Datasets:

bigbio

/

ddi_corpus

like 5

[ { "id": "Naltrexone_ddi__text", "type": "abstract", "text": [ "Studies to evaluate possible interactions between REVIA and drugs other than opiates have not been performed. Consequently, caution is advised if the concomitant administration of REVIA and other drugs is required. The safety and efficacy of concomitant use of REVIA and disulfiram is unknown, and the concomitant use of two potentially hepatotoxic medications is not ordinarily recommended unless the probable benefits outweigh the known risks. Lethargy and somnolence have been reported following doses of REVIA and thioridazine. Patients taking REVIA may not benefit from opioid containing medicines, such as cough and cold preparations, antidiarrheal preparations, and opioid analgesics. In an emergency situation when opioid analgesia must be administered to a patient receiving REVIA, the amount of opioid required may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged." ], "offsets": [ [ 0, 922 ] ] } ]

[ { "id": "Naltrexone_ddi_T1", "type": "BRAND", "text": [ "REVIA" ], "offsets": [ [ 50, 55 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T2", "type": "GROUP", "text": [ "opiates" ], "offsets": [ [ 77, 84 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T3", "type": "BRAND", "text": [ "REVIA" ], "offsets": [ [ 180, 185 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T4", "type": "BRAND", "text": [ "REVIA" ], "offsets": [ [ 261, 266 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T5", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 271, 281 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T6", "type": "BRAND", "text": [ "REVIA" ], "offsets": [ [ 508, 513 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T7", "type": "DRUG", "text": [ "thioridazine" ], "offsets": [ [ 518, 530 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T8", "type": "BRAND", "text": [ "REVIA" ], "offsets": [ [ 548, 553 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T9", "type": "GROUP", "text": [ "opioid" ], "offsets": [ [ 575, 581 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T10", "type": "GROUP", "text": [ "opioid analgesics" ], "offsets": [ [ 673, 690 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T11", "type": "BRAND", "text": [ "REVIA" ], "offsets": [ [ 784, 789 ] ], "normalized": [] }, { "id": "Naltrexone_ddi_T12", "type": "GROUP", "text": [ "opioid" ], "offsets": [ [ 805, 811 ] ], "normalized": [] } ]

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[ { "id": "Naltrexone_ddi_R1", "type": "EFFECT", "arg1_id": "Naltrexone_ddi_T4", "arg2_id": "Naltrexone_ddi_T5", "normalized": [] }, { "id": "Naltrexone_ddi_R2", "type": "EFFECT", "arg1_id": "Naltrexone_ddi_T6", "arg2_id": "Naltrexone_ddi_T7", "normalized": [] }, { "id": "Naltrexone_ddi_R3", "type": "EFFECT", "arg1_id": "Naltrexone_ddi_T8", "arg2_id": "Naltrexone_ddi_T9", "normalized": [] }, { "id": "Naltrexone_ddi_R4", "type": "EFFECT", "arg1_id": "Naltrexone_ddi_T8", "arg2_id": "Naltrexone_ddi_T10", "normalized": [] }, { "id": "Naltrexone_ddi_R5", "type": "EFFECT", "arg1_id": "Naltrexone_ddi_T11", "arg2_id": "Naltrexone_ddi_T12", "normalized": [] } ]

[ { "id": "Cycloserine_ddi__text", "type": "abstract", "text": [ "May interact with wthionamide (Trecator-SC) and isoniazid (Nydrazid)." ], "offsets": [ [ 0, 69 ] ] } ]

[ { "id": "Cycloserine_ddi_T1", "type": "BRAND", "text": [ "Trecator-SC" ], "offsets": [ [ 31, 42 ] ], "normalized": [] }, { "id": "Cycloserine_ddi_T2", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 48, 57 ] ], "normalized": [] }, { "id": "Cycloserine_ddi_T3", "type": "BRAND", "text": [ "Nydrazid" ], "offsets": [ [ 59, 67 ] ], "normalized": [] } ]

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[ { "id": "Ethinamate_ddi__text", "type": "abstract", "text": [ "May interact with addictive medications, especially central nervous system (CNS) depressants with habituating potential (prolonged concurrent use may increase the risk of habituation), alcohol or CNS depression producing medications (concurrent use may increase the CNS depressant effects of either these medications or ethinamate)." ], "offsets": [ [ 0, 332 ] ] } ]

[ { "id": "Ethinamate_ddi_T1", "type": "GROUP", "text": [ "central nervous system (CNS) depressants" ], "offsets": [ [ 52, 92 ] ], "normalized": [] }, { "id": "Ethinamate_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 185, 192 ] ], "normalized": [] }, { "id": "Ethinamate_ddi_T3", "type": "DRUG", "text": [ "ethinamate" ], "offsets": [ [ 320, 330 ] ], "normalized": [] } ]

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[ { "id": "Nesiritide_ddi__text", "type": "abstract", "text": [ "No trials specifically examining potential drug interactions with Natrecor were conducted, although many concomitant drugs were used in clinical trials. No drug interactions were detected except for an increase in symptomatic hypotension in patients receiving oral ACE inhibitors. The co-administration of Natrecor with IV vasodilators such as nitroglycerin, nitroprusside, milrinone, or IV ACE inhibitors has not been evaluated (these drugs were not co-administered with Natrecor in clinical trials)." ], "offsets": [ [ 0, 501 ] ] } ]

[ { "id": "Nesiritide_ddi_T1", "type": "BRAND", "text": [ "Natrecor" ], "offsets": [ [ 66, 74 ] ], "normalized": [] }, { "id": "Nesiritide_ddi_T2", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 265, 279 ] ], "normalized": [] }, { "id": "Nesiritide_ddi_T3", "type": "BRAND", "text": [ "Natrecor" ], "offsets": [ [ 306, 314 ] ], "normalized": [] }, { "id": "Nesiritide_ddi_T4", "type": "GROUP", "text": [ "vasodilators" ], "offsets": [ [ 323, 335 ] ], "normalized": [] }, { "id": "Nesiritide_ddi_T5", "type": "DRUG", "text": [ "nitroglycerin" ], "offsets": [ [ 344, 357 ] ], "normalized": [] }, { "id": "Nesiritide_ddi_T6", "type": "DRUG", "text": [ "nitroprusside" ], "offsets": [ [ 359, 372 ] ], "normalized": [] }, { "id": "Nesiritide_ddi_T7", "type": "DRUG", "text": [ "milrinone" ], "offsets": [ [ 374, 383 ] ], "normalized": [] }, { "id": "Nesiritide_ddi_T8", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 391, 405 ] ], "normalized": [] }, { "id": "Nesiritide_ddi_T9", "type": "BRAND", "text": [ "Natrecor" ], "offsets": [ [ 472, 480 ] ], "normalized": [] } ]

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[ { "id": "Clomipramine_ddi__text", "type": "abstract", "text": [ "The risks of using Anafranil in combination with other drugs have not been systematically evaluated. Given the primary CNS effects of Anafranil, caution is advised in using it concomitantly with other CNS-active drugs. Anafranil should not be used with MAO inhibitors. Close supervision and careful adjustment of dosage are required when Anafranil is administered with anticholinergic or sympathomimetic drugs. Several tricyclic antidepressants have been reported to block the pharmacologic effects of guanethidine, clonidine, or similar agents, and such an effect may be anticipated with CMI because of its structural similarity to other tricyclic antidepressants. The plasma concentration of CMI has been reported to be increased by the concomitant administration of haloperidol; plasma levels of several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. Administration of CMI has been reported to increase the plasma levels of phenobarbital, if given concomitantly. Drugs Metabolized by P450 2D6: The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the aucasian population (about 7%-10% of Caucasians are so-called poor metabolizers); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected lasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCAmay become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, paroxetine, and fluvoxamine, inhibit P450 2D6, they may vary in the extent of inhibition. Fluvoxamine has also been shown to inhibit P450 1A2, an isoform also involved in TCAmetabolism. The extent to which SSRI-TCAinteractions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCAtreatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of agents in the tricyclic antidepressant class (which includes Anafranil) with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant agent or the other drug. Furthermore, whenever one of these drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant agent may be required. It is desirable to monitor TCAplasma levels whenever an agent of the tricyclic antidepressant class including Anafranil is going to be co-administered with another drug known to be an inhibitor of P450 2D6 (and/or P450 1A2). Because Anafranil is highly bound to serum protein, the administration of Anafranil to patients taking other drugs that are highly bound to protein (e.g., warfarin, digoxin) may cause an increase in plasma concentrations of these drugs, potentially resulting in adverse effects. Conversely, adverse effects may result from displacement of protein-bound Anafranil by other highly bound drugs." ], "offsets": [ [ 0, 4295 ] ] } ]

[ { "id": "Clomipramine_ddi_T1", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 19, 28 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T2", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 134, 143 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T3", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 219, 228 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T4", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 253, 267 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T5", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 338, 347 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T6", "type": "GROUP", "text": [ "anticholinergic" ], "offsets": [ [ 369, 384 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T7", "type": "GROUP", "text": [ "sympathomimetic drugs" ], "offsets": [ [ 388, 409 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T8", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 419, 444 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T9", "type": "DRUG", "text": [ "guanethidine" ], "offsets": [ [ 502, 514 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T10", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 516, 525 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T11", "type": "DRUG", "text": [ "CMI" ], "offsets": [ [ 589, 592 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T12", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 639, 664 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T13", "type": "DRUG", "text": [ "CMI" ], "offsets": [ [ 694, 697 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T14", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 769, 780 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T15", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 823, 848 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T16", "type": "DRUG", "text": [ "methylphenidate" ], "offsets": [ [ 921, 936 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T17", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 973, 983 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T18", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 985, 995 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T19", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 1079, 1091 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T20", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1093, 1102 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T21", "type": "DRUG", "text": [ "CMI" ], "offsets": [ [ 1148, 1151 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T22", "type": "DRUG", "text": [ "CMI" ], "offsets": [ [ 1179, 1182 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T23", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1234, 1247 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T24", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 1728, 1753 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T25", "type": "GROUP", "text": [ "TCAs" ], "offsets": [ [ 1755, 1759 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T26", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 1948, 1951 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T27", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 2122, 2125 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T28", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 2312, 2321 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T29", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2323, 2333 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T30", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 2389, 2404 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T31", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 2406, 2420 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T32", "type": "GROUP", "text": [ "Type 1C antiarrhythmics" ], "offsets": [ [ 2430, 2453 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T33", "type": "DRUG", "text": [ "propafenone" ], "offsets": [ [ 2454, 2465 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T34", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 2470, 2480 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T35", "type": "GROUP", "text": [ "selective serotonin reuptake inhibitors" ], "offsets": [ [ 2497, 2536 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T36", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 2538, 2543 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T37", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 2552, 2562 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T38", "type": "DRUG", "text": [ "sertraline" ], "offsets": [ [ 2564, 2574 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T39", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 2576, 2586 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T40", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 2592, 2603 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T41", "type": "DRUG", "text": [ "Fluvoxamine" ], "offsets": [ [ 2666, 2677 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T42", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 2747, 2750 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T43", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 2782, 2786 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T44", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 2787, 2790 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T45", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 2902, 2906 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T46", "type": "GROUP", "text": [ "TCAs" ], "offsets": [ [ 2980, 2984 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T47", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 3001, 3006 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T48", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 3130, 3133 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T49", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 3177, 3187 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T50", "type": "GROUP", "text": [ "tricyclic antidepressant class" ], "offsets": [ [ 3320, 3350 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T51", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 3367, 3376 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T52", "type": "GROUP", "text": [ "tricyclic antidepressant agent" ], "offsets": [ [ 3489, 3519 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T53", "type": "GROUP", "text": [ "tricyclic antidepressant agent" ], "offsets": [ [ 3631, 3661 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T54", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 3706, 3709 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T55", "type": "GROUP", "text": [ "tricyclic antidepressant class" ], "offsets": [ [ 3748, 3778 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T56", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 3789, 3798 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T57", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 3912, 3921 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T58", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 3978, 3987 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T59", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4059, 4067 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T60", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 4069, 4076 ] ], "normalized": [] }, { "id": "Clomipramine_ddi_T61", "type": "BRAND", "text": [ "Anafranil" ], "offsets": [ [ 4257, 4266 ] ], "normalized": [] } ]

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[ { "id": "Clomipramine_ddi_R1", "type": "ADVISE", "arg1_id": "Clomipramine_ddi_T3", "arg2_id": "Clomipramine_ddi_T4", "normalized": [] }, { "id": "Clomipramine_ddi_R2", "type": "ADVISE", "arg1_id": "Clomipramine_ddi_T5", "arg2_id": "Clomipramine_ddi_T6", "normalized": [] }, { "id": "Clomipramine_ddi_R3", "type": "ADVISE", "arg1_id": "Clomipramine_ddi_T5", "arg2_id": "Clomipramine_ddi_T7", "normalized": [] }, { "id": "Clomipramine_ddi_R4", "type": "EFFECT", "arg1_id": "Clomipramine_ddi_T8", "arg2_id": "Clomipramine_ddi_T9", "normalized": [] }, { "id": "Clomipramine_ddi_R5", "type": "EFFECT", "arg1_id": "Clomipramine_ddi_T8", "arg2_id": "Clomipramine_ddi_T10", "normalized": [] }, { "id": "Clomipramine_ddi_R6", "type": "EFFECT", "arg1_id": "Clomipramine_ddi_T8", "arg2_id": "Clomipramine_ddi_T11", "normalized": [] }, { "id": "Clomipramine_ddi_R7", "type": "EFFECT", "arg1_id": "Clomipramine_ddi_T8", "arg2_id": "Clomipramine_ddi_T12", "normalized": [] }, { "id": "Clomipramine_ddi_R8", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T13", "arg2_id": "Clomipramine_ddi_T14", "normalized": [] }, { "id": "Clomipramine_ddi_R9", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T15", "arg2_id": "Clomipramine_ddi_T16", "normalized": [] }, { "id": "Clomipramine_ddi_R10", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T15", "arg2_id": "Clomipramine_ddi_T17", "normalized": [] }, { "id": "Clomipramine_ddi_R11", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T15", "arg2_id": "Clomipramine_ddi_T18", "normalized": [] }, { "id": "Clomipramine_ddi_R12", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T15", "arg2_id": "Clomipramine_ddi_T19", "normalized": [] }, { "id": "Clomipramine_ddi_R13", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T15", "arg2_id": "Clomipramine_ddi_T20", "normalized": [] }, { "id": "Clomipramine_ddi_R14", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T16", "arg2_id": "Clomipramine_ddi_T21", "normalized": [] }, { "id": "Clomipramine_ddi_R15", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T17", "arg2_id": "Clomipramine_ddi_T21", "normalized": [] }, { "id": "Clomipramine_ddi_R16", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T18", "arg2_id": "Clomipramine_ddi_T21", "normalized": [] }, { "id": "Clomipramine_ddi_R17", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T19", "arg2_id": "Clomipramine_ddi_T21", "normalized": [] }, { "id": "Clomipramine_ddi_R18", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T20", "arg2_id": "Clomipramine_ddi_T21", "normalized": [] }, { "id": "Clomipramine_ddi_R19", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T22", "arg2_id": "Clomipramine_ddi_T23", "normalized": [] }, { "id": "Clomipramine_ddi_R20", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T41", "arg2_id": "Clomipramine_ddi_T42", "normalized": [] }, { "id": "Clomipramine_ddi_R21", "type": "INT", "arg1_id": "Clomipramine_ddi_T43", "arg2_id": "Clomipramine_ddi_T44", "normalized": [] }, { "id": "Clomipramine_ddi_R22", "type": "ADVISE", "arg1_id": "Clomipramine_ddi_T46", "arg2_id": "Clomipramine_ddi_T47", "normalized": [] }, { "id": "Clomipramine_ddi_R23", "type": "ADVISE", "arg1_id": "Clomipramine_ddi_T48", "arg2_id": "Clomipramine_ddi_T49", "normalized": [] }, { "id": "Clomipramine_ddi_R24", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T58", "arg2_id": "Clomipramine_ddi_T59", "normalized": [] }, { "id": "Clomipramine_ddi_R25", "type": "MECHANISM", "arg1_id": "Clomipramine_ddi_T58", "arg2_id": "Clomipramine_ddi_T60", "normalized": [] } ]

[ { "id": "Colesevelam_ddi__text", "type": "abstract", "text": [ "WelChol has been studied in several human drug interaction studies in which it was administered with a meal and the test drug. WelChol was found to have no significant effect on the bioavailability of digoxin, lovastatin, metoprolol, quinidine, valproic acid, and warfarin. WelChol decreased the Cmax and AUC of sustained-release verapamil (Calan SR ) by approximately 31% and 11%, respectively. Since there is a high degree of variability in the bioavailability of verapamil, the clinical significance of this finding is unclear. In clinical studies, coadministration of WelChol with atorvastatin, lovastatin, or simvastatin did not interfere with the lipid-lowering activity of the HMG-CoA reductase inhibitor. Other drugs have not been studied. When administering other drugs for which alterations in blood levels could have a clinically significant effect on safety or efficacy, physicians should consider monitoring drug levels or effects." ], "offsets": [ [ 0, 948 ] ] } ]

[ { "id": "Colesevelam_ddi_T1", "type": "BRAND", "text": [ "WelChol" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T2", "type": "BRAND", "text": [ "WelChol" ], "offsets": [ [ 128, 135 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T3", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 203, 210 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T4", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 212, 222 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T5", "type": "DRUG", "text": [ "metoprolol" ], "offsets": [ [ 224, 234 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T6", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 236, 245 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T7", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 247, 260 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T8", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 266, 274 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T9", "type": "BRAND", "text": [ "WelChol" ], "offsets": [ [ 276, 283 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T10", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 333, 342 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T11", "type": "BRAND", "text": [ "Calan SR" ], "offsets": [ [ 344, 352 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T12", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 469, 478 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T13", "type": "BRAND", "text": [ "WelChol" ], "offsets": [ [ 575, 582 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T14", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 589, 601 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T15", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 603, 613 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T16", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 618, 629 ] ], "normalized": [] }, { "id": "Colesevelam_ddi_T17", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitor" ], "offsets": [ [ 688, 715 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Colesevelam_ddi_R1", "type": "MECHANISM", "arg1_id": "Colesevelam_ddi_T9", "arg2_id": "Colesevelam_ddi_T10", "normalized": [] }, { "id": "Colesevelam_ddi_R2", "type": "MECHANISM", "arg1_id": "Colesevelam_ddi_T9", "arg2_id": "Colesevelam_ddi_T11", "normalized": [] } ]

[ { "id": "Emtricitabine_ddi__text", "type": "abstract", "text": [ "The potential for drug interactions with EMTRIVA has been studied in combination with indinavir, stavudine, famciclovir, and tenofovir disoproxil fumarate. There were no clinically significant drug interactions for any of these drugs ." ], "offsets": [ [ 0, 235 ] ] } ]

[ { "id": "Emtricitabine_ddi_T1", "type": "BRAND", "text": [ "EMTRIVA" ], "offsets": [ [ 41, 48 ] ], "normalized": [] }, { "id": "Emtricitabine_ddi_T2", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 86, 95 ] ], "normalized": [] }, { "id": "Emtricitabine_ddi_T3", "type": "DRUG", "text": [ "stavudine" ], "offsets": [ [ 97, 106 ] ], "normalized": [] }, { "id": "Emtricitabine_ddi_T4", "type": "DRUG", "text": [ "famciclovir" ], "offsets": [ [ 108, 119 ] ], "normalized": [] }, { "id": "Emtricitabine_ddi_T5", "type": "DRUG", "text": [ "tenofovir disoproxil fumarate" ], "offsets": [ [ 125, 154 ] ], "normalized": [] } ]

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[ { "id": "Atorvastatin_ddi__text", "type": "abstract", "text": [ "The risk of myopathy during treatment with drugs of this class is increased with concurrent administration of cyclosporine, fibric acid derivatives, niacin (nicotinic acid), erythromycin, azole antifungals. Antacid: When atorvastatin and Maalox TC suspension were coadministered, plasma concentrations of atorvastatin decreased approximately 35%. However, LDL-C reduction was not altered. Antipyrine: Because atorvastatin does not affect the pharmacokinetics of antipyrine, interactions with other drugs metabolized via the same cytochrome isozymes are not expected. Colestipol: Plasma concentrations of atorvastatin decreased approximately 25% when colestipol and atorvastatin were coadministered. However, LDL-C reduction was greater when atorvastatin and colestipol were coadministered than when either drug was given alone. Cimetidine: Atorvastatin plasma concentrations and LDL-C reduction were not altered by coadministration of cimetidine. Digoxin: When multiple doses of atorvastatin and digoxin were coadministered, steady-state plasma digoxin concentrations increased by approximately 20%. Patients taking digoxin should be monitored appropriately. Erythromycin: In healthy individuals, plasma concentrations of atorvastatin increased approximately 40% with coadministration of atorvastatin and erythromycin, a known inhibitor of cytochrome P450 3A4. Oral Contraceptives: Coadministration of atorvastatin and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol by approximately 30% and 20%. These increases should be considered when selecting an oral contraceptive for a woman taking atorvastatin. Warfarin: Atorvastatin had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment. Endocrine Function HMG-CoA reductase inhibitors interfere with cholesterol synthesis and theoretically might blunt adrenal and/or gonadal steroid production. Clinical studies have shown that atorvastatin does not reduce basal plasma cortisol concentration or impair adrenal reserve. The effects of HMG-CoA reductase inhibitors on male fertility have not been studied in adequate numbers of patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Caution should be exercised if an HMG-CoA reductase inhibitor is administered concomitantly with drugs that may decrease the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine. CNS Toxicity Brain hemorrhage was seen in a female dog treated for 3 months at 120 mg/kg/day. Brain hemorrhage and optic nerve vacuolation were seen in another female dog that was sacrificed in moribund condition after 11 weeks of escalating doses up to 280 mg/kg/day. The 120 mg/kg dose resulted in a systemic exposure approximately 16 times the human plasma area-under-the-curve (AUC, 0-24 hours) based on the maximum human dose of 80 mg/day. A single tonic convulsion was seen in each of 2 male dogs (one treated at 10 mg/kg/day and one at 120 mg/kg/day) in a 2-year study. No CNS lesions have been observed in mice after chronic treatment for up to 2 years at doses up to 400 mg/kg/day or in rats at doses up to 100 mg/kg/day. These doses were 6 to 11 times (mouse) and 8 to 16 times (rat) the human AUC (0-24) based on the maximum recommended human dose of 80 mg/day. CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of perivascular spaces, have been observed in dogs treated with other members of this class. A chemically similar drug in this class produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion at a dose that produced plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose." ], "offsets": [ [ 0, 3892 ] ] } ]

[ { "id": "Atorvastatin_ddi_T1", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 110, 122 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T2", "type": "GROUP", "text": [ "fibric acid derivatives" ], "offsets": [ [ 124, 147 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T3", "type": "DRUG", "text": [ "niacin" ], "offsets": [ [ 149, 155 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T4", "type": "DRUG", "text": [ "nicotinic acid" ], "offsets": [ [ 157, 171 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T5", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 174, 186 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T6", "type": "GROUP", "text": [ "azole antifungals" ], "offsets": [ [ 188, 205 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T7", "type": "GROUP", "text": [ "Antacid" ], "offsets": [ [ 207, 214 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T8", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 221, 233 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T9", "type": "BRAND", "text": [ "Maalox TC" ], "offsets": [ [ 238, 247 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T10", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 305, 317 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T11", "type": "DRUG", "text": [ "Antipyrine" ], "offsets": [ [ 389, 399 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T12", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 409, 421 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T13", "type": "DRUG", "text": [ "antipyrine" ], "offsets": [ [ 462, 472 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T14", "type": "DRUG", "text": [ "drugs" ], "offsets": [ [ 498, 503 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T15", "type": "DRUG", "text": [ "Colestipol" ], "offsets": [ [ 567, 577 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T16", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 604, 616 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T17", "type": "DRUG", "text": [ "colestipol" ], "offsets": [ [ 650, 660 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T18", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 665, 677 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T19", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 741, 753 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T20", "type": "DRUG", "text": [ "colestipol" ], "offsets": [ [ 758, 768 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T21", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 828, 838 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T22", "type": "DRUG", "text": [ "Atorvastatin" ], "offsets": [ [ 840, 852 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T23", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 935, 945 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T24", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 947, 954 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T25", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 979, 991 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T26", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 996, 1003 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T27", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1045, 1052 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T28", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1116, 1123 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T29", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 1159, 1171 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T30", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 1222, 1234 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T31", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 1288, 1300 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T32", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1305, 1317 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T33", "type": "GROUP", "text": [ "Contraceptives" ], "offsets": [ [ 1366, 1380 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T34", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 1402, 1414 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T35", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 1427, 1440 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T36", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 1466, 1479 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T37", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 1484, 1501 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T38", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 1592, 1605 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T39", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 1625, 1637 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T40", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 1639, 1647 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T41", "type": "DRUG", "text": [ "Atorvastatin" ], "offsets": [ [ 1649, 1661 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T42", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1767, 1775 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T43", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 1806, 1834 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T44", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 1978, 1990 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T45", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 2085, 2113 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T46", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitor" ], "offsets": [ [ 2308, 2335 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T47", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 2458, 2470 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T48", "type": "DRUG", "text": [ "spironolactone" ], "offsets": [ [ 2472, 2486 ] ], "normalized": [] }, { "id": "Atorvastatin_ddi_T49", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2492, 2502 ] ], "normalized": [] } ]

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[ { "id": "Atorvastatin_ddi_R1", "type": "MECHANISM", "arg1_id": "Atorvastatin_ddi_T8", "arg2_id": "Atorvastatin_ddi_T9", "normalized": [] }, { "id": "Atorvastatin_ddi_R2", "type": "MECHANISM", "arg1_id": "Atorvastatin_ddi_T17", "arg2_id": "Atorvastatin_ddi_T18", "normalized": [] }, { "id": "Atorvastatin_ddi_R3", "type": "EFFECT", "arg1_id": "Atorvastatin_ddi_T19", "arg2_id": "Atorvastatin_ddi_T20", "normalized": [] }, { "id": "Atorvastatin_ddi_R4", "type": "MECHANISM", "arg1_id": "Atorvastatin_ddi_T25", "arg2_id": "Atorvastatin_ddi_T26", "normalized": [] }, { "id": "Atorvastatin_ddi_R5", "type": "MECHANISM", "arg1_id": "Atorvastatin_ddi_T31", "arg2_id": "Atorvastatin_ddi_T32", "normalized": [] }, { "id": "Atorvastatin_ddi_R6", "type": "MECHANISM", "arg1_id": "Atorvastatin_ddi_T34", "arg2_id": "Atorvastatin_ddi_T35", "normalized": [] }, { "id": "Atorvastatin_ddi_R7", "type": "MECHANISM", "arg1_id": "Atorvastatin_ddi_T34", "arg2_id": "Atorvastatin_ddi_T36", "normalized": [] }, { "id": "Atorvastatin_ddi_R8", "type": "MECHANISM", "arg1_id": "Atorvastatin_ddi_T34", "arg2_id": "Atorvastatin_ddi_T37", "normalized": [] }, { "id": "Atorvastatin_ddi_R9", "type": "ADVISE", "arg1_id": "Atorvastatin_ddi_T38", "arg2_id": "Atorvastatin_ddi_T39", "normalized": [] }, { "id": "Atorvastatin_ddi_R10", "type": "ADVISE", "arg1_id": "Atorvastatin_ddi_T46", "arg2_id": "Atorvastatin_ddi_T47", "normalized": [] }, { "id": "Atorvastatin_ddi_R11", "type": "ADVISE", "arg1_id": "Atorvastatin_ddi_T46", "arg2_id": "Atorvastatin_ddi_T48", "normalized": [] }, { "id": "Atorvastatin_ddi_R12", "type": "ADVISE", "arg1_id": "Atorvastatin_ddi_T46", "arg2_id": "Atorvastatin_ddi_T49", "normalized": [] } ]

[ { "id": "Dornase Alfa_ddi__text", "type": "abstract", "text": [ "Clinical trials have indicated that Pulmozyme can be effectively and safely used in conjunction with standard cystic fibrosis therapies including oral, inhaled and/or parenteral antibiotics, bronchodilators, enzyme supplements, vitamins, oral or inhaled corticosteroids, and analgesics. No formal drug interaction studies have been performed." ], "offsets": [ [ 0, 342 ] ] } ]

[ { "id": "Dornase Alfa_ddi_T1", "type": "BRAND", "text": [ "Pulmozyme" ], "offsets": [ [ 36, 45 ] ], "normalized": [] }, { "id": "Dornase Alfa_ddi_T2", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 178, 189 ] ], "normalized": [] }, { "id": "Dornase Alfa_ddi_T3", "type": "GROUP", "text": [ "bronchodilators" ], "offsets": [ [ 191, 206 ] ], "normalized": [] }, { "id": "Dornase Alfa_ddi_T4", "type": "GROUP", "text": [ "vitamins" ], "offsets": [ [ 228, 236 ] ], "normalized": [] }, { "id": "Dornase Alfa_ddi_T5", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 254, 269 ] ], "normalized": [] }, { "id": "Dornase Alfa_ddi_T6", "type": "GROUP", "text": [ "analgesics" ], "offsets": [ [ 275, 285 ] ], "normalized": [] } ]

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[ { "id": "L-Glutamic Acid_ddi__text", "type": "abstract", "text": [ "No well-known drug interactions with glutamic acid" ], "offsets": [ [ 0, 50 ] ] } ]

[ { "id": "L-Glutamic Acid_ddi_T1", "type": "DRUG", "text": [ "glutamic acid" ], "offsets": [ [ 37, 50 ] ], "normalized": [] } ]

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[ { "id": "Letrozole_ddi__text", "type": "abstract", "text": [ "Clinical interaction studies with cimetidine and warfarin indicated that the coadministration of Femara with these drugs does not result in clinically- significant drug interactions. (See CLINICAL PHARMACOLOGY) Coadministration of Femara and tamoxifen 20 mg daily resulted in a reduction of letrozole plasma levels by 38% on average. There is no clinical experience to date on the use of Femara in combination with other anticancer agents. Drug/Laboratory Test-Interactions None observed." ], "offsets": [ [ 0, 488 ] ] } ]

[ { "id": "Letrozole_ddi_T1", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 34, 44 ] ], "normalized": [] }, { "id": "Letrozole_ddi_T2", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 49, 57 ] ], "normalized": [] }, { "id": "Letrozole_ddi_T3", "type": "BRAND", "text": [ "Femara" ], "offsets": [ [ 97, 103 ] ], "normalized": [] }, { "id": "Letrozole_ddi_T4", "type": "BRAND", "text": [ "Femara" ], "offsets": [ [ 231, 237 ] ], "normalized": [] }, { "id": "Letrozole_ddi_T5", "type": "DRUG", "text": [ "tamoxifen" ], "offsets": [ [ 242, 251 ] ], "normalized": [] }, { "id": "Letrozole_ddi_T6", "type": "DRUG", "text": [ "letrozole" ], "offsets": [ [ 291, 300 ] ], "normalized": [] }, { "id": "Letrozole_ddi_T7", "type": "BRAND", "text": [ "Femara" ], "offsets": [ [ 388, 394 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Letrozole_ddi_R1", "type": "MECHANISM", "arg1_id": "Letrozole_ddi_T4", "arg2_id": "Letrozole_ddi_T5", "normalized": [] } ]

[ { "id": "Dichlorphenamide_ddi__text", "type": "abstract", "text": [ "Caution is advised in patients receiving concomitant high-dose aspirin and carbonic anhydrase inhibitors, as anorexia, tachypnea, lethargy and coma have been rarely reported due to a possible drug interaction." ], "offsets": [ [ 0, 209 ] ] } ]

[ { "id": "Dichlorphenamide_ddi_T1", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 63, 70 ] ], "normalized": [] }, { "id": "Dichlorphenamide_ddi_T2", "type": "GROUP", "text": [ "carbonic anhydrase inhibitors" ], "offsets": [ [ 75, 104 ] ], "normalized": [] } ]

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[]

[ { "id": "Dichlorphenamide_ddi_R1", "type": "ADVISE", "arg1_id": "Dichlorphenamide_ddi_T1", "arg2_id": "Dichlorphenamide_ddi_T2", "normalized": [] } ]

[ { "id": "Nafarelin_ddi__text", "type": "abstract", "text": [ "No pharmacokinetic-based drug-drug interaction studies have been conducted with SYNAREL. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, and the drug is only about 80% bound to plasma proteins at 4 C, drug interactions would not be expected to occur." ], "offsets": [ [ 0, 327 ] ] } ]

[ { "id": "Nafarelin_ddi_T1", "type": "BRAND", "text": [ "SYNAREL" ], "offsets": [ [ 80, 87 ] ], "normalized": [] }, { "id": "Nafarelin_ddi_T2", "type": "DRUG", "text": [ "nafarelin acetate" ], "offsets": [ [ 106, 123 ] ], "normalized": [] } ]

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[ { "id": "Clavulanate_ddi__text", "type": "abstract", "text": [ "The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. In controlled clinical trials of AUGMENTIN XR, 22 patients received concomitant allopurinol and AUGMENTIN XR. No rashes were reported in these patients. However, this sample size is too small to allow for any conclusions to be drawn regarding the risk of rashes with concomitant AUGMENTIN XR and allopurinol use. In common with other broad-spectrum antibiotics, AUGMENTIN XR may reduce the efficacy of oral contraceptives" ], "offsets": [ [ 0, 747 ] ] } ]

[ { "id": "Clavulanate_ddi_T1", "type": "DRUG", "text": [ "allopurinol" ], "offsets": [ [ 33, 44 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T2", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 49, 59 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T3", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 175, 185 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T4", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 238, 248 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T5", "type": "DRUG", "text": [ "allopurinol" ], "offsets": [ [ 266, 277 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T6", "type": "BRAND", "text": [ "AUGMENTIN XR" ], "offsets": [ [ 359, 371 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T7", "type": "DRUG", "text": [ "allopurinol" ], "offsets": [ [ 406, 417 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T8", "type": "BRAND", "text": [ "AUGMENTIN XR" ], "offsets": [ [ 422, 434 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T9", "type": "BRAND", "text": [ "AUGMENTIN XR" ], "offsets": [ [ 605, 617 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T10", "type": "DRUG", "text": [ "allopurinol" ], "offsets": [ [ 622, 633 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T11", "type": "GROUP", "text": [ "broad-spectrum antibiotics" ], "offsets": [ [ 660, 686 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T12", "type": "BRAND", "text": [ "AUGMENTIN XR" ], "offsets": [ [ 688, 700 ] ], "normalized": [] }, { "id": "Clavulanate_ddi_T13", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 733, 747 ] ], "normalized": [] } ]

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[]

[ { "id": "Clavulanate_ddi_R1", "type": "EFFECT", "arg1_id": "Clavulanate_ddi_T1", "arg2_id": "Clavulanate_ddi_T2", "normalized": [] }, { "id": "Clavulanate_ddi_R2", "type": "EFFECT", "arg1_id": "Clavulanate_ddi_T4", "arg2_id": "Clavulanate_ddi_T5", "normalized": [] }, { "id": "Clavulanate_ddi_R3", "type": "EFFECT", "arg1_id": "Clavulanate_ddi_T11", "arg2_id": "Clavulanate_ddi_T13", "normalized": [] }, { "id": "Clavulanate_ddi_R4", "type": "EFFECT", "arg1_id": "Clavulanate_ddi_T12", "arg2_id": "Clavulanate_ddi_T13", "normalized": [] } ]

[ { "id": "Crotamiton_ddi__text", "type": "abstract", "text": [ "None known." ], "offsets": [ [ 0, 11 ] ] } ]

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[ { "id": "Diatrizoate_ddi__text", "type": "abstract", "text": [ "May interact with thyroid medication (e.g., levothyroxine), iodine-containing products, antacids, H2-antagonists (e.g., famotidine, ranitidine), and proton pump inhibitors (e.g., lansoprazole, omeprazole). This product can affect the results of certain lab tests." ], "offsets": [ [ 0, 263 ] ] } ]

[ { "id": "Diatrizoate_ddi_T1", "type": "DRUG", "text": [ "levothyroxine" ], "offsets": [ [ 44, 57 ] ], "normalized": [] }, { "id": "Diatrizoate_ddi_T2", "type": "DRUG", "text": [ "iodine" ], "offsets": [ [ 60, 66 ] ], "normalized": [] }, { "id": "Diatrizoate_ddi_T3", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 88, 96 ] ], "normalized": [] }, { "id": "Diatrizoate_ddi_T4", "type": "GROUP", "text": [ "H2-antagonists" ], "offsets": [ [ 98, 112 ] ], "normalized": [] }, { "id": "Diatrizoate_ddi_T5", "type": "DRUG", "text": [ "famotidine" ], "offsets": [ [ 120, 130 ] ], "normalized": [] }, { "id": "Diatrizoate_ddi_T6", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 132, 142 ] ], "normalized": [] }, { "id": "Diatrizoate_ddi_T7", "type": "GROUP", "text": [ "proton pump inhibitors" ], "offsets": [ [ 149, 171 ] ], "normalized": [] }, { "id": "Diatrizoate_ddi_T8", "type": "DRUG", "text": [ "lansoprazole" ], "offsets": [ [ 179, 191 ] ], "normalized": [] }, { "id": "Diatrizoate_ddi_T9", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 193, 203 ] ], "normalized": [] } ]

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[ { "id": "Glibenclamide_ddi__text", "type": "abstract", "text": [ "The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving MICRONASE, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving MICRONASE, the patient should be observed closely for loss of control. Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phe-nothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimet-ics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving MICRONASE, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving MICRONASE, the patient should be observed closely for hypoglycemia. A possible interaction between glyburide and ciprofloxacin, a fluoroquinolone antibiotic, has been reported, resulting in a potentiation of the hypoglycemic action of glyburide. The mechanism for this interaction is not known. A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical or vaginal preparations of miconazole is not known. Metformin: In a single-dose interaction study in NIDDM subjects, decreases in glyburide AUC and Cmax were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmaco-dynamic effects, makes the clinical significance of this interaction uncertain. Coadministration of gly-buride and metformin did not result in any changes in either metformin pharmacokinetics or pharmaco-dynamics." ], "offsets": [ [ 0, 2052 ] ] } ]

[ { "id": "Glibenclamide_ddi_T1", "type": "GROUP", "text": [ "sulfonylureas" ], "offsets": [ [ 27, 40 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T2", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 87, 124 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T3", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 172, 183 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T4", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 185, 197 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T5", "type": "DRUG", "text": [ "chloramphenicol" ], "offsets": [ [ 199, 214 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T6", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 216, 226 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T7", "type": "GROUP", "text": [ "coumarins" ], "offsets": [ [ 228, 237 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T8", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 239, 267 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T9", "type": "GROUP", "text": [ "beta adrenergic blocking agents" ], "offsets": [ [ 273, 304 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T10", "type": "BRAND", "text": [ "MICRONASE" ], "offsets": [ [ 362, 371 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T11", "type": "BRAND", "text": [ "MICRONASE" ], "offsets": [ [ 485, 494 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T12", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 657, 666 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T13", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 677, 686 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T14", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 688, 703 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T15", "type": "GROUP", "text": [ "thyroid products" ], "offsets": [ [ 722, 738 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T16", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 740, 749 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T17", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 756, 770 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T18", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 772, 781 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T19", "type": "DRUG", "text": [ "nicotinic acid" ], "offsets": [ [ 783, 797 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T20", "type": "GROUP", "text": [ "calcium channel blocking drugs" ], "offsets": [ [ 818, 848 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T21", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 854, 863 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T22", "type": "BRAND", "text": [ "MICRONASE" ], "offsets": [ [ 921, 930 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T23", "type": "BRAND", "text": [ "MICRONASE" ], "offsets": [ [ 1047, 1056 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T24", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 1146, 1155 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T25", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 1160, 1173 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T26", "type": "GROUP", "text": [ "fluoroquinolone antibiotic" ], "offsets": [ [ 1177, 1203 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T27", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 1282, 1291 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T28", "type": "DRUG", "text": [ "miconazole" ], "offsets": [ [ 1379, 1389 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T29", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 1399, 1418 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T30", "type": "DRUG", "text": [ "miconazole" ], "offsets": [ [ 1563, 1573 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T31", "type": "DRUG", "text": [ "Metformin" ], "offsets": [ [ 1588, 1597 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T32", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 1666, 1675 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T33", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 1803, 1812 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T34", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 1954, 1963 ] ], "normalized": [] }, { "id": "Glibenclamide_ddi_T35", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 2004, 2013 ] ], "normalized": [] } ]

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[ { "id": "Glibenclamide_ddi_R1", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T1", "arg2_id": "Glibenclamide_ddi_T2", "normalized": [] }, { "id": "Glibenclamide_ddi_R2", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T1", "arg2_id": "Glibenclamide_ddi_T3", "normalized": [] }, { "id": "Glibenclamide_ddi_R3", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T1", "arg2_id": "Glibenclamide_ddi_T4", "normalized": [] }, { "id": "Glibenclamide_ddi_R4", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T1", "arg2_id": "Glibenclamide_ddi_T5", "normalized": [] }, { "id": "Glibenclamide_ddi_R5", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T1", "arg2_id": "Glibenclamide_ddi_T6", "normalized": [] }, { "id": "Glibenclamide_ddi_R6", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T1", "arg2_id": "Glibenclamide_ddi_T7", "normalized": [] }, { "id": "Glibenclamide_ddi_R7", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T1", "arg2_id": "Glibenclamide_ddi_T8", "normalized": [] }, { "id": "Glibenclamide_ddi_R8", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T1", "arg2_id": "Glibenclamide_ddi_T9", "normalized": [] }, { "id": "Glibenclamide_ddi_R9", "type": "INT", "arg1_id": "Glibenclamide_ddi_T24", "arg2_id": "Glibenclamide_ddi_T25", "normalized": [] }, { "id": "Glibenclamide_ddi_R10", "type": "EFFECT", "arg1_id": "Glibenclamide_ddi_T28", "arg2_id": "Glibenclamide_ddi_T29", "normalized": [] } ]

[ { "id": "Adinazolam_ddi__text", "type": "abstract", "text": [ "Co-administration with antifungal agents such as ketoconazole or itraconazole is not recommended. Nafazodone, fluvoxamine, cimetidine (consider Xanax dose reduction). Fluoxetine, OCs, sertraline, diltiazem, macrolide antibiotics (exercise caution)." ], "offsets": [ [ 0, 248 ] ] } ]

[ { "id": "Adinazolam_ddi_T1", "type": "GROUP", "text": [ "antifungal agents" ], "offsets": [ [ 23, 40 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T2", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 49, 61 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T3", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 65, 77 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T4", "type": "DRUG", "text": [ "Nafazodone" ], "offsets": [ [ 98, 108 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T5", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 110, 121 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T6", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 123, 133 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T7", "type": "BRAND", "text": [ "Xanax" ], "offsets": [ [ 144, 149 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T8", "type": "DRUG", "text": [ "Fluoxetine" ], "offsets": [ [ 167, 177 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T9", "type": "GROUP", "text": [ "OCs" ], "offsets": [ [ 179, 182 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T10", "type": "DRUG", "text": [ "sertraline" ], "offsets": [ [ 184, 194 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T11", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 196, 205 ] ], "normalized": [] }, { "id": "Adinazolam_ddi_T12", "type": "GROUP", "text": [ "macrolide antibiotics" ], "offsets": [ [ 207, 228 ] ], "normalized": [] } ]

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[]

[ { "id": "Adinazolam_ddi_R1", "type": "ADVISE", "arg1_id": "Adinazolam_ddi_T4", "arg2_id": "Adinazolam_ddi_T7", "normalized": [] }, { "id": "Adinazolam_ddi_R2", "type": "ADVISE", "arg1_id": "Adinazolam_ddi_T5", "arg2_id": "Adinazolam_ddi_T7", "normalized": [] }, { "id": "Adinazolam_ddi_R3", "type": "ADVISE", "arg1_id": "Adinazolam_ddi_T6", "arg2_id": "Adinazolam_ddi_T7", "normalized": [] } ]

[ { "id": "Acarbose_ddi__text", "type": "abstract", "text": [ "Certain drugs tend to produce hyperglycemia and may lead to loss of blood glucose control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel-blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Acarbose, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from patients receiving Acarbose in combination with sulfonylureas or insulin, patients should be observed closely for any evidence of hypoglycemia. Intestinal adsorbents (e. g., charcoal) and digestive enzyme preparations containing carbohydrate-splitting enzymes (e. g., amylase, pancreatin) may reduce the effect of Acarbose and should not be taken concomitantly. Acarbose has been shown to change the bioavailabillty digoxin when they are co-administered, which may require digoxin dose adjustment. Studies in healthy volunteers have shown that Acarbose has no effect on either the pharmacokinetics or pharmacodynamics of digoxin, nifedipine, propranolol, or ranitidine. Acarbose did not interfere with the absorption or disposition of the sulfonylurea glyburide in diabetic patients. Acarbose may affect digoxin bioavailabillty and may require dose adjustment of digoxin by 16% (90% confidence interval: 8-23%), decrease mean C max digoxin by 26% (90% confidence interval: 16-34%) and decrease mean trough concentrations of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). The amount of metformin absorbed while taking Acarbose was bioequivalent to the amount absorbed when taking placebo, as indicated by the plasma AUC values. However, the peak plasma level of metformin was reduced by approximately 20% when taking Acarbose due to a slight delay in the absorption of metformin. There is little if any clinically significant interaction between Acarbose and metformin." ], "offsets": [ [ 0, 1984 ] ] } ]

[ { "id": "Acarbose_ddi_T1", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 115, 124 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T2", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 135, 144 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T3", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 146, 161 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T4", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 163, 177 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T5", "type": "GROUP", "text": [ "thyroid products" ], "offsets": [ [ 179, 195 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T6", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 197, 206 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T7", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 213, 227 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T8", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 229, 238 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T9", "type": "DRUG", "text": [ "nicotinic acid" ], "offsets": [ [ 240, 254 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T10", "type": "GROUP", "text": [ "sympathomimetics" ], "offsets": [ [ 256, 272 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T11", "type": "GROUP", "text": [ "calcium channel-blocking drugs" ], "offsets": [ [ 274, 304 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T12", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 310, 319 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T13", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 377, 385 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T14", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 515, 523 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T15", "type": "GROUP", "text": [ "sulfonylureas" ], "offsets": [ [ 544, 557 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T16", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 561, 568 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T17", "type": "GROUP", "text": [ "Intestinal adsorbents" ], "offsets": [ [ 640, 661 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T18", "type": "DRUG", "text": [ "charcoal" ], "offsets": [ [ 670, 678 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T19", "type": "GROUP", "text": [ "digestive enzyme preparations" ], "offsets": [ [ 684, 713 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T20", "type": "DRUG", "text": [ "amylase" ], "offsets": [ [ 764, 771 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T21", "type": "DRUG", "text": [ "pancreatin" ], "offsets": [ [ 773, 783 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T22", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 810, 818 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T23", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 858, 866 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T24", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 912, 919 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T25", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 969, 976 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T26", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 1040, 1048 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T27", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1117, 1124 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T28", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 1126, 1136 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T29", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1138, 1149 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T30", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 1154, 1164 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T31", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 1166, 1174 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T32", "type": "DRUG", "text": [ "sulfonylurea" ], "offsets": [ [ 1235, 1247 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T33", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 1248, 1257 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T34", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 1280, 1288 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T35", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1300, 1307 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T36", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1359, 1366 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T37", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1428, 1435 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T38", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1520, 1527 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T39", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 1601, 1610 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T40", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 1633, 1641 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T41", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 1777, 1786 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T42", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 1832, 1840 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T43", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 1884, 1893 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T44", "type": "DRUG", "text": [ "Acarbose" ], "offsets": [ [ 1961, 1969 ] ], "normalized": [] }, { "id": "Acarbose_ddi_T45", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 1974, 1983 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Acarbose_ddi_R1", "type": "MECHANISM", "arg1_id": "Acarbose_ddi_T17", "arg2_id": "Acarbose_ddi_T22", "normalized": [] }, { "id": "Acarbose_ddi_R2", "type": "MECHANISM", "arg1_id": "Acarbose_ddi_T18", "arg2_id": "Acarbose_ddi_T22", "normalized": [] }, { "id": "Acarbose_ddi_R3", "type": "MECHANISM", "arg1_id": "Acarbose_ddi_T20", "arg2_id": "Acarbose_ddi_T22", "normalized": [] }, { "id": "Acarbose_ddi_R4", "type": "MECHANISM", "arg1_id": "Acarbose_ddi_T21", "arg2_id": "Acarbose_ddi_T22", "normalized": [] }, { "id": "Acarbose_ddi_R5", "type": "MECHANISM", "arg1_id": "Acarbose_ddi_T23", "arg2_id": "Acarbose_ddi_T24", "normalized": [] }, { "id": "Acarbose_ddi_R6", "type": "MECHANISM", "arg1_id": "Acarbose_ddi_T41", "arg2_id": "Acarbose_ddi_T42", "normalized": [] }, { "id": "Acarbose_ddi_R7", "type": "MECHANISM", "arg1_id": "Acarbose_ddi_T42", "arg2_id": "Acarbose_ddi_T43", "normalized": [] } ]

[ { "id": "Labetalol_ddi__text", "type": "abstract", "text": [ "In one survey, 2.3% of patients taking labetalol HCl in combination with tricyclic antidepressants experienced tremor, as compared to 0.7% reported to occur with labetalol HCl alone. The contribution of each of the treatments to this adverse reaction is unknown but the possibility of a drug interaction cannot be excluded. Drugs possessing beta-blocking properties can blunt the bronchodilator effect of beta-receptor agonist drugs in patients with bronchospasm; therefore, doses greater than the normal antiasthmatic dose of beta-agonist bronchodilator drugs may be required. Cimetidine has been shown to increase the bioavailability of labetalol HCl. Since this could be explained either by enhanced absorption or by an alteration of hepatic metabolism of labetalol HCl, special care should be used in establishing the dose required for blood pressure control in such patients. Synergism has been shown between halothane anesthesia and intravenously administered labetalol HCl. During controlled hypotensive anesthesia using labetalol HCl in association with halothane, high concentrations (3% or above) of halothane should not be used because the degree of hypotension will be increased and because of the possibility of a large reduction in cardiac output and an increase in central venous pressure. The anesthesiologist should be informed when a patient is receiving labetalol HCl. Labetalol HCl blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. If labetalol HCl is used with nitroglycerin in patients with angina pectoris, additional antihypertensive effects may occur. Care should be taken if labetalol is used concomitantly with calcium antagonists of the verapamil type. Risk of Anaphylactic Reaction While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. Drug/Laboratory Test Interactions The presence of labetalol metabolites in the urine may result in falsely elevated levels of urinary catecholamines, metanephrine, normetanephrine and vanillylmandelic acid when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with labetalol HCl, a specific method, such as a high performance liquid chromatographic assay with solid phase extraction (e.g., J Chromatogr 385:241,1987) should be employed in determining levels of catecholamines. Labetalol HCl has also been reported to produce a false positive test for amphetamine when screening urine for the presence of drugs using the commercially available assay methods Toxi-Lab A (thin-layer chromatographic assay) and Emit-d.a.u. (radioenzymatic assay). When patients being treated with labetalol have a positive urine test for amphetamine using these techniques confirmation should be made by using more specific methods such as a gas chromatographic-mass spectrometer technique." ], "offsets": [ [ 0, 3112 ] ] } ]

