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[ { "id": "Insulin recombinant_ddi__text", "type": "abstract", "text": [ "A number of substances affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring. The following are examples of substances that may increase the blood-glucose-lowering effect and susceptibility to hypoglycemia: oral antidiabetic products, ACE inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, propoxyphene, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics. The following are examples of substances that may reduce the blood-glucose-lowering effect: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, salbutamol, terbutaline), isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives). Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine, and reserpine, the signs of hypoglycemia may be reduced or absent. Mixing of Insulins A clinical study in healthy male volunteers (n=24) demonstrated that mixing NovoLog with NPH human insulin immediately before injection produced some attenuation in the peak concentration of NovoLog, but that the time to peak and the total bioavailability of NovoLog were not significantly affected. If NovoLog is mixed with NPH human insulin, NovoLog should be drawn into the syringe first. The injection should be made immediately after mixing. Because there are no data on the compatibility of NovoLog and crystalline zinc insulin preparations, NovoLog should not be mixed with these preparations. The effects of mixing NovoLog with insulins of animal source or insulin preparations produced by other manufacturers have not been studied . Mixtures should not be administered intravenously. When used in external subcutaneous infusion pumps for insulin, NovoLog should not be mixed with any other insulins or diluent." ], "offsets": [ [ 0, 2130 ] ] } ]

[ { "id": "Insulin recombinant_ddi_T1", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 65, 72 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T2", "type": "GROUP", "text": [ "antidiabetic products" ], "offsets": [ [ 258, 279 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T3", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 281, 295 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T4", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 297, 309 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T5", "type": "GROUP", "text": [ "fibrates" ], "offsets": [ [ 311, 319 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T6", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 321, 331 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T7", "type": "GROUP", "text": [ "monoamine oxidase (MAO) inhibitors" ], "offsets": [ [ 333, 367 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T8", "type": "DRUG", "text": [ "propoxyphene" ], "offsets": [ [ 369, 381 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T9", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 383, 394 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T10", "type": "GROUP", "text": [ "somatostatin analog" ], "offsets": [ [ 396, 415 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T11", "type": "DRUG", "text": [ "octreotide" ], "offsets": [ [ 423, 433 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T12", "type": "GROUP", "text": [ "sulfonamide antibiotics" ], "offsets": [ [ 436, 459 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T13", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 553, 568 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T14", "type": "DRUG", "text": [ "niacin" ], "offsets": [ [ 570, 576 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T15", "type": "DRUG", "text": [ "danazol" ], "offsets": [ [ 578, 585 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T16", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 587, 596 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T17", "type": "GROUP", "text": [ "sympathomimetic agents" ], "offsets": [ [ 598, 620 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T18", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 628, 639 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T19", "type": "DRUG", "text": [ "salbutamol" ], "offsets": [ [ 641, 651 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T20", "type": "DRUG", "text": [ "terbutaline" ], "offsets": [ [ 653, 664 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T21", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 667, 676 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T22", "type": "GROUP", "text": [ "phenothiazine derivatives" ], "offsets": [ [ 678, 703 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T23", "type": "DRUG", "text": [ "somatropin" ], "offsets": [ [ 705, 715 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T24", "type": "GROUP", "text": [ "thyroid hormones" ], "offsets": [ [ 717, 733 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T25", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 735, 744 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T26", "type": "GROUP", "text": [ "progestogens" ], "offsets": [ [ 746, 758 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T27", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 774, 788 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T28", "type": "GROUP", "text": [ "Beta-blockers" ], "offsets": [ [ 791, 804 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T29", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 806, 815 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T30", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 817, 824 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T31", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 836, 843 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T32", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 913, 920 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T33", "type": "DRUG", "text": [ "Pentamidine" ], "offsets": [ [ 922, 933 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T34", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 1085, 1098 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T35", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 1100, 1109 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T36", "type": "DRUG", "text": [ "guanethidine" ], "offsets": [ [ 1111, 1123 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T37", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 1129, 1138 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T38", "type": "GROUP", "text": [ "Insulins" ], "offsets": [ [ 1202, 1210 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T39", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 1287, 1294 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T40", "type": "DRUG", "text": [ "NPH human insulin" ], "offsets": [ [ 1300, 1317 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T41", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 1402, 1409 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T42", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 1470, 1477 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T43", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 1514, 1521 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T44", "type": "DRUG", "text": [ "NPH human insulin" ], "offsets": [ [ 1536, 1553 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T45", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 1555, 1562 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T46", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 1708, 1715 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T47", "type": "DRUG", "text": [ "zinc insulin" ], "offsets": [ [ 1732, 1744 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T48", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 1759, 1766 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T49", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 1834, 1841 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T50", "type": "GROUP", "text": [ "insulins" ], "offsets": [ [ 1847, 1855 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T51", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 1876, 1883 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T52", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 2058, 2065 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T53", "type": "BRAND", "text": [ "NovoLog" ], "offsets": [ [ 2067, 2074 ] ], "normalized": [] }, { "id": "Insulin recombinant_ddi_T54", "type": "GROUP", "text": [ "insulins" ], "offsets": [ [ 2110, 2118 ] ], "normalized": [] } ]

[]

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[ { "id": "Insulin recombinant_ddi_R1", "type": "EFFECT", "arg1_id": "Insulin recombinant_ddi_T28", "arg2_id": "Insulin recombinant_ddi_T32", "normalized": [] }, { "id": "Insulin recombinant_ddi_R2", "type": "EFFECT", "arg1_id": "Insulin recombinant_ddi_T29", "arg2_id": "Insulin recombinant_ddi_T32", "normalized": [] }, { "id": "Insulin recombinant_ddi_R3", "type": "EFFECT", "arg1_id": "Insulin recombinant_ddi_T30", "arg2_id": "Insulin recombinant_ddi_T32", "normalized": [] }, { "id": "Insulin recombinant_ddi_R4", "type": "EFFECT", "arg1_id": "Insulin recombinant_ddi_T31", "arg2_id": "Insulin recombinant_ddi_T32", "normalized": [] } ]