[ { "id": "Labetalol_ddi_T1", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 39, 52 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T2", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 73, 98 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T3", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 162, 175 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T4", "type": "GROUP", "text": [ "beta-receptor agonist drugs" ], "offsets": [ [ 405, 432 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T5", "type": "GROUP", "text": [ "beta-agonist bronchodilator drugs" ], "offsets": [ [ 527, 560 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T6", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 578, 588 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T7", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 639, 652 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T8", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 759, 772 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T9", "type": "DRUG", "text": [ "halothane" ], "offsets": [ [ 914, 923 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T10", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 966, 979 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T11", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 1028, 1041 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T12", "type": "DRUG", "text": [ "halothane" ], "offsets": [ [ 1062, 1071 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T13", "type": "DRUG", "text": [ "halothane" ], "offsets": [ [ 1110, 1119 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T14", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 1373, 1386 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T15", "type": "DRUG", "text": [ "Labetalol HCl" ], "offsets": [ [ 1388, 1401 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T16", "type": "DRUG", "text": [ "nitroglycerin" ], "offsets": [ [ 1444, 1457 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T17", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 1504, 1517 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T18", "type": "DRUG", "text": [ "nitroglycerin" ], "offsets": [ [ 1531, 1544 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T19", "type": "DRUG", "text": [ "labetalol" ], "offsets": [ [ 1650, 1659 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T20", "type": "GROUP", "text": [ "calcium antagonist" ], "offsets": [ [ 1687, 1705 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T21", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 1714, 1723 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T22", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 1773, 1786 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T23", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 2017, 2028 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T24", "type": "DRUG", "text": [ "labetalol HCl" ], "offsets": [ [ 2406, 2419 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T25", "type": "DRUG", "text": [ "Labetalol HCl" ], "offsets": [ [ 2618, 2631 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T26", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 2692, 2703 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T27", "type": "DRUG", "text": [ "labetalol" ], "offsets": [ [ 2919, 2928 ] ], "normalized": [] }, { "id": "Labetalol_ddi_T28", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 2960, 2971 ] ], "normalized": [] } ]

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[ { "id": "Labetalol_ddi_R1", "type": "EFFECT", "arg1_id": "Labetalol_ddi_T1", "arg2_id": "Labetalol_ddi_T2", "normalized": [] }, { "id": "Labetalol_ddi_R2", "type": "MECHANISM", "arg1_id": "Labetalol_ddi_T6", "arg2_id": "Labetalol_ddi_T7", "normalized": [] }, { "id": "Labetalol_ddi_R3", "type": "EFFECT", "arg1_id": "Labetalol_ddi_T9", "arg2_id": "Labetalol_ddi_T10", "normalized": [] }, { "id": "Labetalol_ddi_R4", "type": "EFFECT", "arg1_id": "Labetalol_ddi_T11", "arg2_id": "Labetalol_ddi_T12", "normalized": [] }, { "id": "Labetalol_ddi_R5", "type": "EFFECT", "arg1_id": "Labetalol_ddi_T15", "arg2_id": "Labetalol_ddi_T16", "normalized": [] }, { "id": "Labetalol_ddi_R6", "type": "EFFECT", "arg1_id": "Labetalol_ddi_T17", "arg2_id": "Labetalol_ddi_T18", "normalized": [] }, { "id": "Labetalol_ddi_R7", "type": "ADVISE", "arg1_id": "Labetalol_ddi_T19", "arg2_id": "Labetalol_ddi_T20", "normalized": [] } ]

[ { "id": "Diphenidol_ddi__text", "type": "abstract", "text": [ "CNS depression producing medications - concurrent use may potentiate the effects of either these medications or diphenidol; anticholinergics or other medications with anticholinergic activity - anticholinergic effects may be potentiated when these medications are used concurrently with diphenidol; apomorphine - prior ingestion of diphenidol may decrease the emetic response to apomorphine in the treatment of poisoning." ], "offsets": [ [ 0, 421 ] ] } ]

[ { "id": "Diphenidol_ddi_T1", "type": "DRUG", "text": [ "diphenidol" ], "offsets": [ [ 112, 122 ] ], "normalized": [] }, { "id": "Diphenidol_ddi_T2", "type": "GROUP", "text": [ "anticholinergics" ], "offsets": [ [ 124, 140 ] ], "normalized": [] }, { "id": "Diphenidol_ddi_T3", "type": "DRUG", "text": [ "diphenidol" ], "offsets": [ [ 287, 297 ] ], "normalized": [] }, { "id": "Diphenidol_ddi_T4", "type": "DRUG", "text": [ "apomorphine" ], "offsets": [ [ 299, 310 ] ], "normalized": [] }, { "id": "Diphenidol_ddi_T5", "type": "DRUG", "text": [ "diphenidol" ], "offsets": [ [ 332, 342 ] ], "normalized": [] }, { "id": "Diphenidol_ddi_T6", "type": "GROUP", "text": [ "emetic" ], "offsets": [ [ 360, 366 ] ], "normalized": [] }, { "id": "Diphenidol_ddi_T7", "type": "DRUG", "text": [ "apomorphine" ], "offsets": [ [ 379, 390 ] ], "normalized": [] } ]

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[ { "id": "Diphenidol_ddi_R1", "type": "EFFECT", "arg1_id": "Diphenidol_ddi_T5", "arg2_id": "Diphenidol_ddi_T7", "normalized": [] } ]

[ { "id": "Fondaparinux sodium_ddi__text", "type": "abstract", "text": [ "In clinical studies performed with Fondaparinux, the concomitant use of oral anticoagulants (warfarin), platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam), and digoxin did not significantly affect the pharmacokinetics/pharmacodynamics of fondaparinux sodium. In addition, Fondaparinux neither influenced the pharmacodynamics of warfarin, acetylsalicylic acid, piroxicam, and digoxin, nor the pharmacokinetics of digoxin at steady state. Agents that may enhance the risk of hemorrhage should be discontinued prior to initiation of Fondaparinux therapy. If co-administration is essential, close monitoring may be appropriate. In an in vitro study in human liver microsomes, inhibition of CYP2A6 hydroxylation of coumarin by fondaparinux (200 m m M i.e., 350 mg/L) was 17-28%. Inhibition of the other isozymes evaluated (CYPs 2A1, 2C9, 2C19, 2D6, 3A4, and 3E1) was 0-16%. Since fondaparinux does not markedly inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4) in vitro, fondaparinux sodium is not expected to significantly interact with other drugs in vivo by inhibition of metabolism mediated by these isozymes. Since fondaparinux sodium does not bind significantly to plasma proteins other than ATIII, no drug interactions by protein-binding displacement are expected." ], "offsets": [ [ 0, 1305 ] ] } ]

[ { "id": "Fondaparinux sodium_ddi_T1", "type": "DRUG", "text": [ "Fondaparinux" ], "offsets": [ [ 35, 47 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T2", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 77, 91 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 93, 101 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T4", "type": "GROUP", "text": [ "platelet inhibitors" ], "offsets": [ [ 104, 123 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T5", "type": "DRUG", "text": [ "acetylsalicylic acid" ], "offsets": [ [ 125, 145 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T6", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 148, 154 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T7", "type": "DRUG", "text": [ "piroxicam" ], "offsets": [ [ 156, 165 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T8", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 172, 179 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T9", "type": "DRUG", "text": [ "fondaparinux sodium" ], "offsets": [ [ 250, 269 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T10", "type": "DRUG", "text": [ "Fondaparinux" ], "offsets": [ [ 284, 296 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T11", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 340, 348 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T12", "type": "DRUG", "text": [ "acetylsalicylic acid" ], "offsets": [ [ 350, 370 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T13", "type": "DRUG", "text": [ "piroxicam" ], "offsets": [ [ 372, 381 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T14", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 387, 394 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T15", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 424, 431 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T16", "type": "DRUG", "text": [ "Fondaparinux" ], "offsets": [ [ 542, 554 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T17", "type": "GROUP", "text": [ "coumarin" ], "offsets": [ [ 722, 730 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T18", "type": "DRUG", "text": [ "fondaparinux" ], "offsets": [ [ 734, 746 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T19", "type": "DRUG", "text": [ "fondaparinux" ], "offsets": [ [ 887, 899 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T20", "type": "DRUG", "text": [ "fondaparinux sodium" ], "offsets": [ [ 1005, 1024 ] ], "normalized": [] }, { "id": "Fondaparinux sodium_ddi_T21", "type": "DRUG", "text": [ "fondaparinux sodium" ], "offsets": [ [ 1154, 1173 ] ], "normalized": [] } ]

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[ { "id": "Fondaparinux sodium_ddi_R1", "type": "MECHANISM", "arg1_id": "Fondaparinux sodium_ddi_T17", "arg2_id": "Fondaparinux sodium_ddi_T18", "normalized": [] } ]

[ { "id": "Famotidine_ddi__text", "type": "abstract", "text": [ "No drug interactions have been identified. Studies with famotidine in man, in animal models, and in vitro have shown no significant interference with the disposition of compounds metabolized by the hepatic microsomal enzymes, e.g., cytochrome P450 system. Compounds tested in man include warfarin, theophylline, phenytoin, diazepam, aminopyrine and antipyrine. Indocyanine green as an index of hepatic drug extraction has been tested and no significant effects have been found." ], "offsets": [ [ 0, 477 ] ] } ]

[ { "id": "Famotidine_ddi_T1", "type": "DRUG", "text": [ "famotidine" ], "offsets": [ [ 56, 66 ] ], "normalized": [] }, { "id": "Famotidine_ddi_T2", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 288, 296 ] ], "normalized": [] }, { "id": "Famotidine_ddi_T3", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 298, 310 ] ], "normalized": [] }, { "id": "Famotidine_ddi_T4", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 312, 321 ] ], "normalized": [] }, { "id": "Famotidine_ddi_T5", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 323, 331 ] ], "normalized": [] }, { "id": "Famotidine_ddi_T6", "type": "DRUG", "text": [ "aminopyrine" ], "offsets": [ [ 333, 344 ] ], "normalized": [] }, { "id": "Famotidine_ddi_T7", "type": "DRUG", "text": [ "antipyrine" ], "offsets": [ [ 349, 359 ] ], "normalized": [] }, { "id": "Famotidine_ddi_T8", "type": "DRUG_N", "text": [ "Indocyanine green" ], "offsets": [ [ 361, 378 ] ], "normalized": [] } ]

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[ { "id": "Estazolam_ddi__text", "type": "abstract", "text": [ "If ProSom is given concomitantly with other drugs acting on the central nervous system, careful consideration should be given to the pharmacology of all agents. The action of the benzodiazepines may be potentiated by anticonvulsants, antihistamines, alcohol, barbiturates, monoamine oxidase inhibitors, narcotics, phenothiazines, psychotropic medications, or other drugs that produce CNS depression. Smokers have an increased clearance of benzodiazepines as compared to nonsmokers; this was seen in studies with estazolam. While no in vivo drug-drug interaction studies were conducted between estazolam and inducers of CYP3A, compounds that are potent CYP3A inducers (such as carbamazepine, phenytoin, rifampin, and barbiturates) would be expected to decrease estazolam concentrations. Estazolam: Interaction with Drugs that Inhibit Metabolism via Cytochrome P450 3A (CYP3A): The metabolism of estazolam to the major circulating metabolite 4-hydroxy-estazolam and the metabolism of other triazolobenzodiazepines is catalyzed by CYP3A. Consequently, estazolam should be avoided in patients receiving ketoconazole and itraconazole, which are very potent inhibitors of CYP3A. With drugs inhibiting CYP3A to a lesser, but still significant degree, estazolam should be used only with caution and consideration of appropriate dosage reduction. The following are examples of drugs known to inhibit the metabolism of other related benzodiazepines, presumably through inhibition of CYP3A: nefazodone, fluvoxamine, cimetidine, diltiazem, isoniazide, and some macrolide antibiotics. Drug Interaction with Fluoxetine: A multiple-dose study was conducted to assess the effect of fluoxetine 20 mg BID on the pharmacokinetics of estazolam 2 mg QHS after seven days. The pharmacokinetics of estazolam (Cmax and AUC) were not affected during multiple-dose fluoxetine, suggesting no clinically significant pharmacokinetic interaction. Estazolam: Interaction with Other Drugs that are Metabolized by Cytochrome P450 (CYP): At clinically relevant concentrations, in vitro studies indicate that estazolam (0.6 M) was not inhibitory towards the major cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A. Therefore, based on these in vitro data, estazolam is very unlikely to inhibit the biotransformation of other drugs metabolized by these CYP isoforms ." ], "offsets": [ [ 0, 2365 ] ] } ]

[ { "id": "Estazolam_ddi_T1", "type": "BRAND", "text": [ "ProSom" ], "offsets": [ [ 3, 9 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T2", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 179, 194 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T3", "type": "GROUP", "text": [ "anticonvulsants" ], "offsets": [ [ 217, 232 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T4", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 234, 248 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T5", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 250, 257 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T6", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 259, 271 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T7", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 273, 301 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T8", "type": "GROUP", "text": [ "narcotics" ], "offsets": [ [ 303, 312 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T9", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 314, 328 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T10", "type": "GROUP", "text": [ "psychotropic medications" ], "offsets": [ [ 330, 354 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T11", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 439, 454 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T12", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 512, 521 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T13", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 593, 602 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T14", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 676, 689 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T15", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 691, 700 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T16", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 702, 710 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T17", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 716, 728 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T18", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 760, 769 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T19", "type": "DRUG", "text": [ "Estazolam" ], "offsets": [ [ 786, 795 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T20", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 894, 903 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T21", "type": "DRUG_N", "text": [ "4-hydroxy-estazolam" ], "offsets": [ [ 940, 959 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T22", "type": "GROUP", "text": [ "triazolobenzodiazepines" ], "offsets": [ [ 988, 1011 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T23", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 1049, 1058 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T24", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1099, 1111 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T25", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1116, 1128 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T26", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 1244, 1253 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T27", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 1423, 1438 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T28", "type": "DRUG", "text": [ "nefazodone" ], "offsets": [ [ 1480, 1490 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T29", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 1492, 1503 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T30", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1505, 1515 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T31", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 1517, 1526 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T32", "type": "DRUG", "text": [ "isoniazide" ], "offsets": [ [ 1528, 1538 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T33", "type": "GROUP", "text": [ "macrolide antibiotics" ], "offsets": [ [ 1549, 1570 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T34", "type": "DRUG", "text": [ "Fluoxetine" ], "offsets": [ [ 1594, 1604 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T35", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1666, 1676 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T36", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 1714, 1723 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T37", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 1775, 1784 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T38", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1839, 1849 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T39", "type": "DRUG", "text": [ "Estazolam" ], "offsets": [ [ 1917, 1926 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T40", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 2074, 2083 ] ], "normalized": [] }, { "id": "Estazolam_ddi_T41", "type": "DRUG", "text": [ "estazolam" ], "offsets": [ [ 2255, 2264 ] ], "normalized": [] } ]

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[ { "id": "Estazolam_ddi_R1", "type": "EFFECT", "arg1_id": "Estazolam_ddi_T2", "arg2_id": "Estazolam_ddi_T3", "normalized": [] }, { "id": "Estazolam_ddi_R2", "type": "EFFECT", "arg1_id": "Estazolam_ddi_T2", "arg2_id": "Estazolam_ddi_T4", "normalized": [] }, { "id": "Estazolam_ddi_R3", "type": "EFFECT", "arg1_id": "Estazolam_ddi_T2", "arg2_id": "Estazolam_ddi_T5", "normalized": [] }, { "id": "Estazolam_ddi_R4", "type": "EFFECT", "arg1_id": "Estazolam_ddi_T2", "arg2_id": "Estazolam_ddi_T6", "normalized": [] }, { "id": "Estazolam_ddi_R5", "type": "EFFECT", "arg1_id": "Estazolam_ddi_T2", "arg2_id": "Estazolam_ddi_T7", "normalized": [] }, { "id": "Estazolam_ddi_R6", "type": "EFFECT", "arg1_id": "Estazolam_ddi_T2", "arg2_id": "Estazolam_ddi_T8", "normalized": [] }, { "id": "Estazolam_ddi_R7", "type": "EFFECT", "arg1_id": "Estazolam_ddi_T2", "arg2_id": "Estazolam_ddi_T9", "normalized": [] }, { "id": "Estazolam_ddi_R8", "type": "EFFECT", "arg1_id": "Estazolam_ddi_T2", "arg2_id": "Estazolam_ddi_T10", "normalized": [] }, { "id": "Estazolam_ddi_R9", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T13", "arg2_id": "Estazolam_ddi_T14", "normalized": [] }, { "id": "Estazolam_ddi_R10", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T13", "arg2_id": "Estazolam_ddi_T15", "normalized": [] }, { "id": "Estazolam_ddi_R11", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T13", "arg2_id": "Estazolam_ddi_T16", "normalized": [] }, { "id": "Estazolam_ddi_R12", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T13", "arg2_id": "Estazolam_ddi_T17", "normalized": [] }, { "id": "Estazolam_ddi_R13", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T13", "arg2_id": "Estazolam_ddi_T18", "normalized": [] }, { "id": "Estazolam_ddi_R14", "type": "ADVISE", "arg1_id": "Estazolam_ddi_T23", "arg2_id": "Estazolam_ddi_T24", "normalized": [] }, { "id": "Estazolam_ddi_R15", "type": "ADVISE", "arg1_id": "Estazolam_ddi_T23", "arg2_id": "Estazolam_ddi_T25", "normalized": [] }, { "id": "Estazolam_ddi_R16", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T27", "arg2_id": "Estazolam_ddi_T28", "normalized": [] }, { "id": "Estazolam_ddi_R17", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T27", "arg2_id": "Estazolam_ddi_T29", "normalized": [] }, { "id": "Estazolam_ddi_R18", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T27", "arg2_id": "Estazolam_ddi_T30", "normalized": [] }, { "id": "Estazolam_ddi_R19", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T27", "arg2_id": "Estazolam_ddi_T31", "normalized": [] }, { "id": "Estazolam_ddi_R20", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T27", "arg2_id": "Estazolam_ddi_T32", "normalized": [] }, { "id": "Estazolam_ddi_R21", "type": "MECHANISM", "arg1_id": "Estazolam_ddi_T27", "arg2_id": "Estazolam_ddi_T33", "normalized": [] } ]

[ { "id": "Abciximab_ddi__text", "type": "abstract", "text": [ "Formal drug interaction studies with Abciximab have not been conducted. Abciximab has been administered to patients with ischemic heart disease treated concomitantly with a broad range of medications used in the treatment of angina myocardial infarction and hypertension. These medications have included heparin, warfarin, beta-adrenergic receptor blockers, calcium channel antagonists, angiotensin converting enzyme inhibitors, intravenous and oral nitrates, ticlopidine, and aspirin. Heparin, other anticoagulants, thrombolytics, and anti platelet agents are associated with an increase in bleeding. Patients with HACA titers may have allergic or hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies." ], "offsets": [ [ 0, 748 ] ] } ]

[ { "id": "Abciximab_ddi_T1", "type": "DRUG", "text": [ "Abciximab" ], "offsets": [ [ 37, 46 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T2", "type": "DRUG", "text": [ "Abciximab" ], "offsets": [ [ 72, 81 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T3", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 304, 311 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T4", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 313, 321 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T5", "type": "GROUP", "text": [ "beta-adrenergic receptor blockers" ], "offsets": [ [ 323, 356 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T6", "type": "GROUP", "text": [ "calcium channel antagonists" ], "offsets": [ [ 358, 385 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T7", "type": "GROUP", "text": [ "angiotensin converting enzyme inhibitors" ], "offsets": [ [ 387, 427 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T8", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 450, 458 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T9", "type": "DRUG", "text": [ "ticlopidine" ], "offsets": [ [ 460, 471 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T10", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 477, 484 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T11", "type": "DRUG", "text": [ "Heparin" ], "offsets": [ [ 486, 493 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T12", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 501, 515 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T13", "type": "GROUP", "text": [ "thrombolytics" ], "offsets": [ [ 517, 530 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T14", "type": "GROUP", "text": [ "anti platelet agents" ], "offsets": [ [ 536, 556 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T15", "type": "GROUP", "text": [ "diagnostic", "monoclonal antibodies" ], "offsets": [ [ 700, 710 ], [ 726, 747 ] ], "normalized": [] }, { "id": "Abciximab_ddi_T16", "type": "GROUP", "text": [ "therapeutic monoclonal antibodies" ], "offsets": [ [ 714, 747 ] ], "normalized": [] } ]

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[ { "id": "Cyanocobalamin_ddi__text", "type": "abstract", "text": [ "Persons taking most antibiotics, methotrexate and pyrimethamine invalidate folic acid and vitamin B12 diagnostic blood assays. Colchicine para-aminosalicylic acid and heavy alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B12." ], "offsets": [ [ 0, 253 ] ] } ]

[ { "id": "Cyanocobalamin_ddi_T1", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 20, 31 ] ], "normalized": [] }, { "id": "Cyanocobalamin_ddi_T2", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 33, 45 ] ], "normalized": [] }, { "id": "Cyanocobalamin_ddi_T3", "type": "DRUG", "text": [ "pyrimethamine" ], "offsets": [ [ 50, 63 ] ], "normalized": [] }, { "id": "Cyanocobalamin_ddi_T4", "type": "DRUG", "text": [ "folic acid" ], "offsets": [ [ 75, 85 ] ], "normalized": [] }, { "id": "Cyanocobalamin_ddi_T5", "type": "DRUG", "text": [ "vitamin B12" ], "offsets": [ [ 90, 101 ] ], "normalized": [] }, { "id": "Cyanocobalamin_ddi_T6", "type": "DRUG", "text": [ "Colchicine" ], "offsets": [ [ 127, 137 ] ], "normalized": [] }, { "id": "Cyanocobalamin_ddi_T7", "type": "DRUG", "text": [ "para-aminosalicylic acid" ], "offsets": [ [ 138, 162 ] ], "normalized": [] }, { "id": "Cyanocobalamin_ddi_T8", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 173, 180 ] ], "normalized": [] }, { "id": "Cyanocobalamin_ddi_T9", "type": "DRUG", "text": [ "vitamin B12" ], "offsets": [ [ 241, 252 ] ], "normalized": [] } ]

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[ { "id": "Cyanocobalamin_ddi_R1", "type": "MECHANISM", "arg1_id": "Cyanocobalamin_ddi_T6", "arg2_id": "Cyanocobalamin_ddi_T9", "normalized": [] }, { "id": "Cyanocobalamin_ddi_R2", "type": "MECHANISM", "arg1_id": "Cyanocobalamin_ddi_T7", "arg2_id": "Cyanocobalamin_ddi_T9", "normalized": [] }, { "id": "Cyanocobalamin_ddi_R3", "type": "MECHANISM", "arg1_id": "Cyanocobalamin_ddi_T8", "arg2_id": "Cyanocobalamin_ddi_T9", "normalized": [] } ]

[ { "id": "Aminolevulinic acid_ddi__text", "type": "abstract", "text": [ "There have been no formal studies of the interaction of LEVULAN KERASTICK for Topical Solution with any other drugs, and no drug-specific interactions were noted during any of the controlled clinical trials. It is, however, possible that concomitant use of other known photosensitizing agents such as griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides and tetracyclines might increase the photosensitivity reaction of actinic keratoses treated with the LEVULAN KERASTICK for Topical Solution." ], "offsets": [ [ 0, 519 ] ] } ]

[ { "id": "Aminolevulinic acid_ddi_T1", "type": "BRAND", "text": [ "LEVULAN KERASTICK" ], "offsets": [ [ 56, 73 ] ], "normalized": [] }, { "id": "Aminolevulinic acid_ddi_T2", "type": "GROUP", "text": [ "photosensitizing agents" ], "offsets": [ [ 269, 292 ] ], "normalized": [] }, { "id": "Aminolevulinic acid_ddi_T3", "type": "DRUG", "text": [ "griseofulvin" ], "offsets": [ [ 301, 313 ] ], "normalized": [] }, { "id": "Aminolevulinic acid_ddi_T4", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 315, 333 ] ], "normalized": [] }, { "id": "Aminolevulinic acid_ddi_T5", "type": "GROUP", "text": [ "sulfonylureas" ], "offsets": [ [ 335, 348 ] ], "normalized": [] }, { "id": "Aminolevulinic acid_ddi_T6", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 350, 364 ] ], "normalized": [] }, { "id": "Aminolevulinic acid_ddi_T7", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 366, 378 ] ], "normalized": [] }, { "id": "Aminolevulinic acid_ddi_T8", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 383, 396 ] ], "normalized": [] }, { "id": "Aminolevulinic acid_ddi_T9", "type": "BRAND", "text": [ "LEVULAN KERASTICK" ], "offsets": [ [ 480, 497 ] ], "normalized": [] } ]

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[ { "id": "Aminolevulinic acid_ddi_R1", "type": "EFFECT", "arg1_id": "Aminolevulinic acid_ddi_T2", "arg2_id": "Aminolevulinic acid_ddi_T9", "normalized": [] }, { "id": "Aminolevulinic acid_ddi_R2", "type": "EFFECT", "arg1_id": "Aminolevulinic acid_ddi_T3", "arg2_id": "Aminolevulinic acid_ddi_T9", "normalized": [] }, { "id": "Aminolevulinic acid_ddi_R3", "type": "EFFECT", "arg1_id": "Aminolevulinic acid_ddi_T4", "arg2_id": "Aminolevulinic acid_ddi_T9", "normalized": [] }, { "id": "Aminolevulinic acid_ddi_R4", "type": "EFFECT", "arg1_id": "Aminolevulinic acid_ddi_T5", "arg2_id": "Aminolevulinic acid_ddi_T9", "normalized": [] }, { "id": "Aminolevulinic acid_ddi_R5", "type": "EFFECT", "arg1_id": "Aminolevulinic acid_ddi_T6", "arg2_id": "Aminolevulinic acid_ddi_T9", "normalized": [] }, { "id": "Aminolevulinic acid_ddi_R6", "type": "EFFECT", "arg1_id": "Aminolevulinic acid_ddi_T7", "arg2_id": "Aminolevulinic acid_ddi_T9", "normalized": [] }, { "id": "Aminolevulinic acid_ddi_R7", "type": "EFFECT", "arg1_id": "Aminolevulinic acid_ddi_T8", "arg2_id": "Aminolevulinic acid_ddi_T9", "normalized": [] } ]

[ { "id": "Frovatriptan_ddi__text", "type": "abstract", "text": [ "Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Due to a theoretical risk of a pharmacodynamic interaction, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and FROVA within 24 hours of each other should be avoided (see a href= frova_od.htm#CI CONTRAINDICATIONS). Concomitant use of other 5-HT1B/1D agonists within 24 hours of FROVA treatment is not recommended. Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been reported, rarely, to cause weakness, hyperreflexia, and incoordination when coadministered with 5-HT1 agonists. If concomitant treatment with frovatriptan and an SSRI is clinically warranted, appropriate observation of the patient is advised. Drug/Laboratory Test Interactions FROVA is not known to interfere with commonly employed clinical laboratory tests." ], "offsets": [ [ 0, 919 ] ] } ]

[ { "id": "Frovatriptan_ddi_T1", "type": "DRUG", "text": [ "ergotamine" ], "offsets": [ [ 151, 161 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T2", "type": "GROUP", "text": [ "ergot-type medications" ], "offsets": [ [ 176, 198 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T3", "type": "DRUG", "text": [ "dihydroergotamine" ], "offsets": [ [ 205, 222 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T4", "type": "DRUG", "text": [ "methysergide" ], "offsets": [ [ 226, 238 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T5", "type": "BRAND", "text": [ "FROVA" ], "offsets": [ [ 244, 249 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T6", "type": "BRAND", "text": [ "FROVA" ], "offsets": [ [ 411, 416 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T7", "type": "GROUP", "text": [ "Selective serotonin reuptake inhibitors" ], "offsets": [ [ 447, 486 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T8", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 488, 493 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T9", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 502, 512 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T10", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 514, 525 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T11", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 527, 537 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T12", "type": "DRUG", "text": [ "sertraline" ], "offsets": [ [ 539, 549 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T13", "type": "GROUP", "text": [ "5-HT1 agonists" ], "offsets": [ [ 657, 671 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T14", "type": "DRUG", "text": [ "frovatriptan" ], "offsets": [ [ 703, 715 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T15", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 723, 727 ] ], "normalized": [] }, { "id": "Frovatriptan_ddi_T16", "type": "BRAND", "text": [ "FROVA" ], "offsets": [ [ 838, 843 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Frovatriptan_ddi_R1", "type": "ADVISE", "arg1_id": "Frovatriptan_ddi_T1", "arg2_id": "Frovatriptan_ddi_T5", "normalized": [] }, { "id": "Frovatriptan_ddi_R2", "type": "ADVISE", "arg1_id": "Frovatriptan_ddi_T2", "arg2_id": "Frovatriptan_ddi_T5", "normalized": [] }, { "id": "Frovatriptan_ddi_R3", "type": "ADVISE", "arg1_id": "Frovatriptan_ddi_T3", "arg2_id": "Frovatriptan_ddi_T5", "normalized": [] }, { "id": "Frovatriptan_ddi_R4", "type": "ADVISE", "arg1_id": "Frovatriptan_ddi_T4", "arg2_id": "Frovatriptan_ddi_T5", "normalized": [] }, { "id": "Frovatriptan_ddi_R5", "type": "EFFECT", "arg1_id": "Frovatriptan_ddi_T7", "arg2_id": "Frovatriptan_ddi_T13", "normalized": [] }, { "id": "Frovatriptan_ddi_R6", "type": "EFFECT", "arg1_id": "Frovatriptan_ddi_T8", "arg2_id": "Frovatriptan_ddi_T13", "normalized": [] }, { "id": "Frovatriptan_ddi_R7", "type": "EFFECT", "arg1_id": "Frovatriptan_ddi_T9", "arg2_id": "Frovatriptan_ddi_T13", "normalized": [] }, { "id": "Frovatriptan_ddi_R8", "type": "EFFECT", "arg1_id": "Frovatriptan_ddi_T10", "arg2_id": "Frovatriptan_ddi_T13", "normalized": [] }, { "id": "Frovatriptan_ddi_R9", "type": "EFFECT", "arg1_id": "Frovatriptan_ddi_T11", "arg2_id": "Frovatriptan_ddi_T13", "normalized": [] }, { "id": "Frovatriptan_ddi_R10", "type": "EFFECT", "arg1_id": "Frovatriptan_ddi_T12", "arg2_id": "Frovatriptan_ddi_T13", "normalized": [] }, { "id": "Frovatriptan_ddi_R11", "type": "ADVISE", "arg1_id": "Frovatriptan_ddi_T14", "arg2_id": "Frovatriptan_ddi_T15", "normalized": [] } ]

[ { "id": "Efalizumab_ddi__text", "type": "abstract", "text": [ "No formal drug interaction studies have been performed with RAPTIVA. RAPTIVA should not be used with other immunosuppressive drugs. Acellular, live and live-attenuated vaccines should not be administered during RAPTIVA treatment. Drug/Laboratory Test Interactions Increases in lymphocyte counts related to the pharmacologic mechanism of action are frequently observed during RAPTIVA treatment." ], "offsets": [ [ 0, 393 ] ] } ]

[ { "id": "Efalizumab_ddi_T1", "type": "BRAND", "text": [ "RAPTIVA" ], "offsets": [ [ 60, 67 ] ], "normalized": [] }, { "id": "Efalizumab_ddi_T2", "type": "BRAND", "text": [ "RAPTIVA" ], "offsets": [ [ 69, 76 ] ], "normalized": [] }, { "id": "Efalizumab_ddi_T3", "type": "GROUP", "text": [ "immunosuppressive drugs" ], "offsets": [ [ 107, 130 ] ], "normalized": [] }, { "id": "Efalizumab_ddi_T4", "type": "GROUP", "text": [ "Acellular", "vaccines" ], "offsets": [ [ 132, 141 ], [ 168, 176 ] ], "normalized": [] }, { "id": "Efalizumab_ddi_T5", "type": "GROUP", "text": [ "live", "vaccines" ], "offsets": [ [ 143, 147 ], [ 168, 176 ] ], "normalized": [] }, { "id": "Efalizumab_ddi_T6", "type": "GROUP", "text": [ "live-attenuated vaccines" ], "offsets": [ [ 152, 176 ] ], "normalized": [] }, { "id": "Efalizumab_ddi_T7", "type": "BRAND", "text": [ "RAPTIVA" ], "offsets": [ [ 211, 218 ] ], "normalized": [] }, { "id": "Efalizumab_ddi_T8", "type": "BRAND", "text": [ "RAPTIVA" ], "offsets": [ [ 375, 382 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Efalizumab_ddi_R1", "type": "ADVISE", "arg1_id": "Efalizumab_ddi_T2", "arg2_id": "Efalizumab_ddi_T3", "normalized": [] }, { "id": "Efalizumab_ddi_R2", "type": "ADVISE", "arg1_id": "Efalizumab_ddi_T4", "arg2_id": "Efalizumab_ddi_T7", "normalized": [] }, { "id": "Efalizumab_ddi_R3", "type": "ADVISE", "arg1_id": "Efalizumab_ddi_T5", "arg2_id": "Efalizumab_ddi_T7", "normalized": [] }, { "id": "Efalizumab_ddi_R4", "type": "ADVISE", "arg1_id": "Efalizumab_ddi_T6", "arg2_id": "Efalizumab_ddi_T7", "normalized": [] } ]

[ { "id": "Acetazolamide_ddi__text", "type": "abstract", "text": [ "DIAMOX modifies phenytoin metabolism with increased serum levels of phenytoin. This may increase or enhance the occurrence of osteomalacia in some patients receiving chronic phenytoin therapy. Caution is advised in patients receiving chronic concomitant therapy. By decreasing the gastrointestinal absorption of primidone, DIAMOX may decrease serum concentrations of primidone and its metabolites, with a consequent possible decrease in anticonvulsant effect. Caution is advised when beginning, discontinuing, or changing the dose of DIAMOX in patients receiving primidone. Because of possible additive effects with other carbonic anhydrase inhibitors, concomitant use is not advisable. Acetazolamide may increase the effects of other folic acid antagonists. Acetazolamide may increase or decrease blood glucose levels. Consideration should be taken in patients being treated with antidiabetic agents. Acetazolamide decreases urinary excretion of amphetamine and may enhance the magnitude and duration of their effect. Acetazolamide reduces urinary excretion of quinidine and may enhance its effect. Acetazolamide may prevent the urinary antiseptic effect of methenamine. Acetazolamide increases lithium excretion and the lithium may be decreased. Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation. Acetazolamide may elevate cyclosporine levels." ], "offsets": [ [ 0, 1397 ] ] } ]

[ { "id": "Acetazolamide_ddi_T1", "type": "BRAND", "text": [ "DIAMOX" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T2", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 16, 25 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T3", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 68, 77 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T4", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 174, 183 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T5", "type": "DRUG", "text": [ "primidone" ], "offsets": [ [ 312, 321 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T6", "type": "BRAND", "text": [ "DIAMOX" ], "offsets": [ [ 323, 329 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T7", "type": "DRUG", "text": [ "primidone" ], "offsets": [ [ 367, 376 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T8", "type": "BRAND", "text": [ "DIAMOX" ], "offsets": [ [ 534, 540 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T9", "type": "DRUG", "text": [ "primidone" ], "offsets": [ [ 563, 572 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T10", "type": "GROUP", "text": [ "carbonic anhydrase inhibitors" ], "offsets": [ [ 622, 651 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T11", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 687, 700 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T12", "type": "GROUP", "text": [ "folic acid antagonists" ], "offsets": [ [ 735, 757 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T13", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 759, 772 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T14", "type": "DRUG", "text": [ "antidiabetic" ], "offsets": [ [ 881, 893 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T15", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 902, 915 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T16", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 947, 958 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T17", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 1019, 1032 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T18", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1062, 1071 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T19", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 1100, 1113 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T20", "type": "DRUG", "text": [ "methenamine" ], "offsets": [ [ 1159, 1170 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T21", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 1172, 1185 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T22", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1196, 1203 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T23", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1222, 1229 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T24", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 1248, 1261 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T25", "type": "DRUG", "text": [ "sodium bicarbonate" ], "offsets": [ [ 1266, 1284 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T26", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 1351, 1364 ] ], "normalized": [] }, { "id": "Acetazolamide_ddi_T27", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1377, 1389 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Acetazolamide_ddi_R1", "type": "MECHANISM", "arg1_id": "Acetazolamide_ddi_T1", "arg2_id": "Acetazolamide_ddi_T2", "normalized": [] }, { "id": "Acetazolamide_ddi_R2", "type": "MECHANISM", "arg1_id": "Acetazolamide_ddi_T1", "arg2_id": "Acetazolamide_ddi_T3", "normalized": [] }, { "id": "Acetazolamide_ddi_R3", "type": "MECHANISM", "arg1_id": "Acetazolamide_ddi_T6", "arg2_id": "Acetazolamide_ddi_T7", "normalized": [] }, { "id": "Acetazolamide_ddi_R4", "type": "ADVISE", "arg1_id": "Acetazolamide_ddi_T8", "arg2_id": "Acetazolamide_ddi_T9", "normalized": [] }, { "id": "Acetazolamide_ddi_R5", "type": "EFFECT", "arg1_id": "Acetazolamide_ddi_T11", "arg2_id": "Acetazolamide_ddi_T12", "normalized": [] }, { "id": "Acetazolamide_ddi_R6", "type": "MECHANISM", "arg1_id": "Acetazolamide_ddi_T15", "arg2_id": "Acetazolamide_ddi_T16", "normalized": [] }, { "id": "Acetazolamide_ddi_R7", "type": "MECHANISM", "arg1_id": "Acetazolamide_ddi_T17", "arg2_id": "Acetazolamide_ddi_T18", "normalized": [] }, { "id": "Acetazolamide_ddi_R8", "type": "EFFECT", "arg1_id": "Acetazolamide_ddi_T19", "arg2_id": "Acetazolamide_ddi_T20", "normalized": [] }, { "id": "Acetazolamide_ddi_R9", "type": "MECHANISM", "arg1_id": "Acetazolamide_ddi_T21", "arg2_id": "Acetazolamide_ddi_T22", "normalized": [] }, { "id": "Acetazolamide_ddi_R10", "type": "EFFECT", "arg1_id": "Acetazolamide_ddi_T24", "arg2_id": "Acetazolamide_ddi_T25", "normalized": [] }, { "id": "Acetazolamide_ddi_R11", "type": "MECHANISM", "arg1_id": "Acetazolamide_ddi_T26", "arg2_id": "Acetazolamide_ddi_T27", "normalized": [] } ]

[ { "id": "Grepafloxacin_ddi__text", "type": "abstract", "text": [ "Antacids, Sucralfate, Metal Cations, Multivitamins Quinolones form chelates with alkaline earth and transition metal cations. Administration of quinolones with antacids containing aluminum, magnesium, or calcium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as VIDEX (didanosine) chewable/buffered tablets or the pediatric powder for oral solution, may substantially interfere with the absorption of quinolones, resulting in systemic concentrations considerably lower than desired. These agents should not be taken within 4 hours before or 4 hours after grepafloxacin administration. Caffeine Theobromine Grepafloxacin, like other quinolones, may inhibit the metabolism of caffeine and theobromine. These stimulants are commonly found in coffee and tea, respectively. In some patients, this may lead to reduced clearance, prolongation of plasma half-life, and enhanced effects of caffeine and theobromine. Theophylline: Grepafloxacin is a competitive inhibitor of the metabolism of theophylline. Serum theophylline concentrations increase when grepafloxacin is initiated in a patient maintained on theophylline. When initiating a multi-day course of grepafloxacin in a patient maintained on theophylline, the theophylline maintenance dose should be halved for the period of concurrent use of grepafloxacin and monitoring of serum theophylline concentrations should be initiated as a guide to further dosage adjustments. Warfarin: In subjects receiving warfarin, no significant change in clotting time was observed when grepafloxacin was coadministered. However, because some quinolones have been reported to enhance the effects of warfarin or its derivatives, prothrombin time or other suitable anticoagulation test should be monitored closely if a quinolone antimicrobial is administered with warfarin or its derivatives. Drugs Metabolized by Cytochrome P450 Enzymes The drug interaction study evaluating the effect of grepafloxacin on theophylline indicates that grepafloxacin inhibits theophylline metabolism, which is mediated by CYP1A2. While no clinical studies have been conducted to evaluate the effect of grepafloxacin on the metabolism of C.P.A. substrates, in vitro data suggest similar effects of grepafloxacin in CYP3A4 mediated metabolism and theophylline metabolism. In addition, other quinolones have been reported to decrease the CYP3A4-mediated metabolism of cyclosporine. Other drugs metabolized by C.P.A. include terfenadine, astemizole, cisapride, midazolam, and triazolam. The clinical relevance of the potential effect of grepafloxacin on the metabolism of C.P.A. substrates is not known. Patients receiving concurrent administration of substrates of C.P.A. were not excluded from clinical trials of grepafloxacin. Nonsteroidal Anti-inflammatory Drugs (NSAIDs): The concomitant administration of a nonsteroidal anti inflammatory drug with a quinolone may increase the risks of CNS stimulation and convulsions. Antidiabetic Agents: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are coadministered." ], "offsets": [ [ 0, 3342 ] ] } ]

[ { "id": "Grepafloxacin_ddi_T1", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T2", "type": "DRUG", "text": [ "Sucralfate" ], "offsets": [ [ 10, 20 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T3", "type": "GROUP", "text": [ "Multivitamins" ], "offsets": [ [ 37, 50 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T4", "type": "GROUP", "text": [ "Quinolones" ], "offsets": [ [ 51, 61 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T5", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 144, 154 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T6", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 160, 168 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T7", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 180, 188 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T8", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 190, 199 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T9", "type": "DRUG", "text": [ "calcium" ], "offsets": [ [ 204, 211 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T10", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 218, 228 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T11", "type": "DRUG", "text": [ "iron" ], "offsets": [ [ 257, 261 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T12", "type": "GROUP", "text": [ "multivitamins" ], "offsets": [ [ 271, 284 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T13", "type": "DRUG", "text": [ "iron" ], "offsets": [ [ 296, 300 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T14", "type": "DRUG", "text": [ "zinc" ], "offsets": [ [ 304, 308 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T15", "type": "BRAND", "text": [ "VIDEX" ], "offsets": [ [ 381, 386 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T16", "type": "DRUG", "text": [ "didanosine" ], "offsets": [ [ 388, 398 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T17", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 520, 530 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T18", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 674, 687 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T19", "type": "DRUG", "text": [ "Caffeine" ], "offsets": [ [ 704, 712 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T20", "type": "DRUG", "text": [ "Theobromine" ], "offsets": [ [ 713, 724 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T21", "type": "DRUG", "text": [ "Grepafloxacin" ], "offsets": [ [ 725, 738 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T22", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 751, 761 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T23", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 793, 801 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T24", "type": "DRUG", "text": [ "theobromine" ], "offsets": [ [ 806, 817 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T25", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 1000, 1008 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T26", "type": "DRUG", "text": [ "theobromine" ], "offsets": [ [ 1013, 1024 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T27", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 1026, 1038 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T28", "type": "DRUG", "text": [ "Grepafloxacin" ], "offsets": [ [ 1040, 1053 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T29", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1102, 1114 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T30", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1122, 1134 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T31", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 1164, 1177 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T32", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1218, 1230 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T33", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 1270, 1283 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T34", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1311, 1323 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T35", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1329, 1341 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T36", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 1412, 1425 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T37", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1450, 1462 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T38", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 1540, 1548 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T39", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1572, 1580 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T40", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 1639, 1652 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T41", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 1695, 1705 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T42", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1751, 1759 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T43", "type": "GROUP", "text": [ "quinolone antimicrobial" ], "offsets": [ [ 1869, 1892 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T44", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1914, 1922 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T45", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 2040, 2053 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T46", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2057, 2069 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T47", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 2085, 2098 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T48", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2108, 2120 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T49", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 2234, 2247 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T50", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 2329, 2342 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T51", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2377, 2389 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T52", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 2421, 2431 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T53", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2497, 2509 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T54", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 2553, 2564 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T55", "type": "DRUG", "text": [ "astemizole" ], "offsets": [ [ 2566, 2576 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T56", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 2578, 2587 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T57", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 2589, 2598 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T58", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 2604, 2613 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T59", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 2665, 2678 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T60", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 2843, 2856 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T61", "type": "GROUP", "text": [ "Nonsteroidal Anti-inflammatory Drugs" ], "offsets": [ [ 2858, 2894 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T62", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2896, 2902 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T63", "type": "GROUP", "text": [ "nonsteroidal anti inflammatory drug" ], "offsets": [ [ 2941, 2976 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T64", "type": "GROUP", "text": [ "quinolone" ], "offsets": [ [ 2984, 2993 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T65", "type": "GROUP", "text": [ "Antidiabetic Agents" ], "offsets": [ [ 3053, 3072 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T66", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 3205, 3215 ] ], "normalized": [] }, { "id": "Grepafloxacin_ddi_T67", "type": "GROUP", "text": [ "antidiabetic agent" ], "offsets": [ [ 3223, 3241 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Grepafloxacin_ddi_R1", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T7", "normalized": [] }, { "id": "Grepafloxacin_ddi_R2", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T8", "normalized": [] }, { "id": "Grepafloxacin_ddi_R3", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T9", "normalized": [] }, { "id": "Grepafloxacin_ddi_R4", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T10", "normalized": [] }, { "id": "Grepafloxacin_ddi_R5", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T11", "normalized": [] }, { "id": "Grepafloxacin_ddi_R6", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T12", "normalized": [] }, { "id": "Grepafloxacin_ddi_R7", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T13", "normalized": [] }, { "id": "Grepafloxacin_ddi_R8", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T14", "normalized": [] }, { "id": "Grepafloxacin_ddi_R9", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T15", "normalized": [] }, { "id": "Grepafloxacin_ddi_R10", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T5", "arg2_id": "Grepafloxacin_ddi_T16", "normalized": [] }, { "id": "Grepafloxacin_ddi_R11", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T21", "arg2_id": "Grepafloxacin_ddi_T23", "normalized": [] }, { "id": "Grepafloxacin_ddi_R12", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T21", "arg2_id": "Grepafloxacin_ddi_T24", "normalized": [] }, { "id": "Grepafloxacin_ddi_R13", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T22", "arg2_id": "Grepafloxacin_ddi_T23", "normalized": [] }, { "id": "Grepafloxacin_ddi_R14", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T22", "arg2_id": "Grepafloxacin_ddi_T24", "normalized": [] }, { "id": "Grepafloxacin_ddi_R15", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T28", "arg2_id": "Grepafloxacin_ddi_T29", "normalized": [] }, { "id": "Grepafloxacin_ddi_R16", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T31", "arg2_id": "Grepafloxacin_ddi_T32", "normalized": [] }, { "id": "Grepafloxacin_ddi_R17", "type": "ADVISE", "arg1_id": "Grepafloxacin_ddi_T35", "arg2_id": "Grepafloxacin_ddi_T36", "normalized": [] }, { "id": "Grepafloxacin_ddi_R18", "type": "EFFECT", "arg1_id": "Grepafloxacin_ddi_T41", "arg2_id": "Grepafloxacin_ddi_T42", "normalized": [] }, { "id": "Grepafloxacin_ddi_R19", "type": "ADVISE", "arg1_id": "Grepafloxacin_ddi_T43", "arg2_id": "Grepafloxacin_ddi_T44", "normalized": [] }, { "id": "Grepafloxacin_ddi_R20", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T47", "arg2_id": "Grepafloxacin_ddi_T48", "normalized": [] }, { "id": "Grepafloxacin_ddi_R21", "type": "MECHANISM", "arg1_id": "Grepafloxacin_ddi_T52", "arg2_id": "Grepafloxacin_ddi_T53", "normalized": [] }, { "id": "Grepafloxacin_ddi_R22", "type": "EFFECT", "arg1_id": "Grepafloxacin_ddi_T63", "arg2_id": "Grepafloxacin_ddi_T64", "normalized": [] }, { "id": "Grepafloxacin_ddi_R23", "type": "EFFECT", "arg1_id": "Grepafloxacin_ddi_T66", "arg2_id": "Grepafloxacin_ddi_T67", "normalized": [] } ]

[ { "id": "Furosemide_ddi__text", "type": "abstract", "text": [ "Furosemide may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function. Except in life-threatening situations, avoid this combination. Furosemide should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity. Patients receiving high doses of salicylates concomitantly with furosemide, as in rheumatic disease, may experience salicylate toxicity at lower doses because of competitive renal excretory sites. Furosemide has a tendency to antagonize the skeletal muscle relaxing effect of tubocurarine and may potentiate the action of succinylcholine. Lithium generally should not be given with diuretics because they reduce lithiums renal clearance and add a high risk of lithium toxicity. Furosemide may add to or potentiate the therapeutic effect of other antihypertensive drugs. Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs. Furosemide may decrease arterial responsiveness to norepinephrine. However, norepinephrine may still be used effectively. Tablets Simultaneous administration of sucralfate and furosemide tablets may reduce the natriuretic and antihypertensive effects of furosemide. Patients receiving both drugs should be observed closely to determine if the desired diuretic and/or antihypertensive effect of furosemide is achieved. The intake of furosemide and sucralfate should be separated by at least two hours. Tablets, Injection, and Oral Solution One study in six subjects demonstrated that the combination of furosemide and acetylsalicylic acid temporarily reduced creatinine clearance in patients with chronic renal insufficiency. There are case reports of patients who developed increased BUN, serum creatinine and serum potassium levels, and weight gain when furosemide was used in conjunction with NSAIDs. Literature reports indicate that coadministration of indomethacin may reduce the natriuretic and antihypertensive effects of furosemide in some patients by inhibiting prostaglandin synthesis. Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation. Patients receiving both indomethacin and furosemide should be observed closely to determine if the desired diuretic and/or antihypertensive effect of furosemide is achieved." ], "offsets": [ [ 0, 2322 ] ] } ]

[ { "id": "Furosemide_ddi_T1", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T2", "type": "GROUP", "text": [ "aminoglycoside antibiotics" ], "offsets": [ [ 50, 76 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T3", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 196, 206 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T4", "type": "DRUG", "text": [ "ethacrynic acid" ], "offsets": [ [ 245, 260 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T5", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 337, 348 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T6", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 368, 378 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T7", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 420, 430 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T8", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 501, 511 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T9", "type": "DRUG", "text": [ "tubocurarine" ], "offsets": [ [ 580, 592 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T10", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 626, 641 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T11", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 643, 650 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T12", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 686, 695 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T13", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 716, 723 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T14", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 764, 771 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T15", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 782, 792 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T16", "type": "GROUP", "text": [ "antihypertensive drugs" ], "offsets": [ [ 850, 872 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T17", "type": "GROUP", "text": [ "ganglionic", "adrenergic blocking drugs" ], "offsets": [ [ 899, 909 ], [ 924, 949 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T18", "type": "GROUP", "text": [ "peripheral adrenergic blocking drugs" ], "offsets": [ [ 913, 949 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T19", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 951, 961 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T20", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 1002, 1016 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T21", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 1027, 1041 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T22", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 1112, 1122 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T23", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1127, 1137 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T24", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1205, 1215 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T25", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1345, 1355 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T26", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1383, 1393 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T27", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 1398, 1408 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T28", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1553, 1563 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T29", "type": "DRUG", "text": [ "acetylsalicylic acid" ], "offsets": [ [ 1568, 1588 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T30", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1806, 1816 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T31", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1846, 1852 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T32", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 1907, 1919 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T33", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1979, 1989 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T34", "type": "DRUG", "text": [ "Indomethacin" ], "offsets": [ [ 2046, 2058 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T35", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 2173, 2185 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T36", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 2190, 2200 ] ], "normalized": [] }, { "id": "Furosemide_ddi_T37", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 2299, 2309 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Furosemide_ddi_R1", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T1", "arg2_id": "Furosemide_ddi_T2", "normalized": [] }, { "id": "Furosemide_ddi_R2", "type": "ADVISE", "arg1_id": "Furosemide_ddi_T3", "arg2_id": "Furosemide_ddi_T4", "normalized": [] }, { "id": "Furosemide_ddi_R3", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T5", "arg2_id": "Furosemide_ddi_T6", "normalized": [] }, { "id": "Furosemide_ddi_R4", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T8", "arg2_id": "Furosemide_ddi_T9", "normalized": [] }, { "id": "Furosemide_ddi_R5", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T8", "arg2_id": "Furosemide_ddi_T10", "normalized": [] }, { "id": "Furosemide_ddi_R6", "type": "ADVISE", "arg1_id": "Furosemide_ddi_T11", "arg2_id": "Furosemide_ddi_T12", "normalized": [] }, { "id": "Furosemide_ddi_R7", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T15", "arg2_id": "Furosemide_ddi_T16", "normalized": [] }, { "id": "Furosemide_ddi_R8", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T19", "arg2_id": "Furosemide_ddi_T20", "normalized": [] }, { "id": "Furosemide_ddi_R9", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T22", "arg2_id": "Furosemide_ddi_T23", "normalized": [] }, { "id": "Furosemide_ddi_R10", "type": "ADVISE", "arg1_id": "Furosemide_ddi_T26", "arg2_id": "Furosemide_ddi_T27", "normalized": [] }, { "id": "Furosemide_ddi_R11", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T28", "arg2_id": "Furosemide_ddi_T29", "normalized": [] }, { "id": "Furosemide_ddi_R12", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T30", "arg2_id": "Furosemide_ddi_T31", "normalized": [] }, { "id": "Furosemide_ddi_R13", "type": "EFFECT", "arg1_id": "Furosemide_ddi_T32", "arg2_id": "Furosemide_ddi_T33", "normalized": [] }, { "id": "Furosemide_ddi_R14", "type": "ADVISE", "arg1_id": "Furosemide_ddi_T35", "arg2_id": "Furosemide_ddi_T36", "normalized": [] } ]

[ { "id": "Indomethacin_ddi__text", "type": "abstract", "text": [ "In normal volunteers receiving indomethacin, the administration of diflunisal decreased the renal clearance and significantly increased the plasma levels of indomethacin. In some patients, combined use of INDOCIN and diflunisal has been associated with fatal gastrointestinal hemorrhage. Therefore, diflunisal and INDOCIN should not be used concomitantly. In a study in normal volunteers, it was found that chronic concurrent administration of 3.6 g of aspirin per day decreases indomethacin blood levels approximately 20%. The concomitant use of INDOCIN with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy. Clinical studies have shown that INDOCIN does not influence the hypoprothrombinemia produced by anticoagulants. However, when any additional drug, including INDOCIN, is added to the treatment of patients on anticoagulant therapy, the patients should be observed for alterations of the prothrombin time. In post-marketing experience, bleeding has been reported in patients on concomitant treatment with anticoagulants and INDOCIN. Caution should be exercised when INDOCIN and anticoagulants are administered concomitantly. When INDOCIN is given to patients receiving probenecid, the plasma levels of indomethacin are likely to be increased. Therefore, a lower total daily dosage of INDOCIN may produce a satisfactory therapeutic effect. When increases in the dose of INDOCIN are made, they should be made carefully and in small increments. Caution should be used if INDOCIN is administered simultaneously with methotrexate. INDOCIN has been reported to decrease the tubular secretion of methotrexate and to potentiate its toxicity. Administration of non-steroidal anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine, and renal function should be carefully monitored. Capsules INDOCIN 50 mg t.i.d. produced a clinically relevant elevation of plasma lithium and reduction in renal lithium clearance in psychiatric patients and normal subjects with steady state plasma lithium concentrations. This effect has been attributed to inhibition of prostaglandin synthesis. As a consequence, when INDOCIN and lithium are given concomitantly, the patient should be carefully observed for signs of lithium toxicity. (Read circulars for lithium preparations before use of such concomitant therapy.) In addition, the frequency of monitoring serum lithium concentration should be increased at the outset of such combination drug treatment. INDOCIN given concomitantly with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Therefore, when INDOCIN and digoxin are used concomitantly, serum digoxin levels should be closely monitored. In some patients, the administration of INDOCIN can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. Therefore, when INDOCIN and INDOCIN. (Indomethacin) diuretics are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained. INDOCIN reduces basal plasma renin activity (PRA), as well as those elevations of PRA induced by furosemide administration, or salt or volume depletion. These facts should be considered when evaluating plasma renin activity in hypertensive patients. It has been reported that the addition of triamterene to a maintenance schedule of INDOCIN resulted in reversible acute renal failure in two of four healthy volunteers. INDOCIN and triamterene should not be administered together. INDOCIN and potassium-sparing diuretics each may be associated with increased serum potassium levels. The potential effects of INDOCIN and potassium-sparing diuretics on potassium kinetics and renal function should be considered when these agents are administered concurrently. Most of the above effects concerning diuretics have been attributed, at least in part, to mechanisms involving inhibition of prostaglandin synthesis by INDOCIN. Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by non-steroidal antiinflammatory drugs including INDOCIN has been reported. Therefore, when using these blocking agents to treat hypertension, patients should be observed carefully in order to confirm that the desired therapeutic effect has been obtained. INDOCIN can reduce the antihypertensive effects of captopril and losartan. False-negative results in the dexamethasone suppression test (DST) in patients being treated with INDOCIN have been reported. Thus, results of the DST should be interpreted with caution in these patients." ], "offsets": [ [ 0, 4851 ] ] } ]

[ { "id": "Indomethacin_ddi_T1", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 31, 43 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T2", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 67, 77 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T3", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 157, 169 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T4", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 205, 212 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T5", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 217, 227 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T6", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 299, 309 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T7", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 314, 321 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T8", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 453, 460 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T9", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 479, 491 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T10", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 547, 554 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T11", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 566, 572 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T12", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 728, 735 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T13", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 791, 805 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T14", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 852, 859 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T15", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 902, 915 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T16", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1097, 1111 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T17", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 1116, 1123 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T18", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 1158, 1165 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T19", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1170, 1184 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T20", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 1222, 1229 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T21", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 1261, 1271 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T22", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 1294, 1306 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T23", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 1376, 1383 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T24", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 1461, 1468 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T25", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 1560, 1567 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T26", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1604, 1616 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T27", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 1618, 1625 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T28", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1681, 1693 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T29", "type": "GROUP", "text": [ "non-steroidal anti-inflammatory drugs" ], "offsets": [ [ 1744, 1781 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T30", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1801, 1813 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T31", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1854, 1866 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T32", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1944, 1950 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T33", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1998, 2010 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T34", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 2071, 2078 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T35", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2143, 2150 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T36", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2174, 2181 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T37", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2261, 2268 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T38", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 2382, 2389 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T39", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2394, 2401 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T40", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2481, 2488 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T41", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2519, 2526 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T42", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2628, 2635 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T43", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 2720, 2727 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T44", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2753, 2760 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T45", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2844, 2851 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T46", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 2869, 2876 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T47", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2881, 2888 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T48", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2919, 2926 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T49", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 3003, 3010 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T50", "type": "GROUP", "text": [ "loop", "diuretics" ], "offsets": [ [ 3081, 3085 ], [ 3119, 3128 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T51", "type": "GROUP", "text": [ "potassium-sparing", "diuretics" ], "offsets": [ [ 3087, 3104 ], [ 3119, 3128 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T52", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 3110, 3128 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T53", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 3146, 3153 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T54", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 3158, 3165 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T55", "type": "DRUG", "text": [ "Indomethacin" ], "offsets": [ [ 3168, 3180 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T56", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 3182, 3191 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T57", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 3297, 3305 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T58", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 3319, 3326 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T59", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 3416, 3426 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T60", "type": "DRUG", "text": [ "triamterene" ], "offsets": [ [ 3611, 3622 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T61", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 3652, 3659 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T62", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 3738, 3745 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T63", "type": "DRUG", "text": [ "triamterene" ], "offsets": [ [ 3750, 3761 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T64", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 3799, 3806 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T65", "type": "GROUP", "text": [ "potassium-sparing diuretics" ], "offsets": [ [ 3811, 3838 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T66", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 3926, 3933 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T67", "type": "GROUP", "text": [ "potassium-sparing diuretics" ], "offsets": [ [ 3938, 3965 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T68", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 4114, 4123 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T69", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 4229, 4236 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T70", "type": "GROUP", "text": [ "beta-adrenoceptor blocking agents" ], "offsets": [ [ 4281, 4314 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T71", "type": "GROUP", "text": [ "non-steroidal antiinflammatory drugs" ], "offsets": [ [ 4318, 4354 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T72", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 4365, 4372 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T73", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 4572, 4579 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T74", "type": "DRUG", "text": [ "captopril" ], "offsets": [ [ 4623, 4632 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T75", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 4637, 4645 ] ], "normalized": [] }, { "id": "Indomethacin_ddi_T76", "type": "BRAND", "text": [ "INDOCIN" ], "offsets": [ [ 4745, 4752 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Indomethacin_ddi_R1", "type": "MECHANISM", "arg1_id": "Indomethacin_ddi_T2", "arg2_id": "Indomethacin_ddi_T3", "normalized": [] }, { "id": "Indomethacin_ddi_R2", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T4", "arg2_id": "Indomethacin_ddi_T5", "normalized": [] }, { "id": "Indomethacin_ddi_R3", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T6", "arg2_id": "Indomethacin_ddi_T7", "normalized": [] }, { "id": "Indomethacin_ddi_R4", "type": "MECHANISM", "arg1_id": "Indomethacin_ddi_T8", "arg2_id": "Indomethacin_ddi_T9", "normalized": [] }, { "id": "Indomethacin_ddi_R5", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T10", "arg2_id": "Indomethacin_ddi_T11", "normalized": [] }, { "id": "Indomethacin_ddi_R6", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T14", "arg2_id": "Indomethacin_ddi_T15", "normalized": [] }, { "id": "Indomethacin_ddi_R7", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T16", "arg2_id": "Indomethacin_ddi_T17", "normalized": [] }, { "id": "Indomethacin_ddi_R8", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T18", "arg2_id": "Indomethacin_ddi_T19", "normalized": [] }, { "id": "Indomethacin_ddi_R9", "type": "MECHANISM", "arg1_id": "Indomethacin_ddi_T20", "arg2_id": "Indomethacin_ddi_T21", "normalized": [] }, { "id": "Indomethacin_ddi_R10", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T25", "arg2_id": "Indomethacin_ddi_T26", "normalized": [] }, { "id": "Indomethacin_ddi_R11", "type": "MECHANISM", "arg1_id": "Indomethacin_ddi_T27", "arg2_id": "Indomethacin_ddi_T28", "normalized": [] }, { "id": "Indomethacin_ddi_R12", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T29", "arg2_id": "Indomethacin_ddi_T30", "normalized": [] }, { "id": "Indomethacin_ddi_R13", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T32", "arg2_id": "Indomethacin_ddi_T33", "normalized": [] }, { "id": "Indomethacin_ddi_R14", "type": "MECHANISM", "arg1_id": "Indomethacin_ddi_T34", "arg2_id": "Indomethacin_ddi_T35", "normalized": [] }, { "id": "Indomethacin_ddi_R15", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T38", "arg2_id": "Indomethacin_ddi_T39", "normalized": [] }, { "id": "Indomethacin_ddi_R16", "type": "MECHANISM", "arg1_id": "Indomethacin_ddi_T43", "arg2_id": "Indomethacin_ddi_T44", "normalized": [] }, { "id": "Indomethacin_ddi_R17", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T46", "arg2_id": "Indomethacin_ddi_T47", "normalized": [] }, { "id": "Indomethacin_ddi_R18", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T49", "arg2_id": "Indomethacin_ddi_T50", "normalized": [] }, { "id": "Indomethacin_ddi_R19", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T49", "arg2_id": "Indomethacin_ddi_T51", "normalized": [] }, { "id": "Indomethacin_ddi_R20", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T49", "arg2_id": "Indomethacin_ddi_T52", "normalized": [] }, { "id": "Indomethacin_ddi_R21", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T60", "arg2_id": "Indomethacin_ddi_T61", "normalized": [] }, { "id": "Indomethacin_ddi_R22", "type": "ADVISE", "arg1_id": "Indomethacin_ddi_T62", "arg2_id": "Indomethacin_ddi_T63", "normalized": [] }, { "id": "Indomethacin_ddi_R23", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T66", "arg2_id": "Indomethacin_ddi_T67", "normalized": [] }, { "id": "Indomethacin_ddi_R24", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T68", "arg2_id": "Indomethacin_ddi_T69", "normalized": [] }, { "id": "Indomethacin_ddi_R25", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T70", "arg2_id": "Indomethacin_ddi_T71", "normalized": [] }, { "id": "Indomethacin_ddi_R26", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T70", "arg2_id": "Indomethacin_ddi_T72", "normalized": [] }, { "id": "Indomethacin_ddi_R27", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T73", "arg2_id": "Indomethacin_ddi_T74", "normalized": [] }, { "id": "Indomethacin_ddi_R28", "type": "EFFECT", "arg1_id": "Indomethacin_ddi_T73", "arg2_id": "Indomethacin_ddi_T75", "normalized": [] } ]

[ { "id": "Saquinavir_ddi__text", "type": "abstract", "text": [ "DRUG INTERACTIONS Several drug interaction studies have been completed with both INVIRASE and FORTOVASE. Observations from drug interaction studies with FORTOVASE may not be predictive for INVIRASE. Because ritonavir is coadministered, prescribers should also refer to the prescribing information for ritonavir regarding drug interactions associated with this agent. The metabolism of saquinavir is mediated by cytochrome P450, with the specific isoenzyme CYP3A4 responsible for 90% of the hepatic metabolism. Additionally, saquinavir is a substrate for P-Glycoprotein (Pgp). Therefore, drugs that affect CYP3A4 and/or Pgp, may modify the pharmacokinetics of saquinavir. Similarly, saquinavir might also modify the pharmacokinetics of other drugs that are substrates for CYP3A4 or Pgp. Drugs that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse events are listed CONTRAINDICATIONS. Additional drugs that are not recommended for coadministration with INVIRASE and ritonavir are included below. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious events or loss of efficacy. With some agents, the metabolism may be induced, resulting in decreased concentrations. Drugs That Should Not Be Coadministered With INVIRASE/Ritonavir Drug Class: Drug Name Clinical Comment Antiarrhythmics: Amiodarone, bepridil, flecainide, propafenone, quinidine CONTRAINDICATED due to potential for serious and/or life-threatening reactions. Antihistamines: astemizole*, terfenadine* CONTRAINDICATED due to potential for serious and/or life-threatening cardiac arrhythmias. Ergot Derivatives: Dihydroergotamine, ergonovine, ergotamine, methylergonovine CONTRAINDICATED due to potential for serious and life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Antimycobacterial Agents: rifampin CONTRAINDICATED since the coadministration of this product with saquinavir in an antiretroviral regimen reduces the plasma concentrations of saquinavir. Garlic Capsules Garlic capsules should not be used while taking saquinavir (FORTOVASE) as the sole protease inhibitor due to the risk of decreased saquinavir plasma concentrations. No data are available for the coadministration of INVIRASE/ritonavir or FORTOVASE/ritonavir and garlic capsules. GI Motility Agent: cisapride* CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. Herbal Products: St. John s wort (hypericum perforatum) WARNING coadministration may lead to loss of virologic response and possible resistance to INVIRASE or to the class of protease inhibitors. HMG-CoA Reductase Inhibitors: lovastatin, simvastatin WARNING potential for serious reactions such as risk of myopathy including rhabdomyolysis. Sedatives/Hypnotics: triazolam, midazolam CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. * No longer marketed in the US. Drugs That Are Mainly Metabolized by CYP3A4 Although specific studies have not been performed, coadministration with drugs that are mainly metabolized by CYP3A4 (eg, calcium channel blockers, dapsone, disopyramide, quinine, amiodarone, quinidine, warfarin, tacrolimus, cyclosporine, ergot derivatives, pimozide, carbamazepine, fentanyl, alfentanyl, alprazolam, and triazolam) may have elevated plasma concentrations when coadministered with saquinavir; therefore, these combinations should be used with caution. Since INVIRASE is coadministered with ritonavir, the ritonavir label should be reviewed for additional drugs that should not be coadministered. Inducers of CYP3A4 Coadministration with compounds that are potent inducers of CYP3A4 (eg, phenobarbital, phenytoin, dexamethasone, carbamazepine) may result in decreased plasma levels of saquinavir." ], "offsets": [ [ 0, 4035 ] ] } ]

[ { "id": "Saquinavir_ddi_T1", "type": "BRAND", "text": [ "INVIRASE" ], "offsets": [ [ 81, 89 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T2", "type": "BRAND", "text": [ "FORTOVASE" ], "offsets": [ [ 94, 103 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T3", "type": "BRAND", "text": [ "FORTOVASE" ], "offsets": [ [ 153, 162 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T4", "type": "BRAND", "text": [ "INVIRASE" ], "offsets": [ [ 189, 197 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T5", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 207, 216 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T6", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 301, 310 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T7", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 385, 395 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T8", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 524, 534 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T9", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 659, 669 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T10", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 682, 692 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T11", "type": "BRAND", "text": [ "INVIRASE" ], "offsets": [ [ 1014, 1022 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T12", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 1027, 1036 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T13", "type": "BRAND", "text": [ "INVIRASE" ], "offsets": [ [ 1382, 1390 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T14", "type": "DRUG", "text": [ "Ritonavir" ], "offsets": [ [ 1391, 1400 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T15", "type": "GROUP", "text": [ "Antiarrhythmics" ], "offsets": [ [ 1440, 1455 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T16", "type": "DRUG", "text": [ "Amiodarone" ], "offsets": [ [ 1457, 1467 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T17", "type": "DRUG", "text": [ "bepridil" ], "offsets": [ [ 1469, 1477 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T18", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1479, 1489 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T19", "type": "DRUG", "text": [ "propafenone" ], "offsets": [ [ 1491, 1502 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T20", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1504, 1513 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T21", "type": "DRUG", "text": [ "Antihistamines" ], "offsets": [ [ 1594, 1608 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T22", "type": "DRUG", "text": [ "astemizole" ], "offsets": [ [ 1610, 1620 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T23", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 1623, 1634 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T24", "type": "GROUP", "text": [ "Ergot Derivatives" ], "offsets": [ [ 1726, 1743 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T25", "type": "DRUG", "text": [ "Dihydroergotamine" ], "offsets": [ [ 1745, 1762 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T26", "type": "DRUG", "text": [ "ergonovine" ], "offsets": [ [ 1764, 1774 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T27", "type": "DRUG", "text": [ "ergotamine" ], "offsets": [ [ 1776, 1786 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T28", "type": "DRUG", "text": [ "methylergonovine" ], "offsets": [ [ 1788, 1804 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T29", "type": "GROUP", "text": [ "ergot" ], "offsets": [ [ 1895, 1900 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T30", "type": "GROUP", "text": [ "Antimycobacterial Agents" ], "offsets": [ [ 1999, 2023 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T31", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 2025, 2033 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T32", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 2098, 2108 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T33", "type": "GROUP", "text": [ "antiretroviral" ], "offsets": [ [ 2115, 2129 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T34", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 2175, 2185 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T35", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 2251, 2261 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T36", "type": "BRAND", "text": [ "FORTOVASE" ], "offsets": [ [ 2263, 2272 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T37", "type": "GROUP", "text": [ "protease inhibitor" ], "offsets": [ [ 2286, 2304 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T38", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 2334, 2344 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T39", "type": "BRAND", "text": [ "INVIRASE" ], "offsets": [ [ 2418, 2426 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T40", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 2427, 2436 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T41", "type": "BRAND", "text": [ "FORTOVASE" ], "offsets": [ [ 2440, 2449 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T42", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 2450, 2459 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T43", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 2500, 2509 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T44", "type": "BRAND", "text": [ "INVIRASE" ], "offsets": [ [ 2766, 2774 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T45", "type": "GROUP", "text": [ "HMG-CoA Reductase Inhibitors" ], "offsets": [ [ 2815, 2843 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T46", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 2845, 2855 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T47", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 2857, 2868 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T48", "type": "GROUP", "text": [ "Sedatives" ], "offsets": [ [ 2960, 2969 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T49", "type": "GROUP", "text": [ "Hypnotics" ], "offsets": [ [ 2970, 2979 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T50", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 2981, 2990 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T51", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 2992, 3001 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T52", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 3346, 3370 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T53", "type": "DRUG", "text": [ "dapsone" ], "offsets": [ [ 3372, 3379 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T54", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 3381, 3393 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T55", "type": "DRUG", "text": [ "quinine" ], "offsets": [ [ 3395, 3402 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T56", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 3404, 3414 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T57", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 3416, 3425 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T58", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3427, 3435 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T59", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 3437, 3447 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T60", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 3449, 3461 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T61", "type": "GROUP", "text": [ "ergot derivatives" ], "offsets": [ [ 3463, 3480 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T62", "type": "DRUG", "text": [ "pimozide" ], "offsets": [ [ 3482, 3490 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T63", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 3492, 3505 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T64", "type": "DRUG", "text": [ "fentanyl" ], "offsets": [ [ 3507, 3515 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T65", "type": "DRUG", "text": [ "alfentanyl" ], "offsets": [ [ 3517, 3527 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T66", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 3529, 3539 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T67", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 3545, 3554 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T68", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 3621, 3631 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T69", "type": "BRAND", "text": [ "INVIRASE" ], "offsets": [ [ 3698, 3706 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T70", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 3730, 3739 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T71", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 3745, 3754 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T72", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 3927, 3940 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T73", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3942, 3951 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T74", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 3953, 3966 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T75", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 3968, 3981 ] ], "normalized": [] }, { "id": "Saquinavir_ddi_T76", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 4024, 4034 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Saquinavir_ddi_R1", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T52", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R2", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T53", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R3", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T54", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R4", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T55", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R5", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T56", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R6", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T57", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R7", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T58", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R8", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T59", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R9", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T60", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R10", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T61", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R11", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T62", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R12", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T63", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R13", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T64", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R14", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T65", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R15", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T66", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R16", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T67", "arg2_id": "Saquinavir_ddi_T68", "normalized": [] }, { "id": "Saquinavir_ddi_R17", "type": "ADVISE", "arg1_id": "Saquinavir_ddi_T69", "arg2_id": "Saquinavir_ddi_T70", "normalized": [] }, { "id": "Saquinavir_ddi_R18", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T72", "arg2_id": "Saquinavir_ddi_T76", "normalized": [] }, { "id": "Saquinavir_ddi_R19", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T73", "arg2_id": "Saquinavir_ddi_T76", "normalized": [] }, { "id": "Saquinavir_ddi_R20", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T74", "arg2_id": "Saquinavir_ddi_T76", "normalized": [] }, { "id": "Saquinavir_ddi_R21", "type": "MECHANISM", "arg1_id": "Saquinavir_ddi_T75", "arg2_id": "Saquinavir_ddi_T76", "normalized": [] } ]

[ { "id": "Conivaptan_ddi__text", "type": "abstract", "text": [ "Digoxin: Coadministration of digoxin, a P-glycoprotein substrate, with oral conivaptan resulted in a reduction in clearance and an increase in digoxin Cmax and AUC values. Therefore, if digoxin is administered with VAPRISOL, the clinician should be alert to the possibility of increases in digoxin levels." ], "offsets": [ [ 0, 305 ] ] } ]

[ { "id": "Conivaptan_ddi_T1", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Conivaptan_ddi_T2", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 29, 36 ] ], "normalized": [] }, { "id": "Conivaptan_ddi_T3", "type": "DRUG", "text": [ "conivaptan" ], "offsets": [ [ 76, 86 ] ], "normalized": [] }, { "id": "Conivaptan_ddi_T4", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 143, 150 ] ], "normalized": [] }, { "id": "Conivaptan_ddi_T5", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 186, 193 ] ], "normalized": [] }, { "id": "Conivaptan_ddi_T6", "type": "BRAND", "text": [ "VAPRISOL" ], "offsets": [ [ 215, 223 ] ], "normalized": [] }, { "id": "Conivaptan_ddi_T7", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 290, 297 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Conivaptan_ddi_R1", "type": "MECHANISM", "arg1_id": "Conivaptan_ddi_T2", "arg2_id": "Conivaptan_ddi_T3", "normalized": [] }, { "id": "Conivaptan_ddi_R2", "type": "MECHANISM", "arg1_id": "Conivaptan_ddi_T5", "arg2_id": "Conivaptan_ddi_T6", "normalized": [] } ]

[ { "id": "Hydroxocobalamin_ddi__text", "type": "abstract", "text": [ "No formal drug interaction studies have been conducted with Cyanokit." ], "offsets": [ [ 0, 69 ] ] } ]

[ { "id": "Hydroxocobalamin_ddi_T1", "type": "BRAND", "text": [ "Cyanokit" ], "offsets": [ [ 60, 68 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Denileukin diftitox_ddi__text", "type": "abstract", "text": [ "No clinical drug interaction studies have been conducted. However, in a single in vivo rodent study denileukin diftitox had no effect on P450 levels." ], "offsets": [ [ 0, 149 ] ] } ]

[ { "id": "Denileukin diftitox_ddi_T1", "type": "DRUG", "text": [ "denileukin diftitox" ], "offsets": [ [ 100, 119 ] ], "normalized": [] } ]

[]

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[ { "id": "Diltiazem_ddi__text", "type": "abstract", "text": [ "Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem hydrochloride concomitantly with other agents known to affect cardiac contractility and/or conduction. Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with Tiazac. As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem is both a substrate and an inhibitor of the cytochrome P-450 3A4 enzyme system. Other drugs that are specific substrates, inhibitors, or inducers of the enzyme system may have a significant impact on the efficacy and side effect profile of diltiazem. Patients taking other drugs that are substrates of CYP450 3A4, especially patients with renal and/or hepatic impairment, may require dosage adjustment when starting or stopping concomitantly administered diltiazem in order to maintain optimum therapeutic blood levels. Beta Blockers Controlled and uncontrolled domestic studies suggest that concomitant use of diltiazem hydrochloride and beta-blockers is usually well tolerated, but available data are not sufficient to predict the effects of concomitant treatment in patients with left ventricular dysfunction or cardiac conduction abnormalities. Administration of diltiazem hydrochloride concomitantly with propranolol in five normal volunteers resulted in increased propranolol levels in all subjects and bioavailability of propranolol was increased approximately 50%. In vitro, propranolol appears to be displaced from its binding sites by diltiazem. If combination therapy is initiated or withdrawn in conjunction with propranolol, an adjustment in the propranolol dose may be warranted. Cimetidine A study in six healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and AUC (53%) after a 1-week course of cimetidine 1200 mg/day and a single dose of diltiazem 60mg. Ranitidine produced smaller, nonsignificant increases. The effect may be mediated by cimetidines known inhibition of hepatic cytochrome P-450, the enzyme system responsible for the first-pass metabolism of diltiazem. Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with cimetidine. An adjustment in the diltiazem dose may be warranted. Digitalis Administration of diltiazem hydrochloride with digoxin in 24 healthy male subjects increased plasma digoxin concentrations approximately 20%. Another investigator found no increase in digoxin levels in 12 patients with coronary artery disease. Since there have been conflicting results regarding the effect of digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing diltiazem hydrochloride therapy to avoid possible over- or under-digitalization. Anesthetics The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with anesthetics may be potentiated by calcium channel blockers. When used concomitantly, anesthetics and calcium channel blockers should be titrated carefully. Cyclosporine A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporine dose ranging from 15% to 48% was necessary to maintain cyclosporine trough concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted, or discontinued. The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated. Carbamazepine Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of carbamazepine (40% to 72% increase), resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction. Benzodiazepines Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3-4 fold and the Cmax by 2-fold, compared to placebo. The elimination half life of midazolam and triazolam also increased (1.5-2.5 fold) during coadministration with diltiazem. These pharmacokinetic effects seen during diltiazem coadministration can result in increased clinical effects (e.g., prolonged sodation)of both midazolam and triazolam. Lovastatin In a ten-subject study, coadministration of diltiazem (120 mg bid) with lovastatin resulted in a 3-4 times increase in mean lovastatin AUC and Cmax vs. lovastatin alone; no change in pravastatin AUC and Cmax was observed during diltiazem coadministration. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin. Rifampin Coadministration of rifampin with diltiazem lowered the diltiazem plasma concentrations to undetectable levels. Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered." ], "offsets": [ [ 0, 5241 ] ] } ]

[ { "id": "Diltiazem_ddi_T1", "type": "DRUG", "text": [ "diltiazem hydrochloride" ], "offsets": [ [ 109, 132 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T2", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 327, 340 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T3", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 344, 353 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T4", "type": "BRAND", "text": [ "Tiazac" ], "offsets": [ [ 373, 379 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T5", "type": "DRUG", "text": [ "Diltiazem" ], "offsets": [ [ 475, 484 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T6", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 725, 734 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T7", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 940, 949 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T8", "type": "GROUP", "text": [ "Beta Blockers" ], "offsets": [ [ 1005, 1018 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T9", "type": "DRUG", "text": [ "diltiazem hydrochloride" ], "offsets": [ [ 1096, 1119 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T10", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 1124, 1137 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T11", "type": "DRUG", "text": [ "diltiazem hydrochloride" ], "offsets": [ [ 1352, 1375 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T12", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1395, 1406 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T13", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1455, 1466 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T14", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1513, 1524 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T15", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1568, 1579 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T16", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 1630, 1639 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T17", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1710, 1721 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T18", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1744, 1755 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T19", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 1779, 1789 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T20", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 1865, 1874 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T21", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1934, 1944 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T22", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 1978, 1987 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T23", "type": "DRUG", "text": [ "Ranitidine" ], "offsets": [ [ 1994, 2004 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T24", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2079, 2089 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T25", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 2200, 2209 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T26", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 2240, 2249 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T27", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2374, 2384 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T28", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 2407, 2416 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T29", "type": "GROUP", "text": [ "Digitalis" ], "offsets": [ [ 2440, 2449 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T30", "type": "DRUG", "text": [ "diltiazem hydrochloride" ], "offsets": [ [ 2468, 2491 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T31", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2497, 2504 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T32", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2550, 2557 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T33", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2634, 2641 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T34", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2760, 2767 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T35", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2799, 2806 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T36", "type": "DRUG", "text": [ "diltiazem hydrochloride" ], "offsets": [ [ 2873, 2896 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T37", "type": "GROUP", "text": [ "Anesthetics" ], "offsets": [ [ 2954, 2965 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T38", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 3087, 3098 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T39", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 3121, 3145 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T40", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 3172, 3183 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T41", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 3188, 3212 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T42", "type": "DRUG", "text": [ "Cyclosporine" ], "offsets": [ [ 3243, 3255 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T43", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 3294, 3303 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T44", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 3308, 3320 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T45", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 3462, 3474 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T46", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 3530, 3542 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T47", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 3612, 3621 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T48", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 3676, 3688 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T49", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 3741, 3750 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T50", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 3814, 3826 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T51", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 3830, 3839 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T52", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 3886, 3899 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T53", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 3930, 3939 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T54", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 3945, 3958 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T55", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 4015, 4028 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T56", "type": "GROUP", "text": [ "Benzodiazepines" ], "offsets": [ [ 4187, 4202 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T57", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 4223, 4232 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T58", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4254, 4263 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T59", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 4268, 4277 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T60", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4364, 4373 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T61", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 4378, 4387 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T62", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 4447, 4456 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T63", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 4500, 4509 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T64", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4602, 4611 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T65", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 4616, 4625 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T66", "type": "DRUG", "text": [ "Lovastatin" ], "offsets": [ [ 4627, 4637 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T67", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 4682, 4691 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T68", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 4710, 4720 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T69", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 4762, 4772 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T70", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 4790, 4800 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T71", "type": "DRUG", "text": [ "pravastatin" ], "offsets": [ [ 4821, 4832 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T72", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 4866, 4875 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T73", "type": "DRUG", "text": [ "Diltiazem" ], "offsets": [ [ 4894, 4903 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T74", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 4953, 4963 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T75", "type": "DRUG", "text": [ "pravastatin" ], "offsets": [ [ 4967, 4978 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T76", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 4980, 4988 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T77", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 5009, 5017 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T78", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 5023, 5032 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T79", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 5045, 5054 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T80", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 5121, 5130 ] ], "normalized": [] }, { "id": "Diltiazem_ddi_T81", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 5136, 5144 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Diltiazem_ddi_R1", "type": "EFFECT", "arg1_id": "Diltiazem_ddi_T2", "arg2_id": "Diltiazem_ddi_T4", "normalized": [] }, { "id": "Diltiazem_ddi_R2", "type": "EFFECT", "arg1_id": "Diltiazem_ddi_T3", "arg2_id": "Diltiazem_ddi_T4", "normalized": [] }, { "id": "Diltiazem_ddi_R3", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T11", "arg2_id": "Diltiazem_ddi_T12", "normalized": [] }, { "id": "Diltiazem_ddi_R4", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T15", "arg2_id": "Diltiazem_ddi_T16", "normalized": [] }, { "id": "Diltiazem_ddi_R5", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T21", "arg2_id": "Diltiazem_ddi_T22", "normalized": [] }, { "id": "Diltiazem_ddi_R6", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T24", "arg2_id": "Diltiazem_ddi_T25", "normalized": [] }, { "id": "Diltiazem_ddi_R7", "type": "ADVISE", "arg1_id": "Diltiazem_ddi_T26", "arg2_id": "Diltiazem_ddi_T27", "normalized": [] }, { "id": "Diltiazem_ddi_R8", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T30", "arg2_id": "Diltiazem_ddi_T31", "normalized": [] }, { "id": "Diltiazem_ddi_R9", "type": "ADVISE", "arg1_id": "Diltiazem_ddi_T35", "arg2_id": "Diltiazem_ddi_T36", "normalized": [] }, { "id": "Diltiazem_ddi_R10", "type": "EFFECT", "arg1_id": "Diltiazem_ddi_T38", "arg2_id": "Diltiazem_ddi_T39", "normalized": [] }, { "id": "Diltiazem_ddi_R11", "type": "ADVISE", "arg1_id": "Diltiazem_ddi_T40", "arg2_id": "Diltiazem_ddi_T41", "normalized": [] }, { "id": "Diltiazem_ddi_R12", "type": "INT", "arg1_id": "Diltiazem_ddi_T43", "arg2_id": "Diltiazem_ddi_T44", "normalized": [] }, { "id": "Diltiazem_ddi_R13", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T45", "arg2_id": "Diltiazem_ddi_T47", "normalized": [] }, { "id": "Diltiazem_ddi_R14", "type": "ADVISE", "arg1_id": "Diltiazem_ddi_T48", "arg2_id": "Diltiazem_ddi_T49", "normalized": [] }, { "id": "Diltiazem_ddi_R15", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T53", "arg2_id": "Diltiazem_ddi_T54", "normalized": [] }, { "id": "Diltiazem_ddi_R16", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T57", "arg2_id": "Diltiazem_ddi_T58", "normalized": [] }, { "id": "Diltiazem_ddi_R17", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T57", "arg2_id": "Diltiazem_ddi_T59", "normalized": [] }, { "id": "Diltiazem_ddi_R18", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T60", "arg2_id": "Diltiazem_ddi_T62", "normalized": [] }, { "id": "Diltiazem_ddi_R19", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T61", "arg2_id": "Diltiazem_ddi_T62", "normalized": [] }, { "id": "Diltiazem_ddi_R20", "type": "EFFECT", "arg1_id": "Diltiazem_ddi_T63", "arg2_id": "Diltiazem_ddi_T64", "normalized": [] }, { "id": "Diltiazem_ddi_R21", "type": "EFFECT", "arg1_id": "Diltiazem_ddi_T63", "arg2_id": "Diltiazem_ddi_T65", "normalized": [] }, { "id": "Diltiazem_ddi_R22", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T67", "arg2_id": "Diltiazem_ddi_T68", "normalized": [] }, { "id": "Diltiazem_ddi_R23", "type": "MECHANISM", "arg1_id": "Diltiazem_ddi_T77", "arg2_id": "Diltiazem_ddi_T78", "normalized": [] }, { "id": "Diltiazem_ddi_R24", "type": "ADVISE", "arg1_id": "Diltiazem_ddi_T80", "arg2_id": "Diltiazem_ddi_T81", "normalized": [] } ]

[ { "id": "Fluoxetine_ddi__text", "type": "abstract", "text": [ "Do not take this medicine with thioridizine, or within 5 weeks of taking fluoxetine. Talk to your doctor if you are taking certain antibiotics such as erythromycin, clarithromycin or azithromycin. This medicine should not be taken with MAO inhibitors. Caution should be exercised when taking this medicine certain antibiotics, such as erythromycin, clarithromycin, or azithromycin. This medicine should not be taken with MAO inhibitors. If you think you are taking an MAO inhibitor talk to your doctor or pharmacist. Do not take this medicine with St. Johns Wort because of the additive effects of sertonin. This medication should not be taken with MAO inhibitors. Your doctor or pharmacist can give you more information on MAO inhibitors. Wait 5 weeks after stopping escitalopram before starting a non-selective MAO inhibitor. Wait 2 weeks after stopping an MAO inhibitor before starting escitalopram. If you are taking medications for migraines such as Imitrex, talk to your doctor before starting this medicine. If you are taking a tricyclic antidepressant, talk to your doctor before taking this medicine. St. John s Wort should be avoided while taking this medicine due to the additive effects of serotonin. Tell your doctor if you are taking any of the following drugs: blood thinners (Coumadin) other antidepressants metoprolol antihistamines carbamazepine (Tegretol) cimetidine (Tagamet) estrogens fluoxetine (Prozac) intraconazole (Sporanox) ketoconazole (Nizoral) levodopa lithium muscle relaxants birth control pills sleeping pills thyroid medications" ], "offsets": [ [ 0, 1563 ] ] } ]

[ { "id": "Fluoxetine_ddi_T1", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 73, 83 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T2", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 131, 142 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T3", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 151, 163 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T4", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 165, 179 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T5", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 183, 195 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T6", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 236, 250 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T7", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 314, 325 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T8", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 335, 347 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T9", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 349, 363 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T10", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 368, 380 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T11", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 421, 435 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T12", "type": "GROUP", "text": [ "MAO inhibitor" ], "offsets": [ [ 468, 481 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T13", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 649, 663 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T14", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 724, 738 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T15", "type": "DRUG", "text": [ "escitalopram" ], "offsets": [ [ 768, 780 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T16", "type": "GROUP", "text": [ "non-selective MAO inhibitor" ], "offsets": [ [ 799, 826 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T17", "type": "GROUP", "text": [ "MAO inhibitor" ], "offsets": [ [ 859, 872 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T18", "type": "DRUG", "text": [ "escitalopram" ], "offsets": [ [ 889, 901 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T19", "type": "BRAND", "text": [ "Imitrex" ], "offsets": [ [ 955, 962 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T20", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 1035, 1059 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T21", "type": "GROUP", "text": [ "blood thinner" ], "offsets": [ [ 1277, 1290 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T22", "type": "BRAND", "text": [ "Coumadin" ], "offsets": [ [ 1293, 1301 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T23", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 1309, 1324 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T24", "type": "DRUG", "text": [ "metoprolol" ], "offsets": [ [ 1325, 1335 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T25", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 1336, 1350 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T26", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1351, 1364 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T27", "type": "BRAND", "text": [ "Tegretol" ], "offsets": [ [ 1366, 1374 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T28", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1376, 1386 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T29", "type": "BRAND", "text": [ "Tagamet" ], "offsets": [ [ 1388, 1395 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T30", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 1397, 1406 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T31", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1407, 1417 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T32", "type": "BRAND", "text": [ "Prozac" ], "offsets": [ [ 1419, 1425 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T33", "type": "BRAND", "text": [ "Sporanox" ], "offsets": [ [ 1442, 1450 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T34", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1452, 1464 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T35", "type": "BRAND", "text": [ "Nizoral" ], "offsets": [ [ 1466, 1473 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T36", "type": "DRUG", "text": [ "levodopa" ], "offsets": [ [ 1475, 1483 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T37", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1484, 1491 ] ], "normalized": [] }, { "id": "Fluoxetine_ddi_T38", "type": "GROUP", "text": [ "muscle relaxants" ], "offsets": [ [ 1492, 1508 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Fluoxetine_ddi_R1", "type": "ADVISE", "arg1_id": "Fluoxetine_ddi_T15", "arg2_id": "Fluoxetine_ddi_T16", "normalized": [] }, { "id": "Fluoxetine_ddi_R2", "type": "ADVISE", "arg1_id": "Fluoxetine_ddi_T17", "arg2_id": "Fluoxetine_ddi_T18", "normalized": [] } ]

[ { "id": "Acitretin_ddi__text", "type": "abstract", "text": [ "Ethanol:Clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and ethanol. Glibenclamide: In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with Soriatane is recommended. Hormonal Contraceptives: It has not been established if there is a pharmacokinetic interaction between acitretin and combined oral contraceptives. However, it has been established that acitretin interferes with the contraceptive effect of microdosed progestin minipill preparations. Microdosed minipill progestin preparations are not recommended for use with Soriatane. It is not known whether other progestational contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy. Methotrexate: An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. Consequently, the combination of methotrexate with acitretin is also contraindicated. Phenytoin: If acitretin is given concurrently with phenytoin, the protein binding of phenytoin may be reduced. Tetracyclines: Since both acitretin and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated. Vitamin A and oral retinoids: Concomitant administration of vitamin A and/or other oral retinoids with acitretin must be avoided because of the risk of hypervitaminosis A. Other: There appears to be no pharmacokinetic interaction between acitretin and cimetidine, digoxin, or glyburide. Investigations into the effect of acitretin on the protein binding of anticoagulants of the coumarin type (warfarin) revealed no interaction. Laboratory Tests If significant abnormal laboratory results are obtained, either dosage reduction with careful monitoring or treatment discontinuation is recommended, depending on clinical judgement. Blood Sugar: Some patients receiving retinoids have experienced problems with blood sugar control. In addition, new cases of diabetes have been diagnosed during retinoid therapy, including diabetic ketoacidosis. In diabetics, blood-sugar levels should be monitored very carefully. Lipids: In clinical studies, the incidence of hypertriglyceridemia was 66%, hypercholesterolemia was 33% and that of decreased HDL was 40%. Pretreatment and follow-up measurements should be obtained under fasting conditions. It is recommended that these tests be performed weekly or every other week until the lipid response to Soriatane has stabilized. Liver Function Tests: Elevations of AST (SGOT), ALT (SGPT) or LDH were experienced by approximately 1 in 3 patients treated with Soriatane. It is recommended that these tests be performed prior to initiation of Soriatane therapy, at 1- to 2-week intervals until stable and thereafter at intervals as clinically indicated." ], "offsets": [ [ 0, 3125 ] ] } ]

[ { "id": "Acitretin_ddi_T1", "type": "DRUG", "text": [ "Ethanol" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T2", "type": "DRUG", "text": [ "etretinate" ], "offsets": [ [ 41, 51 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T3", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 95, 104 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T4", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 109, 116 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T5", "type": "DRUG", "text": [ "Glibenclamide" ], "offsets": [ [ 118, 131 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T6", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 174, 183 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T7", "type": "DRUG", "text": [ "glibenclamide" ], "offsets": [ [ 243, 256 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T8", "type": "GROUP", "text": [ "sulfonylurea" ], "offsets": [ [ 260, 272 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T9", "type": "DRUG", "text": [ "chlorpropamide" ], "offsets": [ [ 284, 298 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T10", "type": "DRUG", "text": [ "glibenclamide" ], "offsets": [ [ 393, 406 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T11", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 435, 444 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T12", "type": "BRAND", "text": [ "Soriatane" ], "offsets": [ [ 529, 538 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T13", "type": "GROUP", "text": [ "Hormonal Contraceptives" ], "offsets": [ [ 555, 578 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T14", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 658, 667 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T15", "type": "GROUP", "text": [ "combined oral contraceptives" ], "offsets": [ [ 672, 700 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T16", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 740, 749 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T17", "type": "DRUG", "text": [ "progestin" ], "offsets": [ [ 805, 814 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T18", "type": "DRUG", "text": [ "progestin" ], "offsets": [ [ 858, 867 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T19", "type": "DRUG", "text": [ "Soriatane" ], "offsets": [ [ 914, 923 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T20", "type": "GROUP", "text": [ "progestational contraceptives" ], "offsets": [ [ 955, 984 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T21", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 1065, 1074 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T22", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 1084, 1096 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T23", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1178, 1190 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T24", "type": "DRUG", "text": [ "etretinate" ], "offsets": [ [ 1195, 1205 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T25", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1240, 1252 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T26", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 1258, 1267 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T27", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 1293, 1302 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T28", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 1307, 1316 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T29", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1344, 1353 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T30", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1378, 1387 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T31", "type": "GROUP", "text": [ "Tetracyclines" ], "offsets": [ [ 1404, 1417 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T32", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 1430, 1439 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T33", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 1444, 1457 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T34", "type": "GROUP", "text": [ "Vitamin A" ], "offsets": [ [ 1540, 1549 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T35", "type": "GROUP", "text": [ "retinoids" ], "offsets": [ [ 1559, 1568 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T36", "type": "GROUP", "text": [ "vitamin A" ], "offsets": [ [ 1600, 1609 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T37", "type": "GROUP", "text": [ "retinoids" ], "offsets": [ [ 1628, 1637 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T38", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 1643, 1652 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T39", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 1778, 1787 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T40", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1792, 1802 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T41", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1804, 1811 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T42", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 1816, 1825 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T43", "type": "DRUG", "text": [ "acitretin" ], "offsets": [ [ 1861, 1870 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T44", "type": "GROUP", "text": [ "anticoagulants of the coumarin type" ], "offsets": [ [ 1897, 1932 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T45", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1934, 1942 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T46", "type": "GROUP", "text": [ "retinoids" ], "offsets": [ [ 2206, 2215 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T47", "type": "GROUP", "text": [ "retinoid" ], "offsets": [ [ 2330, 2338 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T48", "type": "BRAND", "text": [ "Soriatane" ], "offsets": [ [ 2778, 2787 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T49", "type": "BRAND", "text": [ "Soriatane" ], "offsets": [ [ 2933, 2942 ] ], "normalized": [] }, { "id": "Acitretin_ddi_T50", "type": "BRAND", "text": [ "Soriatane" ], "offsets": [ [ 3015, 3024 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Acitretin_ddi_R1", "type": "MECHANISM", "arg1_id": "Acitretin_ddi_T3", "arg2_id": "Acitretin_ddi_T4", "normalized": [] }, { "id": "Acitretin_ddi_R2", "type": "EFFECT", "arg1_id": "Acitretin_ddi_T6", "arg2_id": "Acitretin_ddi_T7", "normalized": [] }, { "id": "Acitretin_ddi_R3", "type": "EFFECT", "arg1_id": "Acitretin_ddi_T16", "arg2_id": "Acitretin_ddi_T17", "normalized": [] }, { "id": "Acitretin_ddi_R4", "type": "ADVISE", "arg1_id": "Acitretin_ddi_T18", "arg2_id": "Acitretin_ddi_T19", "normalized": [] }, { "id": "Acitretin_ddi_R5", "type": "EFFECT", "arg1_id": "Acitretin_ddi_T23", "arg2_id": "Acitretin_ddi_T24", "normalized": [] }, { "id": "Acitretin_ddi_R6", "type": "ADVISE", "arg1_id": "Acitretin_ddi_T25", "arg2_id": "Acitretin_ddi_T26", "normalized": [] }, { "id": "Acitretin_ddi_R7", "type": "MECHANISM", "arg1_id": "Acitretin_ddi_T28", "arg2_id": "Acitretin_ddi_T29", "normalized": [] }, { "id": "Acitretin_ddi_R8", "type": "EFFECT", "arg1_id": "Acitretin_ddi_T32", "arg2_id": "Acitretin_ddi_T33", "normalized": [] }, { "id": "Acitretin_ddi_R9", "type": "ADVISE", "arg1_id": "Acitretin_ddi_T36", "arg2_id": "Acitretin_ddi_T38", "normalized": [] }, { "id": "Acitretin_ddi_R10", "type": "ADVISE", "arg1_id": "Acitretin_ddi_T37", "arg2_id": "Acitretin_ddi_T38", "normalized": [] } ]

[ { "id": "Alprazolam_ddi__text", "type": "abstract", "text": [ "The benzodiazepines, including alprazolam, produce additive CNS depressant effects when co-administered with other psychotropic medications, anticonvulsants, antihistaminics, ethanol, and other drugs which themselves produce CNS depression. The steady state plasma concentrations of imipramine and desipramine have been reported to be increased an average of 31% and 20%, respectively, by the concomitant administration of alprazolam tablets in doses up to 4 mg/day. The clinical significance of these changes is unknown. Drugs That Inhibit Alprazolam Metabolism Via Cytochrome P450 3A: The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP 3A). Drugs which inhibit this metabolic pathway may have a profound effect on the clearance of alprazolam . Drugs Demonstrated to be CYP 3A Inhibitors of Possible Clinical Significance on the Basis of Clinical Studies Involving Alprazolam (caution is recommended during coadministration with alprazolam): Coadministration of fluoxetine with alprazolam increased the maximum plasma concentration of alprazolam by 46%, decreased clearance by 21%, increased half-life by 17%, and decreased measured psychomotor performance. Coadministration of propoxyphene decreased the maximum plasma concentration of alprazolam by 6%, decreased clearance by 38%, and increased half-life by 58%. Coadministration of oral contraceptives increased the maximum plasma concentration of alprazolam by 18%, decreased clearance by 22%, and increased half-life by 29%. Drugs and other substances demonstrated to be CYP 3A inhibitors on the basis of clinical studies involving benzodiazepines metabolized similarly to alprazolam or on the basis of in vitro studies with alprazolam or other benzodiazepines (caution is recommended during coadministration with alprazolam): Available data from clinical studies of benzodiazepines other than alprazolam suggest a possible drug interaction with alprazolam for the following: diltiazem, isoniazid, macrolide antibiotics such as erythromycin and clarithromycin, and grapefruit juice. Data from in vitro studies of alprazolam suggest a possible drug interaction with alprazolam for the following: sertraline and paroxetine. Data from in vitro studies of benzodiazepines other than alprazolam suggest a possible drug interaction for the following: ergotamine, cyclosporine, amiodarone, nicardipine, and nifedipine. Caution is recommended during the coadministration of any of these with alprazolam." ], "offsets": [ [ 0, 2496 ] ] } ]

[ { "id": "Alprazolam_ddi_T1", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 4, 19 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T2", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 31, 41 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T3", "type": "GROUP", "text": [ "psychotropic medications" ], "offsets": [ [ 115, 139 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T4", "type": "GROUP", "text": [ "anticonvulsants" ], "offsets": [ [ 141, 156 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T5", "type": "GROUP", "text": [ "antihistaminics" ], "offsets": [ [ 158, 173 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T6", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 175, 182 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T7", "type": "DRUG", "text": [ "imipramine" ], "offsets": [ [ 283, 293 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T8", "type": "DRUG", "text": [ "desipramine" ], "offsets": [ [ 298, 309 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T9", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 423, 433 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T10", "type": "DRUG", "text": [ "Alprazolam" ], "offsets": [ [ 541, 551 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T11", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 607, 617 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T12", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 778, 788 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T13", "type": "DRUG", "text": [ "Alprazolam" ], "offsets": [ [ 911, 921 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T14", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 975, 985 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T15", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1008, 1018 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T16", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1024, 1034 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T17", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1081, 1091 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T18", "type": "DRUG", "text": [ "propoxyphene" ], "offsets": [ [ 1224, 1236 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T19", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1283, 1293 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T20", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 1386, 1400 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T21", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1447, 1457 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T22", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 1633, 1648 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T23", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1674, 1684 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T24", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1726, 1736 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T25", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 1746, 1761 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T26", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1815, 1825 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T27", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 1868, 1883 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T28", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1895, 1905 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T29", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1947, 1957 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T30", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 1977, 1986 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T31", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 1988, 1997 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T32", "type": "GROUP", "text": [ "macrolide antibiotics" ], "offsets": [ [ 1999, 2020 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T33", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 2029, 2041 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T34", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 2046, 2060 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T35", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 2114, 2124 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T36", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 2166, 2176 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T37", "type": "DRUG", "text": [ "sertraline" ], "offsets": [ [ 2196, 2206 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T38", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 2211, 2221 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T39", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 2253, 2268 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T40", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 2280, 2290 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T41", "type": "DRUG", "text": [ "ergotamine" ], "offsets": [ [ 2346, 2356 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T42", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2358, 2370 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T43", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 2372, 2382 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T44", "type": "DRUG", "text": [ "nicardipine" ], "offsets": [ [ 2384, 2395 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T45", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 2401, 2411 ] ], "normalized": [] }, { "id": "Alprazolam_ddi_T46", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 2485, 2495 ] ], "normalized": [] } ]