[ { "id": "Candesartan_ddi__text", "type": "abstract", "text": [ "No significant drug interactions have been reported in studies of candesartan cilexetil given with other drugs such as glyburide, nifedipine, digoxin, warfarin, hydrochlorothiazide, and oral contraceptives in healthy volunteers, or given with enalapril to patients with heart failure (NYHA class II and III). Because candesartan is not significantly metabolized by the cytochrome P450 system and at therapeutic concentrations has no effects on P450 enzymes, interactions with drugs that inhibit or are metabolized by those enzymes would not be expected. Lithium Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors, and with some angiotensin II receptor antagonists. An increase in serum lithium concentration has been reported during concomitant administration of lithium with ATACAND, so careful monitoring of serum lithium levels is recommended during concomitant use." ], "offsets": [ [ 0, 968 ] ] } ]

[ { "id": "Candesartan_ddi_T1", "type": "DRUG", "text": [ "candesartan cilexetil" ], "offsets": [ [ 66, 87 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T2", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 119, 128 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T3", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 130, 140 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T4", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 142, 149 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T5", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 151, 159 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T6", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 161, 180 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T7", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 191, 205 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T8", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 243, 252 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T9", "type": "DRUG", "text": [ "candesartan" ], "offsets": [ [ 317, 328 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T10", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 554, 561 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T11", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 592, 599 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T12", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 684, 691 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T13", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 697, 711 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T14", "type": "GROUP", "text": [ "angiotensin II receptor antagonists" ], "offsets": [ [ 727, 762 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T15", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 785, 792 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T16", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 862, 869 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T17", "type": "BRAND", "text": [ "ATACAND" ], "offsets": [ [ 875, 882 ] ], "normalized": [] }, { "id": "Candesartan_ddi_T18", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 915, 922 ] ], "normalized": [] } ]

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[ { "id": "Candesartan_ddi_R1", "type": "MECHANISM", "arg1_id": "Candesartan_ddi_T12", "arg2_id": "Candesartan_ddi_T13", "normalized": [] }, { "id": "Candesartan_ddi_R2", "type": "MECHANISM", "arg1_id": "Candesartan_ddi_T12", "arg2_id": "Candesartan_ddi_T14", "normalized": [] }, { "id": "Candesartan_ddi_R3", "type": "MECHANISM", "arg1_id": "Candesartan_ddi_T16", "arg2_id": "Candesartan_ddi_T17", "normalized": [] } ]

[ { "id": "Indinavir_ddi__text", "type": "abstract", "text": [ "Indinavir is an inhibitor of the cytochrome P450 isoform CYP3A4. Coadministration of CRIXIVAN and drugs primarily metabolized by CYP3A4 may result in increased plasma concentrations of the other drug, which could increase or prolong its therapeutic and adverse effects. Indinavir is metabolized by CYP3A4. Drugs that induce CYP3A4 activity would be expected to increase the clearance of indinavir, resulting in lowered plasma concentrations of indinavir. Coadministration of CRIXIVAN and other drugs that inhibit CYP3A4 may decrease the clearance of indinavir and may result in increased plasma concentrations of indinavir. Table 8 Drugs That Should Not Be Coadministered with CRIXIVAN Drug Class: Drug Name Clinical Comment Antiarrhythmics: amiodarone CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Sedative/hypnotics: midazolam, triazolam CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. GI motility agents: cisapride CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. Neuroleptic: pimozide CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. Herbal products: St. John s wort (Hypericum perforatum) May lead to loss of virologic response and possible resistance to CRIXIVAN or to the class of protease inhibitors. Antimycobacterial: rifampin May lead to loss of virologic response and possible resistance to CRIXIVAN or to the class of protease inhibitors or other coadministered antiretroviral agents. HMG-CoA Reductase inhibitors: lovastatin, simvastatin Potential for serious reactions such as risk of myopathy including rhabdomyolysis. Protease inhibitor: atazanavir Both CRIXIVAN and atazanavir are associated with indirect (unconjugated) hyperbilirubinemia. Combinations of these drugs have not been studied and coadministration of CRIXIVAN and atazanavir is not recommended. Table 9 Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction Drug Name Effect Clinical Comment HIV Antiviral Agents Delavirdine indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered when taking delavirdine 400 mg three times a day. Didanosine Indinavir and didanosine formulations containing buffer should be administered at least one hour apart on an empty stomach. Efavirenz indinavir concentration The optimal dose of indinavir, when given in combination with efavirenz, is not known. Increasing the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to efavirenz. Nelfinavir indinavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Nevirapine indinavir concentration Indinavir concentrations may be decreased in the presence of nevirapine. The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Ritonavir indinavir concentration ritonavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Preliminary clinical data suggest that the incidence of nephrolithiasis is higher in patients receiving indinavir in combination with ritonavir than those receiving CRIXIVAN 800 mg q8h. Saquinavir saquinavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established. Other Agents Antiarrhythmics: bepridil, lidocaine (systemic) and quinidine antiarrhythmic agents concentration Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics when coadministered with CRIXIVAN. Anticonvulsants: carbamazepine, phenobarbital, phenytoin indinavir concentration Use with caution. CRIXIVAN may not be effective due to decreased indinavir concentrations in patients taking these agents concomitantly. Calcium Channel Blockers, Dihydropyridine: e.g., felodipine, nifedipine, nicardipine dihydropyridine calcium channel blockers concentration Caution is warranted and clinical monitoring of patients is recommended. Clarithromycin clarithromycin concentration indinavir concentration The appropriate doses for this combination, with respect to efficacy and safety, have not been established. HMG-CoA Reductase Inhibitor: atorvastatin atorvastatin concentration Use lowest possible dose of atorvastatin with careful monitoring, or consider HMG-CoA reductase inhibitors that are not primarily metabolized by CYP3A4, such as pravastatin, fluvastatin, or rosuvastatin in combination with CRIXIVAN. Immunosuppressants: cyclosporine, tacrolimus, sirolimus immunosuppressant agents concentration Plasma concentrations may be increased by CRIXIVAN. Itraconazole indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours is recommended when administering itraconazole concurrently. Ketoconazole indinavir concentration Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered. Rifabutin indinavir concentration rifabutin concentration Dose reduction of rifabutin to half the standard dose and a dose increase of CRIXIVAN to 1000 mg (three 333-mg capsules) every 8 hours are recommended when rifabutin and CRIXIVAN are coadministered. Sildenafil sildenafil concentration Sildenafil dose should not exceed a maximum of 25 mg in a 48- hour period in patients receiving concomitant indinavir therapy. Tadalafil tadalafil concentration Tadalafil dose should not exceed a maximum of 10 mg in a 72- hour period in patients receiving concomitant indinavir therapy. Vardenafil vardenafil concentration Vardenafil dose should not exceed a maximum of 2.5 mg in a 24-hour period in patients receiving concomitant indinavir therapy. Note: = increase; = decrease" ], "offsets": [ [ 0, 6303 ] ] } ]