[]

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[ { "id": "Alprazolam_ddi_R1", "type": "EFFECT", "arg1_id": "Alprazolam_ddi_T1", "arg2_id": "Alprazolam_ddi_T3", "normalized": [] }, { "id": "Alprazolam_ddi_R2", "type": "EFFECT", "arg1_id": "Alprazolam_ddi_T1", "arg2_id": "Alprazolam_ddi_T4", "normalized": [] }, { "id": "Alprazolam_ddi_R3", "type": "EFFECT", "arg1_id": "Alprazolam_ddi_T1", "arg2_id": "Alprazolam_ddi_T5", "normalized": [] }, { "id": "Alprazolam_ddi_R4", "type": "EFFECT", "arg1_id": "Alprazolam_ddi_T1", "arg2_id": "Alprazolam_ddi_T6", "normalized": [] }, { "id": "Alprazolam_ddi_R5", "type": "EFFECT", "arg1_id": "Alprazolam_ddi_T2", "arg2_id": "Alprazolam_ddi_T3", "normalized": [] }, { "id": "Alprazolam_ddi_R6", "type": "EFFECT", "arg1_id": "Alprazolam_ddi_T2", "arg2_id": "Alprazolam_ddi_T4", "normalized": [] }, { "id": "Alprazolam_ddi_R7", "type": "EFFECT", "arg1_id": "Alprazolam_ddi_T2", "arg2_id": "Alprazolam_ddi_T5", "normalized": [] }, { "id": "Alprazolam_ddi_R8", "type": "EFFECT", "arg1_id": "Alprazolam_ddi_T2", "arg2_id": "Alprazolam_ddi_T6", "normalized": [] }, { "id": "Alprazolam_ddi_R9", "type": "MECHANISM", "arg1_id": "Alprazolam_ddi_T7", "arg2_id": "Alprazolam_ddi_T9", "normalized": [] }, { "id": "Alprazolam_ddi_R10", "type": "MECHANISM", "arg1_id": "Alprazolam_ddi_T8", "arg2_id": "Alprazolam_ddi_T9", "normalized": [] }, { "id": "Alprazolam_ddi_R11", "type": "MECHANISM", "arg1_id": "Alprazolam_ddi_T15", "arg2_id": "Alprazolam_ddi_T16", "normalized": [] }, { "id": "Alprazolam_ddi_R12", "type": "MECHANISM", "arg1_id": "Alprazolam_ddi_T18", "arg2_id": "Alprazolam_ddi_T19", "normalized": [] }, { "id": "Alprazolam_ddi_R13", "type": "MECHANISM", "arg1_id": "Alprazolam_ddi_T20", "arg2_id": "Alprazolam_ddi_T21", "normalized": [] }, { "id": "Alprazolam_ddi_R14", "type": "INT", "arg1_id": "Alprazolam_ddi_T29", "arg2_id": "Alprazolam_ddi_T30", "normalized": [] }, { "id": "Alprazolam_ddi_R15", "type": "INT", "arg1_id": "Alprazolam_ddi_T29", "arg2_id": "Alprazolam_ddi_T31", "normalized": [] }, { "id": "Alprazolam_ddi_R16", "type": "INT", "arg1_id": "Alprazolam_ddi_T29", "arg2_id": "Alprazolam_ddi_T32", "normalized": [] }, { "id": "Alprazolam_ddi_R17", "type": "INT", "arg1_id": "Alprazolam_ddi_T29", "arg2_id": "Alprazolam_ddi_T33", "normalized": [] }, { "id": "Alprazolam_ddi_R18", "type": "INT", "arg1_id": "Alprazolam_ddi_T29", "arg2_id": "Alprazolam_ddi_T34", "normalized": [] }, { "id": "Alprazolam_ddi_R19", "type": "INT", "arg1_id": "Alprazolam_ddi_T36", "arg2_id": "Alprazolam_ddi_T37", "normalized": [] }, { "id": "Alprazolam_ddi_R20", "type": "INT", "arg1_id": "Alprazolam_ddi_T36", "arg2_id": "Alprazolam_ddi_T38", "normalized": [] }, { "id": "Alprazolam_ddi_R21", "type": "INT", "arg1_id": "Alprazolam_ddi_T39", "arg2_id": "Alprazolam_ddi_T41", "normalized": [] }, { "id": "Alprazolam_ddi_R22", "type": "INT", "arg1_id": "Alprazolam_ddi_T39", "arg2_id": "Alprazolam_ddi_T42", "normalized": [] }, { "id": "Alprazolam_ddi_R23", "type": "INT", "arg1_id": "Alprazolam_ddi_T39", "arg2_id": "Alprazolam_ddi_T43", "normalized": [] }, { "id": "Alprazolam_ddi_R24", "type": "INT", "arg1_id": "Alprazolam_ddi_T39", "arg2_id": "Alprazolam_ddi_T44", "normalized": [] }, { "id": "Alprazolam_ddi_R25", "type": "INT", "arg1_id": "Alprazolam_ddi_T39", "arg2_id": "Alprazolam_ddi_T45", "normalized": [] }, { "id": "Alprazolam_ddi_R26", "type": "INT", "arg1_id": "Alprazolam_ddi_T40", "arg2_id": "Alprazolam_ddi_T41", "normalized": [] }, { "id": "Alprazolam_ddi_R27", "type": "INT", "arg1_id": "Alprazolam_ddi_T40", "arg2_id": "Alprazolam_ddi_T42", "normalized": [] }, { "id": "Alprazolam_ddi_R28", "type": "INT", "arg1_id": "Alprazolam_ddi_T40", "arg2_id": "Alprazolam_ddi_T43", "normalized": [] }, { "id": "Alprazolam_ddi_R29", "type": "INT", "arg1_id": "Alprazolam_ddi_T40", "arg2_id": "Alprazolam_ddi_T44", "normalized": [] }, { "id": "Alprazolam_ddi_R30", "type": "INT", "arg1_id": "Alprazolam_ddi_T40", "arg2_id": "Alprazolam_ddi_T45", "normalized": [] } ]

[ { "id": "Dipyridamole_ddi__text", "type": "abstract", "text": [ "No pharmacokinetic drug-drug interaction studies were conducted with PERSANTINE (dipyridamole USP) Tablets. The following information was obtained from the literature. Adenosine: Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Cholinesterase Inhibitors: Dipyridamole may counteract the anticholinesterase effect of cholinesterase inhibitors, thereby potentially aggravating myasthenia gravis." ], "offsets": [ [ 0, 496 ] ] } ]

[ { "id": "Dipyridamole_ddi_T1", "type": "BRAND", "text": [ "PERSANTINE" ], "offsets": [ [ 69, 79 ] ], "normalized": [] }, { "id": "Dipyridamole_ddi_T2", "type": "DRUG", "text": [ "dipyridamole" ], "offsets": [ [ 82, 94 ] ], "normalized": [] }, { "id": "Dipyridamole_ddi_T3", "type": "DRUG", "text": [ "Adenosine" ], "offsets": [ [ 169, 178 ] ], "normalized": [] }, { "id": "Dipyridamole_ddi_T4", "type": "DRUG", "text": [ "Dipyridamole" ], "offsets": [ [ 180, 192 ] ], "normalized": [] }, { "id": "Dipyridamole_ddi_T5", "type": "DRUG", "text": [ "adenosine" ], "offsets": [ [ 271, 280 ] ], "normalized": [] }, { "id": "Dipyridamole_ddi_T6", "type": "DRUG", "text": [ "adenosine" ], "offsets": [ [ 296, 305 ] ], "normalized": [] }, { "id": "Dipyridamole_ddi_T7", "type": "GROUP", "text": [ "Cholinesterase Inhibitors" ], "offsets": [ [ 331, 356 ] ], "normalized": [] }, { "id": "Dipyridamole_ddi_T8", "type": "DRUG", "text": [ "Dipyridamole" ], "offsets": [ [ 358, 370 ] ], "normalized": [] }, { "id": "Dipyridamole_ddi_T9", "type": "GROUP", "text": [ "cholinesterase inhibitors" ], "offsets": [ [ 419, 444 ] ], "normalized": [] } ]

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[ { "id": "Dipyridamole_ddi_R1", "type": "MECHANISM", "arg1_id": "Dipyridamole_ddi_T4", "arg2_id": "Dipyridamole_ddi_T5", "normalized": [] }, { "id": "Dipyridamole_ddi_R2", "type": "EFFECT", "arg1_id": "Dipyridamole_ddi_T8", "arg2_id": "Dipyridamole_ddi_T9", "normalized": [] } ]

[ { "id": "Daunorubicin_ddi__text", "type": "abstract", "text": [ "Use of Cerubidine in a patient who has previously received doxorubicin increases the risk of cardiotoxicity. Cerubidine should not be used in patients who have previously received the recommended maximum cumulative doses of doxorubicin or Cerubidine. Cyclophosphamide used concurrently with Cerubidine may also result in increased cardiotoxicity. Dosage reduction of Cerubidine may be required when used concurrently with other myelosuppressive agents. Hepatotoxic medications, such as high-dose methotrexate, may impair liver function and increase the risk of toxicity." ], "offsets": [ [ 0, 570 ] ] } ]

[ { "id": "Daunorubicin_ddi_T1", "type": "BRAND", "text": [ "Cerubidine" ], "offsets": [ [ 7, 17 ] ], "normalized": [] }, { "id": "Daunorubicin_ddi_T2", "type": "DRUG", "text": [ "doxorubicin" ], "offsets": [ [ 59, 70 ] ], "normalized": [] }, { "id": "Daunorubicin_ddi_T3", "type": "BRAND", "text": [ "Cerubidine" ], "offsets": [ [ 109, 119 ] ], "normalized": [] }, { "id": "Daunorubicin_ddi_T4", "type": "DRUG", "text": [ "doxorubicin" ], "offsets": [ [ 224, 235 ] ], "normalized": [] }, { "id": "Daunorubicin_ddi_T5", "type": "BRAND", "text": [ "Cerubidine" ], "offsets": [ [ 239, 249 ] ], "normalized": [] }, { "id": "Daunorubicin_ddi_T6", "type": "DRUG", "text": [ "Cyclophosphamide" ], "offsets": [ [ 251, 267 ] ], "normalized": [] }, { "id": "Daunorubicin_ddi_T7", "type": "BRAND", "text": [ "Cerubidine" ], "offsets": [ [ 291, 301 ] ], "normalized": [] }, { "id": "Daunorubicin_ddi_T8", "type": "BRAND", "text": [ "Cerubidine" ], "offsets": [ [ 367, 377 ] ], "normalized": [] }, { "id": "Daunorubicin_ddi_T9", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 496, 508 ] ], "normalized": [] } ]

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[ { "id": "Daunorubicin_ddi_R1", "type": "EFFECT", "arg1_id": "Daunorubicin_ddi_T1", "arg2_id": "Daunorubicin_ddi_T2", "normalized": [] }, { "id": "Daunorubicin_ddi_R2", "type": "ADVISE", "arg1_id": "Daunorubicin_ddi_T3", "arg2_id": "Daunorubicin_ddi_T4", "normalized": [] }, { "id": "Daunorubicin_ddi_R3", "type": "EFFECT", "arg1_id": "Daunorubicin_ddi_T6", "arg2_id": "Daunorubicin_ddi_T7", "normalized": [] } ]

[ { "id": "Echothiophate Iodide_ddi__text", "type": "abstract", "text": [ "Phospholine Iodide potentiates other cholinesterase inhibitors such as succinylcholine or organophosphate and carbamate insecticides. Patients undergoing systemic anticholinesterase treatment should be warned of the possible additive effects of Phospholine Iodide." ], "offsets": [ [ 0, 264 ] ] } ]

[ { "id": "Echothiophate Iodide_ddi_T1", "type": "DRUG", "text": [ "Phospholine Iodide" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "Echothiophate Iodide_ddi_T2", "type": "GROUP", "text": [ "cholinesterase inhibitors" ], "offsets": [ [ 37, 62 ] ], "normalized": [] }, { "id": "Echothiophate Iodide_ddi_T3", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 71, 86 ] ], "normalized": [] }, { "id": "Echothiophate Iodide_ddi_T4", "type": "DRUG_N", "text": [ "organophosphate", "insecticide" ], "offsets": [ [ 90, 105 ], [ 120, 131 ] ], "normalized": [] }, { "id": "Echothiophate Iodide_ddi_T5", "type": "DRUG_N", "text": [ "carbamate insecticide" ], "offsets": [ [ 110, 131 ] ], "normalized": [] }, { "id": "Echothiophate Iodide_ddi_T6", "type": "DRUG", "text": [ "Phospholine Iodide" ], "offsets": [ [ 245, 263 ] ], "normalized": [] } ]

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[ { "id": "Echothiophate Iodide_ddi_R1", "type": "EFFECT", "arg1_id": "Echothiophate Iodide_ddi_T1", "arg2_id": "Echothiophate Iodide_ddi_T2", "normalized": [] }, { "id": "Echothiophate Iodide_ddi_R2", "type": "EFFECT", "arg1_id": "Echothiophate Iodide_ddi_T1", "arg2_id": "Echothiophate Iodide_ddi_T3", "normalized": [] }, { "id": "Echothiophate Iodide_ddi_R3", "type": "EFFECT", "arg1_id": "Echothiophate Iodide_ddi_T1", "arg2_id": "Echothiophate Iodide_ddi_T4", "normalized": [] }, { "id": "Echothiophate Iodide_ddi_R4", "type": "EFFECT", "arg1_id": "Echothiophate Iodide_ddi_T1", "arg2_id": "Echothiophate Iodide_ddi_T5", "normalized": [] } ]

[ { "id": "Loratadine_ddi__text", "type": "abstract", "text": [ "Loratadine (10 mg once daily) has been coadministered with therapeutic doses of erythromycin, cimetidine, and ketoconazole in controlled clinical pharmacology studies in adult volunteers. Although increased plasma concentrations (AUC 0-24 hrs) of loratadine and/or descarboethoxyloratadine were observed following coadministration of loratadine with each of these drugs in normal volunteers (n = 24 in each study), there were no clinically relevant changes in the safety profile of loratadine, as assessed by electrocardiographic parameters, clinical laboratory tests, vital signs, and adverse events. There were no significant effects on QTc intervals, and no reports of sedation or syncope. No effects on plasma concentrations of cimetidine or ketoconazole were observed. Plasma concentrations (AUC 0-24 hrs) of erythromycin decreased 15% with coadministration of loratadine relative to that observed with erythromycin alone. The clinical relevance of this difference is unknown. These above findings are summarized in TABLE 1. TABLE 1 Effects on Plasma Concentrations (AUC 0-24 hrs) of Loratadine and Descarboethoxyloratadine After 10 Days of Coadministration (Loratadine 10 mg) in Normal Volunteers Loratadine Descarboethoxyloratadine Erythromycin (500 mg q8h) + 40% +46% Cimetidine (300 mg qid) +103% + 6% Ketoconazole (200 mg q12h) +307% +73% There does not appear to be an increase in adverse events in subjects who received oral contraceptives and loratadine." ], "offsets": [ [ 0, 1467 ] ] } ]

[ { "id": "Loratadine_ddi_T1", "type": "DRUG", "text": [ "Loratadine" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T2", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 80, 92 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T3", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 94, 104 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T4", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 110, 122 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T5", "type": "DRUG", "text": [ "loratadine" ], "offsets": [ [ 247, 257 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T6", "type": "DRUG", "text": [ "descarboethoxyloratadine" ], "offsets": [ [ 265, 289 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T7", "type": "DRUG", "text": [ "loratadine" ], "offsets": [ [ 334, 344 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T8", "type": "DRUG", "text": [ "loratadine" ], "offsets": [ [ 482, 492 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T9", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 732, 742 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T10", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 746, 758 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T11", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 814, 826 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T12", "type": "DRUG", "text": [ "loratadine" ], "offsets": [ [ 866, 876 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T13", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 908, 920 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T14", "type": "DRUG", "text": [ "Loratadine" ], "offsets": [ [ 1089, 1099 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T15", "type": "DRUG", "text": [ "Descarboethoxyloratadine" ], "offsets": [ [ 1104, 1128 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T16", "type": "DRUG", "text": [ "Loratadine" ], "offsets": [ [ 1164, 1174 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T17", "type": "DRUG", "text": [ "Loratadine" ], "offsets": [ [ 1203, 1213 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T18", "type": "DRUG", "text": [ "Descarboethoxyloratadine" ], "offsets": [ [ 1214, 1238 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T19", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 1239, 1251 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T20", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 1276, 1286 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T21", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 1311, 1323 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T22", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 1437, 1451 ] ], "normalized": [] }, { "id": "Loratadine_ddi_T23", "type": "DRUG", "text": [ "loratadine" ], "offsets": [ [ 1456, 1466 ] ], "normalized": [] } ]

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[ { "id": "Loratadine_ddi_R1", "type": "MECHANISM", "arg1_id": "Loratadine_ddi_T11", "arg2_id": "Loratadine_ddi_T12", "normalized": [] } ]

[ { "id": "Haloperidol_ddi__text", "type": "abstract", "text": [ "An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN, and FBS) followed by irreversible brain damage has occurred in a few patients treated with lithium plus HALDOL. A causal relationship between these events and the concomitant administration of lithium and HALDOL has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear. As with other antipsychotic agents, it should be noted that HALDOL may be capable of potentiating CNS depressants such as anesthetics, opiates, and alcohol. In a study of 12 schizophrenic patients coadministered oral haloperidol and rifampin, plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. In 5 other schizophrenic patients treated with oral haloperidol and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations. Thus, careful monitoring of clinical status is warranted when rifampin is administered or discontinued in haloperidol-treated patients." ], "offsets": [ [ 0, 1279 ] ] } ]

[ { "id": "Haloperidol_ddi_T1", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 261, 268 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T2", "type": "BRAND", "text": [ "HALDOL" ], "offsets": [ [ 274, 280 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T3", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 363, 370 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T4", "type": "BRAND", "text": [ "HALDOL" ], "offsets": [ [ 375, 381 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T5", "type": "GROUP", "text": [ "antipsychotic agents" ], "offsets": [ [ 602, 622 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T6", "type": "BRAND", "text": [ "HALDOL" ], "offsets": [ [ 648, 654 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T7", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 686, 701 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T8", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 710, 721 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T9", "type": "GROUP", "text": [ "opiates" ], "offsets": [ [ 723, 730 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T10", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 736, 743 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T11", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 805, 816 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T12", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 821, 829 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T13", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 838, 849 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T14", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 1025, 1036 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T15", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1041, 1049 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T16", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1070, 1078 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T17", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 1116, 1127 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T18", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1206, 1214 ] ], "normalized": [] }, { "id": "Haloperidol_ddi_T19", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 1250, 1261 ] ], "normalized": [] } ]

[]

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[ { "id": "Haloperidol_ddi_R1", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T1", "arg2_id": "Haloperidol_ddi_T2", "normalized": [] }, { "id": "Haloperidol_ddi_R2", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T5", "arg2_id": "Haloperidol_ddi_T7", "normalized": [] }, { "id": "Haloperidol_ddi_R3", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T5", "arg2_id": "Haloperidol_ddi_T8", "normalized": [] }, { "id": "Haloperidol_ddi_R4", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T5", "arg2_id": "Haloperidol_ddi_T9", "normalized": [] }, { "id": "Haloperidol_ddi_R5", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T5", "arg2_id": "Haloperidol_ddi_T10", "normalized": [] }, { "id": "Haloperidol_ddi_R6", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T6", "arg2_id": "Haloperidol_ddi_T7", "normalized": [] }, { "id": "Haloperidol_ddi_R7", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T6", "arg2_id": "Haloperidol_ddi_T8", "normalized": [] }, { "id": "Haloperidol_ddi_R8", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T6", "arg2_id": "Haloperidol_ddi_T9", "normalized": [] }, { "id": "Haloperidol_ddi_R9", "type": "EFFECT", "arg1_id": "Haloperidol_ddi_T6", "arg2_id": "Haloperidol_ddi_T10", "normalized": [] }, { "id": "Haloperidol_ddi_R10", "type": "MECHANISM", "arg1_id": "Haloperidol_ddi_T11", "arg2_id": "Haloperidol_ddi_T12", "normalized": [] }, { "id": "Haloperidol_ddi_R11", "type": "MECHANISM", "arg1_id": "Haloperidol_ddi_T16", "arg2_id": "Haloperidol_ddi_T17", "normalized": [] }, { "id": "Haloperidol_ddi_R12", "type": "ADVISE", "arg1_id": "Haloperidol_ddi_T18", "arg2_id": "Haloperidol_ddi_T19", "normalized": [] } ]

[ { "id": "Atovaquone_ddi__text", "type": "abstract", "text": [ "Atovaquone is highly bound to plasma protein (99.9%). Therefore, caution should be used when administering MEPRON concurrently with other highly plasma protein- bound drugs with narrow therapeutic indices, as competition for binding sites may occur. The extent of plasma protein binding of atovaquone in human plasma is not affected by the presence of therapeutic concentrations of phenytoin (15 mcg/ mL), nor is the binding of phenytoin affected by the presence of atovaquone. Rifampin: Coadministration of rifampin and MEPRON Suspension results in a significant decrease in average steady- state plasma atovaquone concentrations. Alternatives to rifampin should be considered during the course of PCP treatment with MEPRON. Rifabutin, another rifamycin, is structurally similar to rifampin and may possibly have some of the same drug interactions as rifampin. No interaction trials have been conducted with MEPRON and rifabutin. Drug/ Laboratory Test Interactions: It is not known if MEPRON interferes with clinical laboratory test or assay results." ], "offsets": [ [ 0, 1051 ] ] } ]

[ { "id": "Atovaquone_ddi_T1", "type": "DRUG", "text": [ "Atovaquone" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T2", "type": "BRAND", "text": [ "MEPRON" ], "offsets": [ [ 107, 113 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T3", "type": "DRUG", "text": [ "atovaquone" ], "offsets": [ [ 290, 300 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T4", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 382, 391 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T5", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 428, 437 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T6", "type": "DRUG", "text": [ "atovaquone" ], "offsets": [ [ 466, 476 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T7", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 478, 486 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T8", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 508, 516 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T9", "type": "BRAND", "text": [ "MEPRON" ], "offsets": [ [ 521, 527 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T10", "type": "DRUG", "text": [ "atovaquone" ], "offsets": [ [ 605, 615 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T11", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 648, 656 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T12", "type": "BRAND", "text": [ "MEPRON" ], "offsets": [ [ 718, 724 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T13", "type": "DRUG", "text": [ "Rifabutin" ], "offsets": [ [ 726, 735 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T14", "type": "DRUG", "text": [ "rifamycin" ], "offsets": [ [ 745, 754 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T15", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 783, 791 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T16", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 852, 860 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T17", "type": "BRAND", "text": [ "MEPRON" ], "offsets": [ [ 909, 915 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T18", "type": "DRUG", "text": [ "rifabutin" ], "offsets": [ [ 920, 929 ] ], "normalized": [] }, { "id": "Atovaquone_ddi_T19", "type": "BRAND", "text": [ "MEPRON" ], "offsets": [ [ 986, 992 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Atovaquone_ddi_R1", "type": "MECHANISM", "arg1_id": "Atovaquone_ddi_T8", "arg2_id": "Atovaquone_ddi_T9", "normalized": [] }, { "id": "Atovaquone_ddi_R2", "type": "ADVISE", "arg1_id": "Atovaquone_ddi_T11", "arg2_id": "Atovaquone_ddi_T12", "normalized": [] } ]

[ { "id": "Nortriptyline_ddi__text", "type": "abstract", "text": [ "Steady-state serum concentrations of tricyclic antidepressants are reported to fluctuate significantly when cimetidine is either added or deleted from the drug regimen. Serious anticholinergic symptoms (severe dry mouth, urinary retention, blurred vision) have been associated with elevations in the serum levels of tricyclic antidepressants when cimetidine is added to the drug regimen. In addition, higher-than expected steady-state serum concentrations of tricyclic antidepressants have been observed when therapy is initiated in patients already taking cimetidine. In well-controlled patients undergoing concurrent therapy with cimetidine, a decrease in the steady-state serum concentrations of tricyclic antidepressants may occur when cime-tidine therapy is discontinued. The therapeutic efficacy of tricyclic antidepressants may be compromised in these patients when cimetidine is discontinued. Several of the tricyclic antidepressants have been cited in these reports. There have been greater than 2-fold increases in previously stable plasma levels of other antidepressants, including nortriptyline, when fluoxetine hydrochloride has been administered in combination with these agents. Fluoxetine and its active metabolite, norfluoxe-tine, have long half-lives (4 to 16 days for norfluoxetine), that may affect strategies during conversion from one drug to the other. Administration of reserpine during therapy with a tricyclic antidepressant has been shown to produce a stimulating effect in some depressed patients. Close supervision and careful adjustment of the dosage are required when nortriptyline hydrochloride is used with other anticholinergic drugs or sympathomimetic drugs. The patient should be informed that the response to alcohol may be exaggerated. Drugs Metabolized by P450IID6 A subset (3% to 10%) of the population has reduced activity of certain drug metabolizing enzymes such as the cytochrome P450 isoenzyme P450IID6. Such individuals are referred to as poor metabolizers of drugs such as debrisoquin, dextromethorphan, and the tricyclic antidepressants. These individuals may have higher than expected plasma concentrations of tricyclic antidepressants when given usual doses. In addition, certain drugs that are metabolized by this isoenzyme, including many antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, and others), may inhibit the activity of this isoenzyme, and thus may make normal metab-olizers resemble poor metabolizers with regard to concomitant therapy with other drugs metabolized by this enzyme system, leading to drug interactions. Concomitant use of tricyclic antidepressants with other drugs metabolized by cytochrome P450IID6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Therefore, co-administration of tricyclic antidepressants with other drugs that are metabolized by this isoenzyme, including other antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (eg, propafenone, flecainide, and encainide), or that inhibit this enzyme (eg, quinidine), should be approached with caution." ], "offsets": [ [ 0, 3157 ] ] } ]

[ { "id": "Nortriptyline_ddi_T1", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 37, 62 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T2", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 108, 118 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T3", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 316, 341 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T4", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 347, 357 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T5", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 459, 484 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T6", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 557, 567 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T7", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 632, 642 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T8", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 699, 724 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T9", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 805, 830 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T10", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 873, 883 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T11", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 916, 941 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T12", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 1066, 1081 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T13", "type": "DRUG", "text": [ "nortriptyline" ], "offsets": [ [ 1093, 1106 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T14", "type": "DRUG", "text": [ "fluoxetine hydrochloride" ], "offsets": [ [ 1113, 1137 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T15", "type": "DRUG", "text": [ "Fluoxetine" ], "offsets": [ [ 1194, 1204 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T16", "type": "DRUG_N", "text": [ "norfluoxetine" ], "offsets": [ [ 1287, 1300 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T17", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 1394, 1403 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T18", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 1426, 1450 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T19", "type": "DRUG", "text": [ "nortriptyline hydrochloride" ], "offsets": [ [ 1601, 1628 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T20", "type": "GROUP", "text": [ "anticholinergic drugs" ], "offsets": [ [ 1648, 1669 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T21", "type": "GROUP", "text": [ "sympathomimetic drugs" ], "offsets": [ [ 1673, 1694 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T22", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 1748, 1755 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T23", "type": "DRUG", "text": [ "debrisoquin" ], "offsets": [ [ 2025, 2036 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T24", "type": "DRUG", "text": [ "dextromethorphan" ], "offsets": [ [ 2038, 2054 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T25", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 2064, 2089 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T26", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 2164, 2189 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T27", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 2296, 2311 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T28", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 2313, 2338 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T29", "type": "GROUP", "text": [ "selective serotonin reuptake inhibitors" ], "offsets": [ [ 2340, 2379 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T30", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 2640, 2665 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T31", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 2781, 2805 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T32", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 2857, 2882 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T33", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 2956, 2971 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T34", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 2973, 2987 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T35", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2989, 3002 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T36", "type": "GROUP", "text": [ "Type 1C antiarrhythmics" ], "offsets": [ [ 3008, 3031 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T37", "type": "DRUG", "text": [ "propafenone" ], "offsets": [ [ 3037, 3048 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T38", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 3050, 3060 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T39", "type": "DRUG", "text": [ "encainide" ], "offsets": [ [ 3066, 3075 ] ], "normalized": [] }, { "id": "Nortriptyline_ddi_T40", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 3111, 3120 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Nortriptyline_ddi_R1", "type": "MECHANISM", "arg1_id": "Nortriptyline_ddi_T1", "arg2_id": "Nortriptyline_ddi_T2", "normalized": [] }, { "id": "Nortriptyline_ddi_R2", "type": "EFFECT", "arg1_id": "Nortriptyline_ddi_T3", "arg2_id": "Nortriptyline_ddi_T4", "normalized": [] }, { "id": "Nortriptyline_ddi_R3", "type": "MECHANISM", "arg1_id": "Nortriptyline_ddi_T5", "arg2_id": "Nortriptyline_ddi_T6", "normalized": [] }, { "id": "Nortriptyline_ddi_R4", "type": "MECHANISM", "arg1_id": "Nortriptyline_ddi_T7", "arg2_id": "Nortriptyline_ddi_T8", "normalized": [] }, { "id": "Nortriptyline_ddi_R5", "type": "EFFECT", "arg1_id": "Nortriptyline_ddi_T9", "arg2_id": "Nortriptyline_ddi_T10", "normalized": [] }, { "id": "Nortriptyline_ddi_R6", "type": "MECHANISM", "arg1_id": "Nortriptyline_ddi_T12", "arg2_id": "Nortriptyline_ddi_T14", "normalized": [] }, { "id": "Nortriptyline_ddi_R7", "type": "MECHANISM", "arg1_id": "Nortriptyline_ddi_T13", "arg2_id": "Nortriptyline_ddi_T14", "normalized": [] }, { "id": "Nortriptyline_ddi_R8", "type": "EFFECT", "arg1_id": "Nortriptyline_ddi_T17", "arg2_id": "Nortriptyline_ddi_T18", "normalized": [] }, { "id": "Nortriptyline_ddi_R9", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T19", "arg2_id": "Nortriptyline_ddi_T20", "normalized": [] }, { "id": "Nortriptyline_ddi_R10", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T19", "arg2_id": "Nortriptyline_ddi_T21", "normalized": [] }, { "id": "Nortriptyline_ddi_R11", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T32", "arg2_id": "Nortriptyline_ddi_T33", "normalized": [] }, { "id": "Nortriptyline_ddi_R12", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T32", "arg2_id": "Nortriptyline_ddi_T34", "normalized": [] }, { "id": "Nortriptyline_ddi_R13", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T32", "arg2_id": "Nortriptyline_ddi_T35", "normalized": [] }, { "id": "Nortriptyline_ddi_R14", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T32", "arg2_id": "Nortriptyline_ddi_T36", "normalized": [] }, { "id": "Nortriptyline_ddi_R15", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T32", "arg2_id": "Nortriptyline_ddi_T37", "normalized": [] }, { "id": "Nortriptyline_ddi_R16", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T32", "arg2_id": "Nortriptyline_ddi_T38", "normalized": [] }, { "id": "Nortriptyline_ddi_R17", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T32", "arg2_id": "Nortriptyline_ddi_T39", "normalized": [] }, { "id": "Nortriptyline_ddi_R18", "type": "ADVISE", "arg1_id": "Nortriptyline_ddi_T32", "arg2_id": "Nortriptyline_ddi_T40", "normalized": [] } ]

[ { "id": "Cefditoren_ddi__text", "type": "abstract", "text": [ "Oral Contraceptives Multiple doses of cefditoren pivoxil had no effect on the pharmacokinetics of ethinyl estradiol, the estrogenic component in most oral contraceptives. Although the clinical significance is not known, it is not recommended that cefditoren pivoxil be taken concomitantly with antacids. H2-Receptor Antagonists: Co-administration of a single dose of intravenously administered famotidine (20 mg) reduced the oral absorption of a single 400 mg dose of cefditoren pivoxil administered following a meal, as evidenced by a 27% decrease in mean Cmax and a 22% decrease in mean AUC. Although the clinical significance is not known, it is not recommended that cefditoren pivoxil be taken concomitantly with H2 receptor antagonists. Probenecid: As with other b-lactam antibiotics, co-administration of probenecid with cefditoren pivoxil resulted in an increase in the plasma exposure of cefditoren, with a 49% increase in mean Cmax, a 122% increase in mean AUC, and a 53% increase in half-life. Drug/Laboratory Test Interactions Cephalosporins are known to occasionally induce a positive direct Coombs test. A false-positive reaction for glucose in the urine may occur with copper reduction tests (Benedicts or Fehlings solution or with CLINITEST tablets), but not with enzyme-based tests for glycosuria (e.g., CLINISTIX, TES-TAPE). As a false-negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase method be used to determine blood/plasma glucose levels in patients receiving cefditoren pivoxil." ], "offsets": [ [ 0, 1566 ] ] } ]

[ { "id": "Cefditoren_ddi_T1", "type": "GROUP", "text": [ "Contraceptives" ], "offsets": [ [ 5, 19 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T2", "type": "DRUG", "text": [ "cefditoren pivoxil" ], "offsets": [ [ 38, 56 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T3", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 98, 115 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T4", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 155, 169 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T5", "type": "DRUG", "text": [ "cefditoren pivoxil" ], "offsets": [ [ 247, 265 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T6", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 294, 302 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T7", "type": "GROUP", "text": [ "H2-Receptor Antagonists" ], "offsets": [ [ 304, 327 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T8", "type": "DRUG", "text": [ "famotidine" ], "offsets": [ [ 394, 404 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T9", "type": "DRUG", "text": [ "cefditoren pivoxil" ], "offsets": [ [ 468, 486 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T10", "type": "DRUG", "text": [ "cefditoren pivoxil" ], "offsets": [ [ 670, 688 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T11", "type": "GROUP", "text": [ "H2 receptor antagonists" ], "offsets": [ [ 717, 740 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T12", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 742, 752 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T13", "type": "GROUP", "text": [ "b-lactam antibiotics" ], "offsets": [ [ 768, 788 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T14", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 811, 821 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T15", "type": "DRUG", "text": [ "cefditoren pivoxil" ], "offsets": [ [ 827, 845 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T16", "type": "DRUG", "text": [ "cefditoren" ], "offsets": [ [ 896, 906 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T17", "type": "GROUP", "text": [ "Cephalosporins" ], "offsets": [ [ 1038, 1052 ] ], "normalized": [] }, { "id": "Cefditoren_ddi_T18", "type": "DRUG", "text": [ "cefditoren pivoxil" ], "offsets": [ [ 1547, 1565 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cefditoren_ddi_R1", "type": "ADVISE", "arg1_id": "Cefditoren_ddi_T5", "arg2_id": "Cefditoren_ddi_T6", "normalized": [] }, { "id": "Cefditoren_ddi_R2", "type": "MECHANISM", "arg1_id": "Cefditoren_ddi_T8", "arg2_id": "Cefditoren_ddi_T9", "normalized": [] }, { "id": "Cefditoren_ddi_R3", "type": "MECHANISM", "arg1_id": "Cefditoren_ddi_T13", "arg2_id": "Cefditoren_ddi_T15", "normalized": [] }, { "id": "Cefditoren_ddi_R4", "type": "MECHANISM", "arg1_id": "Cefditoren_ddi_T14", "arg2_id": "Cefditoren_ddi_T15", "normalized": [] } ]

[ { "id": "Auranofin_ddi__text", "type": "abstract", "text": [ "Auranofin should be avoided by patients with a history of serious reaction to any gold medication, including Solganal and Myochrysine. Auranofin should not be used together with penicillamine (Depen, Cuprimine), another arthritis medication. It should also be avoided in patients with blood, liver or kidney diseases, recent radiation treatment, or uncontrolled diabetes. Patients should report to their practitioners any new rashes, itching, mouth sores, or unusual taste while taking auranofin. Gold is excreted slowly from the body. Safety and effectiveness in children has not been established." ], "offsets": [ [ 0, 598 ] ] } ]

[ { "id": "Auranofin_ddi_T1", "type": "DRUG", "text": [ "Auranofin" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T2", "type": "GROUP", "text": [ "gold medication" ], "offsets": [ [ 82, 97 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T3", "type": "BRAND", "text": [ "Solganal" ], "offsets": [ [ 109, 117 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T4", "type": "BRAND", "text": [ "Myochrysine" ], "offsets": [ [ 122, 133 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T5", "type": "DRUG", "text": [ "Auranofin" ], "offsets": [ [ 135, 144 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T6", "type": "DRUG", "text": [ "penicillamine" ], "offsets": [ [ 178, 191 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T7", "type": "BRAND", "text": [ "Depen" ], "offsets": [ [ 193, 198 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T8", "type": "BRAND", "text": [ "Cuprimine" ], "offsets": [ [ 200, 209 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T9", "type": "DRUG", "text": [ "auranofin" ], "offsets": [ [ 486, 495 ] ], "normalized": [] }, { "id": "Auranofin_ddi_T10", "type": "GROUP", "text": [ "Gold" ], "offsets": [ [ 497, 501 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Auranofin_ddi_R1", "type": "ADVISE", "arg1_id": "Auranofin_ddi_T1", "arg2_id": "Auranofin_ddi_T2", "normalized": [] }, { "id": "Auranofin_ddi_R2", "type": "ADVISE", "arg1_id": "Auranofin_ddi_T1", "arg2_id": "Auranofin_ddi_T3", "normalized": [] }, { "id": "Auranofin_ddi_R3", "type": "ADVISE", "arg1_id": "Auranofin_ddi_T1", "arg2_id": "Auranofin_ddi_T4", "normalized": [] }, { "id": "Auranofin_ddi_R4", "type": "ADVISE", "arg1_id": "Auranofin_ddi_T5", "arg2_id": "Auranofin_ddi_T6", "normalized": [] }, { "id": "Auranofin_ddi_R5", "type": "ADVISE", "arg1_id": "Auranofin_ddi_T5", "arg2_id": "Auranofin_ddi_T7", "normalized": [] }, { "id": "Auranofin_ddi_R6", "type": "ADVISE", "arg1_id": "Auranofin_ddi_T5", "arg2_id": "Auranofin_ddi_T8", "normalized": [] } ]

[ { "id": "Ethynodiol Diacetate_ddi__text", "type": "abstract", "text": [ "Ethinyl estradiol: Substrate of CYP3A4 (major), 3A5-7 (minor); Inhibits CYP1A2 (weak), 2B6 (weak), 2C19 (weak), 3A4 (weak). Acetaminophen: May increase plasma concentration of synthetic estrogens, possibly by inhibiting conjugation. Combination hormonal contraceptives may also decrease the plasma concentration of acetaminophen. Acitretin: Interferes with the contraceptive effect of microdosed progestin-containing minipill preparations. The effect on other progestational contraceptives (eg, implants, injectables) is unknown. Aminoglutethimide: May increase CYP metabolism of progestins leading to possible decrease in contraceptive effectiveness. Use of a nonhormonal contraceptive product is recommended. Antibiotics (ampicillin, tetracycline): Pregnancy has been reported following concomitant use, however, pharmacokinetic studies have not shown consistent effects with these antibiotics on plasma concentrations of synthetic steroids. Use of a nonhormonal contraceptive product is recommended. Anticoagulants: Combination hormonal contraceptives may increase or decrease the effects of coumarin derivatives. Combination hormonal contraceptives may also increase risk of thromboembolic disorders. Anticonvulsants (carbamazepine, felbamate, phenobarbital, phenytoin, topiramate): Increase the metabolism of ethinyl estradiol and/or some progestins, leading to possible decrease in contraceptive effectiveness. Use of a nonhormonal contraceptive product is recommended. Ascorbic acid: Doses of ascorbic acid (vitamin C) 1 g/day have been reported to increase plasma concentration of synthetic estrogens by ~47%, possibly by inhibiting conjugation; clinical implications are unclear. Atorvastatin: Atorvastatin increases the AUC for norethindrone and ethinyl estradiol. Benzodiazepines: Combination hormonal contraceptives may decrease the clearance of some benzodiazepines (alprazolam, chlordiazepoxide, diazepam) and increase the clearance of others (lorazepam, oxazepam, temazepam). Clofibric acid: Combination hormonal contraceptives may increase the clearance of clofibric acid. Cyclosporine: Combination hormonal contraceptives may inhibit the metabolism of cyclosporine, leading to increased plasma concentrations; monitor cyclosporine levels. CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of ethinyl estradiol. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins. Griseofulvin: Griseofulvin may induce the metabolism of combination hormonal contraceptives causing menstrual changes; pregnancies have been reported. Use of barrier form of contraception is suggested while on griseofulvin therapy. Morphine: Combination hormonal contraceptives may increase the clearance of morphine. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Nevirapine may decrease plasma levels of combination hormonal contraceptives; use of a nonhormonal contraceptive product is recommended. No data for delavirdine; incomplete data for efavirenz. Prednisolone: Ethinyl estradiol may inhibit the metabolism of prednisolone, leading to increased plasma concentrations. Protease inhibitors: Amprenavir, lopinavir, nelfinavir, and ritonavir have been shown to decrease plasma levels of combination hormonal contraceptives; use of a nonhormonal contraceptive product is recommended. Indinavir has been shown to increase plasma levels of combination hormonal contraceptives. No data for saquinavir. Rifampin: Rifampin increases the metabolism of ethinyl estradiol and some progestins (norethindrone) resulting in decreased contraceptive effectiveness and increased menstrual irregularities. Use of a nonhormonal contraceptive product is recommended. Salicylic acid: Combination hormonal contraceptives may increase the clearance of salicylic acid. Selegiline: Combination hormonal contraceptives may increase the serum concentration of selegiline. Theophylline: Ethinyl estradiol may inhibit the metabolism of theophylline, leading to increased plasma concentrations. Tricyclic antidepressants (amitriptyline, imipramine, nortriptyline): Metabolism may be inhibited by combination hormonal contraceptives, increasing plasma levels of antidepressant; use caution. ETHANOL / NUTRITION / HERB INTERACTIONS: Food: CNS effects of caffeine may be enhanced if combination hormonal contraceptives are used concurrently with caffeine. Grapefruit juice increases ethinyl estradiol concentrations and would be expected to increase progesterone serum levels as well; clinical implications are unclear. Herb/Nutraceutical: St Johns wort may decrease the effectiveness of combination hormonal contraceptives by inducing hepatic enzymes. Avoid dong quai and black cohosh (have estrogen activity). Avoid saw palmetto, red clover, ginseng." ], "offsets": [ [ 0, 4805 ] ] } ]

[ { "id": "Ethynodiol Diacetate_ddi_T1", "type": "DRUG", "text": [ "Ethinyl estradiol" ], "offsets": [ [ 0, 17 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T2", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 124, 137 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T3", "type": "GROUP", "text": [ "synthetic estrogens" ], "offsets": [ [ 176, 195 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T4", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 245, 268 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T5", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 315, 328 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T6", "type": "DRUG", "text": [ "Acitretin" ], "offsets": [ [ 330, 339 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T7", "type": "GROUP", "text": [ "progestin" ], "offsets": [ [ 396, 405 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T8", "type": "GROUP", "text": [ "progestational contraceptives" ], "offsets": [ [ 460, 489 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T9", "type": "DRUG", "text": [ "Aminoglutethimide" ], "offsets": [ [ 530, 547 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T10", "type": "GROUP", "text": [ "progestins" ], "offsets": [ [ 580, 590 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T11", "type": "GROUP", "text": [ "nonhormonal contraceptive product" ], "offsets": [ [ 661, 694 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T12", "type": "GROUP", "text": [ "Antibiotics" ], "offsets": [ [ 711, 722 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T13", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 724, 734 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T14", "type": "DRUG", "text": [ "tetracycline" ], "offsets": [ [ 736, 748 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T15", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 884, 895 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T16", "type": "GROUP", "text": [ "synthetic steroids" ], "offsets": [ [ 924, 942 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T17", "type": "GROUP", "text": [ "nonhormonal contraceptive product" ], "offsets": [ [ 953, 986 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T18", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 1003, 1017 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T19", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 1031, 1054 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T20", "type": "GROUP", "text": [ "coumarin derivatives" ], "offsets": [ [ 1095, 1115 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T21", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 1129, 1152 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T22", "type": "GROUP", "text": [ "Anticonvulsants" ], "offsets": [ [ 1205, 1220 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T23", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1222, 1235 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T24", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 1237, 1246 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T25", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1248, 1261 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T26", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1263, 1272 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T27", "type": "DRUG", "text": [ "topiramate" ], "offsets": [ [ 1274, 1284 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T28", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 1314, 1331 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T29", "type": "GROUP", "text": [ "progestins" ], "offsets": [ [ 1344, 1354 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T30", "type": "GROUP", "text": [ "nonhormonal contraceptive product" ], "offsets": [ [ 1426, 1459 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T31", "type": "DRUG", "text": [ "Ascorbic acid" ], "offsets": [ [ 1476, 1489 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T32", "type": "DRUG", "text": [ "ascorbic acid" ], "offsets": [ [ 1500, 1513 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T33", "type": "DRUG", "text": [ "vitamin C" ], "offsets": [ [ 1515, 1524 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T34", "type": "GROUP", "text": [ "synthetic estrogens" ], "offsets": [ [ 1589, 1608 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T35", "type": "DRUG", "text": [ "Atorvastatin" ], "offsets": [ [ 1689, 1701 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T36", "type": "DRUG", "text": [ "Atorvastatin" ], "offsets": [ [ 1703, 1715 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T37", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 1738, 1751 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T38", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 1756, 1773 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T39", "type": "GROUP", "text": [ "Benzodiazepines" ], "offsets": [ [ 1775, 1790 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T40", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 1804, 1827 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T41", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 1863, 1878 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T42", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 1880, 1890 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T43", "type": "DRUG", "text": [ "chlordiazepoxide" ], "offsets": [ [ 1892, 1908 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T44", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 1910, 1918 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T45", "type": "DRUG", "text": [ "lorazepam" ], "offsets": [ [ 1958, 1967 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T46", "type": "DRUG", "text": [ "oxazepam" ], "offsets": [ [ 1969, 1977 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T47", "type": "DRUG", "text": [ "temazepam" ], "offsets": [ [ 1979, 1988 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T48", "type": "DRUG_N", "text": [ "Clofibric acid" ], "offsets": [ [ 1991, 2005 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T49", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 2019, 2042 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T50", "type": "DRUG_N", "text": [ "clofibric acid" ], "offsets": [ [ 2073, 2087 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T51", "type": "DRUG", "text": [ "Cyclosporine" ], "offsets": [ [ 2089, 2101 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T52", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 2115, 2138 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T53", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2169, 2181 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T54", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2235, 2247 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T55", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 2324, 2341 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T56", "type": "DRUG", "text": [ "aminoglutethimide" ], "offsets": [ [ 2368, 2385 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T57", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2387, 2400 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T58", "type": "DRUG", "text": [ "nafcillin" ], "offsets": [ [ 2402, 2411 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T59", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 2413, 2423 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T60", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 2425, 2438 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T61", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2440, 2449 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T62", "type": "GROUP", "text": [ "rifamycins" ], "offsets": [ [ 2455, 2465 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T63", "type": "DRUG", "text": [ "Griseofulvin" ], "offsets": [ [ 2467, 2479 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T64", "type": "DRUG", "text": [ "Griseofulvin" ], "offsets": [ [ 2481, 2493 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T65", "type": "GROUP", "text": [ "combination hormonal contraceptives" ], "offsets": [ [ 2523, 2558 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T66", "type": "DRUG", "text": [ "griseofulvin" ], "offsets": [ [ 2677, 2689 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T67", "type": "DRUG", "text": [ "Morphine" ], "offsets": [ [ 2699, 2707 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T68", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 2721, 2744 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T69", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 2775, 2783 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T70", "type": "GROUP", "text": [ "Non-nucleoside reverse transcriptase inhibitors" ], "offsets": [ [ 2785, 2832 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T71", "type": "GROUP", "text": [ "NNRTIs" ], "offsets": [ [ 2834, 2840 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T72", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 2843, 2853 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T73", "type": "GROUP", "text": [ "combination hormonal contraceptives" ], "offsets": [ [ 2884, 2919 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T74", "type": "GROUP", "text": [ "nonhormonal contraceptive product" ], "offsets": [ [ 2930, 2963 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T75", "type": "DRUG", "text": [ "delavirdine" ], "offsets": [ [ 2992, 3003 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T76", "type": "DRUG", "text": [ "efavirenz" ], "offsets": [ [ 3025, 3034 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T77", "type": "DRUG", "text": [ "Prednisolone" ], "offsets": [ [ 3036, 3048 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T78", "type": "DRUG", "text": [ "Ethinyl estradiol" ], "offsets": [ [ 3050, 3067 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T79", "type": "DRUG", "text": [ "prednisolone" ], "offsets": [ [ 3098, 3110 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T80", "type": "GROUP", "text": [ "Protease inhibitors" ], "offsets": [ [ 3156, 3175 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T81", "type": "DRUG", "text": [ "Amprenavir" ], "offsets": [ [ 3177, 3187 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T82", "type": "DRUG", "text": [ "lopinavir" ], "offsets": [ [ 3189, 3198 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T83", "type": "DRUG", "text": [ "nelfinavir" ], "offsets": [ [ 3200, 3210 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T84", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 3216, 3225 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T85", "type": "GROUP", "text": [ "combination hormonal contraceptives" ], "offsets": [ [ 3271, 3306 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T86", "type": "GROUP", "text": [ "nonhormonal contraceptive product" ], "offsets": [ [ 3317, 3350 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T87", "type": "DRUG", "text": [ "Indinavir" ], "offsets": [ [ 3367, 3376 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T88", "type": "GROUP", "text": [ "combination hormonal contraceptives" ], "offsets": [ [ 3421, 3456 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T89", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 3470, 3480 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T90", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 3482, 3490 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T91", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 3492, 3500 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T92", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 3529, 3546 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T93", "type": "GROUP", "text": [ "progestins" ], "offsets": [ [ 3556, 3566 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T94", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 3568, 3581 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T95", "type": "GROUP", "text": [ "nonhormonal contraceptive product" ], "offsets": [ [ 3683, 3716 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T96", "type": "DRUG", "text": [ "Salicylic acid" ], "offsets": [ [ 3733, 3747 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T97", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 3761, 3784 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T98", "type": "DRUG", "text": [ "salicylic acid" ], "offsets": [ [ 3815, 3829 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T99", "type": "DRUG", "text": [ "Selegiline" ], "offsets": [ [ 3831, 3841 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T100", "type": "GROUP", "text": [ "Combination hormonal contraceptives" ], "offsets": [ [ 3843, 3878 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T101", "type": "DRUG", "text": [ "selegiline" ], "offsets": [ [ 3919, 3929 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T102", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 3931, 3943 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T103", "type": "DRUG", "text": [ "Ethinyl estradiol" ], "offsets": [ [ 3945, 3962 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T104", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 3993, 4005 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T105", "type": "GROUP", "text": [ "Tricyclic antidepressants" ], "offsets": [ [ 4051, 4076 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T106", "type": "DRUG", "text": [ "amitriptyline" ], "offsets": [ [ 4078, 4091 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T107", "type": "DRUG", "text": [ "imipramine" ], "offsets": [ [ 4093, 4103 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T108", "type": "DRUG", "text": [ "nortriptyline" ], "offsets": [ [ 4105, 4118 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T109", "type": "GROUP", "text": [ "combination hormonal contraceptives" ], "offsets": [ [ 4152, 4187 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T110", "type": "GROUP", "text": [ "antidepressant" ], "offsets": [ [ 4217, 4231 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T111", "type": "DRUG", "text": [ "ETHANOL" ], "offsets": [ [ 4246, 4253 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T112", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 4308, 4316 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T113", "type": "GROUP", "text": [ "combination hormonal contraceptives" ], "offsets": [ [ 4336, 4371 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T114", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 4399, 4407 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T115", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 4436, 4453 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T116", "type": "DRUG", "text": [ "progesterone" ], "offsets": [ [ 4503, 4515 ] ], "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_T117", "type": "GROUP", "text": [ "combination hormonal contraceptives" ], "offsets": [ [ 4641, 4676 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ethynodiol Diacetate_ddi_R1", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T2", "arg2_id": "Ethynodiol Diacetate_ddi_T3", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R2", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T4", "arg2_id": "Ethynodiol Diacetate_ddi_T5", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R3", "type": "EFFECT", "arg1_id": "Ethynodiol Diacetate_ddi_T6", "arg2_id": "Ethynodiol Diacetate_ddi_T7", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R4", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T9", "arg2_id": "Ethynodiol Diacetate_ddi_T10", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R5", "type": "EFFECT", "arg1_id": "Ethynodiol Diacetate_ddi_T19", "arg2_id": "Ethynodiol Diacetate_ddi_T20", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R6", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T22", "arg2_id": "Ethynodiol Diacetate_ddi_T28", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R7", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T22", "arg2_id": "Ethynodiol Diacetate_ddi_T29", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R8", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T23", "arg2_id": "Ethynodiol Diacetate_ddi_T28", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R9", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T23", "arg2_id": "Ethynodiol Diacetate_ddi_T29", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R10", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T24", "arg2_id": "Ethynodiol Diacetate_ddi_T28", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R11", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T24", "arg2_id": "Ethynodiol Diacetate_ddi_T29", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R12", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T25", "arg2_id": "Ethynodiol Diacetate_ddi_T28", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R13", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T25", "arg2_id": "Ethynodiol Diacetate_ddi_T29", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R14", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T26", "arg2_id": "Ethynodiol Diacetate_ddi_T28", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R15", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T26", "arg2_id": "Ethynodiol Diacetate_ddi_T29", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R16", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T27", "arg2_id": "Ethynodiol Diacetate_ddi_T28", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R17", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T27", "arg2_id": "Ethynodiol Diacetate_ddi_T29", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R18", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T32", "arg2_id": "Ethynodiol Diacetate_ddi_T34", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R19", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T33", "arg2_id": "Ethynodiol Diacetate_ddi_T34", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R20", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T36", "arg2_id": "Ethynodiol Diacetate_ddi_T37", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R21", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T36", "arg2_id": "Ethynodiol Diacetate_ddi_T38", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R22", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T40", "arg2_id": "Ethynodiol Diacetate_ddi_T41", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R23", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T40", "arg2_id": "Ethynodiol Diacetate_ddi_T42", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R24", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T40", "arg2_id": "Ethynodiol Diacetate_ddi_T43", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R25", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T40", "arg2_id": "Ethynodiol Diacetate_ddi_T44", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R26", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T40", "arg2_id": "Ethynodiol Diacetate_ddi_T45", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R27", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T40", "arg2_id": "Ethynodiol Diacetate_ddi_T46", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R28", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T40", "arg2_id": "Ethynodiol Diacetate_ddi_T47", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R29", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T49", "arg2_id": "Ethynodiol Diacetate_ddi_T50", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R30", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T52", "arg2_id": "Ethynodiol Diacetate_ddi_T53", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R31", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T64", "arg2_id": "Ethynodiol Diacetate_ddi_T65", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R32", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T68", "arg2_id": "Ethynodiol Diacetate_ddi_T69", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R33", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T72", "arg2_id": "Ethynodiol Diacetate_ddi_T73", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R34", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T78", "arg2_id": "Ethynodiol Diacetate_ddi_T79", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R35", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T81", "arg2_id": "Ethynodiol Diacetate_ddi_T85", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R36", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T82", "arg2_id": "Ethynodiol Diacetate_ddi_T85", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R37", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T83", "arg2_id": "Ethynodiol Diacetate_ddi_T85", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R38", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T84", "arg2_id": "Ethynodiol Diacetate_ddi_T85", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R39", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T87", "arg2_id": "Ethynodiol Diacetate_ddi_T88", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R40", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T91", "arg2_id": "Ethynodiol Diacetate_ddi_T92", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R41", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T91", "arg2_id": "Ethynodiol Diacetate_ddi_T93", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R42", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T91", "arg2_id": "Ethynodiol Diacetate_ddi_T94", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R43", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T97", "arg2_id": "Ethynodiol Diacetate_ddi_T98", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R44", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T100", "arg2_id": "Ethynodiol Diacetate_ddi_T101", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R45", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T103", "arg2_id": "Ethynodiol Diacetate_ddi_T104", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R46", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T105", "arg2_id": "Ethynodiol Diacetate_ddi_T109", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R47", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T106", "arg2_id": "Ethynodiol Diacetate_ddi_T109", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R48", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T107", "arg2_id": "Ethynodiol Diacetate_ddi_T109", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R49", "type": "MECHANISM", "arg1_id": "Ethynodiol Diacetate_ddi_T108", "arg2_id": "Ethynodiol Diacetate_ddi_T109", "normalized": [] }, { "id": "Ethynodiol Diacetate_ddi_R50", "type": "EFFECT", "arg1_id": "Ethynodiol Diacetate_ddi_T113", "arg2_id": "Ethynodiol Diacetate_ddi_T114", "normalized": [] } ]