[ { "id": "Indinavir_ddi_T1", "type": "DRUG", "text": [ "Indinavir" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T2", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 85, 93 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T3", "type": "DRUG", "text": [ "Indinavir" ], "offsets": [ [ 270, 279 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T4", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 387, 396 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T5", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 444, 453 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T6", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 475, 483 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T7", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 550, 559 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T8", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 613, 622 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T9", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 677, 685 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T10", "type": "GROUP", "text": [ "Antiarrhythmics" ], "offsets": [ [ 725, 740 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T11", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 742, 752 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T12", "type": "DRUG", "text": [ "dihydroergotamine" ], "offsets": [ [ 880, 897 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T13", "type": "DRUG", "text": [ "ergonovine" ], "offsets": [ [ 899, 909 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T14", "type": "DRUG", "text": [ "ergotamine" ], "offsets": [ [ 911, 921 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T15", "type": "DRUG", "text": [ "methylergonovine" ], "offsets": [ [ 923, 939 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T16", "type": "GROUP", "text": [ "Sedative" ], "offsets": [ [ 1137, 1145 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T17", "type": "GROUP", "text": [ "hypnotics" ], "offsets": [ [ 1146, 1155 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T18", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 1157, 1166 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T19", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 1168, 1177 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T20", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1344, 1353 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T21", "type": "GROUP", "text": [ "Neuroleptic" ], "offsets": [ [ 1462, 1473 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T22", "type": "DRUG", "text": [ "pimozide" ], "offsets": [ [ 1475, 1483 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T23", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 1714, 1722 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T24", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 1742, 1761 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T25", "type": "GROUP", "text": [ "Antimycobacterial" ], "offsets": [ [ 1763, 1780 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T26", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1782, 1790 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T27", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 1857, 1865 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T28", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 1885, 1904 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T29", "type": "GROUP", "text": [ "antiretroviral agents" ], "offsets": [ [ 1929, 1950 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T30", "type": "GROUP", "text": [ "HMG-CoA Reductase inhibitors" ], "offsets": [ [ 1952, 1980 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T31", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 1982, 1992 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T32", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 1994, 2005 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T33", "type": "GROUP", "text": [ "Protease inhibitor" ], "offsets": [ [ 2089, 2107 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T34", "type": "DRUG", "text": [ "atazanavir" ], "offsets": [ [ 2109, 2119 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T35", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 2125, 2133 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T36", "type": "DRUG", "text": [ "atazanavir" ], "offsets": [ [ 2138, 2148 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T37", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 2287, 2295 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T38", "type": "DRUG", "text": [ "atazanavir" ], "offsets": [ [ 2300, 2310 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T39", "type": "GROUP", "text": [ "HIV Antiviral Agents" ], "offsets": [ [ 2546, 2566 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T40", "type": "DRUG", "text": [ "Delavirdine" ], "offsets": [ [ 2567, 2578 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T41", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 2579, 2588 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T42", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 2621, 2629 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T43", "type": "DRUG", "text": [ "delavirdine" ], "offsets": [ [ 2687, 2698 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T44", "type": "DRUG", "text": [ "Didanosine" ], "offsets": [ [ 2725, 2735 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T45", "type": "DRUG", "text": [ "Indinavir" ], "offsets": [ [ 2736, 2745 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T46", "type": "DRUG", "text": [ "didanosine" ], "offsets": [ [ 2750, 2760 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T47", "type": "DRUG", "text": [ "Efavirenz" ], "offsets": [ [ 2860, 2869 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T48", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 2870, 2879 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T49", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 2914, 2923 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T50", "type": "DRUG", "text": [ "efavirenz" ], "offsets": [ [ 2956, 2965 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T51", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 2996, 3005 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T52", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 3074, 3083 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T53", "type": "DRUG", "text": [ "efavirenz" ], "offsets": [ [ 3102, 3111 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T54", "type": "DRUG", "text": [ "Nelfinavir" ], "offsets": [ [ 3113, 3123 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T55", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 3124, 3133 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T56", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 3256, 3266 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T57", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 3267, 3276 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T58", "type": "DRUG", "text": [ "Indinavir" ], "offsets": [ [ 3291, 3300 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T59", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 3352, 3362 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T60", "type": "DRUG", "text": [ "Ritonavir" ], "offsets": [ [ 3472, 3481 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T61", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 3482, 3491 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T62", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 3508, 3517 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T63", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 3744, 3753 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T64", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 3774, 3783 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T65", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 3805, 3813 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T66", "type": "DRUG", "text": [ "Saquinavir" ], "offsets": [ [ 3826, 3836 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T67", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 3837, 3847 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T68", "type": "GROUP", "text": [ "Antiarrhythmics" ], "offsets": [ [ 3983, 3998 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T69", "type": "DRUG", "text": [ "bepridil" ], "offsets": [ [ 4000, 4008 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T70", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 4010, 4019 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T71", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 4035, 4044 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T72", "type": "GROUP", "text": [ "antiarrhythmic agents" ], "offsets": [ [ 4045, 4066 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T73", "type": "GROUP", "text": [ "antiarrhythmics" ], "offsets": [ [ 4162, 4177 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T74", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 4203, 4211 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T75", "type": "GROUP", "text": [ "Anticonvulsants" ], "offsets": [ [ 4213, 4228 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T76", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 4230, 4243 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T77", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 4245, 4258 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T78", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 4260, 4269 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T79", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 4270, 4279 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T80", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 4312, 4320 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T81", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 4359, 4368 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T82", "type": "GROUP", "text": [ "Calcium Channel Blockers" ], "offsets": [ [ 4431, 4455 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T83", "type": "GROUP", "text": [ "Dihydropyridine" ], "offsets": [ [ 4457, 4472 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T84", "type": "DRUG", "text": [ "felodipine" ], "offsets": [ [ 4480, 4490 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T85", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 4492, 4502 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T86", "type": "DRUG", "text": [ "nicardipine" ], "offsets": [ [ 4504, 4515 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T87", "type": "GROUP", "text": [ "dihydropyridine calcium channel blockers" ], "offsets": [ [ 4516, 4556 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T88", "type": "DRUG", "text": [ "Clarithromycin" ], "offsets": [ [ 4644, 4658 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T89", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 4659, 4673 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T90", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 4690, 4699 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T91", "type": "GROUP", "text": [ "HMG-CoA Reductase Inhibitor" ], "offsets": [ [ 4822, 4849 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T92", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 4851, 4863 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T93", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 4864, 4876 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T94", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 4919, 4931 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T95", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 4969, 4997 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T96", "type": "DRUG", "text": [ "pravastatin" ], "offsets": [ [ 5052, 5063 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T97", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 5065, 5076 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T98", "type": "DRUG", "text": [ "rosuvastatin" ], "offsets": [ [ 5081, 5093 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T99", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 5114, 5122 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T100", "type": "GROUP", "text": [ "Immunosuppressants" ], "offsets": [ [ 5124, 5142 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T101", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 5144, 5156 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T102", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 5158, 5168 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T103", "type": "DRUG", "text": [ "sirolimus" ], "offsets": [ [ 5170, 5179 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T104", "type": "GROUP", "text": [ "immunosuppressant agents" ], "offsets": [ [ 5180, 5204 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T105", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 5261, 5269 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T106", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 5271, 5283 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T107", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 5284, 5293 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T108", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 5326, 5334 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T109", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 5393, 5405 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T110", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 5420, 5432 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T111", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 5433, 5442 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T112", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 5475, 5483 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T113", "type": "DRUG", "text": [ "Rifabutin" ], "offsets": [ [ 5530, 5539 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T114", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 5540, 5549 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T115", "type": "DRUG", "text": [ "rifabutin" ], "offsets": [ [ 5566, 5575 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T116", "type": "DRUG", "text": [ "rifabutin" ], "offsets": [ [ 5608, 5617 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T117", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 5667, 5675 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T118", "type": "DRUG", "text": [ "rifabutin" ], "offsets": [ [ 5746, 5755 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T119", "type": "BRAND", "text": [ "CRIXIVAN" ], "offsets": [ [ 5760, 5768 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T120", "type": "DRUG", "text": [ "Sildenafil" ], "offsets": [ [ 5789, 5799 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T121", "type": "DRUG", "text": [ "sildenafil" ], "offsets": [ [ 5800, 5810 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T122", "type": "DRUG", "text": [ "Sildenafil" ], "offsets": [ [ 5825, 5835 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T123", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 5933, 5942 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T124", "type": "DRUG", "text": [ "Tadalafil" ], "offsets": [ [ 5952, 5961 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T125", "type": "DRUG", "text": [ "tadalafil" ], "offsets": [ [ 5962, 5971 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T126", "type": "DRUG", "text": [ "Tadalafil" ], "offsets": [ [ 5986, 5995 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T127", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 6093, 6102 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T128", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 6112, 6122 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T129", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 6123, 6133 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T130", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 6148, 6158 ] ], "normalized": [] }, { "id": "Indinavir_ddi_T131", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 6256, 6265 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Indinavir_ddi_R1", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T37", "arg2_id": "Indinavir_ddi_T38", "normalized": [] }, { "id": "Indinavir_ddi_R2", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T42", "arg2_id": "Indinavir_ddi_T43", "normalized": [] }, { "id": "Indinavir_ddi_R3", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T45", "arg2_id": "Indinavir_ddi_T46", "normalized": [] }, { "id": "Indinavir_ddi_R4", "type": "MECHANISM", "arg1_id": "Indinavir_ddi_T52", "arg2_id": "Indinavir_ddi_T53", "normalized": [] }, { "id": "Indinavir_ddi_R5", "type": "MECHANISM", "arg1_id": "Indinavir_ddi_T58", "arg2_id": "Indinavir_ddi_T59", "normalized": [] }, { "id": "Indinavir_ddi_R6", "type": "EFFECT", "arg1_id": "Indinavir_ddi_T63", "arg2_id": "Indinavir_ddi_T64", "normalized": [] }, { "id": "Indinavir_ddi_R7", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T73", "arg2_id": "Indinavir_ddi_T74", "normalized": [] }, { "id": "Indinavir_ddi_R8", "type": "EFFECT", "arg1_id": "Indinavir_ddi_T80", "arg2_id": "Indinavir_ddi_T81", "normalized": [] }, { "id": "Indinavir_ddi_R9", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T94", "arg2_id": "Indinavir_ddi_T99", "normalized": [] }, { "id": "Indinavir_ddi_R10", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T95", "arg2_id": "Indinavir_ddi_T99", "normalized": [] }, { "id": "Indinavir_ddi_R11", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T108", "arg2_id": "Indinavir_ddi_T109", "normalized": [] }, { "id": "Indinavir_ddi_R12", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T118", "arg2_id": "Indinavir_ddi_T119", "normalized": [] }, { "id": "Indinavir_ddi_R13", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T122", "arg2_id": "Indinavir_ddi_T123", "normalized": [] }, { "id": "Indinavir_ddi_R14", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T126", "arg2_id": "Indinavir_ddi_T127", "normalized": [] }, { "id": "Indinavir_ddi_R15", "type": "ADVISE", "arg1_id": "Indinavir_ddi_T130", "arg2_id": "Indinavir_ddi_T131", "normalized": [] } ]

[ { "id": "Darifenacin_ddi__text", "type": "abstract", "text": [ "The daily dose of ENABLEX should not exceed 7.5 mg when coadministered with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin and nefazadone) . Caution should be taken when ENABLEX is used concomitantly with medications that are predominantly metabolized by CYP2D6 and which have a narrow therapeutic window, such as flecainide, thioridazine and tricyclic antidepressants (see CLINICAL PHARMACOLOGY). The concomitant use of ENABLEX with other anticholinergic agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision and other anticholinergic pharmacological effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to effects on gastrointestinal motility. Drug Laboratory Test Interactions Interactions between darifenacin and laboratory tests have not been studied." ], "offsets": [ [ 0, 907 ] ] } ]

[ { "id": "Darifenacin_ddi_T1", "type": "BRAND", "text": [ "ENABLEX" ], "offsets": [ [ 18, 25 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T2", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 108, 120 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T3", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 122, 134 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T4", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 136, 145 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T5", "type": "DRUG", "text": [ "nelfinavir" ], "offsets": [ [ 147, 157 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T6", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 159, 173 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T7", "type": "BRAND", "text": [ "ENABLEX" ], "offsets": [ [ 221, 228 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T8", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 365, 375 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T9", "type": "DRUG", "text": [ "thioridazine" ], "offsets": [ [ 377, 389 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T10", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 394, 419 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T11", "type": "BRAND", "text": [ "ENABLEX" ], "offsets": [ [ 472, 479 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T12", "type": "GROUP", "text": [ "anticholinergic agents" ], "offsets": [ [ 491, 513 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T13", "type": "GROUP", "text": [ "Anticholinergic agents" ], "offsets": [ [ 651, 673 ] ], "normalized": [] }, { "id": "Darifenacin_ddi_T14", "type": "DRUG", "text": [ "darifenacin" ], "offsets": [ [ 852, 863 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Darifenacin_ddi_R1", "type": "ADVISE", "arg1_id": "Darifenacin_ddi_T1", "arg2_id": "Darifenacin_ddi_T2", "normalized": [] }, { "id": "Darifenacin_ddi_R2", "type": "ADVISE", "arg1_id": "Darifenacin_ddi_T1", "arg2_id": "Darifenacin_ddi_T3", "normalized": [] }, { "id": "Darifenacin_ddi_R3", "type": "ADVISE", "arg1_id": "Darifenacin_ddi_T1", "arg2_id": "Darifenacin_ddi_T4", "normalized": [] }, { "id": "Darifenacin_ddi_R4", "type": "ADVISE", "arg1_id": "Darifenacin_ddi_T1", "arg2_id": "Darifenacin_ddi_T5", "normalized": [] }, { "id": "Darifenacin_ddi_R5", "type": "ADVISE", "arg1_id": "Darifenacin_ddi_T1", "arg2_id": "Darifenacin_ddi_T6", "normalized": [] }, { "id": "Darifenacin_ddi_R6", "type": "ADVISE", "arg1_id": "Darifenacin_ddi_T7", "arg2_id": "Darifenacin_ddi_T8", "normalized": [] }, { "id": "Darifenacin_ddi_R7", "type": "ADVISE", "arg1_id": "Darifenacin_ddi_T7", "arg2_id": "Darifenacin_ddi_T9", "normalized": [] }, { "id": "Darifenacin_ddi_R8", "type": "ADVISE", "arg1_id": "Darifenacin_ddi_T7", "arg2_id": "Darifenacin_ddi_T10", "normalized": [] }, { "id": "Darifenacin_ddi_R9", "type": "EFFECT", "arg1_id": "Darifenacin_ddi_T11", "arg2_id": "Darifenacin_ddi_T12", "normalized": [] } ]