[ { "id": "Infliximab_ddi__text", "type": "abstract", "text": [ "Concurrent administration of etanercept (another TNF -blocking agent) and anakinra (an interleukin-1 antagonist) has been associated with an increased risk of serious infections, and increased risk of neutropenia and no additional benefit compared to these medicinal products alone. Other TNFa-blocking agents (including REMICADE) used in combination with anakinra may also result in similar toxicities. Specific drug interaction studies, including interactions with MTX, have not been conducted. The majority of patients in rheumatoid arthritis or Crohn s disease clinical studies received one or more concomitant medications. In rheumatoid arthritis, concomitant medications besides MTX were nonsteroidal anti-inflammatory agents, folic acid, corticosteroids and/or narcotics. Concomitant Crohn s disease medications were antibiotics, antivirals, corticosteroids, 6-MP/AZA and aminosalicylates. In psoriatic arthritis clinical trials, concomitant medications included MTX in approximately half of the patients as well as nonsteroidal anti-inflammatory agents, folic acid and corticosteroids. Patients with Crohn s disease who received immunosuppressants tended to experience fewer infusion reactions compared to patients on no immunosuppressants. Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of Crohn s disease including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates." ], "offsets": [ [ 0, 1468 ] ] } ]

[ { "id": "Infliximab_ddi_T1", "type": "DRUG", "text": [ "etanercept" ], "offsets": [ [ 29, 39 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T2", "type": "DRUG", "text": [ "anakinra" ], "offsets": [ [ 74, 82 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T3", "type": "GROUP", "text": [ "interleukin-1 antagonist" ], "offsets": [ [ 87, 111 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T4", "type": "GROUP", "text": [ "TNFa-blocking agents" ], "offsets": [ [ 289, 309 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T5", "type": "BRAND", "text": [ "REMICADE" ], "offsets": [ [ 321, 329 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T6", "type": "DRUG", "text": [ "anakinra" ], "offsets": [ [ 356, 364 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T7", "type": "DRUG", "text": [ "MTX" ], "offsets": [ [ 467, 470 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T8", "type": "DRUG", "text": [ "MTX" ], "offsets": [ [ 685, 688 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T9", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 694, 731 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T10", "type": "DRUG", "text": [ "folic acid" ], "offsets": [ [ 733, 743 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T11", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 745, 760 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T12", "type": "GROUP", "text": [ "narcotics" ], "offsets": [ [ 768, 777 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T13", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 824, 835 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T14", "type": "GROUP", "text": [ "antivirals" ], "offsets": [ [ 837, 847 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T15", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 849, 864 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T16", "type": "DRUG", "text": [ "6-MP" ], "offsets": [ [ 866, 870 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T17", "type": "DRUG", "text": [ "AZA" ], "offsets": [ [ 871, 874 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T18", "type": "DRUG", "text": [ "MTX" ], "offsets": [ [ 970, 973 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T19", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 1023, 1060 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T20", "type": "DRUG", "text": [ "folic acid" ], "offsets": [ [ 1062, 1072 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T21", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 1077, 1092 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T22", "type": "GROUP", "text": [ "immunosuppressants" ], "offsets": [ [ 1137, 1155 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T23", "type": "GROUP", "text": [ "immunosuppressants" ], "offsets": [ [ 1229, 1247 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T24", "type": "DRUG", "text": [ "infliximab" ], "offsets": [ [ 1255, 1265 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T25", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 1385, 1400 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T26", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 1402, 1413 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T27", "type": "DRUG", "text": [ "metronidazole" ], "offsets": [ [ 1415, 1428 ] ], "normalized": [] }, { "id": "Infliximab_ddi_T28", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 1432, 1445 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Infliximab_ddi_R1", "type": "EFFECT", "arg1_id": "Infliximab_ddi_T1", "arg2_id": "Infliximab_ddi_T2", "normalized": [] }, { "id": "Infliximab_ddi_R2", "type": "EFFECT", "arg1_id": "Infliximab_ddi_T4", "arg2_id": "Infliximab_ddi_T6", "normalized": [] }, { "id": "Infliximab_ddi_R3", "type": "EFFECT", "arg1_id": "Infliximab_ddi_T5", "arg2_id": "Infliximab_ddi_T6", "normalized": [] } ]

[ { "id": "Decamethonium_ddi__text", "type": "abstract", "text": [ "Potentially fatal drug interactions may occur when coadministered with digoxin, as this may enhance cardiovascular depression and bradyarrhythmias may occur. Anticholinesterases (neostgmine, physostigmine), lignocaine, quinine, procainamide can enhance toxicity and cause cardio respiratory depression. In addition, neuromuscular blocking action is enhanced by general anesthetics, local anesthetics like lidocaine, procaine, beta-blockers, metaclopramide, lithium carbonate, and terbutaline." ], "offsets": [ [ 0, 492 ] ] } ]

[ { "id": "Decamethonium_ddi_T1", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 71, 78 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T2", "type": "GROUP", "text": [ "Anticholinesterases" ], "offsets": [ [ 158, 177 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T3", "type": "DRUG", "text": [ "physostigmine" ], "offsets": [ [ 191, 204 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T4", "type": "DRUG", "text": [ "lignocaine" ], "offsets": [ [ 207, 217 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T5", "type": "DRUG", "text": [ "quinine" ], "offsets": [ [ 219, 226 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T6", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 228, 240 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T7", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 369, 380 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T8", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 388, 399 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T9", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 405, 414 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T10", "type": "DRUG", "text": [ "procaine" ], "offsets": [ [ 416, 424 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T11", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 426, 439 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T12", "type": "DRUG", "text": [ "metaclopramide" ], "offsets": [ [ 441, 455 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T13", "type": "DRUG", "text": [ "lithium carbonate" ], "offsets": [ [ 457, 474 ] ], "normalized": [] }, { "id": "Decamethonium_ddi_T14", "type": "DRUG", "text": [ "terbutaline" ], "offsets": [ [ 480, 491 ] ], "normalized": [] } ]

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[ { "id": "Norfloxacin_ddi__text", "type": "abstract", "text": [ "Elevated plasma levels of theophylline have been reported with concomitant quinolone use. There have been reports of theophylline-related side effects in patients on concomitant therapy with norfloxacin and theophylline. Therefore, monitoring of theophylline plasma levels should be considered and dosage of theophylline adjusted as required. Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with norfloxacin. Therefore, cyclosporine serum levels should be monitored and appropriate cyclosporine dosage adjustments made when these drugs are used concomitantly. Quinolones, including norfloxacin, may enhance the effects of oral anticoagulants, including warfarin or its derivatives or similar agents. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be closely monitored. The concomitant administration of quinolones including norfloxacin with glyburide (a sulfonylurea agent) has, on rare occasions, resulted in severe hypoglycemia. Therefore, monitoring of blood glucose is recommended when these agents are co-administered. Diminished urinary excretion of norfloxacin has been reported during the concomitant administration of probenecid and norfloxacin. The concomitant use of nitrofurantoin is not recommended since nitrofurantoin may antagonize the antibacterial effect of Norfloxacin in the urinary tract. Multivitamins, or other products containing iron or zinc, antacids or sucralfate should not be administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because they may interfere with absorption resulting in lower serum and urine levels of norfloxacin. Videx (Didanosine) chewable/buffered tablets or the pediatric powder for oral solution should not be administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because these products may interfere with absorption resulting in lower serum and urine levels of norfloxacin. Some quinolones have also been shown to interfere with the metabolism of caffeine. This may lead to reduced clearance of caffeine and a prolongation of its plasma half-life." ], "offsets": [ [ 0, 2182 ] ] } ]

[ { "id": "Norfloxacin_ddi_T1", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 26, 38 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T2", "type": "GROUP", "text": [ "quinolone" ], "offsets": [ [ 75, 84 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T3", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 117, 129 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T4", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 191, 202 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T5", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 207, 219 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T6", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 246, 258 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T7", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 308, 320 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T8", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 368, 380 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T9", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 424, 436 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T10", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 442, 453 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T11", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 466, 478 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T12", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 528, 540 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T13", "type": "GROUP", "text": [ "Quinolones" ], "offsets": [ [ 606, 616 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T14", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 628, 639 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T15", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 673, 687 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T16", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 699, 707 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T17", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 914, 924 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T18", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 935, 946 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T19", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 952, 961 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T20", "type": "GROUP", "text": [ "sulfonylurea agent" ], "offsets": [ [ 965, 983 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T21", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 1167, 1178 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T22", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 1238, 1248 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T23", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 1253, 1264 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T24", "type": "DRUG", "text": [ "nitrofurantoin" ], "offsets": [ [ 1289, 1303 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T25", "type": "DRUG", "text": [ "nitrofurantoin" ], "offsets": [ [ 1329, 1343 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T26", "type": "DRUG", "text": [ "Norfloxacin" ], "offsets": [ [ 1387, 1398 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T27", "type": "GROUP", "text": [ "Multivitamins" ], "offsets": [ [ 1421, 1434 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T28", "type": "DRUG", "text": [ "iron" ], "offsets": [ [ 1465, 1469 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T29", "type": "DRUG", "text": [ "zinc" ], "offsets": [ [ 1473, 1477 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T30", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 1479, 1487 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T31", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 1491, 1501 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T32", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 1593, 1604 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T33", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 1694, 1705 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T34", "type": "BRAND", "text": [ "Videx" ], "offsets": [ [ 1707, 1712 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T35", "type": "DRUG", "text": [ "Didanosine" ], "offsets": [ [ 1714, 1724 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T36", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 1885, 1896 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T37", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 1996, 2007 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T38", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 2014, 2024 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T39", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 2082, 2090 ] ], "normalized": [] }, { "id": "Norfloxacin_ddi_T40", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 2130, 2138 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Norfloxacin_ddi_R1", "type": "MECHANISM", "arg1_id": "Norfloxacin_ddi_T1", "arg2_id": "Norfloxacin_ddi_T2", "normalized": [] }, { "id": "Norfloxacin_ddi_R2", "type": "EFFECT", "arg1_id": "Norfloxacin_ddi_T4", "arg2_id": "Norfloxacin_ddi_T5", "normalized": [] }, { "id": "Norfloxacin_ddi_R3", "type": "MECHANISM", "arg1_id": "Norfloxacin_ddi_T9", "arg2_id": "Norfloxacin_ddi_T10", "normalized": [] }, { "id": "Norfloxacin_ddi_R4", "type": "EFFECT", "arg1_id": "Norfloxacin_ddi_T13", "arg2_id": "Norfloxacin_ddi_T15", "normalized": [] }, { "id": "Norfloxacin_ddi_R5", "type": "EFFECT", "arg1_id": "Norfloxacin_ddi_T13", "arg2_id": "Norfloxacin_ddi_T16", "normalized": [] }, { "id": "Norfloxacin_ddi_R6", "type": "EFFECT", "arg1_id": "Norfloxacin_ddi_T14", "arg2_id": "Norfloxacin_ddi_T15", "normalized": [] }, { "id": "Norfloxacin_ddi_R7", "type": "EFFECT", "arg1_id": "Norfloxacin_ddi_T14", "arg2_id": "Norfloxacin_ddi_T16", "normalized": [] }, { "id": "Norfloxacin_ddi_R8", "type": "EFFECT", "arg1_id": "Norfloxacin_ddi_T17", "arg2_id": "Norfloxacin_ddi_T19", "normalized": [] }, { "id": "Norfloxacin_ddi_R9", "type": "EFFECT", "arg1_id": "Norfloxacin_ddi_T18", "arg2_id": "Norfloxacin_ddi_T19", "normalized": [] }, { "id": "Norfloxacin_ddi_R10", "type": "MECHANISM", "arg1_id": "Norfloxacin_ddi_T22", "arg2_id": "Norfloxacin_ddi_T23", "normalized": [] }, { "id": "Norfloxacin_ddi_R11", "type": "EFFECT", "arg1_id": "Norfloxacin_ddi_T25", "arg2_id": "Norfloxacin_ddi_T26", "normalized": [] }, { "id": "Norfloxacin_ddi_R12", "type": "ADVISE", "arg1_id": "Norfloxacin_ddi_T27", "arg2_id": "Norfloxacin_ddi_T32", "normalized": [] }, { "id": "Norfloxacin_ddi_R13", "type": "ADVISE", "arg1_id": "Norfloxacin_ddi_T28", "arg2_id": "Norfloxacin_ddi_T32", "normalized": [] }, { "id": "Norfloxacin_ddi_R14", "type": "ADVISE", "arg1_id": "Norfloxacin_ddi_T29", "arg2_id": "Norfloxacin_ddi_T32", "normalized": [] }, { "id": "Norfloxacin_ddi_R15", "type": "ADVISE", "arg1_id": "Norfloxacin_ddi_T30", "arg2_id": "Norfloxacin_ddi_T32", "normalized": [] }, { "id": "Norfloxacin_ddi_R16", "type": "ADVISE", "arg1_id": "Norfloxacin_ddi_T31", "arg2_id": "Norfloxacin_ddi_T32", "normalized": [] }, { "id": "Norfloxacin_ddi_R17", "type": "ADVISE", "arg1_id": "Norfloxacin_ddi_T34", "arg2_id": "Norfloxacin_ddi_T36", "normalized": [] }, { "id": "Norfloxacin_ddi_R18", "type": "ADVISE", "arg1_id": "Norfloxacin_ddi_T35", "arg2_id": "Norfloxacin_ddi_T36", "normalized": [] }, { "id": "Norfloxacin_ddi_R19", "type": "MECHANISM", "arg1_id": "Norfloxacin_ddi_T38", "arg2_id": "Norfloxacin_ddi_T39", "normalized": [] } ]

[ { "id": "Isosorbide Mononitrate_ddi__text", "type": "abstract", "text": [ "The vasodilating effects of isosorbide mononitrate may be additive with those of other vasodilators. Alcohol, in particular, has been found to exhibit additive effects of this variety. Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination. Dose adjustments of either class of agents may be necessary." ], "offsets": [ [ 0, 383 ] ] } ]

[ { "id": "Isosorbide Mononitrate_ddi_T1", "type": "DRUG", "text": [ "isosorbide mononitrate" ], "offsets": [ [ 28, 50 ] ], "normalized": [] }, { "id": "Isosorbide Mononitrate_ddi_T2", "type": "GROUP", "text": [ "vasodilators" ], "offsets": [ [ 87, 99 ] ], "normalized": [] }, { "id": "Isosorbide Mononitrate_ddi_T3", "type": "DRUG", "text": [ "Alcohol" ], "offsets": [ [ 101, 108 ] ], "normalized": [] }, { "id": "Isosorbide Mononitrate_ddi_T4", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 251, 275 ] ], "normalized": [] }, { "id": "Isosorbide Mononitrate_ddi_T5", "type": "GROUP", "text": [ "organic nitrates" ], "offsets": [ [ 280, 296 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Isosorbide Mononitrate_ddi_R1", "type": "EFFECT", "arg1_id": "Isosorbide Mononitrate_ddi_T1", "arg2_id": "Isosorbide Mononitrate_ddi_T2", "normalized": [] }, { "id": "Isosorbide Mononitrate_ddi_R2", "type": "EFFECT", "arg1_id": "Isosorbide Mononitrate_ddi_T4", "arg2_id": "Isosorbide Mononitrate_ddi_T5", "normalized": [] } ]

[ { "id": "Cefazolin_ddi__text", "type": "abstract", "text": [ "Probenecid may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood levels. Drug/Laboratory Test Interactions A false positive reaction for glucose in the urine may occur with Benedicts solution, Fehlings solution or with CLINITEST tablets, but not with enzyme-based tests such as CLINISTIX . Positive direct and indirect antiglobulin (Coombs) tests have occurred; these may also occur in neonates whose mothers received cephalosporins before delivery." ], "offsets": [ [ 0, 537 ] ] } ]

[ { "id": "Cefazolin_ddi_T1", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Cefazolin_ddi_T2", "type": "GROUP", "text": [ "cephalosporins" ], "offsets": [ [ 51, 65 ] ], "normalized": [] }, { "id": "Cefazolin_ddi_T3", "type": "GROUP", "text": [ "cephalosporin" ], "offsets": [ [ 132, 145 ] ], "normalized": [] }, { "id": "Cefazolin_ddi_T4", "type": "GROUP", "text": [ "cephalosporins" ], "offsets": [ [ 506, 520 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cefazolin_ddi_R1", "type": "MECHANISM", "arg1_id": "Cefazolin_ddi_T1", "arg2_id": "Cefazolin_ddi_T2", "normalized": [] } ]

[ { "id": "Eszopiclone_ddi__text", "type": "abstract", "text": [ "CNS-Active Drugs Ethanol An additive effect on psychomotor performance was seen with coadministration of eszopiclone and ethanol 0.70 g/kg for up to 4 hours after ethanol administration. Paroxetine: Coadministration of single doses of eszopiclone 3 mg and paroxetine 20 mg daily for 7 days produced no pharmacokinetic or pharmacodynamic interaction. Lorazepam: Coadministration of single doses of eszopiclone 3 mg and lorazepam 2 mg did not have clinically relevant effects on the pharmacodynamics or pharmacokinetics of either drug. Olanzapine: Coadministration of eszopiclone 3 mg and olanzapine 10 mg produced a decrease in DSST scores. The interaction was pharmacodynamic; there was no alteration in the pharmacokinetics of either drug. Drugs That Inhibit CYP3A4 (Ketoconazole) CYP3A4 is a major metabolic pathway for elimination of eszopiclone. The AUC of eszopiclone was increased 2.2-fold by coadministration of ketoconazole, a potent inhibitor of CYP3A4, 400 mg daily for 5 days. Cmax and t1/2 were increased 1.4-fold and 1.3-fold, respectively. Other strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, nefazodone, troleandomycin, ritonavir, nelfinavir) would be expected to behave similarly. Drugs That Induce CYP3A4 (Rifampicin) Racemic zopiclone exposure was decreased 80% by concomitant useof rifampicin, a potent inducer of CYP3A4. A similar effect would be expected with eszopiclone. Drugs Highly Bound To Plasma Protein Eszopiclone is not highly bound to plasma proteins (52-59% bound); therefore, the disposition of eszopiclone is not expected to be sensitive to alterations in protein binding. Administration of eszopiclone 3 mg to a patient taking another drug that is highly protein-bound would not be expected to cause an alteration in the free concentration of either drug. Drugs With A Narrow Therapeutic Index Digoxin A single dose of eszopiclone 3 mg did not affect the pharmacokinetics of digoxin measured at steady state following dosing of 0.5 mg twice daily for one day and 0.25 mg daily for the next 6 days. Warfarin: Eszopiclone 3 mg administered daily for 5 days did not affect the pharmacokinetics of (R)- or (S)-warfarin, nor were there any changes in the pharmacodynamic profile (prothrombin time) following a single 25 mg oral dose of warfarin ." ], "offsets": [ [ 0, 2294 ] ] } ]

[ { "id": "Eszopiclone_ddi_T1", "type": "DRUG", "text": [ "Ethanol" ], "offsets": [ [ 17, 24 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T2", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 105, 116 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T3", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 121, 128 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T4", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 163, 170 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T5", "type": "DRUG", "text": [ "Paroxetine" ], "offsets": [ [ 187, 197 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T6", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 235, 246 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T7", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 256, 266 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T8", "type": "DRUG", "text": [ "Lorazepam" ], "offsets": [ [ 350, 359 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T9", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 397, 408 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T10", "type": "DRUG", "text": [ "lorazepam" ], "offsets": [ [ 418, 427 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T11", "type": "DRUG", "text": [ "Olanzapine" ], "offsets": [ [ 534, 544 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T12", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 566, 577 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T13", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 587, 597 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T14", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 768, 780 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T15", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 837, 848 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T16", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 861, 872 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T17", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 919, 931 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T18", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1095, 1107 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T19", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 1109, 1123 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T20", "type": "DRUG", "text": [ "nefazodone" ], "offsets": [ [ 1125, 1135 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T21", "type": "DRUG", "text": [ "troleandomycin" ], "offsets": [ [ 1137, 1151 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T22", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 1153, 1162 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T23", "type": "DRUG", "text": [ "nelfinavir" ], "offsets": [ [ 1164, 1174 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T24", "type": "DRUG", "text": [ "Rifampicin" ], "offsets": [ [ 1241, 1251 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T25", "type": "DRUG", "text": [ "zopiclone" ], "offsets": [ [ 1261, 1270 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T26", "type": "DRUG", "text": [ "rifampicin" ], "offsets": [ [ 1319, 1329 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T27", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 1399, 1410 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T28", "type": "DRUG", "text": [ "Eszopiclone" ], "offsets": [ [ 1449, 1460 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T29", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 1546, 1557 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T30", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 1643, 1654 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T31", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 1847, 1854 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T32", "type": "DRUG", "text": [ "eszopiclone" ], "offsets": [ [ 1872, 1883 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T33", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1928, 1935 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T34", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 2051, 2059 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T35", "type": "DRUG", "text": [ "Eszopiclone" ], "offsets": [ [ 2061, 2072 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T36", "type": "DRUG", "text": [ "(R)-w", "arfarin" ], "offsets": [ [ 2146, 2151 ], [ 2159, 2167 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T37", "type": "DRUG", "text": [ "(S)-warfarin" ], "offsets": [ [ 2155, 2167 ] ], "normalized": [] }, { "id": "Eszopiclone_ddi_T38", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2284, 2292 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Eszopiclone_ddi_R1", "type": "EFFECT", "arg1_id": "Eszopiclone_ddi_T2", "arg2_id": "Eszopiclone_ddi_T3", "normalized": [] }, { "id": "Eszopiclone_ddi_R2", "type": "EFFECT", "arg1_id": "Eszopiclone_ddi_T12", "arg2_id": "Eszopiclone_ddi_T13", "normalized": [] }, { "id": "Eszopiclone_ddi_R3", "type": "MECHANISM", "arg1_id": "Eszopiclone_ddi_T16", "arg2_id": "Eszopiclone_ddi_T17", "normalized": [] }, { "id": "Eszopiclone_ddi_R4", "type": "MECHANISM", "arg1_id": "Eszopiclone_ddi_T25", "arg2_id": "Eszopiclone_ddi_T26", "normalized": [] } ]

[ { "id": "Ergotamine_ddi__text", "type": "abstract", "text": [ "The effects of ERGOMAR may be potentiated by triacetyloleandomycin which inhibits the metabolism of ergotamine. The pressor effects of ERGOMAR and other vasoconstrictor drugs can combine to cause dangerous hypertension." ], "offsets": [ [ 0, 219 ] ] } ]

[ { "id": "Ergotamine_ddi_T1", "type": "BRAND", "text": [ "ERGOMAR" ], "offsets": [ [ 15, 22 ] ], "normalized": [] }, { "id": "Ergotamine_ddi_T2", "type": "DRUG", "text": [ "triacetyloleandomycin" ], "offsets": [ [ 45, 66 ] ], "normalized": [] }, { "id": "Ergotamine_ddi_T3", "type": "DRUG", "text": [ "ergotamine" ], "offsets": [ [ 100, 110 ] ], "normalized": [] }, { "id": "Ergotamine_ddi_T4", "type": "BRAND", "text": [ "ERGOMAR" ], "offsets": [ [ 135, 142 ] ], "normalized": [] }, { "id": "Ergotamine_ddi_T5", "type": "GROUP", "text": [ "vasoconstrictor drugs" ], "offsets": [ [ 153, 174 ] ], "normalized": [] } ]

[]

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[ { "id": "Ergotamine_ddi_R1", "type": "MECHANISM", "arg1_id": "Ergotamine_ddi_T1", "arg2_id": "Ergotamine_ddi_T2", "normalized": [] }, { "id": "Ergotamine_ddi_R2", "type": "MECHANISM", "arg1_id": "Ergotamine_ddi_T2", "arg2_id": "Ergotamine_ddi_T3", "normalized": [] }, { "id": "Ergotamine_ddi_R3", "type": "EFFECT", "arg1_id": "Ergotamine_ddi_T4", "arg2_id": "Ergotamine_ddi_T5", "normalized": [] } ]

[ { "id": "Irbesartan_ddi__text", "type": "abstract", "text": [ "No significant drug-drug pharmacokinetic (or pharmacodynamic) interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, and nifedipine. In vitro studies show significant inhibition of the formation of oxidized irbesartan metabolites with the known cytochrome CYP 2C9 substrates/inhibitors sulphenazole, tolbutamide and nifedipine. However, in clinical studies the consequences of concomitant irbesartan on the pharmacodynamics of warfarin were negligible. Based on in vitro data, no interaction would be expected with drugs whose metabolism is dependent upon cytochrome P450 isozymes 1A1, 1A2,2A6,2B6,2D6,2E1,or 3A4. In separate studies of patients receiving maintenance doses of warfarin, hydrochlorothiazide, or digoxin, irbesartan administration for 7 days had no effect on the pharmacodynamics of warfarin (prothrombin time) or pharmacokinetics of digoxin. The pharmacokinetics of irbesartan were not affected by coadministration of nifedipine or hydrochlorothiazide ." ], "offsets": [ [ 0, 1011 ] ] } ]

[ { "id": "Irbesartan_ddi_T1", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 119, 138 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T2", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 140, 147 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 149, 157 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T4", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 163, 173 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T5", "type": "DRUG", "text": [ "sulphenazole" ], "offsets": [ [ 328, 340 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T6", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 342, 353 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T7", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 358, 368 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T8", "type": "DRUG", "text": [ "irbesartan" ], "offsets": [ [ 431, 441 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T9", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 469, 477 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T10", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 719, 727 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T11", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 729, 748 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T12", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 753, 760 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T13", "type": "DRUG", "text": [ "irbesartan" ], "offsets": [ [ 762, 772 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T14", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 840, 848 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T15", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 891, 898 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T16", "type": "DRUG", "text": [ "irbesartan" ], "offsets": [ [ 924, 934 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T17", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 976, 986 ] ], "normalized": [] }, { "id": "Irbesartan_ddi_T18", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 990, 1009 ] ], "normalized": [] } ]

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[ { "id": "Ibritumomab_ddi__text", "type": "abstract", "text": [ "No formal drug interaction studies have been performed with ZEVALIN. Due to the frequent occurrence of severe and prolonged thrombocytopenia, the potential benefits of medications which interfere with platelet function and/or anticoagulation should be weighed against the potential increased risks of bleeding and hemorrhage. Patients receiving medications that interfere with platelet function or coagulation should have more frequent laboratory monitoring for thrombocytopenia. In addition, the transfusion practices for such patients may need to be modified given the increased risk of bleeding. Patients in clinical studies were prohibited from receiving growth factor treatment for 2 weeks prior to the ZEVALIN therapeutic regimen as well as for 2 weeks following completion of the regimen." ], "offsets": [ [ 0, 795 ] ] } ]

[ { "id": "Ibritumomab_ddi_T1", "type": "BRAND", "text": [ "ZEVALIN" ], "offsets": [ [ 60, 67 ] ], "normalized": [] }, { "id": "Ibritumomab_ddi_T2", "type": "BRAND", "text": [ "ZEVALIN" ], "offsets": [ [ 708, 715 ] ], "normalized": [] } ]

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[ { "id": "Cimetidine_ddi__text", "type": "abstract", "text": [ "Tagamet, apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline and metronidazole, thereby delaying elimination and increasing blood levels of these drugs. Clinically significant effects have been reported with the warfarin anticoagulants; therefore, close monitoring of prothrombin time is recommended, and adjustment of the anticoagulant dose may be necessary when Tagamet is administered concomitantly. Interaction with phenytoin, lidocaine and theophylline has also been reported to produce adverse clinical effects. However, a crossover study in healthy subjects receiving either Tagamet 300 mg q.i.d. or 800 mg h.s. concomitantly with a 300 mg b.i.d. dosage of theophylline (Theo-Dur , Key Pharmaceuticals, Inc.) demonstrated less alteration in steady-state theophylline peak serum levels with the 800 mg h.s. regimen, particularly in subjects aged 54 years and older. Data beyond 10 days are not available. (Note: All patients receiving theophylline should be monitored appropriately, regardless of concomitant drug therapy.) Dosage of the drugs mentioned above and other similarly metabolized drugs, particularly those of low therapeutic ratio or in patients with renal and/or hepatic impairment, may require adjustment when starting or stopping concomitantly administered Tagamet to maintain optimum therapeutic blood levels. Alteration of pH may affect absorption of certain drugs (e.g., ketoconazole). If these products are needed, they should be given at least 2 hours before cimetidine administration. Additional clinical experience may reveal other drugs affected by the concomitant administration of Tagamet." ], "offsets": [ [ 0, 1842 ] ] } ]

[ { "id": "Cimetidine_ddi_T1", "type": "BRAND", "text": [ "Tagamet" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T2", "type": "GROUP", "text": [ "warfarin-type anticoagulants" ], "offsets": [ [ 130, 158 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T3", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 160, 169 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T4", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 171, 182 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T5", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 184, 194 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T6", "type": "DRUG", "text": [ "chlordiazepoxide" ], "offsets": [ [ 196, 212 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T7", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 214, 222 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T8", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 232, 257 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T9", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 259, 268 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T10", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 270, 282 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T11", "type": "DRUG", "text": [ "metronidazole" ], "offsets": [ [ 287, 300 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T12", "type": "GROUP", "text": [ "warfarin anticoagulants" ], "offsets": [ [ 434, 457 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T13", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 545, 558 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T14", "type": "BRAND", "text": [ "Tagamet" ], "offsets": [ [ 586, 593 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T15", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 642, 651 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T16", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 653, 662 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T17", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 667, 679 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T18", "type": "BRAND", "text": [ "Tagamet" ], "offsets": [ [ 804, 811 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T19", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 886, 898 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T20", "type": "BRAND", "text": [ "Theo-Dur" ], "offsets": [ [ 900, 908 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T21", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 983, 995 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T22", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1163, 1175 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T23", "type": "BRAND", "text": [ "Tagamet" ], "offsets": [ [ 1500, 1507 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T24", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1617, 1629 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T25", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1707, 1717 ] ], "normalized": [] }, { "id": "Cimetidine_ddi_T26", "type": "BRAND", "text": [ "Tagamet" ], "offsets": [ [ 1834, 1841 ] ], "normalized": [] } ]

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[ { "id": "Cimetidine_ddi_R1", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T2", "normalized": [] }, { "id": "Cimetidine_ddi_R2", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T3", "normalized": [] }, { "id": "Cimetidine_ddi_R3", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T4", "normalized": [] }, { "id": "Cimetidine_ddi_R4", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T5", "normalized": [] }, { "id": "Cimetidine_ddi_R5", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T6", "normalized": [] }, { "id": "Cimetidine_ddi_R6", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T7", "normalized": [] }, { "id": "Cimetidine_ddi_R7", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T8", "normalized": [] }, { "id": "Cimetidine_ddi_R8", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T9", "normalized": [] }, { "id": "Cimetidine_ddi_R9", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T10", "normalized": [] }, { "id": "Cimetidine_ddi_R10", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T1", "arg2_id": "Cimetidine_ddi_T11", "normalized": [] }, { "id": "Cimetidine_ddi_R11", "type": "ADVISE", "arg1_id": "Cimetidine_ddi_T13", "arg2_id": "Cimetidine_ddi_T14", "normalized": [] }, { "id": "Cimetidine_ddi_R12", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T18", "arg2_id": "Cimetidine_ddi_T19", "normalized": [] }, { "id": "Cimetidine_ddi_R13", "type": "MECHANISM", "arg1_id": "Cimetidine_ddi_T18", "arg2_id": "Cimetidine_ddi_T20", "normalized": [] } ]

[ { "id": "Alteplase_ddi__text", "type": "abstract", "text": [ "The interaction of Activase with other cardioactive or cerebroactive drugs has not been studied. In addition to bleeding associated with heparin and vitamin K antagonists, drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole and Abciximab) may increase the risk of bleeding if administered prior to, during, or after Activase therapy. Use of Antithrombotics Aspirin and heparin have been administered concomitantly with and following infusions of Activase in the management of acute myocardial infarction or pulmonary embolism. Because heparin, aspirin, or Activase may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites. The concomitant use of heparin or aspirin during the first 24 hours following symptom onset were prohibited in The NINDS t-PA Stroke Trial. The safety of such concomitant use with Activase for the management of acute ischemic stroke is unknown." ], "offsets": [ [ 0, 953 ] ] } ]

[ { "id": "Alteplase_ddi_T1", "type": "BRAND", "text": [ "Activase" ], "offsets": [ [ 19, 27 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T2", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 137, 144 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T3", "type": "GROUP", "text": [ "vitamin K antagonists" ], "offsets": [ [ 149, 170 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T4", "type": "DRUG", "text": [ "acetylsalicylic acid" ], "offsets": [ [ 216, 236 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T5", "type": "DRUG", "text": [ "dipyridamole" ], "offsets": [ [ 238, 250 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T6", "type": "DRUG", "text": [ "Abciximab" ], "offsets": [ [ 255, 264 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T7", "type": "BRAND", "text": [ "Activase" ], "offsets": [ [ 343, 351 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T8", "type": "GROUP", "text": [ "Antithrombotics" ], "offsets": [ [ 368, 383 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T9", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 384, 391 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T10", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 396, 403 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T11", "type": "BRAND", "text": [ "Activase" ], "offsets": [ [ 473, 481 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T12", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 562, 569 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T13", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 571, 578 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T14", "type": "BRAND", "text": [ "Activase" ], "offsets": [ [ 583, 591 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T15", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 732, 739 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T16", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 743, 750 ] ], "normalized": [] }, { "id": "Alteplase_ddi_T17", "type": "BRAND", "text": [ "Activase" ], "offsets": [ [ 889, 897 ] ], "normalized": [] } ]

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[ { "id": "Alteplase_ddi_R1", "type": "EFFECT", "arg1_id": "Alteplase_ddi_T2", "arg2_id": "Alteplase_ddi_T7", "normalized": [] }, { "id": "Alteplase_ddi_R2", "type": "EFFECT", "arg1_id": "Alteplase_ddi_T3", "arg2_id": "Alteplase_ddi_T7", "normalized": [] }, { "id": "Alteplase_ddi_R3", "type": "INT", "arg1_id": "Alteplase_ddi_T4", "arg2_id": "Alteplase_ddi_T7", "normalized": [] }, { "id": "Alteplase_ddi_R4", "type": "EFFECT", "arg1_id": "Alteplase_ddi_T5", "arg2_id": "Alteplase_ddi_T7", "normalized": [] }, { "id": "Alteplase_ddi_R5", "type": "EFFECT", "arg1_id": "Alteplase_ddi_T6", "arg2_id": "Alteplase_ddi_T7", "normalized": [] } ]

[ { "id": "Kanamycin_ddi__text", "type": "abstract", "text": [ "In vitro mixing of an aminoglycoside with beta-lactamtype antibiotics (penicillins or cephalosporins) may result in a significant mutual inactivation. Even when an aminoglycoside and a penicillin-type drug are administered separately by different routes, a reduction in aminoglycoside serum half-life or serum levels has been reported in patients with impaired renal function and in some patients with normal renal function. Usually, such inactivation of the aminoglycoside is clinically significant only in patients with severely impaired renal function.. See" ], "offsets": [ [ 0, 560 ] ] } ]

[ { "id": "Kanamycin_ddi_T1", "type": "GROUP", "text": [ "aminoglycoside" ], "offsets": [ [ 22, 36 ] ], "normalized": [] }, { "id": "Kanamycin_ddi_T2", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 58, 69 ] ], "normalized": [] }, { "id": "Kanamycin_ddi_T3", "type": "GROUP", "text": [ "penicillins" ], "offsets": [ [ 71, 82 ] ], "normalized": [] }, { "id": "Kanamycin_ddi_T4", "type": "GROUP", "text": [ "cephalosporins" ], "offsets": [ [ 86, 100 ] ], "normalized": [] }, { "id": "Kanamycin_ddi_T5", "type": "GROUP", "text": [ "aminoglycoside" ], "offsets": [ [ 164, 178 ] ], "normalized": [] }, { "id": "Kanamycin_ddi_T6", "type": "GROUP", "text": [ "penicillin" ], "offsets": [ [ 185, 195 ] ], "normalized": [] }, { "id": "Kanamycin_ddi_T7", "type": "GROUP", "text": [ "aminoglycoside" ], "offsets": [ [ 270, 284 ] ], "normalized": [] }, { "id": "Kanamycin_ddi_T8", "type": "GROUP", "text": [ "aminoglycoside" ], "offsets": [ [ 459, 473 ] ], "normalized": [] } ]

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[ { "id": "Kanamycin_ddi_R1", "type": "EFFECT", "arg1_id": "Kanamycin_ddi_T1", "arg2_id": "Kanamycin_ddi_T2", "normalized": [] }, { "id": "Kanamycin_ddi_R2", "type": "EFFECT", "arg1_id": "Kanamycin_ddi_T1", "arg2_id": "Kanamycin_ddi_T3", "normalized": [] }, { "id": "Kanamycin_ddi_R3", "type": "EFFECT", "arg1_id": "Kanamycin_ddi_T1", "arg2_id": "Kanamycin_ddi_T4", "normalized": [] }, { "id": "Kanamycin_ddi_R4", "type": "MECHANISM", "arg1_id": "Kanamycin_ddi_T5", "arg2_id": "Kanamycin_ddi_T6", "normalized": [] } ]

[ { "id": "Ibutilide_ddi__text", "type": "abstract", "text": [ "No specific pharmacokinetic or other formal drug interaction studies were conducted. Digoxin: Supraventricular arrhythmias may mask the cardiotoxicity associated with excessive digoxin levels. Therefore, it is advisable to be particularly cautious in patients whose plasma digoxin levels are above or suspected to be above the usual therapeutic range. Coadministration of digoxin did not have effects on either the safety or efficacy of ibutilide in the clinical trials. Calcium channel blocking agents: Coadministration of calcium channel blockers did not have any effect on either the safety or efficacy of ibutilide in the clinical trials. Beta-adrenergic blocking agents: Coadministration of beta-adrenergic blocking agents did not have any effect on either the safety or efficacy of ibutilide in the clinical trials." ], "offsets": [ [ 0, 821 ] ] } ]

[ { "id": "Ibutilide_ddi_T1", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 85, 92 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T2", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 177, 184 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T3", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 273, 280 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T4", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 372, 379 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T5", "type": "DRUG", "text": [ "ibutilide" ], "offsets": [ [ 437, 446 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T6", "type": "GROUP", "text": [ "Calcium channel blocking agents" ], "offsets": [ [ 471, 502 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T7", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 524, 548 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T8", "type": "DRUG", "text": [ "ibutilide" ], "offsets": [ [ 609, 618 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T9", "type": "GROUP", "text": [ "Beta-adrenergic blocking agents" ], "offsets": [ [ 643, 674 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T10", "type": "GROUP", "text": [ "beta-adrenergic blocking agents" ], "offsets": [ [ 696, 727 ] ], "normalized": [] }, { "id": "Ibutilide_ddi_T11", "type": "DRUG", "text": [ "ibutilide" ], "offsets": [ [ 788, 797 ] ], "normalized": [] } ]

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[]

[ { "id": "Nifedipine_ddi__text", "type": "abstract", "text": [ "Beta-adrenergic Blocking Agents: Experience in over 1400 patients in a non-comparative clinical trial has shown that concomitant administration of nifedipine and beta-blocking agents is usually well tolerated, but there have been occasional literature reports suggesting that the combination may increase the likelihood of congestive heart failure, severe hypotension or exacerbation of angina. Long Acting Nitrates: Nifedipine may be safely co-administered with nitrates, but there have been no controlled studies to evaluate the antianginal effectiveness of this combination. Digitalis: Immediate Release Capsules: Since there have been isolated reports of patients with elevated digoxin levels, and there is a possible interaction between digoxin and nifedipine, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing nifedipine to avoid possible over- or under-digitalization. Extended Release Tablets: Administration of nifedipine with digoxin increased digoxin levels in 9 of 12 normal volunteers. The average increase was 45%. Another investigator found no increase in digoxin levels in 13 patients with coronary artery disease. In an uncontrolled study of over 200 patients with congestive heart failure during which digoxin blood levels were not measured, digitalis toxicity was not observed. Since there have been isolated reports of patients with elevated digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing nifedipine to avoid possible over- or under-digitalization. Quinidine: Immediate Release Capsules: There have been rare reports of an interaction between quinidine and nifedipine (with a decreased plasma level of quinidine). Coumarin Anticoagulants: There have been rare reports of increased prothrombin time in patients taking coumarin anticoagulants to whom nifedipine was administered. However, the relationship to nifedipine therapy is uncertain. Cimetidine: A study in 6 healthy volunteers has shown a significant increase in peak nifedipine plasma levels (80%) and area-under-the-curve (74%) after a 1 week course of cimetidine at 1000 mg per day and nifedipine at 40 mg per day. Ranitidine produced smaller, non-significant increases. The effect may be mediated by the known inhibition of cimetidine on hepatic cytochrome P-450, the enzyme system probably responsible for the first-pass metabolism of nifedipine. If nifedipine therapy is initiated in a patient currently receiving cimetidine, cautious titration is advised." ], "offsets": [ [ 0, 2552 ] ] } ]

[ { "id": "Nifedipine_ddi_T1", "type": "GROUP", "text": [ "Beta-adrenergic Blocking Agents" ], "offsets": [ [ 0, 31 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T2", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 147, 157 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T3", "type": "GROUP", "text": [ "beta-blocking agents" ], "offsets": [ [ 162, 182 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T4", "type": "GROUP", "text": [ "Nitrates" ], "offsets": [ [ 407, 415 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T5", "type": "DRUG", "text": [ "Nifedipine" ], "offsets": [ [ 417, 427 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T6", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 463, 471 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T7", "type": "GROUP", "text": [ "Digitalis" ], "offsets": [ [ 578, 587 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T8", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 682, 689 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T9", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 742, 749 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T10", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 754, 764 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T11", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 789, 796 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T12", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 863, 873 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T13", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 967, 977 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T14", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 983, 990 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T15", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1001, 1008 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T16", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1118, 1125 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T17", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1267, 1274 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T18", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1409, 1416 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T19", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1448, 1455 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T20", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 1522, 1532 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T21", "type": "DRUG", "text": [ "Quinidine" ], "offsets": [ [ 1582, 1591 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T22", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1676, 1685 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T23", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 1690, 1700 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T24", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1735, 1744 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T25", "type": "GROUP", "text": [ "Coumarin Anticoagulants" ], "offsets": [ [ 1747, 1770 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T26", "type": "GROUP", "text": [ "coumarin anticoagulants" ], "offsets": [ [ 1850, 1873 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T27", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 1882, 1892 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T28", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 1940, 1950 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T29", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 1973, 1983 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T30", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 2058, 2068 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T31", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2145, 2155 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T32", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 2179, 2189 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T33", "type": "DRUG", "text": [ "Ranitidine" ], "offsets": [ [ 2208, 2218 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T34", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2318, 2328 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T35", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 2430, 2440 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T36", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 2445, 2455 ] ], "normalized": [] }, { "id": "Nifedipine_ddi_T37", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2510, 2520 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Nifedipine_ddi_R1", "type": "EFFECT", "arg1_id": "Nifedipine_ddi_T2", "arg2_id": "Nifedipine_ddi_T3", "normalized": [] }, { "id": "Nifedipine_ddi_R2", "type": "INT", "arg1_id": "Nifedipine_ddi_T9", "arg2_id": "Nifedipine_ddi_T10", "normalized": [] }, { "id": "Nifedipine_ddi_R3", "type": "ADVISE", "arg1_id": "Nifedipine_ddi_T11", "arg2_id": "Nifedipine_ddi_T12", "normalized": [] }, { "id": "Nifedipine_ddi_R4", "type": "MECHANISM", "arg1_id": "Nifedipine_ddi_T14", "arg2_id": "Nifedipine_ddi_T15", "normalized": [] }, { "id": "Nifedipine_ddi_R5", "type": "ADVISE", "arg1_id": "Nifedipine_ddi_T19", "arg2_id": "Nifedipine_ddi_T20", "normalized": [] }, { "id": "Nifedipine_ddi_R6", "type": "MECHANISM", "arg1_id": "Nifedipine_ddi_T22", "arg2_id": "Nifedipine_ddi_T23", "normalized": [] }, { "id": "Nifedipine_ddi_R7", "type": "EFFECT", "arg1_id": "Nifedipine_ddi_T26", "arg2_id": "Nifedipine_ddi_T27", "normalized": [] }, { "id": "Nifedipine_ddi_R8", "type": "MECHANISM", "arg1_id": "Nifedipine_ddi_T31", "arg2_id": "Nifedipine_ddi_T32", "normalized": [] }, { "id": "Nifedipine_ddi_R9", "type": "ADVISE", "arg1_id": "Nifedipine_ddi_T36", "arg2_id": "Nifedipine_ddi_T37", "normalized": [] } ]

[ { "id": "Doxycycline_ddi__text", "type": "abstract", "text": [ "Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines in conjunction with penicillin. Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and iron-containing preparations. Absorption of tetracycline is impaired by bismuth subsalicylate. Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. The concurrent use of tetracycline and Penthrane (methoxyflurane) has been reported to result in fatal renal toxicity. Concurrent use of tetracycline may render oral contraceptives less effective. Drug/Laboratory Test Interactions False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test." ], "offsets": [ [ 0, 960 ] ] } ]

[ { "id": "Doxycycline_ddi_T1", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 8, 21 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T2", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 98, 111 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T3", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 161, 174 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T4", "type": "DRUG", "text": [ "penicillin" ], "offsets": [ [ 256, 266 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T5", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 300, 313 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T6", "type": "GROUP", "text": [ "penicillin" ], "offsets": [ [ 334, 344 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T7", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 360, 373 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T8", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 389, 397 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T9", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 409, 417 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T10", "type": "DRUG", "text": [ "calcium" ], "offsets": [ [ 419, 426 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T11", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 431, 440 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T12", "type": "DRUG", "text": [ "iron" ], "offsets": [ [ 446, 450 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T13", "type": "DRUG", "text": [ "tetracycline" ], "offsets": [ [ 490, 502 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T14", "type": "DRUG", "text": [ "bismuth subsalicylate" ], "offsets": [ [ 518, 539 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T15", "type": "GROUP", "text": [ "Barbiturates" ], "offsets": [ [ 541, 553 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T16", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 555, 568 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T17", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 574, 583 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T18", "type": "DRUG", "text": [ "doxycycline" ], "offsets": [ [ 610, 621 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T19", "type": "DRUG", "text": [ "tetracycline" ], "offsets": [ [ 645, 657 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T20", "type": "BRAND", "text": [ "Penthrane" ], "offsets": [ [ 662, 671 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T21", "type": "DRUG", "text": [ "methoxyflurane" ], "offsets": [ [ 673, 687 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T22", "type": "DRUG", "text": [ "tetracycline" ], "offsets": [ [ 760, 772 ] ], "normalized": [] }, { "id": "Doxycycline_ddi_T23", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 789, 803 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Doxycycline_ddi_R1", "type": "ADVISE", "arg1_id": "Doxycycline_ddi_T1", "arg2_id": "Doxycycline_ddi_T2", "normalized": [] }, { "id": "Doxycycline_ddi_R2", "type": "ADVISE", "arg1_id": "Doxycycline_ddi_T5", "arg2_id": "Doxycycline_ddi_T6", "normalized": [] }, { "id": "Doxycycline_ddi_R3", "type": "MECHANISM", "arg1_id": "Doxycycline_ddi_T7", "arg2_id": "Doxycycline_ddi_T9", "normalized": [] }, { "id": "Doxycycline_ddi_R4", "type": "MECHANISM", "arg1_id": "Doxycycline_ddi_T7", "arg2_id": "Doxycycline_ddi_T10", "normalized": [] }, { "id": "Doxycycline_ddi_R5", "type": "MECHANISM", "arg1_id": "Doxycycline_ddi_T7", "arg2_id": "Doxycycline_ddi_T11", "normalized": [] }, { "id": "Doxycycline_ddi_R6", "type": "MECHANISM", "arg1_id": "Doxycycline_ddi_T7", "arg2_id": "Doxycycline_ddi_T12", "normalized": [] }, { "id": "Doxycycline_ddi_R7", "type": "MECHANISM", "arg1_id": "Doxycycline_ddi_T13", "arg2_id": "Doxycycline_ddi_T14", "normalized": [] }, { "id": "Doxycycline_ddi_R8", "type": "MECHANISM", "arg1_id": "Doxycycline_ddi_T15", "arg2_id": "Doxycycline_ddi_T18", "normalized": [] }, { "id": "Doxycycline_ddi_R9", "type": "MECHANISM", "arg1_id": "Doxycycline_ddi_T16", "arg2_id": "Doxycycline_ddi_T18", "normalized": [] }, { "id": "Doxycycline_ddi_R10", "type": "MECHANISM", "arg1_id": "Doxycycline_ddi_T17", "arg2_id": "Doxycycline_ddi_T18", "normalized": [] }, { "id": "Doxycycline_ddi_R11", "type": "EFFECT", "arg1_id": "Doxycycline_ddi_T19", "arg2_id": "Doxycycline_ddi_T20", "normalized": [] }, { "id": "Doxycycline_ddi_R12", "type": "EFFECT", "arg1_id": "Doxycycline_ddi_T19", "arg2_id": "Doxycycline_ddi_T21", "normalized": [] }, { "id": "Doxycycline_ddi_R13", "type": "EFFECT", "arg1_id": "Doxycycline_ddi_T22", "arg2_id": "Doxycycline_ddi_T23", "normalized": [] } ]

[ { "id": "Clindamycin_ddi__text", "type": "abstract", "text": [ "Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents. Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently." ], "offsets": [ [ 0, 393 ] ] } ]

[ { "id": "Clindamycin_ddi_T1", "type": "DRUG", "text": [ "Clindamycin" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "Clindamycin_ddi_T2", "type": "GROUP", "text": [ "neuromuscular blocking agents" ], "offsets": [ [ 106, 135 ] ], "normalized": [] }, { "id": "Clindamycin_ddi_T3", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 255, 266 ] ], "normalized": [] }, { "id": "Clindamycin_ddi_T4", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 271, 283 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Clindamycin_ddi_R1", "type": "EFFECT", "arg1_id": "Clindamycin_ddi_T1", "arg2_id": "Clindamycin_ddi_T2", "normalized": [] }, { "id": "Clindamycin_ddi_R2", "type": "EFFECT", "arg1_id": "Clindamycin_ddi_T3", "arg2_id": "Clindamycin_ddi_T4", "normalized": [] } ]

[ { "id": "Imipramine_ddi__text", "type": "abstract", "text": [ "In occasional susceptible patients or in those receiving anticholinergic drugs (including antiparkinsonism agents) in addition, the atropine-like effects may become more pronounced (e.g., paralytic ileus). Close supervision and careful adjustment of dosage is required when this drug is administered concomitantly with anticholinergic drugs. Avoid the use of preparations such as decongestants and local anesthetics which contain any sympathomimetic amine (e.g., epinephrine, norepinephrine), since it has been reported that tricyclic antidepressants can potentiate the effects of catecholamines. Caution should be exercised when imipramine hydrochloride is used with agents that lower blood pressure. Imipramine hydrochloride may potentiate the effects of CNS depressant drugs. The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary. Drugs Metabolized by P450 2D6 The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of caucasians are so called poor metabolizers); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble p.o. metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e. g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition, and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCA5 with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from cotherapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6." ], "offsets": [ [ 0, 3502 ] ] } ]

[ { "id": "Imipramine_ddi_T1", "type": "GROUP", "text": [ "anticholinergic drugs" ], "offsets": [ [ 57, 78 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T2", "type": "GROUP", "text": [ "anticholinergic drugs" ], "offsets": [ [ 319, 340 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T3", "type": "GROUP", "text": [ "decongestants" ], "offsets": [ [ 380, 393 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T4", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 404, 415 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T5", "type": "GROUP", "text": [ "sympathomimetic amine" ], "offsets": [ [ 434, 455 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T6", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 463, 474 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T7", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 476, 490 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T8", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 525, 550 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T9", "type": "DRUG", "text": [ "imipramine hydrochloride" ], "offsets": [ [ 630, 654 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T10", "type": "DRUG", "text": [ "Imipramine hydrochloride" ], "offsets": [ [ 702, 726 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T11", "type": "GROUP", "text": [ "CNS depressant drugs" ], "offsets": [ [ 757, 777 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T12", "type": "DRUG", "text": [ "imipramine" ], "offsets": [ [ 807, 817 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T13", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 906, 916 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T14", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 918, 928 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T15", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 1007, 1019 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T16", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1021, 1030 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T17", "type": "DRUG", "text": [ "imipramine" ], "offsets": [ [ 1065, 1075 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T18", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 1562, 1587 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T19", "type": "GROUP", "text": [ "TCAs" ], "offsets": [ [ 1589, 1593 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T20", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 1782, 1785 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T21", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 1956, 1959 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T22", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 2147, 2156 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T23", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2158, 2168 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T24", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 2224, 2239 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T25", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 2241, 2255 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T26", "type": "GROUP", "text": [ "Type 1C antiarrhythmics" ], "offsets": [ [ 2265, 2288 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T27", "type": "DRUG", "text": [ "propafenone" ], "offsets": [ [ 2289, 2300 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T28", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 2305, 2315 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T29", "type": "GROUP", "text": [ "selective serotonin reuptake inhibitors" ], "offsets": [ [ 2332, 2371 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T30", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 2373, 2378 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T31", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 2388, 2398 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T32", "type": "DRUG", "text": [ "sertraline" ], "offsets": [ [ 2400, 2410 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T33", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 2416, 2426 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T34", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 2509, 2513 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T35", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 2514, 2517 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T36", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 2631, 2635 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T37", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 2730, 2735 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T38", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 2907, 2917 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T39", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3036, 3061 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T40", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 3173, 3197 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T41", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 3314, 3338 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T42", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 3383, 3386 ] ], "normalized": [] }, { "id": "Imipramine_ddi_T43", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 3412, 3415 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Imipramine_ddi_R1", "type": "ADVISE", "arg1_id": "Imipramine_ddi_T3", "arg2_id": "Imipramine_ddi_T8", "normalized": [] }, { "id": "Imipramine_ddi_R2", "type": "ADVISE", "arg1_id": "Imipramine_ddi_T4", "arg2_id": "Imipramine_ddi_T8", "normalized": [] }, { "id": "Imipramine_ddi_R3", "type": "ADVISE", "arg1_id": "Imipramine_ddi_T5", "arg2_id": "Imipramine_ddi_T8", "normalized": [] }, { "id": "Imipramine_ddi_R4", "type": "ADVISE", "arg1_id": "Imipramine_ddi_T6", "arg2_id": "Imipramine_ddi_T8", "normalized": [] }, { "id": "Imipramine_ddi_R5", "type": "ADVISE", "arg1_id": "Imipramine_ddi_T7", "arg2_id": "Imipramine_ddi_T8", "normalized": [] }, { "id": "Imipramine_ddi_R6", "type": "EFFECT", "arg1_id": "Imipramine_ddi_T10", "arg2_id": "Imipramine_ddi_T11", "normalized": [] }, { "id": "Imipramine_ddi_R7", "type": "MECHANISM", "arg1_id": "Imipramine_ddi_T12", "arg2_id": "Imipramine_ddi_T13", "normalized": [] }, { "id": "Imipramine_ddi_R8", "type": "MECHANISM", "arg1_id": "Imipramine_ddi_T12", "arg2_id": "Imipramine_ddi_T14", "normalized": [] }, { "id": "Imipramine_ddi_R9", "type": "MECHANISM", "arg1_id": "Imipramine_ddi_T12", "arg2_id": "Imipramine_ddi_T15", "normalized": [] }, { "id": "Imipramine_ddi_R10", "type": "MECHANISM", "arg1_id": "Imipramine_ddi_T12", "arg2_id": "Imipramine_ddi_T16", "normalized": [] }, { "id": "Imipramine_ddi_R11", "type": "INT", "arg1_id": "Imipramine_ddi_T34", "arg2_id": "Imipramine_ddi_T35", "normalized": [] } ]

[ { "id": "Glimepiride_ddi__text", "type": "abstract", "text": [ "Many other medicines may increase or decrease the effects of glimepiride or affect your condition. Before taking glimepiride, tell your doctor if you are taking any of the following medicines: - aspirin or another salicylate such as magnesium/choline salicylate (Trilisate), salsalate (Disalcid, others), choline salicylate (Arthropan), magnesium salicylate (Magan), or bismuth subsalicylate (Pepto-Bismol); - a nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen (Motrin, Advil, Nuprin, others), ketoprofen (Orudis, Orudis KT, Oruvail), diclofenac (Voltaren, Cataflam), etodolac (Lodine), indomethacin (Indocin), nabumetone (Relafen), oxaprozin (Daypro), and naproxen (Anaprox, Naprosyn, Aleve); - a sulfa-based drug such as sulfamethoxazole-trimethoprim (Bactrim, Septra), sulfisoxazole (Gantrisin), or sulfasalazine (Azulfidine); - a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), tranylcypromine (Parnate), or phenelzine (Nardil); - a beta-blocker such as propranolol (Inderal), atenolol (Tenormin), acebutolol (Sectral), metoprolol (Lopressor), and others; - a diuretic (water pill) such as hydrochlorothiazide (HCTZ, Hydrodiuril), chlorothiazide (Diuril), and others; - a steroid medicine such as prednisone (Deltasone, Orasone, others), methylprednisolone (Medrol, others), prednisolone (Prelone, Pediapred, others), and others; - a phenothiazine such as chlorpromazine (Thorazine), fluphenazine (Prolixin, Permitil), prochlorperazine (Compazine), promethazine (Phenergan), and others; - phenytoin (Dilantin); - isoniazid (Nydrazid); - rifampin (Rifadin, Rifamate); or - over-the-counter cough, cold, allergy, or weight loss medications. You may require a dosage adjustment or special monitoring if you are taking any of the medicines listed above. Drugs other than those listed here may also interact with glimepiride or affect your condition. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products." ], "offsets": [ [ 0, 2006 ] ] } ]

[ { "id": "Glimepiride_ddi_T1", "type": "DRUG", "text": [ "glimepiride" ], "offsets": [ [ 61, 72 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T2", "type": "DRUG", "text": [ "glimepiride" ], "offsets": [ [ 113, 124 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T3", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 195, 202 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T4", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 214, 224 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T5", "type": "DRUG", "text": [ "magnesium/choline salicylate" ], "offsets": [ [ 233, 261 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T6", "type": "BRAND", "text": [ "Trilisate" ], "offsets": [ [ 263, 272 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T7", "type": "DRUG", "text": [ "salsalate" ], "offsets": [ [ 275, 284 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T8", "type": "BRAND", "text": [ "Disalcid" ], "offsets": [ [ 286, 294 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T9", "type": "DRUG", "text": [ "choline salicylate" ], "offsets": [ [ 305, 323 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T10", "type": "DRUG", "text": [ "Arthropan" ], "offsets": [ [ 325, 334 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T11", "type": "DRUG", "text": [ "magnesium salicylate" ], "offsets": [ [ 337, 357 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T12", "type": "BRAND", "text": [ "Magan" ], "offsets": [ [ 359, 364 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T13", "type": "DRUG", "text": [ "bismuth subsalicylate" ], "offsets": [ [ 370, 391 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T14", "type": "BRAND", "text": [ "Pepto-Bismol" ], "offsets": [ [ 393, 405 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T15", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory drug" ], "offsets": [ [ 412, 447 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T16", "type": "GROUP", "text": [ "NSAID" ], "offsets": [ [ 449, 454 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T17", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 464, 473 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T18", "type": "BRAND", "text": [ "Motrin" ], "offsets": [ [ 475, 481 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T19", "type": "BRAND", "text": [ "Advil" ], "offsets": [ [ 483, 488 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T20", "type": "BRAND", "text": [ "Nuprin" ], "offsets": [ [ 490, 496 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T21", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 507, 517 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T22", "type": "BRAND", "text": [ "Orudis" ], "offsets": [ [ 519, 525 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T23", "type": "BRAND", "text": [ "Orudis KT" ], "offsets": [ [ 527, 536 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T24", "type": "BRAND", "text": [ "Oruvail" ], "offsets": [ [ 538, 545 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T25", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 548, 558 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T26", "type": "BRAND", "text": [ "Voltaren" ], "offsets": [ [ 560, 568 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T27", "type": "BRAND", "text": [ "Cataflam" ], "offsets": [ [ 570, 578 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T28", "type": "DRUG", "text": [ "etodolac" ], "offsets": [ [ 581, 589 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T29", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 591, 597 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T30", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 600, 612 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T31", "type": "BRAND", "text": [ "Indocin" ], "offsets": [ [ 614, 621 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T32", "type": "DRUG", "text": [ "nabumetone" ], "offsets": [ [ 624, 634 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T33", "type": "BRAND", "text": [ "Relafen" ], "offsets": [ [ 636, 643 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T34", "type": "DRUG", "text": [ "oxaprozin" ], "offsets": [ [ 646, 655 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T35", "type": "BRAND", "text": [ "Daypro" ], "offsets": [ [ 657, 663 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T36", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 670, 678 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T37", "type": "BRAND", "text": [ "Anaprox" ], "offsets": [ [ 680, 687 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T38", "type": "BRAND", "text": [ "Naprosyn" ], "offsets": [ [ 689, 697 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T39", "type": "BRAND", "text": [ "Aleve" ], "offsets": [ [ 699, 704 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T40", "type": "DRUG", "text": [ "sulfamethoxazole" ], "offsets": [ [ 736, 752 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T41", "type": "DRUG", "text": [ "trimethoprim" ], "offsets": [ [ 753, 765 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T42", "type": "BRAND", "text": [ "Bactrim" ], "offsets": [ [ 767, 774 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T43", "type": "BRAND", "text": [ "Septra" ], "offsets": [ [ 776, 782 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T44", "type": "DRUG", "text": [ "sulfisoxazole" ], "offsets": [ [ 785, 798 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T45", "type": "BRAND", "text": [ "Gantrisin" ], "offsets": [ [ 800, 809 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T46", "type": "DRUG", "text": [ "sulfasalazine" ], "offsets": [ [ 815, 828 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T47", "type": "BRAND", "text": [ "Azulfidine" ], "offsets": [ [ 830, 840 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T48", "type": "GROUP", "text": [ "monoamine oxidase inhibitor" ], "offsets": [ [ 847, 874 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T49", "type": "GROUP", "text": [ "MAOI" ], "offsets": [ [ 876, 880 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T50", "type": "DRUG", "text": [ "isocarboxazid" ], "offsets": [ [ 890, 903 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T51", "type": "BRAND", "text": [ "Marplan" ], "offsets": [ [ 905, 912 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T52", "type": "DRUG", "text": [ "tranylcypromine" ], "offsets": [ [ 915, 930 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T53", "type": "BRAND", "text": [ "Parnate" ], "offsets": [ [ 932, 939 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T54", "type": "DRUG", "text": [ "phenelzine" ], "offsets": [ [ 945, 955 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T55", "type": "BRAND", "text": [ "Nardil" ], "offsets": [ [ 957, 963 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T56", "type": "GROUP", "text": [ "beta-blocker" ], "offsets": [ [ 970, 982 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T57", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 991, 1002 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T58", "type": "BRAND", "text": [ "Inderal" ], "offsets": [ [ 1004, 1011 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T59", "type": "DRUG", "text": [ "atenolol" ], "offsets": [ [ 1014, 1022 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T60", "type": "BRAND", "text": [ "Tenormin" ], "offsets": [ [ 1024, 1032 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T61", "type": "DRUG", "text": [ "acebutolol" ], "offsets": [ [ 1035, 1045 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T62", "type": "BRAND", "text": [ "Sectral" ], "offsets": [ [ 1047, 1054 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T63", "type": "DRUG", "text": [ "metoprolol" ], "offsets": [ [ 1057, 1067 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T64", "type": "BRAND", "text": [ "Lopressor" ], "offsets": [ [ 1069, 1078 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T65", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 1097, 1105 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T66", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 1127, 1146 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T67", "type": "DRUG", "text": [ "HCTZ" ], "offsets": [ [ 1148, 1152 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T68", "type": "BRAND", "text": [ "Hydrodiuril" ], "offsets": [ [ 1154, 1165 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T69", "type": "DRUG", "text": [ "chlorothiazide" ], "offsets": [ [ 1168, 1182 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T70", "type": "BRAND", "text": [ "Diuril" ], "offsets": [ [ 1184, 1190 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T71", "type": "GROUP", "text": [ "steroid medicine" ], "offsets": [ [ 1209, 1225 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T72", "type": "DRUG", "text": [ "prednisone" ], "offsets": [ [ 1234, 1244 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T73", "type": "BRAND", "text": [ "Deltasone" ], "offsets": [ [ 1246, 1255 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T74", "type": "BRAND", "text": [ "Orasone" ], "offsets": [ [ 1257, 1264 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T75", "type": "DRUG", "text": [ "methylprednisolone" ], "offsets": [ [ 1275, 1293 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T76", "type": "BRAND", "text": [ "Medrol" ], "offsets": [ [ 1295, 1301 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T77", "type": "DRUG", "text": [ "prednisolone" ], "offsets": [ [ 1312, 1324 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T78", "type": "BRAND", "text": [ "Prelone" ], "offsets": [ [ 1326, 1333 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T79", "type": "BRAND", "text": [ "Pediapred" ], "offsets": [ [ 1335, 1344 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T80", "type": "GROUP", "text": [ "phenothiazine" ], "offsets": [ [ 1371, 1384 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T81", "type": "DRUG", "text": [ "chlorpromazine" ], "offsets": [ [ 1393, 1407 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T82", "type": "BRAND", "text": [ "Thorazine" ], "offsets": [ [ 1409, 1418 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T83", "type": "DRUG", "text": [ "fluphenazine" ], "offsets": [ [ 1421, 1433 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T84", "type": "BRAND", "text": [ "Prolixin" ], "offsets": [ [ 1435, 1443 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T85", "type": "BRAND", "text": [ "Permitil" ], "offsets": [ [ 1445, 1453 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T86", "type": "DRUG", "text": [ "prochlorperazine" ], "offsets": [ [ 1456, 1472 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T87", "type": "BRAND", "text": [ "Compazine" ], "offsets": [ [ 1474, 1483 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T88", "type": "DRUG", "text": [ "promethazine" ], "offsets": [ [ 1486, 1498 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T89", "type": "BRAND", "text": [ "Phenergan" ], "offsets": [ [ 1500, 1509 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T90", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1526, 1535 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T91", "type": "BRAND", "text": [ "Dilantin" ], "offsets": [ [ 1537, 1545 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T92", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 1550, 1559 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T93", "type": "BRAND", "text": [ "Nydrazid" ], "offsets": [ [ 1561, 1569 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T94", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1574, 1582 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T95", "type": "BRAND", "text": [ "Rifadin" ], "offsets": [ [ 1584, 1591 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T96", "type": "BRAND", "text": [ "Rifamate" ], "offsets": [ [ 1593, 1601 ] ], "normalized": [] }, { "id": "Glimepiride_ddi_T97", "type": "DRUG", "text": [ "glimepiride" ], "offsets": [ [ 1845, 1856 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Glimepiride_ddi_R1", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T3", "normalized": [] }, { "id": "Glimepiride_ddi_R2", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T4", "normalized": [] }, { "id": "Glimepiride_ddi_R3", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T5", "normalized": [] }, { "id": "Glimepiride_ddi_R4", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T6", "normalized": [] }, { "id": "Glimepiride_ddi_R5", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T7", "normalized": [] }, { "id": "Glimepiride_ddi_R6", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T8", "normalized": [] }, { "id": "Glimepiride_ddi_R7", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T9", "normalized": [] }, { "id": "Glimepiride_ddi_R8", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T10", "normalized": [] }, { "id": "Glimepiride_ddi_R9", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T11", "normalized": [] }, { "id": "Glimepiride_ddi_R10", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T12", "normalized": [] }, { "id": "Glimepiride_ddi_R11", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T13", "normalized": [] }, { "id": "Glimepiride_ddi_R12", "type": "ADVISE", "arg1_id": "Glimepiride_ddi_T2", "arg2_id": "Glimepiride_ddi_T14", "normalized": [] } ]

[ { "id": "Dolasetron_ddi__text", "type": "abstract", "text": [ "The potential for clinically significant drug-drug interactions posed by dolasetron and hydrodolasetron appears to be low for drugs commonly used in chemotherapy or surgery, because hydrodolasetron is eliminated by multiple routes. Blood levels of hydrodolasetron increased 24% when dolasetron was coadministered with cimetidine (nonselective inhibitor of cytochrome P-450) for 7 days, and decreased 28% with coadministration of rifampin (potent inducer of cytochrome P-450) for 7 days. Dolasetron has been safely coadministered with drugs used in chemotherapy and surgery. As with other agents which prolong ECG intervals, caution should be exercised in patients taking drugs which prolong ECG intervals, particularly QTc. In patients taking furosemide, nifedipine, diltiazem, ACE inhibitors, verapamil, glyburide, propranolol, and various chemotherapy agents, no effect was shown on the clearance of hydrodolasetron. Clearance of hydrodolasetron decreased by about 27% when dolasetron mesylate was administered intravenously concomitantly with atenolol. Dolasetron does not influence anesthesia recovery time in patients. Dolasetron mesylate did not inhibit the antitumor activity of four chemotherapeutic agents (cisplatin, 5-fluorouracil, doxorubicin, cyclophosphamide) in four murine models." ], "offsets": [ [ 0, 1296 ] ] } ]

[ { "id": "Dolasetron_ddi_T1", "type": "DRUG", "text": [ "dolasetron" ], "offsets": [ [ 73, 83 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T2", "type": "DRUG_N", "text": [ "hydrodolasetron" ], "offsets": [ [ 88, 103 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T3", "type": "DRUG_N", "text": [ "hydrodolasetron" ], "offsets": [ [ 182, 197 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T4", "type": "DRUG_N", "text": [ "hydrodolasetron" ], "offsets": [ [ 248, 263 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T5", "type": "DRUG", "text": [ "dolasetron" ], "offsets": [ [ 283, 293 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T6", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 318, 328 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T7", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 429, 437 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T8", "type": "DRUG", "text": [ "Dolasetron" ], "offsets": [ [ 487, 497 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T9", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 743, 753 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T10", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 755, 765 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T11", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 767, 776 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T12", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 778, 792 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T13", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 794, 803 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T14", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 805, 814 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T15", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 816, 827 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T16", "type": "DRUG_N", "text": [ "hydrodolasetron" ], "offsets": [ [ 902, 917 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T17", "type": "DRUG_N", "text": [ "hydrodolasetron" ], "offsets": [ [ 932, 947 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T18", "type": "DRUG", "text": [ "dolasetron mesylate" ], "offsets": [ [ 976, 995 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T19", "type": "DRUG", "text": [ "atenolol" ], "offsets": [ [ 1046, 1054 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T20", "type": "DRUG", "text": [ "Dolasetron" ], "offsets": [ [ 1056, 1066 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T21", "type": "DRUG", "text": [ "Dolasetron mesylate" ], "offsets": [ [ 1124, 1143 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T22", "type": "GROUP", "text": [ "chemotherapeutic agents" ], "offsets": [ [ 1191, 1214 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T23", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 1216, 1225 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T24", "type": "DRUG", "text": [ "5-fluorouracil" ], "offsets": [ [ 1227, 1241 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T25", "type": "DRUG", "text": [ "doxorubicin" ], "offsets": [ [ 1243, 1254 ] ], "normalized": [] }, { "id": "Dolasetron_ddi_T26", "type": "DRUG", "text": [ "cyclophosphamide" ], "offsets": [ [ 1256, 1272 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Dolasetron_ddi_R1", "type": "MECHANISM", "arg1_id": "Dolasetron_ddi_T5", "arg2_id": "Dolasetron_ddi_T6", "normalized": [] }, { "id": "Dolasetron_ddi_R2", "type": "MECHANISM", "arg1_id": "Dolasetron_ddi_T5", "arg2_id": "Dolasetron_ddi_T7", "normalized": [] }, { "id": "Dolasetron_ddi_R3", "type": "MECHANISM", "arg1_id": "Dolasetron_ddi_T18", "arg2_id": "Dolasetron_ddi_T19", "normalized": [] } ]

[ { "id": "Diflunisal_ddi__text", "type": "abstract", "text": [ "Oral Anticoagulants: In some normal volunteers, the concomitant administration of diflunisal and warfarin, acenocoumarol, or phenprocoumon resulted in prolongation of prothrombin time. This may occur because diflunisal competitively displaces coumarins from protein binding sites. Accordingly, when diflunisal is administered with oral anticoagulants, the prothrombin time should be closely monitored during and for several days after concomitant drug administration. Adjustment of dosage of oral anticoagulants may be required. Tolbutamide: In diabetic patients receiving diflunisal and tolbutamide, no significant effects were seen on tolbutamide plasma levels or fasting blood glucose. Hydrochlorothiazide: In normal volunteers, concomitant administration of diflunisal and hydrochlorothiazide resulted in significantly increased plasma levels of hydrochlorothiazide. Diflunisal decreased the hyperuricemic effect of hydrochlorothiazide. Furosemide: In normal volunteers, the concomitant administration of diflunisal and furosemide had no effect on the diuretic activity of furosemide. Diflunisal decreased the hyperuricemic effect of furosemide. Antacids: Concomitant administration of antacids may reduce plasma levels of diflunisal. This effect is small with occasional doses of antacids, but may be clinically significant when antacids are used on a continuous schedule. Acetaminophen: In normal volunteers, concomitant administration of diflunisal and acetaminophen resulted in an approximate 50% increase in plasma levels of acetaminophen. Acetaminophen had no effect on plasma levels of diflunisal. Since acetaminophen in high doses has been associated with hepatotoxicity, concomitant administration of diflunisal and acetaminophen should be used cautiously, with careful monitoring of patients. Concomitant administration of diflunisal and acetaminophen in dogs, but not in rats, at approximately 2 times the recommended maximum human therapeutic dose of each (40 to 52 mg/kg/day of diflunisal/acetaminophen) resulted in greater gastrointestinal toxicity than when either drug was administered alone. The clinical significance of these findings has not been established. Methotrexate: Caution should be used if diflunisal is administered concomitantly with methotrexate. Nonsteroidal anti-inflammatory drugs have been reported to decrease the tubular secretion of methotrexate and to potentiate its toxicity. Cyclosporine: Administration of nonsteroial anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine, and renal function should be carefully monitored. Nonsteroidal Anti-Inflammatory Drugs: The administration of diflunisal to normal volunteers receiving indomethacin decreased the renal clearance and significantly increased the plasma levels of indomethacin. In some patients the combined use of indomethacin and diflunisal has been associated with fatal gastrointestinal hemorrhage. Therefore, indomethacin and diflunisal should not be used concomitantly. The concomitant use of diflunisal tablets and other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy. The following information was obtained from studies in normal volunteers. Aspirin: In normal volunteers, a small decrease in diflunisal levels was observed when multiple doses of diflunisal and aspirin were administered concomitantly. Sulindac: The concomitant administration of diflunisal and sulindac in normal volunteers resulted in lowering of the plasma levels of the active sulindac sulfide metabolite by approximately one-third. Naproxen: The concomitant administration of diflunisal and naproxen in normal volunteers had no effect on the plasma levels of naproxen, but significantly decreased the urinary excretion of naproxen and its glucuronide metabolite. Naproxen had no effect on plasma levels of diflunisal. Drug laboratory Test Interactions Serum Salicylate Assays: Caution should be used in interpreting the results of serum salicylate assays when diflunisal is present. Salicylate levels have been found to be falsely elevated with some assay methods." ], "offsets": [ [ 0, 4324 ] ] } ]

[ { "id": "Diflunisal_ddi_T1", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 5, 19 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T2", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 82, 92 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 97, 105 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T4", "type": "DRUG", "text": [ "acenocoumarol" ], "offsets": [ [ 107, 120 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T5", "type": "DRUG", "text": [ "phenprocoumon" ], "offsets": [ [ 125, 138 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T6", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 208, 218 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T7", "type": "GROUP", "text": [ "coumarins" ], "offsets": [ [ 243, 252 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T8", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 299, 309 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T9", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 336, 350 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T10", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 497, 511 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T11", "type": "DRUG", "text": [ "Tolbutamide" ], "offsets": [ [ 529, 540 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T12", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 573, 583 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T13", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 588, 599 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T14", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 637, 648 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T15", "type": "DRUG", "text": [ "Hydrochlorothiazide" ], "offsets": [ [ 689, 708 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T16", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 762, 772 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T17", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 777, 796 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T18", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 850, 869 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T19", "type": "DRUG", "text": [ "Diflunisal" ], "offsets": [ [ 871, 881 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T20", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 920, 939 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T21", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 941, 951 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T22", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 1009, 1019 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T23", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1024, 1034 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T24", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1077, 1087 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T25", "type": "DRUG", "text": [ "Diflunisal" ], "offsets": [ [ 1089, 1099 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T26", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1138, 1148 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T27", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 1150, 1158 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T28", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 1190, 1198 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T29", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 1227, 1237 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T30", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 1285, 1293 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T31", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 1334, 1342 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T32", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 1378, 1391 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T33", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 1445, 1455 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T34", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 1460, 1473 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T35", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 1534, 1547 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T36", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 1549, 1562 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T37", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 1597, 1607 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T38", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 1615, 1628 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T39", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 1714, 1724 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T40", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 1729, 1742 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T41", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 1837, 1847 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T42", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 1852, 1865 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T43", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 1995, 2005 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T44", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 2006, 2019 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T45", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 2183, 2195 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T46", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 2223, 2233 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T47", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2269, 2281 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T48", "type": "GROUP", "text": [ "Nonsteroidal anti-inflammatory drugs" ], "offsets": [ [ 2283, 2319 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T49", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2376, 2388 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T50", "type": "DRUG", "text": [ "Cyclosporine" ], "offsets": [ [ 2421, 2433 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T51", "type": "GROUP", "text": [ "nonsteroial anti-inflammatory drugs" ], "offsets": [ [ 2453, 2488 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T52", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2508, 2520 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T53", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2561, 2573 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T54", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2651, 2657 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T55", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2705, 2717 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T56", "type": "GROUP", "text": [ "Nonsteroidal Anti-Inflammatory Drugs" ], "offsets": [ [ 2769, 2805 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T57", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 2829, 2839 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T58", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 2871, 2883 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T59", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 2963, 2975 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T60", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 3014, 3026 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T61", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 3031, 3041 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T62", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 3113, 3125 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T63", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 3130, 3140 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T64", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 3198, 3208 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T65", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 3227, 3233 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T66", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 3430, 3437 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T67", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 3481, 3491 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T68", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 3535, 3545 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T69", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 3550, 3557 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T70", "type": "DRUG", "text": [ "Sulindac" ], "offsets": [ [ 3591, 3599 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T71", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 3635, 3645 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T72", "type": "DRUG", "text": [ "sulindac" ], "offsets": [ [ 3650, 3658 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T73", "type": "DRUG", "text": [ "Naproxen" ], "offsets": [ [ 3792, 3800 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T74", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 3836, 3846 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T75", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 3851, 3859 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T76", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 3919, 3927 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T77", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 3982, 3990 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T78", "type": "DRUG", "text": [ "Naproxen" ], "offsets": [ [ 4023, 4031 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T79", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 4066, 4076 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T80", "type": "DRUG", "text": [ "diflunisal" ], "offsets": [ [ 4220, 4230 ] ], "normalized": [] }, { "id": "Diflunisal_ddi_T81", "type": "GROUP", "text": [ "Salicylate" ], "offsets": [ [ 4243, 4253 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Diflunisal_ddi_R1", "type": "EFFECT", "arg1_id": "Diflunisal_ddi_T2", "arg2_id": "Diflunisal_ddi_T3", "normalized": [] }, { "id": "Diflunisal_ddi_R2", "type": "EFFECT", "arg1_id": "Diflunisal_ddi_T2", "arg2_id": "Diflunisal_ddi_T4", "normalized": [] }, { "id": "Diflunisal_ddi_R3", "type": "EFFECT", "arg1_id": "Diflunisal_ddi_T2", "arg2_id": "Diflunisal_ddi_T5", "normalized": [] }, { "id": "Diflunisal_ddi_R4", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T6", "arg2_id": "Diflunisal_ddi_T7", "normalized": [] }, { "id": "Diflunisal_ddi_R5", "type": "ADVISE", "arg1_id": "Diflunisal_ddi_T8", "arg2_id": "Diflunisal_ddi_T9", "normalized": [] }, { "id": "Diflunisal_ddi_R6", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T16", "arg2_id": "Diflunisal_ddi_T17", "normalized": [] }, { "id": "Diflunisal_ddi_R7", "type": "EFFECT", "arg1_id": "Diflunisal_ddi_T19", "arg2_id": "Diflunisal_ddi_T20", "normalized": [] }, { "id": "Diflunisal_ddi_R8", "type": "EFFECT", "arg1_id": "Diflunisal_ddi_T25", "arg2_id": "Diflunisal_ddi_T26", "normalized": [] }, { "id": "Diflunisal_ddi_R9", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T28", "arg2_id": "Diflunisal_ddi_T29", "normalized": [] }, { "id": "Diflunisal_ddi_R10", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T33", "arg2_id": "Diflunisal_ddi_T34", "normalized": [] }, { "id": "Diflunisal_ddi_R11", "type": "ADVISE", "arg1_id": "Diflunisal_ddi_T39", "arg2_id": "Diflunisal_ddi_T40", "normalized": [] }, { "id": "Diflunisal_ddi_R12", "type": "EFFECT", "arg1_id": "Diflunisal_ddi_T41", "arg2_id": "Diflunisal_ddi_T42", "normalized": [] }, { "id": "Diflunisal_ddi_R13", "type": "ADVISE", "arg1_id": "Diflunisal_ddi_T46", "arg2_id": "Diflunisal_ddi_T47", "normalized": [] }, { "id": "Diflunisal_ddi_R14", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T48", "arg2_id": "Diflunisal_ddi_T49", "normalized": [] }, { "id": "Diflunisal_ddi_R15", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T51", "arg2_id": "Diflunisal_ddi_T52", "normalized": [] }, { "id": "Diflunisal_ddi_R16", "type": "ADVISE", "arg1_id": "Diflunisal_ddi_T54", "arg2_id": "Diflunisal_ddi_T55", "normalized": [] }, { "id": "Diflunisal_ddi_R17", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T57", "arg2_id": "Diflunisal_ddi_T58", "normalized": [] }, { "id": "Diflunisal_ddi_R18", "type": "EFFECT", "arg1_id": "Diflunisal_ddi_T60", "arg2_id": "Diflunisal_ddi_T61", "normalized": [] }, { "id": "Diflunisal_ddi_R19", "type": "ADVISE", "arg1_id": "Diflunisal_ddi_T62", "arg2_id": "Diflunisal_ddi_T63", "normalized": [] }, { "id": "Diflunisal_ddi_R20", "type": "EFFECT", "arg1_id": "Diflunisal_ddi_T64", "arg2_id": "Diflunisal_ddi_T65", "normalized": [] }, { "id": "Diflunisal_ddi_R21", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T68", "arg2_id": "Diflunisal_ddi_T69", "normalized": [] }, { "id": "Diflunisal_ddi_R22", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T71", "arg2_id": "Diflunisal_ddi_T72", "normalized": [] }, { "id": "Diflunisal_ddi_R23", "type": "MECHANISM", "arg1_id": "Diflunisal_ddi_T74", "arg2_id": "Diflunisal_ddi_T75", "normalized": [] } ]

[ { "id": "Isoetharine_ddi__text", "type": "abstract", "text": [ "May interact with the following: beta-adrenergic blocking agents (these medicines may make your condition worse and prevent the adrenergic bronchodilators from working properly) and disopyramide, quinidine, phenothiazines, and procainamide (these medicines may increase the risk of heart problems)." ], "offsets": [ [ 0, 298 ] ] } ]

[ { "id": "Isoetharine_ddi_T1", "type": "GROUP", "text": [ "beta-adrenergic blocking agents" ], "offsets": [ [ 33, 64 ] ], "normalized": [] }, { "id": "Isoetharine_ddi_T2", "type": "GROUP", "text": [ "adrenergic bronchodilators" ], "offsets": [ [ 128, 154 ] ], "normalized": [] }, { "id": "Isoetharine_ddi_T3", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 182, 194 ] ], "normalized": [] }, { "id": "Isoetharine_ddi_T4", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 196, 205 ] ], "normalized": [] }, { "id": "Isoetharine_ddi_T5", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 207, 221 ] ], "normalized": [] }, { "id": "Isoetharine_ddi_T6", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 227, 239 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Adapalene_ddi__text", "type": "abstract", "text": [ "As DIFFERIN Gel has the potential to produce local irritation in some patients, concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices or lime) should be approached with caution. Particular caution should be exercised in using preparations containing sulfur, resorcinol, or salicylic acid in combination with DIFFERIN Gel. If these preparations have been used it is advisable not to start therapy with DIFFERIN Gel until the effects of such preparations in the skin have subsided." ], "offsets": [ [ 0, 658 ] ] } ]

[ { "id": "Adapalene_ddi_T1", "type": "BRAND", "text": [ "DIFFERIN" ], "offsets": [ [ 3, 11 ] ], "normalized": [] }, { "id": "Adapalene_ddi_T2", "type": "DRUG", "text": [ "sulfur" ], "offsets": [ [ 429, 435 ] ], "normalized": [] }, { "id": "Adapalene_ddi_T3", "type": "DRUG", "text": [ "resorcinol" ], "offsets": [ [ 437, 447 ] ], "normalized": [] }, { "id": "Adapalene_ddi_T4", "type": "DRUG", "text": [ "salicylic acid" ], "offsets": [ [ 452, 466 ] ], "normalized": [] }, { "id": "Adapalene_ddi_T5", "type": "BRAND", "text": [ "DIFFERIN" ], "offsets": [ [ 487, 495 ] ], "normalized": [] }, { "id": "Adapalene_ddi_T6", "type": "BRAND", "text": [ "DIFFERIN" ], "offsets": [ [ 580, 588 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "Oxcarbazepine_ddi__text", "type": "abstract", "text": [ "Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5 with potentially important effects on plasma concentrations of other drugs. In addition, several AED s that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD. Oxcarbazepine was evaluated in human liver microsomes to determine its capacity to inhibit the major cytochrome P450 enzymes responsible for the metabolism of other drugs. Results demonstrate that oxcarbazepine and its pharmacologically active 10-monohydroxy metabolite (MHD) have little or no capacity to function as inhibitors for most of the human cytochrome P450 enzymes evaluated (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP4A9 and CYP4A11) with the exception of CYP2C19 and CYP3A4/5. Although inhibition of CYP 3A4/5 by OXC and MHD did occur at high concentrations, it is not likely to be of clinical significance. The inhibition of CYP-2C19 by OXC and MHD, however, is clinically relevant. In vitro, the UDP-glucuronyl transferase level was increased, indicating induction of this enzyme. Increases of 22% with MHD and 47% with oxcarbazepine were observed. As MHD, the predominant plasma substrate, is only a weak inducer of UDP-glucuronyl transferase, it is unlikely to have an effect on drugs that are mainly eliminated by conjugation through UDP-glucuronyl transferase (e.g., valproic acid, lamotrigine). In addition, oxcarbazepine and MHD induce a subgroup of the cytochrome P450 3A family (CYP3A4 and CYP3A5) responsible for the metabolism of dihydropyridine calcium antagonists and oral contraceptives, resulting in a lower plasma concentration of these drugs. As binding of MHD to plasma proteins is low (40%), clinically significant interactions with other drugs through competition for protein binding sites are unlikely. Antiepileptic drugs: Potential interactions between Trileptal and other AEDs were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarized in Table 2: Table 2: Summary of AED interactions with Trileptal AED Co-administered Dose of AED (mg/day) Trileptal dose (mg/day) Influence of Trileptal on AED Concentration (Mean change, 90% Confidence Interval) Influence of AED On MHD Concentration (Mean change, 90% Confidence Interval) Carbamazepine 400-2000 900 nc1 40% decrease [CI: 17% decrease, 57% decrease] Phenobarbital 100-150 600-1800 14% increase [CI: 2% increase, 24% increase] 25% decrease [CI: 12% decrease, 51% decrease] Phenytoin 250-500 600-1800 nc1,2 30% decrease [CI: 3% decrease, 48 % decrease] 1200-2400 up to 40% increase3 [CI: 12% increase, 60 % increase] Valproic acid 400-2800 600-1800 nc1 18% decrease [CI: 13% decrease, 40 % decrease] 1- nc denotes a mean change of less than 10% 2- Pediatrics 3- Mean increase in adults at high Trileptal doses In vivo, the plasma levels of phenytoin increased by up to 40%, when Trileptal was given at doses above 1200 mg/day. Therefore, when using doses of Trileptal greater than 1200 mg/day during adjunctive therapy, a decrease in the dose of phenytoin may be required. The increase of phenobarbital level, however, is small (15%) when given with Trileptal. Strong inducers of cytochrome P450 enzymes (i.e. carbamazepine, phenytoin and phenobarbital) have been shown to decrease the plasma levels of MHD (29-40%). No autoinduction has been observed with Trileptal. Hormonal contraceptives Co-administration of Trileptal with an oral contraceptive has been shown to influence the plasma concentrations of the two hormonal components, ethinylestradiol (EE) and levonorgestrel (LNG). The mean AUC values of EE were decreased by 48% [90% CI: 22-65] in one study and 52% [90% CI: 38-52] in another study [1,2]. The mean AUC values of LNG were decreased by 32% [90% CI: 20-45] in one study and 52% [90% CI: 42-52] in another study. Therefore, concurrent use of Trileptal with hormonal contraceptives may render these contraceptives less effective. Studies with other oral or implant contraceptives have not been conducted. Calcium Antagonists: After repeated co-administration of Trileptal, the AUC of felodipine was lowered by 28% [90% CI: 20-33]. Verapamil produced a decrease of 20% [90% CI: 18-27] of the plasma levels of MHD. Other drug interactions Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD. Results with warfarin wshow no evidence of interaction with either single or repeated doses of Trileptal." ], "offsets": [ [ 0, 4437 ] ] } ]

[ { "id": "Oxcarbazepine_ddi_T1", "type": "DRUG", "text": [ "Oxcarbazepine" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T2", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 151, 154 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T3", "type": "DRUG", "text": [ "oxcarbazepine" ], "offsets": [ [ 229, 242 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T4", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 247, 250 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T5", "type": "DRUG", "text": [ "Oxcarbazepine" ], "offsets": [ [ 252, 265 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T6", "type": "DRUG", "text": [ "oxcarbazepine" ], "offsets": [ [ 449, 462 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T7", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 523, 526 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T8", "type": "DRUG", "text": [ "OXC" ], "offsets": [ [ 778, 781 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T9", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 786, 789 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T10", "type": "DRUG", "text": [ "OXC" ], "offsets": [ [ 903, 906 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T11", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 911, 914 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T12", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 1070, 1073 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T13", "type": "DRUG", "text": [ "oxcarbazepine" ], "offsets": [ [ 1087, 1100 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T14", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 1119, 1122 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T15", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 1338, 1351 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T16", "type": "DRUG", "text": [ "lamotrigine" ], "offsets": [ [ 1353, 1364 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T17", "type": "DRUG", "text": [ "oxcarbazepine" ], "offsets": [ [ 1380, 1393 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T18", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 1398, 1401 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T19", "type": "GROUP", "text": [ "dihydropyridine calcium antagonists" ], "offsets": [ [ 1507, 1542 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T20", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 1552, 1566 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T21", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 1640, 1643 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T22", "type": "GROUP", "text": [ "Antiepileptic drugs" ], "offsets": [ [ 1790, 1809 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T23", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 1842, 1851 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T24", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 1862, 1866 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T25", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 2026, 2035 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T26", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 2036, 2039 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T27", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 2064, 2067 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T28", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 2077, 2086 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T29", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 2114, 2123 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T30", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 2127, 2130 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T31", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 2197, 2200 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T32", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 2204, 2207 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T33", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 2261, 2274 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T34", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 2338, 2351 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T35", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 2460, 2469 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T36", "type": "DRUG", "text": [ "Valproic acid" ], "offsets": [ [ 2603, 2616 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T37", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 2780, 2789 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T38", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2826, 2835 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T39", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 2865, 2874 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T40", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 2944, 2953 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T41", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3032, 3041 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T42", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 3075, 3088 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T43", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 3136, 3145 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T44", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 3196, 3209 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T45", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3211, 3220 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T46", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 3225, 3238 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T47", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 3289, 3292 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T48", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 3343, 3352 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T49", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 3363, 3377 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T50", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 3399, 3408 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T51", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 3422, 3435 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T52", "type": "DRUG", "text": [ "ethinylestradiol" ], "offsets": [ [ 3522, 3538 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T53", "type": "DRUG", "text": [ "levonorgestrel" ], "offsets": [ [ 3548, 3562 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T54", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 3844, 3853 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T55", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 3859, 3882 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T56", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 3900, 3914 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T57", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 3966, 3980 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T58", "type": "GROUP", "text": [ "Calcium Antagonist" ], "offsets": [ [ 4006, 4024 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T59", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 4063, 4072 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T60", "type": "DRUG", "text": [ "felodipine" ], "offsets": [ [ 4085, 4095 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T61", "type": "DRUG", "text": [ "Verapamil" ], "offsets": [ [ 4132, 4141 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T62", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 4209, 4212 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T63", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 4238, 4248 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T64", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 4250, 4262 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T65", "type": "DRUG", "text": [ "dextropropoxyphene" ], "offsets": [ [ 4267, 4285 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T66", "type": "DRUG_N", "text": [ "MHD" ], "offsets": [ [ 4327, 4330 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T67", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4345, 4353 ] ], "normalized": [] }, { "id": "Oxcarbazepine_ddi_T68", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 4427, 4436 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Oxcarbazepine_ddi_R1", "type": "MECHANISM", "arg1_id": "Oxcarbazepine_ddi_T2", "arg2_id": "Oxcarbazepine_ddi_T3", "normalized": [] }, { "id": "Oxcarbazepine_ddi_R2", "type": "MECHANISM", "arg1_id": "Oxcarbazepine_ddi_T38", "arg2_id": "Oxcarbazepine_ddi_T39", "normalized": [] }, { "id": "Oxcarbazepine_ddi_R3", "type": "ADVISE", "arg1_id": "Oxcarbazepine_ddi_T40", "arg2_id": "Oxcarbazepine_ddi_T41", "normalized": [] }, { "id": "Oxcarbazepine_ddi_R4", "type": "MECHANISM", "arg1_id": "Oxcarbazepine_ddi_T42", "arg2_id": "Oxcarbazepine_ddi_T43", "normalized": [] }, { "id": "Oxcarbazepine_ddi_R5", "type": "MECHANISM", "arg1_id": "Oxcarbazepine_ddi_T50", "arg2_id": "Oxcarbazepine_ddi_T51", "normalized": [] }, { "id": "Oxcarbazepine_ddi_R6", "type": "EFFECT", "arg1_id": "Oxcarbazepine_ddi_T54", "arg2_id": "Oxcarbazepine_ddi_T55", "normalized": [] }, { "id": "Oxcarbazepine_ddi_R7", "type": "MECHANISM", "arg1_id": "Oxcarbazepine_ddi_T59", "arg2_id": "Oxcarbazepine_ddi_T60", "normalized": [] } ]

[ { "id": "Ethacrynic acid_ddi__text", "type": "abstract", "text": [ "Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Read circulars for lithium preparations before use of such concomitant therapy. EDECRIN may increase the ototoxic potential of other drugs such as aminoglycoside and some cephalosporin antibiotics. Their concurrent use should be avoided. A number of drugs, including ethacrynic acid, have been shown to displace warfarin from plasma protein; a reduction in the usual anticoagulant dosage may be required in patients receiving both drugs. In some patients, the administration of a non- steroidal antiinflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium- sparing and thiazide diuretics. Therefore, when EDECRIN and non- steroidal anti- inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained." ], "offsets": [ [ 0, 966 ] ] } ]

[ { "id": "Ethacrynic acid_ddi_T1", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T2", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 43, 52 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T3", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 116, 123 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T4", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 153, 160 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T5", "type": "BRAND", "text": [ "EDECRIN" ], "offsets": [ [ 214, 221 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T6", "type": "GROUP", "text": [ "aminoglycoside" ], "offsets": [ [ 281, 295 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T7", "type": "GROUP", "text": [ "cephalosporin antibiotics" ], "offsets": [ [ 305, 330 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T8", "type": "DRUG", "text": [ "ethacrynic acid" ], "offsets": [ [ 401, 416 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T9", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 446, 454 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T10", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 501, 514 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T11", "type": "GROUP", "text": [ "non- steroidal antiinflammatory agent" ], "offsets": [ [ 614, 651 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T12", "type": "GROUP", "text": [ "loop", "diuretics" ], "offsets": [ [ 722, 726 ], [ 760, 769 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T13", "type": "GROUP", "text": [ "potassium- sparing", "diuretics" ], "offsets": [ [ 728, 746 ], [ 760, 769 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T14", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 751, 769 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T15", "type": "BRAND", "text": [ "EDECRIN" ], "offsets": [ [ 787, 794 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T16", "type": "GROUP", "text": [ "non- steroidal anti- inflammatory agents" ], "offsets": [ [ 799, 839 ] ], "normalized": [] }, { "id": "Ethacrynic acid_ddi_T17", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 945, 953 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ethacrynic acid_ddi_R1", "type": "MECHANISM", "arg1_id": "Ethacrynic acid_ddi_T1", "arg2_id": "Ethacrynic acid_ddi_T2", "normalized": [] }, { "id": "Ethacrynic acid_ddi_R2", "type": "EFFECT", "arg1_id": "Ethacrynic acid_ddi_T5", "arg2_id": "Ethacrynic acid_ddi_T6", "normalized": [] }, { "id": "Ethacrynic acid_ddi_R3", "type": "EFFECT", "arg1_id": "Ethacrynic acid_ddi_T5", "arg2_id": "Ethacrynic acid_ddi_T7", "normalized": [] }, { "id": "Ethacrynic acid_ddi_R4", "type": "MECHANISM", "arg1_id": "Ethacrynic acid_ddi_T8", "arg2_id": "Ethacrynic acid_ddi_T9", "normalized": [] }, { "id": "Ethacrynic acid_ddi_R5", "type": "EFFECT", "arg1_id": "Ethacrynic acid_ddi_T11", "arg2_id": "Ethacrynic acid_ddi_T12", "normalized": [] }, { "id": "Ethacrynic acid_ddi_R6", "type": "EFFECT", "arg1_id": "Ethacrynic acid_ddi_T11", "arg2_id": "Ethacrynic acid_ddi_T13", "normalized": [] }, { "id": "Ethacrynic acid_ddi_R7", "type": "EFFECT", "arg1_id": "Ethacrynic acid_ddi_T11", "arg2_id": "Ethacrynic acid_ddi_T14", "normalized": [] }, { "id": "Ethacrynic acid_ddi_R8", "type": "EFFECT", "arg1_id": "Ethacrynic acid_ddi_T15", "arg2_id": "Ethacrynic acid_ddi_T16", "normalized": [] } ]