[ { "id": "Butalbital_ddi__text", "type": "abstract", "text": [ "The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors. Butalbital, acetaminophen and caffeine may enhance the effects of: other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression. Drug/Laboratory Test Interactions Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid." ], "offsets": [ [ 0, 456 ] ] } ]

[ { "id": "Butalbital_ddi_T1", "type": "DRUG", "text": [ "butalbital" ], "offsets": [ [ 19, 29 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T2", "type": "GROUP", "text": [ "monoamine oxidase (MAO) inhibitors" ], "offsets": [ [ 49, 83 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T3", "type": "DRUG", "text": [ "Butalbital" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T4", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 97, 110 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T5", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 115, 123 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T6", "type": "GROUP", "text": [ "narcotic analgesic" ], "offsets": [ [ 158, 176 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T7", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 179, 186 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T8", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 196, 207 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T9", "type": "GROUP", "text": [ "tranquilizers" ], "offsets": [ [ 209, 222 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T10", "type": "DRUG", "text": [ "chlordiazepoxide" ], "offsets": [ [ 231, 247 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T11", "type": "GROUP", "text": [ "sedative-hypnotics" ], "offsets": [ [ 249, 267 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T12", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 278, 293 ] ], "normalized": [] }, { "id": "Butalbital_ddi_T13", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 363, 376 ] ], "normalized": [] } ]

[]

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[ { "id": "Butalbital_ddi_R1", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T1", "arg2_id": "Butalbital_ddi_T2", "normalized": [] }, { "id": "Butalbital_ddi_R2", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T3", "arg2_id": "Butalbital_ddi_T6", "normalized": [] }, { "id": "Butalbital_ddi_R3", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T3", "arg2_id": "Butalbital_ddi_T7", "normalized": [] }, { "id": "Butalbital_ddi_R4", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T3", "arg2_id": "Butalbital_ddi_T8", "normalized": [] }, { "id": "Butalbital_ddi_R5", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T3", "arg2_id": "Butalbital_ddi_T9", "normalized": [] }, { "id": "Butalbital_ddi_R6", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T3", "arg2_id": "Butalbital_ddi_T10", "normalized": [] }, { "id": "Butalbital_ddi_R7", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T3", "arg2_id": "Butalbital_ddi_T11", "normalized": [] }, { "id": "Butalbital_ddi_R8", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T3", "arg2_id": "Butalbital_ddi_T12", "normalized": [] }, { "id": "Butalbital_ddi_R9", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T4", "arg2_id": "Butalbital_ddi_T6", "normalized": [] }, { "id": "Butalbital_ddi_R10", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T4", "arg2_id": "Butalbital_ddi_T7", "normalized": [] }, { "id": "Butalbital_ddi_R11", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T4", "arg2_id": "Butalbital_ddi_T8", "normalized": [] }, { "id": "Butalbital_ddi_R12", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T4", "arg2_id": "Butalbital_ddi_T9", "normalized": [] }, { "id": "Butalbital_ddi_R13", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T4", "arg2_id": "Butalbital_ddi_T10", "normalized": [] }, { "id": "Butalbital_ddi_R14", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T4", "arg2_id": "Butalbital_ddi_T11", "normalized": [] }, { "id": "Butalbital_ddi_R15", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T4", "arg2_id": "Butalbital_ddi_T12", "normalized": [] }, { "id": "Butalbital_ddi_R16", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T5", "arg2_id": "Butalbital_ddi_T6", "normalized": [] }, { "id": "Butalbital_ddi_R17", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T5", "arg2_id": "Butalbital_ddi_T7", "normalized": [] }, { "id": "Butalbital_ddi_R18", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T5", "arg2_id": "Butalbital_ddi_T8", "normalized": [] }, { "id": "Butalbital_ddi_R19", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T5", "arg2_id": "Butalbital_ddi_T9", "normalized": [] }, { "id": "Butalbital_ddi_R20", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T5", "arg2_id": "Butalbital_ddi_T10", "normalized": [] }, { "id": "Butalbital_ddi_R21", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T5", "arg2_id": "Butalbital_ddi_T11", "normalized": [] }, { "id": "Butalbital_ddi_R22", "type": "EFFECT", "arg1_id": "Butalbital_ddi_T5", "arg2_id": "Butalbital_ddi_T12", "normalized": [] } ]

[ { "id": "Losartan_ddi__text", "type": "abstract", "text": [ "No significant drug-drug pharmacokinetic interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Rifampin, an inducer of drug metabolism, decreased the concentrations of losartan and its active metabolite. In humans, two inhibitors of P450 3A4 have been studied. Ketoconazole did not affect the conversion of losartan to the active metabolite after intravenous administration of losartan, and erythromycin had no clinically significant effect after oral administration. Fluconazole, an inhibitor of P450 2C9, decreased active metabolite concentration and increased losartan concentration. The pharmacodynamic consequences of concomitant use of losartan and inhibitors of P450 2C9 have not been examined. Subjects who do not metabolize losartan to active metabolite have been shown to have a specific, rare defect in cytochrome P450 2C9. These data suggest that the conversion of losartan to its active metabolite is mediated primarily by P450 2C9 and not P450 3A4. As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium. As with other antihypertensive agents, the antihypertensive effect of losartan may be blunted by the non-steroidal anti-inflammatory drug indomethacin ." ], "offsets": [ [ 0, 1451 ] ] } ]