[ { "id": "Itraconazole_ddi__text", "type": "abstract", "text": [ "Both itraconazole and its major metabolite, hydroxyitraconazole, are inhibitors of the cytochrome P450 3A4 enzyme system. Coadministration of Itraconazole and drugs primarily metabolized by the cytochrome P450 3A4 enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic and adverse effects. Therefore, unless otherwise specified, appropriate dosage adjustments may be necessary. Coadministration of terfenadine with Itraconazole has led to elevated plasma concentrations of terfenadine, resulting in rare instances of life- threatening cardiac dysrhythmias and one death. Another oral azole antifungal, ketoconazole, inhibits the metabolism of astemizole, resulting in elevated plasma concentrations of astemizole and its active metabolite desmethylastermizole which may prolong QT intervals. In vitro data suggest that itraconazole, when compared to ketoconazole, has a less pronounced effect on the biotransformation system responsible for the metabolism of astemizole. Based on the chemical resemblance of itraconazole and ketoconazole, coadministration of astemizole with itraconazole is contraindicated. Human pharmacokinetics data indicate that oral ketoconazole potently inhibits the metabolism of cisapride resulting in an eight-fold increase in the mean AUC of cisapride. Data suggest that coadministration of oral ketoconazole and cisapride can result in prolongation of the QT interval on the ECG. In vitro data suggest that itraconazole also markedly inhibits the biotransformation system mainly responsible for the metabolism of cisapride; therefore concomitant administration of Itraconazole with cisapride is contraindicated. Coadministration of Itraconazole with oral midazolam or triazolam has resulted in elevated plasma concentrations of the latter two drugs. This may potentiate and prolong hypnotic and sedative effects. These agents should not be used in patients treated with Itraconazole. If midazolam is administered parenterally, special precaution is required since the sedative effect may be prolonged. Coadministration of Itraconazole and cyclosporine, tacrolimus or digoxin has led to increased plasma concentrations of the latter three drugs. Cyclosporine, tacrolimus and digoxin concentrations should be monitored at the initiation of Itraconazole therapy and frequently thereafter, and the dose of these three drug products adjusted appropriately. Rhabdomyolysis has been observed in patients receiving HMG-CoA reductase inhibitors administered alone (at recommended dosages) or concomitantly with immunosuppressive drugs including cyclosporine. When Itraconazole was coadministered with phenytoin, rifampin, or H2antagonists, reduced plasma concentrations of itraconazole were reported. The physician is advised to monitor the plasma concentrations of itraconazole when any of these drugs is taken concurrently, and to increase the dose of Itraconazole if necessary. Although no studies have been conducted, concomitant administration of Itraconazole and phenytoin may alter the metabolism of phenytoin; therefore, plasma concentrations of phenytoin should also be monitored when it is given concurrently with Itraconazole. It has been reported that Itraconazole enhances the anticoagulant effect of coumarin-like drugs. Therefore, prothrombin time should be carefully monitored in patients receiving Itraconazole and coumarin-like drugs simultaneously. Plasma concentrations of azole antifungal agents are reduced when given concurrently with isoniazid. Itraconazole plasma concentrations should be monitored when Itraconazole and isoniazid are coadministered. Severe hypoglycemia has been reported in patients concomitantly receiving azole antifungal agents and oral hypoglycemic agents. Blood glucose concentrations should be carefully monitored when Itraconazole and oral hypoglycemic agents are coadministered. Tinnitus and decreased hearing have been reported in patients concomitantly receiving Itraconazole and quinidine. Edema has been reported in patients concomitantly receiving Itraconazole and dihydropyridine calcium channel blockers. Appropriate dosage adjustments may be necessary. The results from a study in which eight HIV-infected individuals were treated with zidovudine, 8 +/- 0.4 mg/kg/day, showed that the pharmacokinetics of zidovudine were not affected during concomitant administration of Itraconazole, 100 mg b.i.d." ], "offsets": [ [ 0, 4442 ] ] } ]

[ { "id": "Itraconazole_ddi_T1", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 5, 17 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T2", "type": "DRUG_N", "text": [ "hydroxyitraconazole" ], "offsets": [ [ 44, 63 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T3", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 142, 154 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T4", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 464, 475 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T5", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 481, 493 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T6", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 539, 550 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T7", "type": "GROUP", "text": [ "azole antifungal" ], "offsets": [ [ 650, 666 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T8", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 668, 680 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T9", "type": "DRUG", "text": [ "astemizole" ], "offsets": [ [ 709, 719 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T10", "type": "DRUG", "text": [ "astemizole" ], "offsets": [ [ 768, 778 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T11", "type": "DRUG_N", "text": [ "desmethylastermizole" ], "offsets": [ [ 805, 825 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T12", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 885, 897 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T13", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 916, 928 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T14", "type": "DRUG", "text": [ "astemizole" ], "offsets": [ [ 1025, 1035 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T15", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1074, 1086 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T16", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1091, 1103 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T17", "type": "DRUG", "text": [ "astemizole" ], "offsets": [ [ 1125, 1135 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T18", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1141, 1153 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T19", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1221, 1233 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T20", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1270, 1279 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T21", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1335, 1344 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T22", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1389, 1401 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T23", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1406, 1415 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T24", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1501, 1513 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T25", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1607, 1616 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T26", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 1658, 1670 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T27", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1676, 1685 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T28", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 1726, 1738 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T29", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 1749, 1758 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T30", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 1762, 1771 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T31", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 1964, 1976 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T32", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 1981, 1990 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T33", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 2116, 2128 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T34", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2133, 2145 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T35", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 2147, 2157 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T36", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2161, 2168 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T37", "type": "DRUG", "text": [ "Cyclosporine" ], "offsets": [ [ 2239, 2251 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T38", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 2253, 2263 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T39", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2268, 2275 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T40", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 2332, 2344 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T41", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 2501, 2529 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T42", "type": "GROUP", "text": [ "immunosuppressive drugs" ], "offsets": [ [ 2596, 2619 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T43", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2630, 2642 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T44", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 2649, 2661 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T45", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2686, 2695 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T46", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 2697, 2705 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T47", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 2758, 2770 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T48", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 2851, 2863 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T49", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 2939, 2951 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T50", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 3037, 3049 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T51", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3054, 3063 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T52", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3092, 3101 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T53", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3139, 3148 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T54", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 3209, 3221 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T55", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 3249, 3261 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T56", "type": "GROUP", "text": [ "coumarin" ], "offsets": [ [ 3299, 3307 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T57", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 3400, 3412 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T58", "type": "GROUP", "text": [ "coumarin" ], "offsets": [ [ 3417, 3425 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T59", "type": "GROUP", "text": [ "azole antifungal agents" ], "offsets": [ [ 3478, 3501 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T60", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 3543, 3552 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T61", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 3554, 3566 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T62", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 3614, 3626 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T63", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 3631, 3640 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T64", "type": "GROUP", "text": [ "azole antifungal agents" ], "offsets": [ [ 3735, 3758 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T65", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 3768, 3787 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T66", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 3853, 3865 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T67", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 3875, 3894 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T68", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 4001, 4013 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T69", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 4018, 4027 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T70", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 4089, 4101 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T71", "type": "GROUP", "text": [ "dihydropyridine calcium channel blockers" ], "offsets": [ [ 4106, 4146 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T72", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 4280, 4290 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T73", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 4349, 4359 ] ], "normalized": [] }, { "id": "Itraconazole_ddi_T74", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 4415, 4427 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Itraconazole_ddi_R1", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T4", "arg2_id": "Itraconazole_ddi_T5", "normalized": [] }, { "id": "Itraconazole_ddi_R2", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T8", "arg2_id": "Itraconazole_ddi_T9", "normalized": [] }, { "id": "Itraconazole_ddi_R3", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T12", "arg2_id": "Itraconazole_ddi_T14", "normalized": [] }, { "id": "Itraconazole_ddi_R4", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T17", "arg2_id": "Itraconazole_ddi_T18", "normalized": [] }, { "id": "Itraconazole_ddi_R5", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T19", "arg2_id": "Itraconazole_ddi_T20", "normalized": [] }, { "id": "Itraconazole_ddi_R6", "type": "EFFECT", "arg1_id": "Itraconazole_ddi_T22", "arg2_id": "Itraconazole_ddi_T23", "normalized": [] }, { "id": "Itraconazole_ddi_R7", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T24", "arg2_id": "Itraconazole_ddi_T25", "normalized": [] }, { "id": "Itraconazole_ddi_R8", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T26", "arg2_id": "Itraconazole_ddi_T27", "normalized": [] }, { "id": "Itraconazole_ddi_R9", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T28", "arg2_id": "Itraconazole_ddi_T29", "normalized": [] }, { "id": "Itraconazole_ddi_R10", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T28", "arg2_id": "Itraconazole_ddi_T30", "normalized": [] }, { "id": "Itraconazole_ddi_R11", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T33", "arg2_id": "Itraconazole_ddi_T34", "normalized": [] }, { "id": "Itraconazole_ddi_R12", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T33", "arg2_id": "Itraconazole_ddi_T35", "normalized": [] }, { "id": "Itraconazole_ddi_R13", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T33", "arg2_id": "Itraconazole_ddi_T36", "normalized": [] }, { "id": "Itraconazole_ddi_R14", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T37", "arg2_id": "Itraconazole_ddi_T40", "normalized": [] }, { "id": "Itraconazole_ddi_R15", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T38", "arg2_id": "Itraconazole_ddi_T40", "normalized": [] }, { "id": "Itraconazole_ddi_R16", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T39", "arg2_id": "Itraconazole_ddi_T40", "normalized": [] }, { "id": "Itraconazole_ddi_R17", "type": "EFFECT", "arg1_id": "Itraconazole_ddi_T41", "arg2_id": "Itraconazole_ddi_T42", "normalized": [] }, { "id": "Itraconazole_ddi_R18", "type": "EFFECT", "arg1_id": "Itraconazole_ddi_T41", "arg2_id": "Itraconazole_ddi_T43", "normalized": [] }, { "id": "Itraconazole_ddi_R19", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T44", "arg2_id": "Itraconazole_ddi_T45", "normalized": [] }, { "id": "Itraconazole_ddi_R20", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T44", "arg2_id": "Itraconazole_ddi_T46", "normalized": [] }, { "id": "Itraconazole_ddi_R21", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T50", "arg2_id": "Itraconazole_ddi_T51", "normalized": [] }, { "id": "Itraconazole_ddi_R22", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T53", "arg2_id": "Itraconazole_ddi_T54", "normalized": [] }, { "id": "Itraconazole_ddi_R23", "type": "EFFECT", "arg1_id": "Itraconazole_ddi_T55", "arg2_id": "Itraconazole_ddi_T56", "normalized": [] }, { "id": "Itraconazole_ddi_R24", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T57", "arg2_id": "Itraconazole_ddi_T58", "normalized": [] }, { "id": "Itraconazole_ddi_R25", "type": "MECHANISM", "arg1_id": "Itraconazole_ddi_T59", "arg2_id": "Itraconazole_ddi_T60", "normalized": [] }, { "id": "Itraconazole_ddi_R26", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T62", "arg2_id": "Itraconazole_ddi_T63", "normalized": [] }, { "id": "Itraconazole_ddi_R27", "type": "EFFECT", "arg1_id": "Itraconazole_ddi_T64", "arg2_id": "Itraconazole_ddi_T65", "normalized": [] }, { "id": "Itraconazole_ddi_R28", "type": "ADVISE", "arg1_id": "Itraconazole_ddi_T66", "arg2_id": "Itraconazole_ddi_T67", "normalized": [] }, { "id": "Itraconazole_ddi_R29", "type": "EFFECT", "arg1_id": "Itraconazole_ddi_T68", "arg2_id": "Itraconazole_ddi_T69", "normalized": [] }, { "id": "Itraconazole_ddi_R30", "type": "EFFECT", "arg1_id": "Itraconazole_ddi_T70", "arg2_id": "Itraconazole_ddi_T71", "normalized": [] } ]

[ { "id": "Nitroprusside_ddi__text", "type": "abstract", "text": [ "The hypotensive effect of sodium nitroprusside is augmented by that of most other hypotensive drugs, including ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics." ], "offsets": [ [ 0, 190 ] ] } ]

[ { "id": "Nitroprusside_ddi_T1", "type": "DRUG", "text": [ "sodium nitroprusside" ], "offsets": [ [ 26, 46 ] ], "normalized": [] }, { "id": "Nitroprusside_ddi_T2", "type": "GROUP", "text": [ "hypotensive drugs" ], "offsets": [ [ 82, 99 ] ], "normalized": [] }, { "id": "Nitroprusside_ddi_T3", "type": "GROUP", "text": [ "ganglionic blocking agents" ], "offsets": [ [ 111, 137 ] ], "normalized": [] }, { "id": "Nitroprusside_ddi_T4", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 178, 189 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Nitroprusside_ddi_R1", "type": "EFFECT", "arg1_id": "Nitroprusside_ddi_T1", "arg2_id": "Nitroprusside_ddi_T2", "normalized": [] }, { "id": "Nitroprusside_ddi_R2", "type": "EFFECT", "arg1_id": "Nitroprusside_ddi_T1", "arg2_id": "Nitroprusside_ddi_T3", "normalized": [] }, { "id": "Nitroprusside_ddi_R3", "type": "EFFECT", "arg1_id": "Nitroprusside_ddi_T1", "arg2_id": "Nitroprusside_ddi_T4", "normalized": [] } ]

[ { "id": "Doxacurium chloride_ddi__text", "type": "abstract", "text": [ "Prior administration of succinylcholine has no clinically important effect on the neuromuscular blocking action of NUROMAX. The use of NUROMAX before succinylcholine to attenuate some of the side effects of succinylcholine has not been studied. There are no clinical data on concomitant use of NUROMAX and other nondepolarizing neuromuscular blocking agents. Isoflurane, enflurane, and halothane decrease the ED50 of NUROMAX by 30% to 45%. These agents may also prolong the clinically effective duration of action by up to 25%. Other drugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as NUROMAX include certain antibiotics (e. g., aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, and sodium colistimethate), magnesium salts, lithium, local anesthetics, procainamide, and quinidine. As with some other nondepolarizing neuromuscular blocking agents, the time of onset of neuromuscular block induced by NUROMAX is lengthened and the duration of block is shortened in patients receiving phenytoin or carbamazepine." ], "offsets": [ [ 0, 1091 ] ] } ]

[ { "id": "Doxacurium chloride_ddi_T1", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 24, 39 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T2", "type": "BRAND", "text": [ "NUROMAX" ], "offsets": [ [ 115, 122 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T3", "type": "BRAND", "text": [ "NUROMAX" ], "offsets": [ [ 135, 142 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T4", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 150, 165 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T5", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 207, 222 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T6", "type": "BRAND", "text": [ "NUROMAX" ], "offsets": [ [ 294, 301 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T7", "type": "GROUP", "text": [ "neuromuscular blocking agents" ], "offsets": [ [ 328, 357 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T8", "type": "DRUG", "text": [ "Isoflurane" ], "offsets": [ [ 359, 369 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T9", "type": "DRUG", "text": [ "enflurane" ], "offsets": [ [ 371, 380 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T10", "type": "DRUG", "text": [ "halothane" ], "offsets": [ [ 386, 395 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T11", "type": "BRAND", "text": [ "NUROMAX" ], "offsets": [ [ 417, 424 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T12", "type": "BRAND", "text": [ "NUROMAX" ], "offsets": [ [ 626, 633 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T13", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 650, 661 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T14", "type": "GROUP", "text": [ "aminoglycosides" ], "offsets": [ [ 670, 685 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T15", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 687, 700 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T16", "type": "GROUP", "text": [ "bacitracin" ], "offsets": [ [ 702, 712 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T17", "type": "GROUP", "text": [ "polymyxins" ], "offsets": [ [ 714, 724 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T18", "type": "DRUG", "text": [ "lincomycin" ], "offsets": [ [ 726, 736 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T19", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 738, 749 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T20", "type": "DRUG", "text": [ "colistin" ], "offsets": [ [ 751, 759 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T21", "type": "DRUG", "text": [ "sodium colistimethate" ], "offsets": [ [ 765, 786 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T22", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 789, 798 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T23", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 806, 813 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T24", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 821, 832 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T25", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 834, 846 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T26", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 852, 861 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T27", "type": "GROUP", "text": [ "nondepolarizing neuromuscular blocking agents" ], "offsets": [ [ 882, 927 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T28", "type": "BRAND", "text": [ "NUROMAX" ], "offsets": [ [ 981, 988 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T29", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1064, 1073 ] ], "normalized": [] }, { "id": "Doxacurium chloride_ddi_T30", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1077, 1090 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Doxacurium chloride_ddi_R1", "type": "MECHANISM", "arg1_id": "Doxacurium chloride_ddi_T8", "arg2_id": "Doxacurium chloride_ddi_T11", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R2", "type": "MECHANISM", "arg1_id": "Doxacurium chloride_ddi_T9", "arg2_id": "Doxacurium chloride_ddi_T11", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R3", "type": "MECHANISM", "arg1_id": "Doxacurium chloride_ddi_T10", "arg2_id": "Doxacurium chloride_ddi_T11", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R4", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T13", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R5", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T14", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R6", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T15", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R7", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T16", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R8", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T17", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R9", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T18", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R10", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T19", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R11", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T20", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R12", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T21", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R13", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T22", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R14", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T23", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R15", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T24", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R16", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T25", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R17", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T12", "arg2_id": "Doxacurium chloride_ddi_T26", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R18", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T27", "arg2_id": "Doxacurium chloride_ddi_T29", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R19", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T27", "arg2_id": "Doxacurium chloride_ddi_T30", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R20", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T28", "arg2_id": "Doxacurium chloride_ddi_T29", "normalized": [] }, { "id": "Doxacurium chloride_ddi_R21", "type": "EFFECT", "arg1_id": "Doxacurium chloride_ddi_T28", "arg2_id": "Doxacurium chloride_ddi_T30", "normalized": [] } ]

[ { "id": "Lindane_ddi__text", "type": "abstract", "text": [ "Oils may enhance absorption. Therefore, simultaneous use of creams, ointments or oils should be avoided." ], "offsets": [ [ 0, 104 ] ] } ]

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[ { "id": "Etanercept_ddi__text", "type": "abstract", "text": [ "Specific drug interaction studies have not been conducted with ENBREL . However, it was observed that the pharmacokinetics of ENBREL was unaltered by concomitant methotrexate in rheumatoid arthritis patients. In a study in which patients with active RA were treated for up to 24 weeks with concurrent ENBREL and anakinra therapy, a 7% rate of serious infections was observed, which was higher than that observed with ENBREL alone (0%). Two percent of patients treated concurrently with ENBREL and anakinra developed neutropenia (ANC 1 x 109/L). Patients in a clinical study who were on established therapy with sulfasalazine, to which ENBREL was added, were noted to develop a mild decrease in mean neutrophil counts in comparison to groups treated with either ENBREL CI or sulfasalazine alone. The clinical significance of this observation is unknown." ], "offsets": [ [ 0, 858 ] ] } ]

[ { "id": "Etanercept_ddi_T1", "type": "BRAND", "text": [ "ENBREL" ], "offsets": [ [ 63, 69 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T2", "type": "BRAND", "text": [ "ENBREL" ], "offsets": [ [ 126, 132 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T3", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 163, 175 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T4", "type": "BRAND", "text": [ "ENBREL" ], "offsets": [ [ 302, 308 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T5", "type": "DRUG", "text": [ "anakinra" ], "offsets": [ [ 314, 322 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T6", "type": "BRAND", "text": [ "ENBREL" ], "offsets": [ [ 419, 425 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T7", "type": "BRAND", "text": [ "ENBREL" ], "offsets": [ [ 489, 495 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T8", "type": "DRUG", "text": [ "anakinra" ], "offsets": [ [ 501, 509 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T9", "type": "DRUG", "text": [ "sulfasalazine" ], "offsets": [ [ 617, 630 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T10", "type": "BRAND", "text": [ "ENBREL" ], "offsets": [ [ 641, 647 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T11", "type": "BRAND", "text": [ "ENBREL" ], "offsets": [ [ 767, 773 ] ], "normalized": [] }, { "id": "Etanercept_ddi_T12", "type": "DRUG", "text": [ "sulfasalazine" ], "offsets": [ [ 780, 793 ] ], "normalized": [] } ]

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[ { "id": "Etanercept_ddi_R1", "type": "EFFECT", "arg1_id": "Etanercept_ddi_T4", "arg2_id": "Etanercept_ddi_T5", "normalized": [] }, { "id": "Etanercept_ddi_R2", "type": "EFFECT", "arg1_id": "Etanercept_ddi_T7", "arg2_id": "Etanercept_ddi_T8", "normalized": [] }, { "id": "Etanercept_ddi_R3", "type": "EFFECT", "arg1_id": "Etanercept_ddi_T9", "arg2_id": "Etanercept_ddi_T10", "normalized": [] } ]

[ { "id": "Lorazepam_ddi__text", "type": "abstract", "text": [ "Tablets: The benzodiazepines, including lorazepam, produce CNS-depressant effects when administered with such medications as barbiturates or alcohol. Injection: Lorazepam injection, like other injectable benzodiazepines, produces depression of the central nervous system when administered with ethyl alcohol, phenothiazines, barbiturates, MAO inhibitors, and other antidepressants.When scopolamine is used concomitantly with injectable lorazepam, an increased incidence of sedation, hallucinations, and irrational behavior has been observed." ], "offsets": [ [ 0, 541 ] ] } ]

[ { "id": "Lorazepam_ddi_T1", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 13, 28 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T2", "type": "DRUG", "text": [ "lorazepam" ], "offsets": [ [ 40, 49 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T3", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 125, 137 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T4", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 141, 148 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T5", "type": "DRUG", "text": [ "Lorazepam" ], "offsets": [ [ 161, 170 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T6", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 204, 219 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T7", "type": "DRUG", "text": [ "ethyl alcohol" ], "offsets": [ [ 294, 307 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T8", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 309, 323 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T9", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 325, 337 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T10", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 339, 353 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T11", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 365, 380 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T12", "type": "DRUG", "text": [ "scopolamine" ], "offsets": [ [ 386, 397 ] ], "normalized": [] }, { "id": "Lorazepam_ddi_T13", "type": "DRUG", "text": [ "lorazepam" ], "offsets": [ [ 436, 445 ] ], "normalized": [] } ]

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[ { "id": "Lorazepam_ddi_R1", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T1", "arg2_id": "Lorazepam_ddi_T3", "normalized": [] }, { "id": "Lorazepam_ddi_R2", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T1", "arg2_id": "Lorazepam_ddi_T4", "normalized": [] }, { "id": "Lorazepam_ddi_R3", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T2", "arg2_id": "Lorazepam_ddi_T3", "normalized": [] }, { "id": "Lorazepam_ddi_R4", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T2", "arg2_id": "Lorazepam_ddi_T4", "normalized": [] }, { "id": "Lorazepam_ddi_R5", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T5", "arg2_id": "Lorazepam_ddi_T7", "normalized": [] }, { "id": "Lorazepam_ddi_R6", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T5", "arg2_id": "Lorazepam_ddi_T8", "normalized": [] }, { "id": "Lorazepam_ddi_R7", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T5", "arg2_id": "Lorazepam_ddi_T9", "normalized": [] }, { "id": "Lorazepam_ddi_R8", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T5", "arg2_id": "Lorazepam_ddi_T10", "normalized": [] }, { "id": "Lorazepam_ddi_R9", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T5", "arg2_id": "Lorazepam_ddi_T11", "normalized": [] }, { "id": "Lorazepam_ddi_R10", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T6", "arg2_id": "Lorazepam_ddi_T7", "normalized": [] }, { "id": "Lorazepam_ddi_R11", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T6", "arg2_id": "Lorazepam_ddi_T8", "normalized": [] }, { "id": "Lorazepam_ddi_R12", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T6", "arg2_id": "Lorazepam_ddi_T9", "normalized": [] }, { "id": "Lorazepam_ddi_R13", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T6", "arg2_id": "Lorazepam_ddi_T10", "normalized": [] }, { "id": "Lorazepam_ddi_R14", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T6", "arg2_id": "Lorazepam_ddi_T11", "normalized": [] }, { "id": "Lorazepam_ddi_R15", "type": "EFFECT", "arg1_id": "Lorazepam_ddi_T12", "arg2_id": "Lorazepam_ddi_T13", "normalized": [] } ]

[ { "id": "Clofibrate_ddi__text", "type": "abstract", "text": [ "Caution should be exercised when anticoagulants are given in conjunction with Atromid-S. Usually, the dosage of the anticoagulant should be reduced by one-half (depending on the individual case) to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been determined definitely that the prothrombin level has been stabilized. Atromid-S may displace acidic drugs such as phenytoin or tolbutamide from their binding sites. Caution should be exercised when treating patients with either of these drugs or other highly protein-bound drugs and Atromid-S. The hypoglycemic effect of tolbutamide has been reported to increase when Atromid-S is given concurrently. Fulminant rhabdomyolysis has been seen as early as three weeks after initiation of combined therapy with another fibrate and lovastatin but may be seen after several months. For these reasons, it is felt that, in most subjects who have had an unsatisfactory lipid response to either drug alone, the possible benefits of combined therapy with lovastatin and a fibrate do not outweigh the risks of severe myopathy, rhabdomyolysis, and acute renal failure. While it is not known whether this interaction occurs with fibrates other than gemfibrozil, myopathy and rhabdomyolysis have occasionally been associated with the use of fibrates alone, including clofibrate. Therefore, the combined use of lovastatin with fibrates should generally be avoided." ], "offsets": [ [ 0, 1499 ] ] } ]

[ { "id": "Clofibrate_ddi_T1", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 33, 47 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T2", "type": "BRAND", "text": [ "Atromid-S" ], "offsets": [ [ 78, 87 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T3", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 116, 129 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T4", "type": "BRAND", "text": [ "Atromid-S" ], "offsets": [ [ 422, 431 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T5", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 466, 475 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T6", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 479, 490 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T7", "type": "BRAND", "text": [ "Atromid-S" ], "offsets": [ [ 635, 644 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T8", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 673, 684 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T9", "type": "BRAND", "text": [ "Atromid-S" ], "offsets": [ [ 720, 729 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T10", "type": "GROUP", "text": [ "fibrate" ], "offsets": [ [ 866, 873 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T11", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 878, 888 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T12", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 1095, 1105 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T13", "type": "GROUP", "text": [ "fibrate" ], "offsets": [ [ 1112, 1119 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T14", "type": "GROUP", "text": [ "fibrates" ], "offsets": [ [ 1266, 1274 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T15", "type": "DRUG", "text": [ "gemfibrozil" ], "offsets": [ [ 1286, 1297 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T16", "type": "GROUP", "text": [ "fibrates" ], "offsets": [ [ 1377, 1385 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T17", "type": "DRUG", "text": [ "clofibrate" ], "offsets": [ [ 1403, 1413 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T18", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 1446, 1456 ] ], "normalized": [] }, { "id": "Clofibrate_ddi_T19", "type": "GROUP", "text": [ "fibrates" ], "offsets": [ [ 1462, 1470 ] ], "normalized": [] } ]

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[ { "id": "Clofibrate_ddi_R1", "type": "ADVISE", "arg1_id": "Clofibrate_ddi_T1", "arg2_id": "Clofibrate_ddi_T2", "normalized": [] }, { "id": "Clofibrate_ddi_R2", "type": "MECHANISM", "arg1_id": "Clofibrate_ddi_T4", "arg2_id": "Clofibrate_ddi_T5", "normalized": [] }, { "id": "Clofibrate_ddi_R3", "type": "MECHANISM", "arg1_id": "Clofibrate_ddi_T4", "arg2_id": "Clofibrate_ddi_T6", "normalized": [] }, { "id": "Clofibrate_ddi_R4", "type": "EFFECT", "arg1_id": "Clofibrate_ddi_T8", "arg2_id": "Clofibrate_ddi_T9", "normalized": [] }, { "id": "Clofibrate_ddi_R5", "type": "EFFECT", "arg1_id": "Clofibrate_ddi_T10", "arg2_id": "Clofibrate_ddi_T11", "normalized": [] }, { "id": "Clofibrate_ddi_R6", "type": "EFFECT", "arg1_id": "Clofibrate_ddi_T12", "arg2_id": "Clofibrate_ddi_T13", "normalized": [] }, { "id": "Clofibrate_ddi_R7", "type": "ADVISE", "arg1_id": "Clofibrate_ddi_T18", "arg2_id": "Clofibrate_ddi_T19", "normalized": [] } ]

[ { "id": "Alfuzosin_ddi__text", "type": "abstract", "text": [ "Drug-Drug Interactions: The pharmacokinetic and pharmacodynamic interactions between UROXATRAL and other alpha-blockers have not been determined. However, interactions may be expected, and UROXATRAL should NOT be used in combination with other alpha-blockers." ], "offsets": [ [ 0, 259 ] ] } ]

[ { "id": "Alfuzosin_ddi_T1", "type": "BRAND", "text": [ "UROXATRAL" ], "offsets": [ [ 85, 94 ] ], "normalized": [] }, { "id": "Alfuzosin_ddi_T2", "type": "GROUP", "text": [ "alpha-blockers" ], "offsets": [ [ 105, 119 ] ], "normalized": [] }, { "id": "Alfuzosin_ddi_T3", "type": "BRAND", "text": [ "UROXATRAL" ], "offsets": [ [ 189, 198 ] ], "normalized": [] }, { "id": "Alfuzosin_ddi_T4", "type": "GROUP", "text": [ "alpha-blockers" ], "offsets": [ [ 244, 258 ] ], "normalized": [] } ]

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[ { "id": "Alfuzosin_ddi_R1", "type": "ADVISE", "arg1_id": "Alfuzosin_ddi_T3", "arg2_id": "Alfuzosin_ddi_T4", "normalized": [] } ]

[ { "id": "Chloroxine_ddi__text", "type": "abstract", "text": [ "May interact with skin products or shampoos for dandruff or psoriasis." ], "offsets": [ [ 0, 70 ] ] } ]

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[ { "id": "Flutamide_ddi__text", "type": "abstract", "text": [ "Increases in prothrombin time have been noted in patients receiving long- term warfarin therapy after flutamide was initiated. Therefore, close monitoring of prothrombin time is recommended and adjustment of the anticoagulant dose may be necessary when EULEXIN Capsules are administered concomitantly with warfarin." ], "offsets": [ [ 0, 315 ] ] } ]

[ { "id": "Flutamide_ddi_T1", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 79, 87 ] ], "normalized": [] }, { "id": "Flutamide_ddi_T2", "type": "DRUG", "text": [ "flutamide" ], "offsets": [ [ 102, 111 ] ], "normalized": [] }, { "id": "Flutamide_ddi_T3", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 212, 225 ] ], "normalized": [] }, { "id": "Flutamide_ddi_T4", "type": "BRAND", "text": [ "EULEXIN" ], "offsets": [ [ 253, 260 ] ], "normalized": [] }, { "id": "Flutamide_ddi_T5", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 306, 314 ] ], "normalized": [] } ]

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[ { "id": "Flutamide_ddi_R1", "type": "EFFECT", "arg1_id": "Flutamide_ddi_T1", "arg2_id": "Flutamide_ddi_T2", "normalized": [] }, { "id": "Flutamide_ddi_R2", "type": "ADVISE", "arg1_id": "Flutamide_ddi_T4", "arg2_id": "Flutamide_ddi_T5", "normalized": [] } ]

[ { "id": "Naproxen_ddi__text", "type": "abstract", "text": [ "The use of NSAIDs in patients who are receiving ACE inhibitors may potentiate renal disease states. In vitro studies have shown that naproxen anion, because of its affinity for protein, may displace from their binding sites other drugs which are also albumin-bound . Theoretically, the naproxen anion itself could likewise be displaced. Short-term controlled studies failed to show that taking the drug significantly affects prothrombin times when administered to individuals on coumarin-type anticoagulants. Caution is advised nonetheless, since interactions have been seen with other nonsteroidal agents of this class. Similarly, patients receiving the drug and a hydantoin, sulfonamide or sulfonylurea should be observed for signs of toxicity to these drugs. Concomitant administration of naproxen and aspirin is not recommended because naproxen is displaced from its binding sites during the concomitant administration of aspirin, resulting in lower plasma concentrations and peak plasma levels. The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class. Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations has also been reported. Naproxen and other NSAIDs can reduce the antihypertensive effect of propranolol and other beta-blockers. Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly. Caution should be used if naproxen is administered concomitantly with methotrexate. Naproxen, naproxen sodium and other NSAIDs have been reported to reduce the tubular secretion of methotrexate in an animal model, possibly increasing the toxicity of methotrexate. Drug/Laboratory Test Interactions Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined. The administration of naproxen may result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-dinitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used. Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA)." ], "offsets": [ [ 0, 2445 ] ] } ]

[ { "id": "Naproxen_ddi_T1", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 11, 17 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T2", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 48, 62 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T3", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 133, 141 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T4", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 286, 294 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T5", "type": "GROUP", "text": [ "coumarin-type anticoagulants" ], "offsets": [ [ 479, 507 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T6", "type": "GROUP", "text": [ "hydantoin" ], "offsets": [ [ 666, 675 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T7", "type": "GROUP", "text": [ "sulfonamide" ], "offsets": [ [ 677, 688 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T8", "type": "GROUP", "text": [ "sulfonylurea" ], "offsets": [ [ 692, 704 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T9", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 792, 800 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T10", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 805, 812 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T11", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 840, 848 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T12", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 926, 933 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T13", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1026, 1036 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T14", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1120, 1127 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T15", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1169, 1176 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T16", "type": "DRUG", "text": [ "Naproxen" ], "offsets": [ [ 1216, 1224 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T17", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1235, 1241 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T18", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1284, 1295 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T19", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 1306, 1319 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T20", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 1321, 1331 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T21", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 1361, 1369 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T22", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 1464, 1472 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T23", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1508, 1520 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T24", "type": "DRUG", "text": [ "Naproxen" ], "offsets": [ [ 1522, 1530 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T25", "type": "DRUG", "text": [ "naproxen sodium" ], "offsets": [ [ 1532, 1547 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T26", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1558, 1564 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T27", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1619, 1631 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T28", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1688, 1700 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T29", "type": "DRUG", "text": [ "Naproxen" ], "offsets": [ [ 1736, 1744 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T30", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 1899, 1907 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T31", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 2227, 2235 ] ], "normalized": [] }, { "id": "Naproxen_ddi_T32", "type": "DRUG", "text": [ "Naproxen" ], "offsets": [ [ 2358, 2366 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Naproxen_ddi_R1", "type": "EFFECT", "arg1_id": "Naproxen_ddi_T1", "arg2_id": "Naproxen_ddi_T2", "normalized": [] }, { "id": "Naproxen_ddi_R2", "type": "ADVISE", "arg1_id": "Naproxen_ddi_T9", "arg2_id": "Naproxen_ddi_T10", "normalized": [] }, { "id": "Naproxen_ddi_R3", "type": "ADVISE", "arg1_id": "Naproxen_ddi_T11", "arg2_id": "Naproxen_ddi_T12", "normalized": [] }, { "id": "Naproxen_ddi_R4", "type": "EFFECT", "arg1_id": "Naproxen_ddi_T16", "arg2_id": "Naproxen_ddi_T18", "normalized": [] }, { "id": "Naproxen_ddi_R5", "type": "EFFECT", "arg1_id": "Naproxen_ddi_T16", "arg2_id": "Naproxen_ddi_T19", "normalized": [] }, { "id": "Naproxen_ddi_R6", "type": "EFFECT", "arg1_id": "Naproxen_ddi_T17", "arg2_id": "Naproxen_ddi_T18", "normalized": [] }, { "id": "Naproxen_ddi_R7", "type": "EFFECT", "arg1_id": "Naproxen_ddi_T17", "arg2_id": "Naproxen_ddi_T19", "normalized": [] }, { "id": "Naproxen_ddi_R8", "type": "MECHANISM", "arg1_id": "Naproxen_ddi_T20", "arg2_id": "Naproxen_ddi_T21", "normalized": [] }, { "id": "Naproxen_ddi_R9", "type": "ADVISE", "arg1_id": "Naproxen_ddi_T22", "arg2_id": "Naproxen_ddi_T23", "normalized": [] }, { "id": "Naproxen_ddi_R10", "type": "MECHANISM", "arg1_id": "Naproxen_ddi_T24", "arg2_id": "Naproxen_ddi_T27", "normalized": [] }, { "id": "Naproxen_ddi_R11", "type": "MECHANISM", "arg1_id": "Naproxen_ddi_T25", "arg2_id": "Naproxen_ddi_T27", "normalized": [] }, { "id": "Naproxen_ddi_R12", "type": "MECHANISM", "arg1_id": "Naproxen_ddi_T26", "arg2_id": "Naproxen_ddi_T27", "normalized": [] } ]

[ { "id": "Almotriptan_ddi__text", "type": "abstract", "text": [ "Ergot-Containing Drugs: These drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and AXERT within 24 hours of each other should be avoided. Monoamine Oxidase Inhibitors: Coadministration of moclobemide resulted in a 27% decrease in almotriptan clearance and an increase in Cmax of approximately 6%. No dose adjustment is necessary. Other 5-HT1B/1D Agonists Concomitant use of other 5-HT1B/1D agonists within 24 hours of treatment with AXERT is contraindicated. Propanolol: The pharmacokinetics of almotriptan were not affected by coadministration of propranolol. Selective Serotonin Reuptake Inhibitors (SSRIs): SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been rarely reported to cause weakness, hyperreflexia, and incoordination when coadministered with 5-HT1 agonists. If concomitant treatment with AXERT and an SSRI is clinically warranted, appropriate observation of the patient is advised. Verapamil: Coadministration of almotriptan and verapamil resulted in a 24% increase in plasma concentrations of almotriptan. No dose adjustment is necessary. Coadministration of almotriptan and the potent CYP3A4 inhibitor ketoconazole (400 mg q.d. for 3 days) resulted in an approximately 60% increase in the area under the plasma concentration-time curve and maximal plasma concentrations of almotriptan. Although the interaction between almotriptan and other potent CYP3A4 inhibitors (e.g., itraconazole, ritonavir, and erythromycin) has not been studied, increased exposures to almotriptan may be expected when almotriptan is used concomitantly with these medications. AXERT is not known to interfere with commonly employed clinical laboratory tests." ], "offsets": [ [ 0, 1856 ] ] } ]

[ { "id": "Almotriptan_ddi_T1", "type": "GROUP", "text": [ "Ergot-Containing Drugs" ], "offsets": [ [ 0, 22 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T2", "type": "DRUG", "text": [ "ergotamine" ], "offsets": [ [ 177, 187 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T3", "type": "GROUP", "text": [ "ergot-type medications" ], "offsets": [ [ 202, 224 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T4", "type": "DRUG", "text": [ "dihydroergotamine" ], "offsets": [ [ 231, 248 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T5", "type": "DRUG", "text": [ "methysergide" ], "offsets": [ [ 252, 264 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T6", "type": "BRAND", "text": [ "AXERT" ], "offsets": [ [ 270, 275 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T7", "type": "GROUP", "text": [ "Monoamine Oxidase Inhibitors" ], "offsets": [ [ 325, 353 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T8", "type": "DRUG", "text": [ "moclobemide" ], "offsets": [ [ 375, 386 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T9", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 417, 428 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T10", "type": "GROUP", "text": [ "5-HT1B/1D Agonists" ], "offsets": [ [ 523, 541 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T11", "type": "GROUP", "text": [ "5-HT1B/1D agonists" ], "offsets": [ [ 567, 585 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T12", "type": "BRAND", "text": [ "AXERT" ], "offsets": [ [ 620, 625 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T13", "type": "DRUG", "text": [ "Propanolol" ], "offsets": [ [ 646, 656 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T14", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 682, 693 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T15", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 735, 746 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T16", "type": "GROUP", "text": [ "Selective Serotonin Reuptake Inhibitors" ], "offsets": [ [ 748, 787 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T17", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 789, 794 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T18", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 797, 802 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T19", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 810, 820 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T20", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 822, 833 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T21", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 835, 845 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T22", "type": "DRUG", "text": [ "sertraline" ], "offsets": [ [ 847, 857 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T23", "type": "GROUP", "text": [ "5-HT1 agonists" ], "offsets": [ [ 963, 977 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T24", "type": "BRAND", "text": [ "AXERT" ], "offsets": [ [ 1009, 1014 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T25", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 1022, 1026 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T26", "type": "DRUG", "text": [ "Verapamil" ], "offsets": [ [ 1103, 1112 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T27", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 1134, 1145 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T28", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 1150, 1159 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T29", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 1215, 1226 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T30", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 1281, 1292 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T31", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1325, 1337 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T32", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 1496, 1507 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T33", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 1542, 1553 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T34", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1596, 1608 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T35", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 1610, 1619 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T36", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1625, 1637 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T37", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 1684, 1695 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T38", "type": "DRUG", "text": [ "almotriptan" ], "offsets": [ [ 1717, 1728 ] ], "normalized": [] }, { "id": "Almotriptan_ddi_T39", "type": "BRAND", "text": [ "AXERT" ], "offsets": [ [ 1775, 1780 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Almotriptan_ddi_R1", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T2", "arg2_id": "Almotriptan_ddi_T6", "normalized": [] }, { "id": "Almotriptan_ddi_R2", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T3", "arg2_id": "Almotriptan_ddi_T6", "normalized": [] }, { "id": "Almotriptan_ddi_R3", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T4", "arg2_id": "Almotriptan_ddi_T6", "normalized": [] }, { "id": "Almotriptan_ddi_R4", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T5", "arg2_id": "Almotriptan_ddi_T6", "normalized": [] }, { "id": "Almotriptan_ddi_R5", "type": "MECHANISM", "arg1_id": "Almotriptan_ddi_T8", "arg2_id": "Almotriptan_ddi_T9", "normalized": [] }, { "id": "Almotriptan_ddi_R6", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T11", "arg2_id": "Almotriptan_ddi_T12", "normalized": [] }, { "id": "Almotriptan_ddi_R7", "type": "EFFECT", "arg1_id": "Almotriptan_ddi_T18", "arg2_id": "Almotriptan_ddi_T23", "normalized": [] }, { "id": "Almotriptan_ddi_R8", "type": "EFFECT", "arg1_id": "Almotriptan_ddi_T19", "arg2_id": "Almotriptan_ddi_T23", "normalized": [] }, { "id": "Almotriptan_ddi_R9", "type": "EFFECT", "arg1_id": "Almotriptan_ddi_T20", "arg2_id": "Almotriptan_ddi_T23", "normalized": [] }, { "id": "Almotriptan_ddi_R10", "type": "EFFECT", "arg1_id": "Almotriptan_ddi_T21", "arg2_id": "Almotriptan_ddi_T23", "normalized": [] }, { "id": "Almotriptan_ddi_R11", "type": "EFFECT", "arg1_id": "Almotriptan_ddi_T22", "arg2_id": "Almotriptan_ddi_T23", "normalized": [] }, { "id": "Almotriptan_ddi_R12", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T24", "arg2_id": "Almotriptan_ddi_T25", "normalized": [] }, { "id": "Almotriptan_ddi_R13", "type": "MECHANISM", "arg1_id": "Almotriptan_ddi_T27", "arg2_id": "Almotriptan_ddi_T28", "normalized": [] }, { "id": "Almotriptan_ddi_R14", "type": "MECHANISM", "arg1_id": "Almotriptan_ddi_T30", "arg2_id": "Almotriptan_ddi_T31", "normalized": [] }, { "id": "Almotriptan_ddi_R15", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T34", "arg2_id": "Almotriptan_ddi_T38", "normalized": [] }, { "id": "Almotriptan_ddi_R16", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T35", "arg2_id": "Almotriptan_ddi_T38", "normalized": [] }, { "id": "Almotriptan_ddi_R17", "type": "ADVISE", "arg1_id": "Almotriptan_ddi_T36", "arg2_id": "Almotriptan_ddi_T38", "normalized": [] } ]

[ { "id": "Cabergoline_ddi__text", "type": "abstract", "text": [ "DOSTINEX should not be administered concurrently with D2-antagonists, such as phenothiazines, butyrophenones, thioxanthines, or metoclopramide." ], "offsets": [ [ 0, 143 ] ] } ]

[ { "id": "Cabergoline_ddi_T1", "type": "BRAND", "text": [ "DOSTINEX" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Cabergoline_ddi_T2", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 78, 92 ] ], "normalized": [] }, { "id": "Cabergoline_ddi_T3", "type": "GROUP", "text": [ "butyrophenones" ], "offsets": [ [ 94, 108 ] ], "normalized": [] }, { "id": "Cabergoline_ddi_T4", "type": "GROUP", "text": [ "thioxanthines" ], "offsets": [ [ 110, 123 ] ], "normalized": [] }, { "id": "Cabergoline_ddi_T5", "type": "DRUG", "text": [ "metoclopramide" ], "offsets": [ [ 128, 142 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cabergoline_ddi_R1", "type": "ADVISE", "arg1_id": "Cabergoline_ddi_T1", "arg2_id": "Cabergoline_ddi_T2", "normalized": [] }, { "id": "Cabergoline_ddi_R2", "type": "ADVISE", "arg1_id": "Cabergoline_ddi_T1", "arg2_id": "Cabergoline_ddi_T3", "normalized": [] }, { "id": "Cabergoline_ddi_R3", "type": "ADVISE", "arg1_id": "Cabergoline_ddi_T1", "arg2_id": "Cabergoline_ddi_T4", "normalized": [] }, { "id": "Cabergoline_ddi_R4", "type": "ADVISE", "arg1_id": "Cabergoline_ddi_T1", "arg2_id": "Cabergoline_ddi_T5", "normalized": [] } ]

[ { "id": "Etodolac_ddi__text", "type": "abstract", "text": [ "ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors. Antacids: The concomitant administration of antacids has no apparent effect on the extent of absorption of Lodine. However, antacids can decrease the peak concentration reached by 15% to 20% but have no detectable effect on the time-to-peak. Aspirin: When Lodine is administered with aspirin, its protein binding is reduced, although the clearance of free etodolac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of Lodine and aspirin is not generally recommended because of the potential of increased adverse effects. Cyclosporine, Digoxin, Methotrexate Lodine, like other NSAIDs, through effects on renal prostaglandins, may cause changes in the elimination of these drugs leading to elevated serum levels of cyclosporine, digoxin, methotrexate, and increased toxicity. Nephrotoxicity associated with cyclosporine may also be enhanced. Patients receiving these drugs who are given Lodine, or any other NSAID, and particularly those patients with altered renal function, should be observed for the development of the specific toxicities of these drugs. Diuretics: Etodolac has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide. Nevertheless, clinical studies, as well as postmarketing observations have shown that Lodine can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure, as well as to assure diuretic efficacy. Glyburide: Etodolac has no apparent pharmacokinetic interaction when administered with glyburide. Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. Phenylbutazone: Phenylbutazone causes increase (by about 80%) in the free fraction of etodolac. Although in vivo studies have not been done to see if etodolac clearance is changed by coadministration of phenylbutazone, it is not recommended that they be coadministered. Phenytoin: Etodolac has no apparent pharmacokinetic interaction when administered with phenytoin. Warfarin: The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than that of users of either drug alone. Short-term pharmacokinetic studies have demonstrated that concomitant administration of warfarin and Lodine (etodolac capsules and tablets) results in reduced protein binding of warfarin, but there was no change in the clearance of free warfarin. There was no significant difference in the pharmacodynamic effect of warfarin administered alone and warfarin administered with Lodine as measured by prothrombin time. Thus, concomitant therapy with warfarin and Lodine should not require dosage adjustment of either drug. However, caution should be exercised because there have been a few spontaneous reports of prolonged prothrombin times, with or without bleeding, in etodolac-treated patients receiving concomitant warfarin therapy. Drug/Laboratory Test Interactions The urine of patients who take Lodine can give a false-positive reaction for urinary bilirubin (urobilin) due to the presence of phenolic metabolites of etodolac. Diagnostic dip-stick methodology, used to detect ketone bodies in urine, has resulted in false-positive findings in some patients treated with Lodine. Generally, this phenomenon has not been associated with other clinically significant events. No dose relationship has been observed. Lodine treatment is associated with a small decrease in serum uric acid levels. In clinical trials, mean decreases of 1 to 2 mg/dL were observed in arthritic patients receiving etodolac (600 mg to 1000 mg/day) after 4 weeks of therapy. These levels then remained stable for up to 1 year of therapy." ], "offsets": [ [ 0, 4504 ] ] } ]