[ { "id": "Losartan_ddi_T1", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 98, 117 ] ], "normalized": [] }, { "id": "Losartan_ddi_T2", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 119, 126 ] ], "normalized": [] }, { "id": "Losartan_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 128, 136 ] ], "normalized": [] }, { "id": "Losartan_ddi_T4", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 138, 148 ] ], "normalized": [] }, { "id": "Losartan_ddi_T5", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 153, 166 ] ], "normalized": [] }, { "id": "Losartan_ddi_T6", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 168, 176 ] ], "normalized": [] }, { "id": "Losartan_ddi_T7", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 241, 249 ] ], "normalized": [] }, { "id": "Losartan_ddi_T8", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 334, 346 ] ], "normalized": [] }, { "id": "Losartan_ddi_T9", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 380, 388 ] ], "normalized": [] }, { "id": "Losartan_ddi_T10", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 450, 458 ] ], "normalized": [] }, { "id": "Losartan_ddi_T11", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 464, 476 ] ], "normalized": [] }, { "id": "Losartan_ddi_T12", "type": "DRUG", "text": [ "Fluconazole" ], "offsets": [ [ 541, 552 ] ], "normalized": [] }, { "id": "Losartan_ddi_T13", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 636, 644 ] ], "normalized": [] }, { "id": "Losartan_ddi_T14", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 715, 723 ] ], "normalized": [] }, { "id": "Losartan_ddi_T15", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 806, 814 ] ], "normalized": [] }, { "id": "Losartan_ddi_T16", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 950, 958 ] ], "normalized": [] }, { "id": "Losartan_ddi_T17", "type": "GROUP", "text": [ "potassium-sparing diuretics" ], "offsets": [ [ 1117, 1144 ] ], "normalized": [] }, { "id": "Losartan_ddi_T18", "type": "DRUG", "text": [ "spironolactone" ], "offsets": [ [ 1152, 1166 ] ], "normalized": [] }, { "id": "Losartan_ddi_T19", "type": "DRUG", "text": [ "triamterene" ], "offsets": [ [ 1168, 1179 ] ], "normalized": [] }, { "id": "Losartan_ddi_T20", "type": "DRUG", "text": [ "amiloride" ], "offsets": [ [ 1181, 1190 ] ], "normalized": [] }, { "id": "Losartan_ddi_T21", "type": "DRUG", "text": [ "potassium" ], "offsets": [ [ 1193, 1202 ] ], "normalized": [] }, { "id": "Losartan_ddi_T22", "type": "GROUP", "text": [ "antihypertensive agents" ], "offsets": [ [ 1313, 1336 ] ], "normalized": [] }, { "id": "Losartan_ddi_T23", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 1369, 1377 ] ], "normalized": [] }, { "id": "Losartan_ddi_T24", "type": "GROUP", "text": [ "non-steroidal anti-inflammatory drug" ], "offsets": [ [ 1400, 1436 ] ], "normalized": [] }, { "id": "Losartan_ddi_T25", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 1437, 1449 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Losartan_ddi_R1", "type": "MECHANISM", "arg1_id": "Losartan_ddi_T6", "arg2_id": "Losartan_ddi_T7", "normalized": [] }, { "id": "Losartan_ddi_R2", "type": "MECHANISM", "arg1_id": "Losartan_ddi_T12", "arg2_id": "Losartan_ddi_T13", "normalized": [] }, { "id": "Losartan_ddi_R3", "type": "EFFECT", "arg1_id": "Losartan_ddi_T23", "arg2_id": "Losartan_ddi_T25", "normalized": [] } ]

[ { "id": "Botulinum Toxin Type A_ddi__text", "type": "abstract", "text": [ "Co-administration of BOTOX and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like compounds) should only be performed with caution as the effect of the toxin may be potentiated. The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin." ], "offsets": [ [ 0, 540 ] ] } ]

[ { "id": "Botulinum Toxin Type A_ddi_T1", "type": "BRAND", "text": [ "BOTOX" ], "offsets": [ [ 21, 26 ] ], "normalized": [] }, { "id": "Botulinum Toxin Type A_ddi_T2", "type": "GROUP", "text": [ "aminoglycosides" ], "offsets": [ [ 31, 46 ] ], "normalized": [] }, { "id": "Botulinum Toxin Type A_ddi_T3", "type": "GROUP", "text": [ "curare-like compounds" ], "offsets": [ [ 114, 135 ] ], "normalized": [] }, { "id": "Botulinum Toxin Type A_ddi_T4", "type": "DRUG", "text": [ "toxin" ], "offsets": [ [ 196, 201 ] ], "normalized": [] }, { "id": "Botulinum Toxin Type A_ddi_T5", "type": "GROUP", "text": [ "botulinum neurotoxin" ], "offsets": [ [ 260, 280 ] ], "normalized": [] }, { "id": "Botulinum Toxin Type A_ddi_T6", "type": "GROUP", "text": [ "botulinum toxin" ], "offsets": [ [ 440, 455 ] ], "normalized": [] }, { "id": "Botulinum Toxin Type A_ddi_T7", "type": "GROUP", "text": [ "botulinum toxin" ], "offsets": [ [ 524, 539 ] ], "normalized": [] } ]

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[ { "id": "Botulinum Toxin Type A_ddi_R1", "type": "ADVISE", "arg1_id": "Botulinum Toxin Type A_ddi_T1", "arg2_id": "Botulinum Toxin Type A_ddi_T2", "normalized": [] }, { "id": "Botulinum Toxin Type A_ddi_R2", "type": "ADVISE", "arg1_id": "Botulinum Toxin Type A_ddi_T1", "arg2_id": "Botulinum Toxin Type A_ddi_T3", "normalized": [] }, { "id": "Botulinum Toxin Type A_ddi_R3", "type": "EFFECT", "arg1_id": "Botulinum Toxin Type A_ddi_T6", "arg2_id": "Botulinum Toxin Type A_ddi_T7", "normalized": [] } ]