[ { "id": "Etodolac_ddi_T1", "type": "GROUP", "text": [ "ACE-inhibitors" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T2", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 36, 42 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T3", "type": "GROUP", "text": [ "ACE-inhibitors" ], "offsets": [ [ 87, 101 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T4", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 169, 175 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T5", "type": "GROUP", "text": [ "ACE-inhibitors" ], "offsets": [ [ 195, 209 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T6", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 211, 219 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T7", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 255, 263 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T8", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 318, 324 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T9", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 335, 343 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T10", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 453, 460 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T11", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 467, 473 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T12", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 495, 502 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T13", "type": "DRUG", "text": [ "etodolac" ], "offsets": [ [ 567, 575 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T14", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 675, 681 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T15", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 713, 719 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T16", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 724, 731 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T17", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 852, 858 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T18", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 871, 877 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T19", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1008, 1020 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T20", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1022, 1029 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T21", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1031, 1043 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T22", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1100, 1112 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T23", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 1180, 1186 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T24", "type": "GROUP", "text": [ "NSAID" ], "offsets": [ [ 1201, 1206 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T25", "type": "GROUP", "text": [ "Diuretics" ], "offsets": [ [ 1351, 1360 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T26", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1438, 1448 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T27", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 1452, 1471 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T28", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 1559, 1565 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T29", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1603, 1613 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T30", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 1618, 1627 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T31", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1760, 1766 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T32", "type": "DRUG", "text": [ "Glyburide" ], "offsets": [ [ 1875, 1884 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T33", "type": "DRUG", "text": [ "Etodolac" ], "offsets": [ [ 1886, 1894 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T34", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 1962, 1971 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T35", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 1973, 1980 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T36", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1982, 1988 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T37", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2026, 2033 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T38", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2066, 2073 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T39", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2102, 2109 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T40", "type": "GROUP", "text": [ "NSAID" ], "offsets": [ [ 2287, 2292 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T41", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2305, 2311 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T42", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2316, 2323 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T43", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2406, 2413 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T44", "type": "DRUG", "text": [ "Phenylbutazone" ], "offsets": [ [ 2424, 2438 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T45", "type": "DRUG", "text": [ "Phenylbutazone" ], "offsets": [ [ 2440, 2454 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T46", "type": "DRUG", "text": [ "etodolac" ], "offsets": [ [ 2510, 2518 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T47", "type": "DRUG", "text": [ "etodolac" ], "offsets": [ [ 2574, 2582 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T48", "type": "DRUG", "text": [ "phenylbutazone" ], "offsets": [ [ 2627, 2641 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T49", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 2694, 2703 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T50", "type": "DRUG", "text": [ "Etodolac" ], "offsets": [ [ 2705, 2713 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T51", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2781, 2790 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T52", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 2792, 2800 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T53", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2817, 2825 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T54", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2830, 2836 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T55", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3079, 3087 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T56", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 3092, 3098 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T57", "type": "DRUG", "text": [ "etodolac" ], "offsets": [ [ 3101, 3109 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T58", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3170, 3178 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T59", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3229, 3237 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T60", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3308, 3316 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T61", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3340, 3348 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T62", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 3367, 3373 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T63", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3438, 3446 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T64", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 3451, 3457 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T65", "type": "DRUG", "text": [ "etodolac" ], "offsets": [ [ 3659, 3667 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T66", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3707, 3715 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T67", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 3790, 3796 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T68", "type": "DRUG", "text": [ "etodolac" ], "offsets": [ [ 3912, 3920 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T69", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 4065, 4071 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T70", "type": "BRAND", "text": [ "Lodine" ], "offsets": [ [ 4206, 4212 ] ], "normalized": [] }, { "id": "Etodolac_ddi_T71", "type": "DRUG", "text": [ "etodolac" ], "offsets": [ [ 4383, 4391 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Etodolac_ddi_R1", "type": "EFFECT", "arg1_id": "Etodolac_ddi_T2", "arg2_id": "Etodolac_ddi_T3", "normalized": [] }, { "id": "Etodolac_ddi_R2", "type": "ADVISE", "arg1_id": "Etodolac_ddi_T4", "arg2_id": "Etodolac_ddi_T5", "normalized": [] }, { "id": "Etodolac_ddi_R3", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T11", "arg2_id": "Etodolac_ddi_T12", "normalized": [] }, { "id": "Etodolac_ddi_R4", "type": "ADVISE", "arg1_id": "Etodolac_ddi_T15", "arg2_id": "Etodolac_ddi_T16", "normalized": [] }, { "id": "Etodolac_ddi_R5", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T17", "arg2_id": "Etodolac_ddi_T19", "normalized": [] }, { "id": "Etodolac_ddi_R6", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T17", "arg2_id": "Etodolac_ddi_T20", "normalized": [] }, { "id": "Etodolac_ddi_R7", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T17", "arg2_id": "Etodolac_ddi_T21", "normalized": [] }, { "id": "Etodolac_ddi_R8", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T18", "arg2_id": "Etodolac_ddi_T19", "normalized": [] }, { "id": "Etodolac_ddi_R9", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T18", "arg2_id": "Etodolac_ddi_T20", "normalized": [] }, { "id": "Etodolac_ddi_R10", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T18", "arg2_id": "Etodolac_ddi_T21", "normalized": [] }, { "id": "Etodolac_ddi_R11", "type": "EFFECT", "arg1_id": "Etodolac_ddi_T28", "arg2_id": "Etodolac_ddi_T29", "normalized": [] }, { "id": "Etodolac_ddi_R12", "type": "EFFECT", "arg1_id": "Etodolac_ddi_T28", "arg2_id": "Etodolac_ddi_T30", "normalized": [] }, { "id": "Etodolac_ddi_R13", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T36", "arg2_id": "Etodolac_ddi_T37", "normalized": [] }, { "id": "Etodolac_ddi_R14", "type": "EFFECT", "arg1_id": "Etodolac_ddi_T41", "arg2_id": "Etodolac_ddi_T42", "normalized": [] }, { "id": "Etodolac_ddi_R15", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T45", "arg2_id": "Etodolac_ddi_T46", "normalized": [] }, { "id": "Etodolac_ddi_R16", "type": "ADVISE", "arg1_id": "Etodolac_ddi_T47", "arg2_id": "Etodolac_ddi_T48", "normalized": [] }, { "id": "Etodolac_ddi_R17", "type": "EFFECT", "arg1_id": "Etodolac_ddi_T53", "arg2_id": "Etodolac_ddi_T54", "normalized": [] }, { "id": "Etodolac_ddi_R18", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T55", "arg2_id": "Etodolac_ddi_T56", "normalized": [] }, { "id": "Etodolac_ddi_R19", "type": "MECHANISM", "arg1_id": "Etodolac_ddi_T55", "arg2_id": "Etodolac_ddi_T57", "normalized": [] }, { "id": "Etodolac_ddi_R20", "type": "EFFECT", "arg1_id": "Etodolac_ddi_T65", "arg2_id": "Etodolac_ddi_T66", "normalized": [] } ]

[ { "id": "Amitriptyline_ddi__text", "type": "abstract", "text": [ "Drugs Metabolized by P450 2D6 - The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called poor metabolizers); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6. Monoamine Oxidase Inhibitors: Guanethidine or similarly acting compounds; thyroid medication; alcohol, barbiturates and other CNS depressants; and disulfiram When amitriptyline HCl is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required. Hyperpyrexia has been reported when amitriptyline HCl is administered with anticholinergic agents or with neuroleptic drugs, particularly during hot weather. Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic-type drugs. Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well-controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants. Caution is advised if patients receive large doses of ethchlorvynol concurrently. Transient delirium has been reported in patients who were treated with one gram of ethchlorvynol and 75 - 150 mg of amitriptyline HCl." ], "offsets": [ [ 0, 3938 ] ] } ]

[ { "id": "Amitriptyline_ddi_T1", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 457, 482 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T2", "type": "GROUP", "text": [ "TCAs" ], "offsets": [ [ 484, 488 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T3", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 677, 680 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T4", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 851, 854 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T5", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1042, 1051 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T6", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1053, 1063 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T7", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 1119, 1134 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T8", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 1136, 1150 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T9", "type": "GROUP", "text": [ "Type 1C antiarrhythmics" ], "offsets": [ [ 1160, 1183 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T10", "type": "DRUG", "text": [ "propafenone" ], "offsets": [ [ 1184, 1195 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T11", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1200, 1210 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T12", "type": "GROUP", "text": [ "serotonin reuptake inhibitors" ], "offsets": [ [ 1237, 1266 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T13", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 1268, 1273 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T14", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1282, 1292 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T15", "type": "DRUG", "text": [ "sertraline" ], "offsets": [ [ 1294, 1304 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T16", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 1310, 1320 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T17", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 1403, 1407 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T18", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 1408, 1411 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T19", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 1524, 1528 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T20", "type": "GROUP", "text": [ "TCAs" ], "offsets": [ [ 1601, 1605 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T21", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 1622, 1627 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T22", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1799, 1809 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T23", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 1928, 1953 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T24", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 2065, 2089 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T25", "type": "DRUG", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 2207, 2231 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T26", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 2276, 2279 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T27", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 2305, 2308 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T28", "type": "DRUG", "text": [ "Monoamine Oxidase Inhibitors" ], "offsets": [ [ 2395, 2423 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T29", "type": "DRUG", "text": [ "Guanethidine" ], "offsets": [ [ 2425, 2437 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T30", "type": "DRUG", "text": [ "thyroid" ], "offsets": [ [ 2469, 2476 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T31", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 2489, 2496 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T32", "type": "DRUG", "text": [ "barbiturates" ], "offsets": [ [ 2498, 2510 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T33", "type": "DRUG", "text": [ "CNS depressants" ], "offsets": [ [ 2521, 2536 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T34", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 2542, 2552 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T35", "type": "DRUG", "text": [ "amitriptyline HCl" ], "offsets": [ [ 2558, 2575 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T36", "type": "DRUG", "text": [ "anticholinergic" ], "offsets": [ [ 2590, 2605 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T37", "type": "DRUG", "text": [ "sympathomimetic" ], "offsets": [ [ 2616, 2631 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T38", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 2649, 2660 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T39", "type": "DRUG", "text": [ "anesthetics" ], "offsets": [ [ 2681, 2692 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T40", "type": "DRUG", "text": [ "amitriptyline HCl" ], "offsets": [ [ 2796, 2813 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T41", "type": "DRUG", "text": [ "anticholinergic" ], "offsets": [ [ 2835, 2850 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T42", "type": "DRUG", "text": [ "neuroleptic" ], "offsets": [ [ 2866, 2877 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T43", "type": "DRUG", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 2963, 2988 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T44", "type": "DRUG", "text": [ "anticholinergic" ], "offsets": [ [ 3009, 3024 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T45", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 3037, 3047 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T46", "type": "DRUG", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3100, 3125 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T47", "type": "DRUG", "text": [ "drugs" ], "offsets": [ [ 3208, 3213 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T48", "type": "DRUG", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3274, 3299 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T49", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3329, 3339 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T50", "type": "DRUG", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3371, 3396 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T51", "type": "DRUG", "text": [ "anticholinergic" ], "offsets": [ [ 3462, 3477 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T52", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3503, 3513 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T53", "type": "DRUG", "text": [ "drug" ], "offsets": [ [ 3531, 3535 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T54", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3564, 3574 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T55", "type": "DRUG", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3613, 3638 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T56", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3643, 3653 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T57", "type": "DRUG", "text": [ "antidepressants" ], "offsets": [ [ 3705, 3720 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T58", "type": "DRUG", "text": [ "ethchlorvynol" ], "offsets": [ [ 3776, 3789 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T59", "type": "DRUG", "text": [ "ethchlorvynol" ], "offsets": [ [ 3887, 3900 ] ], "normalized": [] }, { "id": "Amitriptyline_ddi_T60", "type": "DRUG", "text": [ "amitriptyline HCl" ], "offsets": [ [ 3920, 3937 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Amitriptyline_ddi_R1", "type": "EFFECT", "arg1_id": "Amitriptyline_ddi_T17", "arg2_id": "Amitriptyline_ddi_T18", "normalized": [] }, { "id": "Amitriptyline_ddi_R2", "type": "ADVISE", "arg1_id": "Amitriptyline_ddi_T20", "arg2_id": "Amitriptyline_ddi_T21", "normalized": [] }, { "id": "Amitriptyline_ddi_R3", "type": "EFFECT", "arg1_id": "Amitriptyline_ddi_T40", "arg2_id": "Amitriptyline_ddi_T41", "normalized": [] }, { "id": "Amitriptyline_ddi_R4", "type": "EFFECT", "arg1_id": "Amitriptyline_ddi_T43", "arg2_id": "Amitriptyline_ddi_T44", "normalized": [] }, { "id": "Amitriptyline_ddi_R5", "type": "MECHANISM", "arg1_id": "Amitriptyline_ddi_T45", "arg2_id": "Amitriptyline_ddi_T46", "normalized": [] }, { "id": "Amitriptyline_ddi_R6", "type": "EFFECT", "arg1_id": "Amitriptyline_ddi_T48", "arg2_id": "Amitriptyline_ddi_T49", "normalized": [] }, { "id": "Amitriptyline_ddi_R7", "type": "MECHANISM", "arg1_id": "Amitriptyline_ddi_T50", "arg2_id": "Amitriptyline_ddi_T52", "normalized": [] }, { "id": "Amitriptyline_ddi_R8", "type": "MECHANISM", "arg1_id": "Amitriptyline_ddi_T55", "arg2_id": "Amitriptyline_ddi_T56", "normalized": [] }, { "id": "Amitriptyline_ddi_R9", "type": "EFFECT", "arg1_id": "Amitriptyline_ddi_T59", "arg2_id": "Amitriptyline_ddi_T60", "normalized": [] } ]

[ { "id": "Hydralazine_ddi__text", "type": "abstract", "text": [ "MAO inhibitors should be used with caution in patients receiving hydralazine. When other potent parental antihypertensive drugs, such as diazoxide, are used in combination with hydralazine, patients should be continuously observed for several hours for any excessive fall in blood pressure. Profound hypotensive episodes may occur when diazoxide infection and hydralazine are used concomitantly. Beta-blockers (metoprolol, propranolol) serum concentrations and pharmacologic effects may be increased. Monitor cardiovascular status. Propranolol increases hydralazines serum concentrations. Acebutolol, atenolol, and nadolol (low hepatic clearance or no first-pass metabolism) are unlikely to be affected. NSAIDs may decrease the hemodynamic effects of hydralazine; avoid use if possible or closely monitor cardiovascular status at the end of drug interactions" ], "offsets": [ [ 0, 858 ] ] } ]

[ { "id": "Hydralazine_ddi_T1", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T2", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 65, 76 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T3", "type": "GROUP", "text": [ "antihypertensive drugs" ], "offsets": [ [ 105, 127 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T4", "type": "DRUG", "text": [ "diazoxide" ], "offsets": [ [ 137, 146 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T5", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 177, 188 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T6", "type": "DRUG", "text": [ "diazoxide" ], "offsets": [ [ 336, 345 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T7", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 360, 371 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T8", "type": "GROUP", "text": [ "Beta-blockers" ], "offsets": [ [ 396, 409 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T9", "type": "DRUG", "text": [ "metoprolol" ], "offsets": [ [ 411, 421 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T10", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 423, 434 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T11", "type": "DRUG", "text": [ "Propranolol" ], "offsets": [ [ 532, 543 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T12", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 554, 565 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T13", "type": "DRUG", "text": [ "Acebutolol" ], "offsets": [ [ 589, 599 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T14", "type": "DRUG", "text": [ "atenolol" ], "offsets": [ [ 601, 609 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T15", "type": "DRUG", "text": [ "nadolol" ], "offsets": [ [ 615, 622 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T16", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 704, 710 ] ], "normalized": [] }, { "id": "Hydralazine_ddi_T17", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 751, 762 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Hydralazine_ddi_R1", "type": "ADVISE", "arg1_id": "Hydralazine_ddi_T1", "arg2_id": "Hydralazine_ddi_T2", "normalized": [] }, { "id": "Hydralazine_ddi_R2", "type": "EFFECT", "arg1_id": "Hydralazine_ddi_T3", "arg2_id": "Hydralazine_ddi_T4", "normalized": [] }, { "id": "Hydralazine_ddi_R3", "type": "EFFECT", "arg1_id": "Hydralazine_ddi_T3", "arg2_id": "Hydralazine_ddi_T5", "normalized": [] }, { "id": "Hydralazine_ddi_R4", "type": "EFFECT", "arg1_id": "Hydralazine_ddi_T6", "arg2_id": "Hydralazine_ddi_T7", "normalized": [] }, { "id": "Hydralazine_ddi_R5", "type": "MECHANISM", "arg1_id": "Hydralazine_ddi_T11", "arg2_id": "Hydralazine_ddi_T12", "normalized": [] }, { "id": "Hydralazine_ddi_R6", "type": "EFFECT", "arg1_id": "Hydralazine_ddi_T16", "arg2_id": "Hydralazine_ddi_T17", "normalized": [] } ]

[ { "id": "Bepridil_ddi__text", "type": "abstract", "text": [ "Nitrates: The concomitant use of Bepridil with long- and short-acting nitrates has been safely tolerated in patients with stable angina pectoris. Sublingual nitroglycerin may be taken if necessary for the control of acute angina attacks during Bepridil therapy. Beta-blocking Agents: The concomitant use of Bepridil and beta-blocking agents has been well tolerated in patients with stable angina. Available data are not sufficient, however, to predict the effects of concomitant medication on patients with impaired ventricular function or cardiac conduction abnormalities. Digoxin: In controlled studies in healthy volunteers, bepridil hydrochloride either had no effect (one study) or was associated with modest increases, about 30% (two studies) in steady-state serum digoxin concentrations. Limited clinical data in angina patients receiving concomitant bepridil hydrochloride and digoxin therapy indicate no discernible changes in serum digoxin levels. Available data are neither sufficient to rule out possible increases in serum digoxin with concomitant treatment in some patients, nor other possible interactions, particularly in patients with cardiac conduction abnormalities (Also see WARNINGS Congestive Heart Failure). Oral Hypoglycemics: Bepridil has been safely used in diabetic patients without significantly lowering their blood glucose levels or altering their need for insulin or oral hypoglycemic agents. General Interactions: Certain drugs could increase the likelihood of potentially serious adverse effects with bepridil hydrochloride. In general, these are drugs that have one or more pharmacologic activities similar to bepridil hydrochloride, including anti-arrhythmic agents such as quinidine and procainamide, cardiac glycosides and tricyclic anti-depressants. Anti-arrhythmics and tricyclic anti-depressants could exaggerate the prolongation of the QT interval observed with bepridil hydrochloride. Cardiac glycosides could exaggerate the depression of AV nodal conduction observed with bepridil hydrochloride." ], "offsets": [ [ 0, 2038 ] ] } ]

[ { "id": "Bepridil_ddi_T1", "type": "GROUP", "text": [ "Nitrates" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T2", "type": "DRUG", "text": [ "Bepridil" ], "offsets": [ [ 33, 41 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T3", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 70, 78 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T4", "type": "DRUG", "text": [ "nitroglycerin" ], "offsets": [ [ 157, 170 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T5", "type": "DRUG", "text": [ "Bepridil" ], "offsets": [ [ 244, 252 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T6", "type": "GROUP", "text": [ "Beta-blocking Agents" ], "offsets": [ [ 262, 282 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T7", "type": "DRUG", "text": [ "Bepridil" ], "offsets": [ [ 307, 315 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T8", "type": "GROUP", "text": [ "beta-blocking agents" ], "offsets": [ [ 320, 340 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T9", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 574, 581 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T10", "type": "DRUG", "text": [ "bepridil hydrochloride" ], "offsets": [ [ 628, 650 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T11", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 771, 778 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T12", "type": "DRUG", "text": [ "bepridil hydrochloride" ], "offsets": [ [ 858, 880 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T13", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 885, 892 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T14", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1036, 1043 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T15", "type": "GROUP", "text": [ "Hypoglycemics" ], "offsets": [ [ 1236, 1249 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T16", "type": "DRUG", "text": [ "Bepridil" ], "offsets": [ [ 1251, 1259 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T17", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 1387, 1394 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T18", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 1403, 1422 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T19", "type": "DRUG", "text": [ "bepridil hydrochloride" ], "offsets": [ [ 1534, 1556 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T20", "type": "DRUG", "text": [ "bepridil hydrochloride" ], "offsets": [ [ 1644, 1666 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T21", "type": "GROUP", "text": [ "anti-arrhythmic agents" ], "offsets": [ [ 1678, 1700 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T22", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1709, 1718 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T23", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 1723, 1735 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T24", "type": "GROUP", "text": [ "cardiac glycosides" ], "offsets": [ [ 1737, 1755 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T25", "type": "GROUP", "text": [ "tricyclic anti-depressants" ], "offsets": [ [ 1760, 1786 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T26", "type": "GROUP", "text": [ "Anti-arrhythmics" ], "offsets": [ [ 1788, 1804 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T27", "type": "GROUP", "text": [ "tricyclic anti-depressants" ], "offsets": [ [ 1809, 1835 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T28", "type": "DRUG", "text": [ "bepridil hydrochloride" ], "offsets": [ [ 1903, 1925 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T29", "type": "GROUP", "text": [ "Cardiac glycosides" ], "offsets": [ [ 1927, 1945 ] ], "normalized": [] }, { "id": "Bepridil_ddi_T30", "type": "DRUG", "text": [ "bepridil hydrochloride" ], "offsets": [ [ 2015, 2037 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Bepridil_ddi_R1", "type": "MECHANISM", "arg1_id": "Bepridil_ddi_T10", "arg2_id": "Bepridil_ddi_T11", "normalized": [] }, { "id": "Bepridil_ddi_R2", "type": "EFFECT", "arg1_id": "Bepridil_ddi_T26", "arg2_id": "Bepridil_ddi_T28", "normalized": [] }, { "id": "Bepridil_ddi_R3", "type": "EFFECT", "arg1_id": "Bepridil_ddi_T27", "arg2_id": "Bepridil_ddi_T28", "normalized": [] }, { "id": "Bepridil_ddi_R4", "type": "EFFECT", "arg1_id": "Bepridil_ddi_T29", "arg2_id": "Bepridil_ddi_T30", "normalized": [] } ]

[ { "id": "Esmolol_ddi__text", "type": "abstract", "text": [ "Catecholamine-depleting drugs, e.g., reserpine, may have an additive effect when given with beta blocking agents. Patients treated concurrently with BREVIBLOC (esmolol HCl) and a catecholamine depletor should therefore be closely observed for evidence of hypotension or marked bradycardia, which may result in vertigo, syncope, or postural hypotension. A study of interaction between BREVIBLOC and warfarin showed that concomitant administration of BREVIBLOC and warfarin does not alter warfarin plasma levels. BREVIBLOC concentrations were equivocally higher when given with warfarin, but this is not likely to be clinically important. When digoxin and BREVIBLOC were concomitantly administered intravenously to normal volunteers, there was a 10-20% increase in digoxin blood levels at some time points. Digoxin did not affect BREVIBLOC pharmacokinetics. When intravenous morphine and BREVIBLOC were concomitantly administered in normal subjects, no effect on morphine blood levels was seen, but BREVIBLOC steady-state blood levels were increased by 46% in the presence of morphine. No other pharmacokinetic parameters were changed. The effect of BREVIBLOC on the duration of succinylcholine-induced neuromuscular blockade was studied in patients undergoing surgery. The onset of neuromuscular blockade by succinylcholine was unaffected by BREVIBLOC, but the duration of neuromuscular blockade was prolonged from 5 minutes to 8 minutes. Although the interactions observed in these studies do not appear to be of major clinical importance, BREVIBLOC should be titrated with caution in patients being treated concurrently with digoxin, morphine, succinylcholine or warfarin. While taking beta blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. Caution should be exercised when considering the use of BREVIBLOC and verapamil in patients with depressed myocardial function. Fatal cardiac arrests have occurred in patients receiving both drugs. Additionally, BREVIBLOC should not be used to control supraventricular tachycardia in the presence of agents which are vasoconstrictive and inotropic such as dopamine, epinephrine, and norepinephrine because of the danger of blocking cardiac contractility when systemic vascular resistance is high." ], "offsets": [ [ 0, 2472 ] ] } ]

[ { "id": "Esmolol_ddi_T1", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 37, 46 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T2", "type": "GROUP", "text": [ "beta blocking agents" ], "offsets": [ [ 92, 112 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T3", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 149, 158 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T4", "type": "DRUG", "text": [ "esmolol HCl" ], "offsets": [ [ 160, 171 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T5", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 384, 393 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T6", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 398, 406 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T7", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 449, 458 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T8", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 463, 471 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T9", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 487, 495 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T10", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 511, 520 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T11", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 576, 584 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T12", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 642, 649 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T13", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 654, 663 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T14", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 763, 770 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T15", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 805, 812 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T16", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 828, 837 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T17", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 873, 881 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T18", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 886, 895 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T19", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 961, 969 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T20", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 997, 1006 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T21", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 1074, 1082 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T22", "type": "DRUG", "text": [ "BREVIBLOC" ], "offsets": [ [ 1148, 1157 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T23", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 1177, 1192 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T24", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 1307, 1322 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T25", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 1341, 1350 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T26", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 1540, 1549 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T27", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1626, 1633 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T28", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 1635, 1643 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T29", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 1645, 1660 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T30", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1664, 1672 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T31", "type": "GROUP", "text": [ "beta blockers" ], "offsets": [ [ 1687, 1700 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T32", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 1931, 1942 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T33", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 2032, 2041 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T34", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 2046, 2055 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T35", "type": "BRAND", "text": [ "BREVIBLOC" ], "offsets": [ [ 2188, 2197 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T36", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 2332, 2340 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T37", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 2342, 2353 ] ], "normalized": [] }, { "id": "Esmolol_ddi_T38", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 2359, 2373 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Esmolol_ddi_R1", "type": "EFFECT", "arg1_id": "Esmolol_ddi_T1", "arg2_id": "Esmolol_ddi_T2", "normalized": [] }, { "id": "Esmolol_ddi_R2", "type": "MECHANISM", "arg1_id": "Esmolol_ddi_T10", "arg2_id": "Esmolol_ddi_T11", "normalized": [] }, { "id": "Esmolol_ddi_R3", "type": "MECHANISM", "arg1_id": "Esmolol_ddi_T12", "arg2_id": "Esmolol_ddi_T13", "normalized": [] }, { "id": "Esmolol_ddi_R4", "type": "MECHANISM", "arg1_id": "Esmolol_ddi_T20", "arg2_id": "Esmolol_ddi_T21", "normalized": [] }, { "id": "Esmolol_ddi_R5", "type": "EFFECT", "arg1_id": "Esmolol_ddi_T24", "arg2_id": "Esmolol_ddi_T25", "normalized": [] }, { "id": "Esmolol_ddi_R6", "type": "ADVISE", "arg1_id": "Esmolol_ddi_T26", "arg2_id": "Esmolol_ddi_T27", "normalized": [] }, { "id": "Esmolol_ddi_R7", "type": "ADVISE", "arg1_id": "Esmolol_ddi_T26", "arg2_id": "Esmolol_ddi_T28", "normalized": [] }, { "id": "Esmolol_ddi_R8", "type": "ADVISE", "arg1_id": "Esmolol_ddi_T26", "arg2_id": "Esmolol_ddi_T29", "normalized": [] }, { "id": "Esmolol_ddi_R9", "type": "ADVISE", "arg1_id": "Esmolol_ddi_T26", "arg2_id": "Esmolol_ddi_T30", "normalized": [] }, { "id": "Esmolol_ddi_R10", "type": "ADVISE", "arg1_id": "Esmolol_ddi_T33", "arg2_id": "Esmolol_ddi_T34", "normalized": [] }, { "id": "Esmolol_ddi_R11", "type": "ADVISE", "arg1_id": "Esmolol_ddi_T35", "arg2_id": "Esmolol_ddi_T36", "normalized": [] }, { "id": "Esmolol_ddi_R12", "type": "ADVISE", "arg1_id": "Esmolol_ddi_T35", "arg2_id": "Esmolol_ddi_T37", "normalized": [] }, { "id": "Esmolol_ddi_R13", "type": "ADVISE", "arg1_id": "Esmolol_ddi_T35", "arg2_id": "Esmolol_ddi_T38", "normalized": [] } ]

[ { "id": "Etonogestrel_ddi__text", "type": "abstract", "text": [ "Etonogestrel may interact with the following medications: acetaminophen (Tylenol), antibiotics such as ampicillin and tetracycline, anticonvulsants (Dilantin, Phenobarbital, Tegretol, Trileptal, Topamax, Felbatol), antifungals (Gris-PEG, Nizoral, Sporanox), atorvastatin (Lipitor), clofibrate (Atromid-S), cyclosporine (Neoral, Sandimmune), HIV drugs classified as protease inhibitors (Agenerase, Crixivan, Fortovase, Invirase, Kaletra, Norvir, Viracept), morphine (Astramorph, Kadian, MS Contin), phenylbutazone, prednisolone (Prelone), rifadin (rifampin), St. Johns wort, temazepam, theophylline (Theo-Dur), and vitamin C." ], "offsets": [ [ 0, 624 ] ] } ]

[ { "id": "Etonogestrel_ddi_T1", "type": "DRUG", "text": [ "Etonogestrel" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T2", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 58, 71 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T3", "type": "BRAND", "text": [ "Tylenol" ], "offsets": [ [ 73, 80 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T4", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 83, 94 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T5", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 103, 113 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T6", "type": "DRUG", "text": [ "tetracycline" ], "offsets": [ [ 118, 130 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T7", "type": "GROUP", "text": [ "anticonvulsants" ], "offsets": [ [ 132, 147 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T8", "type": "BRAND", "text": [ "Dilantin" ], "offsets": [ [ 149, 157 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T9", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 159, 172 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T10", "type": "BRAND", "text": [ "Tegretol" ], "offsets": [ [ 174, 182 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T11", "type": "BRAND", "text": [ "Trileptal" ], "offsets": [ [ 184, 193 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T12", "type": "BRAND", "text": [ "Topamax" ], "offsets": [ [ 195, 202 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T13", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 204, 212 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T14", "type": "GROUP", "text": [ "antifungals" ], "offsets": [ [ 215, 226 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T15", "type": "BRAND", "text": [ "Gris-PEG" ], "offsets": [ [ 228, 236 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T16", "type": "BRAND", "text": [ "Nizoral" ], "offsets": [ [ 238, 245 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T17", "type": "BRAND", "text": [ "Sporanox" ], "offsets": [ [ 247, 255 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T18", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 258, 270 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T19", "type": "BRAND", "text": [ "Lipitor" ], "offsets": [ [ 272, 279 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T20", "type": "DRUG", "text": [ "clofibrate" ], "offsets": [ [ 282, 292 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T21", "type": "BRAND", "text": [ "Atromid-S" ], "offsets": [ [ 294, 303 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T22", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 306, 318 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T23", "type": "BRAND", "text": [ "Neoral" ], "offsets": [ [ 320, 326 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T24", "type": "BRAND", "text": [ "Sandimmune" ], "offsets": [ [ 328, 338 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T25", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 365, 384 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T26", "type": "BRAND", "text": [ "Agenerase" ], "offsets": [ [ 386, 395 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T27", "type": "BRAND", "text": [ "Crixivan" ], "offsets": [ [ 397, 405 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T28", "type": "BRAND", "text": [ "Fortovase" ], "offsets": [ [ 407, 416 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T29", "type": "BRAND", "text": [ "Invirase" ], "offsets": [ [ 418, 426 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T30", "type": "BRAND", "text": [ "Kaletra" ], "offsets": [ [ 428, 435 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T31", "type": "BRAND", "text": [ "Norvir" ], "offsets": [ [ 437, 443 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T32", "type": "BRAND", "text": [ "Viracept" ], "offsets": [ [ 445, 453 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T33", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 456, 464 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T34", "type": "BRAND", "text": [ "Astramorph" ], "offsets": [ [ 466, 476 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T35", "type": "BRAND", "text": [ "Kadian" ], "offsets": [ [ 478, 484 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T36", "type": "BRAND", "text": [ "MS Contin" ], "offsets": [ [ 486, 495 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T37", "type": "DRUG", "text": [ "phenylbutazone" ], "offsets": [ [ 498, 512 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T38", "type": "DRUG", "text": [ "prednisolone" ], "offsets": [ [ 514, 526 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T39", "type": "BRAND", "text": [ "Prelone" ], "offsets": [ [ 528, 535 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T40", "type": "BRAND", "text": [ "rifadin" ], "offsets": [ [ 538, 545 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T41", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 547, 555 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T42", "type": "DRUG", "text": [ "temazepam" ], "offsets": [ [ 574, 583 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T43", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 585, 597 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T44", "type": "BRAND", "text": [ "Theo-Dur" ], "offsets": [ [ 599, 607 ] ], "normalized": [] }, { "id": "Etonogestrel_ddi_T45", "type": "DRUG", "text": [ "vitamin C" ], "offsets": [ [ 614, 623 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Etonogestrel_ddi_R1", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T2", "normalized": [] }, { "id": "Etonogestrel_ddi_R2", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T3", "normalized": [] }, { "id": "Etonogestrel_ddi_R3", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T4", "normalized": [] }, { "id": "Etonogestrel_ddi_R4", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T5", "normalized": [] }, { "id": "Etonogestrel_ddi_R5", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T6", "normalized": [] }, { "id": "Etonogestrel_ddi_R6", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T7", "normalized": [] }, { "id": "Etonogestrel_ddi_R7", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T8", "normalized": [] }, { "id": "Etonogestrel_ddi_R8", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T9", "normalized": [] }, { "id": "Etonogestrel_ddi_R9", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T10", "normalized": [] }, { "id": "Etonogestrel_ddi_R10", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T11", "normalized": [] }, { "id": "Etonogestrel_ddi_R11", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T12", "normalized": [] }, { "id": "Etonogestrel_ddi_R12", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T13", "normalized": [] }, { "id": "Etonogestrel_ddi_R13", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T14", "normalized": [] }, { "id": "Etonogestrel_ddi_R14", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T15", "normalized": [] }, { "id": "Etonogestrel_ddi_R15", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T16", "normalized": [] }, { "id": "Etonogestrel_ddi_R16", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T17", "normalized": [] }, { "id": "Etonogestrel_ddi_R17", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T18", "normalized": [] }, { "id": "Etonogestrel_ddi_R18", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T19", "normalized": [] }, { "id": "Etonogestrel_ddi_R19", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T20", "normalized": [] }, { "id": "Etonogestrel_ddi_R20", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T21", "normalized": [] }, { "id": "Etonogestrel_ddi_R21", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T22", "normalized": [] }, { "id": "Etonogestrel_ddi_R22", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T23", "normalized": [] }, { "id": "Etonogestrel_ddi_R23", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T24", "normalized": [] }, { "id": "Etonogestrel_ddi_R24", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T25", "normalized": [] }, { "id": "Etonogestrel_ddi_R25", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T26", "normalized": [] }, { "id": "Etonogestrel_ddi_R26", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T27", "normalized": [] }, { "id": "Etonogestrel_ddi_R27", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T28", "normalized": [] }, { "id": "Etonogestrel_ddi_R28", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T29", "normalized": [] }, { "id": "Etonogestrel_ddi_R29", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T30", "normalized": [] }, { "id": "Etonogestrel_ddi_R30", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T31", "normalized": [] }, { "id": "Etonogestrel_ddi_R31", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T32", "normalized": [] }, { "id": "Etonogestrel_ddi_R32", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T33", "normalized": [] }, { "id": "Etonogestrel_ddi_R33", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T34", "normalized": [] }, { "id": "Etonogestrel_ddi_R34", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T35", "normalized": [] }, { "id": "Etonogestrel_ddi_R35", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T36", "normalized": [] }, { "id": "Etonogestrel_ddi_R36", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T37", "normalized": [] }, { "id": "Etonogestrel_ddi_R37", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T38", "normalized": [] }, { "id": "Etonogestrel_ddi_R38", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T39", "normalized": [] }, { "id": "Etonogestrel_ddi_R39", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T40", "normalized": [] }, { "id": "Etonogestrel_ddi_R40", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T41", "normalized": [] }, { "id": "Etonogestrel_ddi_R41", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T42", "normalized": [] }, { "id": "Etonogestrel_ddi_R42", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T43", "normalized": [] }, { "id": "Etonogestrel_ddi_R43", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T44", "normalized": [] }, { "id": "Etonogestrel_ddi_R44", "type": "INT", "arg1_id": "Etonogestrel_ddi_T1", "arg2_id": "Etonogestrel_ddi_T45", "normalized": [] } ]

[ { "id": "Piperazine_ddi__text", "type": "abstract", "text": [ "Phenothiazines - Taking piperazine and a phenothiazine together may increase the risk of convulsions (seizures). Pyrantel (e.g., Antiminth) - Taking piperazine and pyrantel together may decrease the effects of piperazine." ], "offsets": [ [ 0, 221 ] ] } ]

[ { "id": "Piperazine_ddi_T1", "type": "GROUP", "text": [ "Phenothiazines" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "Piperazine_ddi_T2", "type": "DRUG", "text": [ "piperazine" ], "offsets": [ [ 24, 34 ] ], "normalized": [] }, { "id": "Piperazine_ddi_T3", "type": "GROUP", "text": [ "phenothiazine" ], "offsets": [ [ 41, 54 ] ], "normalized": [] }, { "id": "Piperazine_ddi_T4", "type": "DRUG", "text": [ "Pyrantel" ], "offsets": [ [ 113, 121 ] ], "normalized": [] }, { "id": "Piperazine_ddi_T5", "type": "DRUG", "text": [ "Antiminth" ], "offsets": [ [ 129, 138 ] ], "normalized": [] }, { "id": "Piperazine_ddi_T6", "type": "DRUG", "text": [ "piperazine" ], "offsets": [ [ 149, 159 ] ], "normalized": [] }, { "id": "Piperazine_ddi_T7", "type": "DRUG", "text": [ "pyrantel" ], "offsets": [ [ 164, 172 ] ], "normalized": [] }, { "id": "Piperazine_ddi_T8", "type": "DRUG", "text": [ "piperazine" ], "offsets": [ [ 210, 220 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Piperazine_ddi_R1", "type": "EFFECT", "arg1_id": "Piperazine_ddi_T2", "arg2_id": "Piperazine_ddi_T3", "normalized": [] }, { "id": "Piperazine_ddi_R2", "type": "EFFECT", "arg1_id": "Piperazine_ddi_T6", "arg2_id": "Piperazine_ddi_T7", "normalized": [] } ]

[ { "id": "Alosetron_ddi__text", "type": "abstract", "text": [ "Because alosetron is metabolized by a variety of hepatic CYP drug-metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance of alosetron. Fluvoxamine is a known strong inhibitor of CYP1A2 and also inhibits CYP3A4, CYP2C9, and CYP2C19. In a pharmacokinetic study, 40 healthy female subjects received fluvoxamine in escalating doses from 50 to 200 mg per day for 16 days, with coadministration of alosetron 1 mg on the last day. Fluvoxamine increased mean alosetron plasma concentrations (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold. Concomitant administration of alosetron and fluvoxamine is contraindicated. Concomitant administration of alosetron and moderate CYP1A2 inhibitors, including quinolone antibiotics and cimetidine, has not been evaluated, but should be avoided unless clinically necessary because of similar potential drug interactions. Ketoconazole is a known strong inhibitor of CYP3A4. In a pharmacokinetic study, 38 healthy female subjects received ketoconazole 200 mg twice daily for 7 days, with coadministration of alosetron 1 mg on the last day. Ketoconazole increased mean alosetron plasma concentrations (AUC) by 29%. Caution should be used when alosetron and ketoconazole are administered concomitantly. Coadministration of alosetron and strong CYP3A4 inhibitors, such as clarithromycin, telithromycin, protease inhibitors, voriconazole, and itraconazole has not been evaluated but should be undertaken with caution because of similar potential drug interactions. The effect of induction or inhibition of other pathways on exposure to alosetron and its metabolites is not known. In vitro human liver microsome studies and an in vivo metabolic probe study demonstrated that alosetron did not inhibit CYP enzymes 2D6, 3A4, 2C9, or 2C19. In vitro, at total drug concentrations 27-fold higher than peak plasma concentrations observed with the 1-mg dosage, alosetron inhibited CYP enzymes 1A2 (60%) and 2E1 (50%). In an in vivo metabolic probe study, alosetron did not inhibit CYP2E1 but did produce 30% inhibition of both CYP1A2 and N-acetyltransferase. Although not studied with alosetron, inhibition of N-acetyltransferase may have clinically relevant consequences for drugs such as isoniazid, procainamide, and hydralazine. The effect on CYP1A2 was explored further in a clinical interaction study with theophylline and no effect on metabolism was observed. Another study showed that alosetron had no clinically significant effect on plasma concentrations of the oral contraceptive agents ethinyl estradiol and levonorgestrel (CYP3A4 substrates). A clinical interaction study was also conducted with alosetron and the CYP3A4 substrate cisapride. No significant effects on cisapride metabolism or QT interval were noted. The effect of alosetron on monoamine oxidases and on intestinal first pass secondary to high intraluminal concentrations have not been examined. Based on the above data from in vitro and in vivo studies, it is unlikely that alosetron will inhibit the hepatic metabolic clearance of drugs metabolized by the major CYP enzyme 3A4, as well as the CYP enzymes 2D6, 2C9, 2C19, 2E1, or 1A2. Alosetron does not appear to induce the major cytochrome P450 (CYP) drug metabolizing enzyme 3A. Alosetron also does not appear to induce CYP enzymes 2E1 or 2C19. It is not known whether alosetron might induce other enzymes." ], "offsets": [ [ 0, 3415 ] ] } ]

[ { "id": "Alosetron_ddi_T1", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 8, 17 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T2", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 156, 165 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T3", "type": "DRUG", "text": [ "Fluvoxamine" ], "offsets": [ [ 167, 178 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T4", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 328, 339 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T5", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 424, 433 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T6", "type": "DRUG", "text": [ "Fluvoxamine" ], "offsets": [ [ 456, 467 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T7", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 483, 492 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T8", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 625, 634 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T9", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 639, 650 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T10", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 701, 710 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T11", "type": "GROUP", "text": [ "quinolone antibiotics" ], "offsets": [ [ 753, 774 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T12", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 779, 789 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T13", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 913, 925 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T14", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1029, 1041 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T15", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 1098, 1107 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T16", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 1130, 1142 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T17", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 1158, 1167 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T18", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 1232, 1241 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T19", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1246, 1258 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T20", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 1311, 1320 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T21", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 1359, 1373 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T22", "type": "DRUG", "text": [ "telithromycin" ], "offsets": [ [ 1375, 1388 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T23", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 1390, 1409 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T24", "type": "DRUG", "text": [ "voriconazole" ], "offsets": [ [ 1411, 1423 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T25", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1429, 1441 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T26", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 1622, 1631 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T27", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 1760, 1769 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T28", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 1939, 1948 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T29", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 2033, 2042 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T30", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 2163, 2172 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T31", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 2268, 2277 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T32", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 2279, 2291 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T33", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 2297, 2308 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T34", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2389, 2401 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T35", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 2470, 2479 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T36", "type": "GROUP", "text": [ "contraceptive agents" ], "offsets": [ [ 2554, 2574 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T37", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 2575, 2592 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T38", "type": "DRUG", "text": [ "levonorgestrel" ], "offsets": [ [ 2597, 2611 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T39", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 2686, 2695 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T40", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 2721, 2730 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T41", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 2758, 2767 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T42", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 2820, 2829 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T43", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 3030, 3039 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T44", "type": "DRUG", "text": [ "Alosetron" ], "offsets": [ [ 3191, 3200 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T45", "type": "DRUG", "text": [ "Alosetron" ], "offsets": [ [ 3288, 3297 ] ], "normalized": [] }, { "id": "Alosetron_ddi_T46", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 3378, 3387 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Alosetron_ddi_R1", "type": "MECHANISM", "arg1_id": "Alosetron_ddi_T6", "arg2_id": "Alosetron_ddi_T7", "normalized": [] }, { "id": "Alosetron_ddi_R2", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T8", "arg2_id": "Alosetron_ddi_T9", "normalized": [] }, { "id": "Alosetron_ddi_R3", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T10", "arg2_id": "Alosetron_ddi_T11", "normalized": [] }, { "id": "Alosetron_ddi_R4", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T10", "arg2_id": "Alosetron_ddi_T12", "normalized": [] }, { "id": "Alosetron_ddi_R5", "type": "MECHANISM", "arg1_id": "Alosetron_ddi_T16", "arg2_id": "Alosetron_ddi_T17", "normalized": [] }, { "id": "Alosetron_ddi_R6", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T18", "arg2_id": "Alosetron_ddi_T19", "normalized": [] }, { "id": "Alosetron_ddi_R7", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T20", "arg2_id": "Alosetron_ddi_T21", "normalized": [] }, { "id": "Alosetron_ddi_R8", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T20", "arg2_id": "Alosetron_ddi_T22", "normalized": [] }, { "id": "Alosetron_ddi_R9", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T20", "arg2_id": "Alosetron_ddi_T23", "normalized": [] }, { "id": "Alosetron_ddi_R10", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T20", "arg2_id": "Alosetron_ddi_T24", "normalized": [] }, { "id": "Alosetron_ddi_R11", "type": "ADVISE", "arg1_id": "Alosetron_ddi_T20", "arg2_id": "Alosetron_ddi_T25", "normalized": [] }, { "id": "Alosetron_ddi_R12", "type": "EFFECT", "arg1_id": "Alosetron_ddi_T30", "arg2_id": "Alosetron_ddi_T31", "normalized": [] }, { "id": "Alosetron_ddi_R13", "type": "EFFECT", "arg1_id": "Alosetron_ddi_T30", "arg2_id": "Alosetron_ddi_T32", "normalized": [] }, { "id": "Alosetron_ddi_R14", "type": "EFFECT", "arg1_id": "Alosetron_ddi_T30", "arg2_id": "Alosetron_ddi_T33", "normalized": [] } ]

[ { "id": "Cinacalcet_ddi__text", "type": "abstract", "text": [ "and/or Drug/Laboratory Test Interactions See CLINICAL PHARMACOLOGY, Pharmacokinetics and Drug Interactions. Effect of Sensipar on other drugs: Drugs metabolized by cytochrome P450 2D6 (CYP2D6): Sensipar is a strong in vitro inhibitor of CYP2D6. Therefore, dose adjustments of concomitant medications that are predominantly metabolized by CYP2D6 and have a narrow therapeutic index (e.g., flecainide, vinblastine, thioridazine and most tricyclic antidepressants) may be required. Amitriptyline: Concurrent administration of 25 mg or 100 mg cinacalcet with 50 mg amitriptyline increased amitriptyline exposure and nortriptyline (active metabolite) exposure by approximately 20% in CYP2D6 extensive metabolizers. Effect of other drugs on Sensipar : Sensipar is metabolized by multiple cytochrome P450 enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. Ketoconazole: Sensipar is metabolized in part by CYP3A4. Co-administration of ketoconazole, a strong inhibitor of CYP3A4, increased cinacalcet exposure following a single 90 mg dose of Sensipar by 2.3 fold. Dose adjustment of Sensipar may be required and PTH and serum calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g., ketoconazole, erythromycin, itraconazole; see DOSAGE AND ADMINISTRATION)." ], "offsets": [ [ 0, 1325 ] ] } ]

[ { "id": "Cinacalcet_ddi_T1", "type": "BRAND", "text": [ "Sensipar" ], "offsets": [ [ 118, 126 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T2", "type": "BRAND", "text": [ "Sensipar" ], "offsets": [ [ 194, 202 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T3", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 389, 399 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T4", "type": "DRUG", "text": [ "vinblastine" ], "offsets": [ [ 401, 412 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T5", "type": "DRUG", "text": [ "thioridazine" ], "offsets": [ [ 414, 426 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T6", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 436, 461 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T7", "type": "DRUG", "text": [ "Amitriptyline" ], "offsets": [ [ 480, 493 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T8", "type": "DRUG", "text": [ "cinacalcet" ], "offsets": [ [ 540, 550 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T9", "type": "DRUG", "text": [ "amitriptyline" ], "offsets": [ [ 562, 575 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T10", "type": "DRUG", "text": [ "amitriptyline" ], "offsets": [ [ 586, 599 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T11", "type": "DRUG_N", "text": [ "nortriptyline" ], "offsets": [ [ 613, 626 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T12", "type": "BRAND", "text": [ "Sensipar" ], "offsets": [ [ 736, 744 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T13", "type": "BRAND", "text": [ "Sensipar" ], "offsets": [ [ 747, 755 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T14", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 847, 859 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T15", "type": "BRAND", "text": [ "Sensipar" ], "offsets": [ [ 861, 869 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T16", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 925, 937 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T17", "type": "DRUG", "text": [ "cinacalcet" ], "offsets": [ [ 979, 989 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T18", "type": "BRAND", "text": [ "Sensipar" ], "offsets": [ [ 1032, 1040 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T19", "type": "BRAND", "text": [ "Sensipar" ], "offsets": [ [ 1073, 1081 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T20", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1252, 1264 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T21", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1266, 1278 ] ], "normalized": [] }, { "id": "Cinacalcet_ddi_T22", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1280, 1292 ] ], "normalized": [] } ]

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[ { "id": "Cinacalcet_ddi_R1", "type": "MECHANISM", "arg1_id": "Cinacalcet_ddi_T8", "arg2_id": "Cinacalcet_ddi_T9", "normalized": [] }, { "id": "Cinacalcet_ddi_R2", "type": "MECHANISM", "arg1_id": "Cinacalcet_ddi_T16", "arg2_id": "Cinacalcet_ddi_T17", "normalized": [] }, { "id": "Cinacalcet_ddi_R3", "type": "ADVISE", "arg1_id": "Cinacalcet_ddi_T19", "arg2_id": "Cinacalcet_ddi_T20", "normalized": [] }, { "id": "Cinacalcet_ddi_R4", "type": "ADVISE", "arg1_id": "Cinacalcet_ddi_T19", "arg2_id": "Cinacalcet_ddi_T21", "normalized": [] }, { "id": "Cinacalcet_ddi_R5", "type": "ADVISE", "arg1_id": "Cinacalcet_ddi_T19", "arg2_id": "Cinacalcet_ddi_T22", "normalized": [] } ]

[ { "id": "Interferon beta-1a_ddi__text", "type": "abstract", "text": [ "No formal drug interaction studies have been conducted with Rebif . Due to its potential to cause neutropenia and lymphopenia, proper monitoring of patients is required if Rebif is given in combination with myelosuppressive agents. Also, the potential for hepatic injury should be considered when Rebif is used in combination with other products associated with hepatic injury, or when new agents are added to the regimen of patients already on Rebif ." ], "offsets": [ [ 0, 454 ] ] } ]

[ { "id": "Interferon beta-1a_ddi_T1", "type": "BRAND", "text": [ "Rebif" ], "offsets": [ [ 60, 65 ] ], "normalized": [] }, { "id": "Interferon beta-1a_ddi_T2", "type": "BRAND", "text": [ "Rebif" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "Interferon beta-1a_ddi_T3", "type": "BRAND", "text": [ "Rebif" ], "offsets": [ [ 298, 303 ] ], "normalized": [] }, { "id": "Interferon beta-1a_ddi_T4", "type": "BRAND", "text": [ "Rebif" ], "offsets": [ [ 447, 452 ] ], "normalized": [] } ]

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[ { "id": "Latanoprost_ddi__text", "type": "abstract", "text": [ "In vitro studies have shown that precipitation occurs when eye drops containing thimerosal are mixed with latanoprost. If such drugs are used they should be administered with an interval of at least 5 minutes between applications." ], "offsets": [ [ 0, 230 ] ] } ]

[ { "id": "Latanoprost_ddi_T1", "type": "DRUG_N", "text": [ "thimerosal" ], "offsets": [ [ 80, 90 ] ], "normalized": [] }, { "id": "Latanoprost_ddi_T2", "type": "DRUG", "text": [ "latanoprost" ], "offsets": [ [ 106, 117 ] ], "normalized": [] } ]

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[ { "id": "Codeine_ddi__text", "type": "abstract", "text": [ "Codeine in combination with other narcotic analgesics, general anesthetics, phenothiazines, tranquilizers, sedative-hypnotics, or other CNS depressants (including alcohol) has additive depressant effects. When s.c. combination therapy is contemplated, the dosage of one or both agents should be reduced." ], "offsets": [ [ 0, 303 ] ] } ]

[ { "id": "Codeine_ddi_T1", "type": "DRUG", "text": [ "Codeine" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Codeine_ddi_T2", "type": "GROUP", "text": [ "narcotic analgesics" ], "offsets": [ [ 34, 53 ] ], "normalized": [] }, { "id": "Codeine_ddi_T3", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 63, 74 ] ], "normalized": [] }, { "id": "Codeine_ddi_T4", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 76, 90 ] ], "normalized": [] }, { "id": "Codeine_ddi_T5", "type": "GROUP", "text": [ "tranquilizers" ], "offsets": [ [ 92, 105 ] ], "normalized": [] }, { "id": "Codeine_ddi_T6", "type": "GROUP", "text": [ "sedative-hypnotics" ], "offsets": [ [ 107, 125 ] ], "normalized": [] }, { "id": "Codeine_ddi_T7", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 136, 151 ] ], "normalized": [] }, { "id": "Codeine_ddi_T8", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 163, 170 ] ], "normalized": [] } ]

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[ { "id": "Codeine_ddi_R1", "type": "EFFECT", "arg1_id": "Codeine_ddi_T1", "arg2_id": "Codeine_ddi_T2", "normalized": [] }, { "id": "Codeine_ddi_R2", "type": "EFFECT", "arg1_id": "Codeine_ddi_T1", "arg2_id": "Codeine_ddi_T3", "normalized": [] }, { "id": "Codeine_ddi_R3", "type": "EFFECT", "arg1_id": "Codeine_ddi_T1", "arg2_id": "Codeine_ddi_T4", "normalized": [] }, { "id": "Codeine_ddi_R4", "type": "EFFECT", "arg1_id": "Codeine_ddi_T1", "arg2_id": "Codeine_ddi_T5", "normalized": [] }, { "id": "Codeine_ddi_R5", "type": "EFFECT", "arg1_id": "Codeine_ddi_T1", "arg2_id": "Codeine_ddi_T6", "normalized": [] }, { "id": "Codeine_ddi_R6", "type": "EFFECT", "arg1_id": "Codeine_ddi_T1", "arg2_id": "Codeine_ddi_T7", "normalized": [] }, { "id": "Codeine_ddi_R7", "type": "EFFECT", "arg1_id": "Codeine_ddi_T1", "arg2_id": "Codeine_ddi_T8", "normalized": [] } ]