[ { "id": "Meclofenamic acid_ddi__text", "type": "abstract", "text": [ "Warfarin: Meclofenamate sodium enhances the effect of warfarin. Therefore, when meclofenamate sodium is given to a patient receiving warfarin, the dosage of warfarin should be reduced to prevent excessive prolongation of the prothrombin time. Aspirin: Concurrent administration of aspirin may lower meclofenamate sodium plasma levels, possibly by competing for protein-binding sites. The urinary excretion of meclofenamate sodium is unaffected by aspirin, indicating no change in meclofenamate sodium absorption. Meclofenamate sodium does not affect serum salicylate levels. Greater fecal blood loss results from concomitant administration of both drugs than from either drug alone. Propoxyphene: The concurrent administration of propoxyphene hydrochloride does not affect the bioavailability of meclofenamate sodium. Antacids: Concomitant administration of aluminum and magnesium hydroxides does not interfere with absorption of meclofenamate sodium." ], "offsets": [ [ 0, 951 ] ] } ]

[ { "id": "Meclofenamic acid_ddi_T1", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T2", "type": "DRUG", "text": [ "Meclofenamate sodium" ], "offsets": [ [ 10, 30 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 54, 62 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T4", "type": "DRUG", "text": [ "meclofenamate sodium" ], "offsets": [ [ 80, 100 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T5", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 133, 141 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T6", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 157, 165 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T7", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 243, 250 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T8", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 281, 288 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T9", "type": "DRUG", "text": [ "meclofenamate sodium" ], "offsets": [ [ 299, 319 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T10", "type": "DRUG", "text": [ "meclofenamate sodium" ], "offsets": [ [ 409, 429 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T11", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 447, 454 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T12", "type": "DRUG", "text": [ "meclofenamate sodium" ], "offsets": [ [ 480, 500 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T13", "type": "DRUG", "text": [ "Meclofenamate sodium" ], "offsets": [ [ 513, 533 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T14", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 556, 566 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T15", "type": "DRUG", "text": [ "Propoxyphene" ], "offsets": [ [ 683, 695 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T16", "type": "DRUG", "text": [ "propoxyphene hydrochloride" ], "offsets": [ [ 730, 756 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T17", "type": "DRUG", "text": [ "meclofenamate sodium" ], "offsets": [ [ 796, 816 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T18", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 818, 826 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T19", "type": "DRUG", "text": [ "aluminum", "hydroxide" ], "offsets": [ [ 858, 866 ], [ 881, 890 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T20", "type": "DRUG", "text": [ "magnesium hydroxide" ], "offsets": [ [ 871, 890 ] ], "normalized": [] }, { "id": "Meclofenamic acid_ddi_T21", "type": "DRUG", "text": [ "meclofenamate sodium" ], "offsets": [ [ 930, 950 ] ], "normalized": [] } ]

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[ { "id": "Meclofenamic acid_ddi_R1", "type": "EFFECT", "arg1_id": "Meclofenamic acid_ddi_T1", "arg2_id": "Meclofenamic acid_ddi_T2", "normalized": [] }, { "id": "Meclofenamic acid_ddi_R2", "type": "ADVISE", "arg1_id": "Meclofenamic acid_ddi_T4", "arg2_id": "Meclofenamic acid_ddi_T5", "normalized": [] }, { "id": "Meclofenamic acid_ddi_R3", "type": "MECHANISM", "arg1_id": "Meclofenamic acid_ddi_T8", "arg2_id": "Meclofenamic acid_ddi_T9", "normalized": [] } ]

[ { "id": "Nateglinide_ddi__text", "type": "abstract", "text": [ "In vitro drug metabolism studies indicate that Starlix is predominantly metabolized by the cytochrome P450 isozyme CYP2C9 (70%) and to a lesser extent CYP3A4 (30%). Starlix is a potential inhibitor of the CYP2C9 isoenzyme in vivo as indicated by its ability to inhibit the in vitro metabolism of tolbutamide. Inhibition of CYP3A4 metabolic reactions was not detected in in vitro experiments. Glyburide: In a randomized, multiple-dose crossover study, patients with Type 2 diabetes were administered 120 mg Starlix three times a day before meals for 1 day in combination with glyburide 10 mg daily. There were no clinically relevant alterations in the pharmacokinetics of either agent. Metformin: When Starlix 120 mg three times daily before meals was administered in combination with metformin 500 mg three times daily to patients with Type 2 diabetes, there were no clinically relevant changes in the pharmacokinetics of either agent. Digoxin: When Starlix 120 mg before meals was administered in combination with a single 1-mg dose of digoxin to healthy volunteers, there were no clinically relevant changes in the pharmacokinetics of either agent. Warfarin: When healthy subjects were administered Starlix 120 mg three times daily before meals for four days in combination with a single dose of warfarin 30 mg on day 2, there were no alterations in the pharmacokinetics of either agent. Prothrombin time was not affected. Diclofenac: Administration of morning and lunch doses of Starlix 120 mg in combination with a single 75-mg dose of diclofenac in healthy volunteers resulted in no significant changes to the pharmacokinetics of either agent. Nateglinide is highly bound to plasma proteins (98%), mainly albumin. In vitro displacement studies with highly protein-bound drugs such as furosemide, propranolol, captopril, nicardipine, pravastatin, glyburide, warfarin, phenytoin, acetylsalicylic acid, tolbutamide, and metformin showed no influence on the extent of nateglinide protein binding. Similarly, nateglinide had no influence on the serum protein binding of propranolol, glyburide, nicardipine, warfarin, phenytoin, acetylsalicylic acid, and tolbutamide in vitro . However, prudent evaluation of individual cases is warranted in the clinical setting. Certain drugs, including nonsteroidal anti-inflammatory agents (NSAIDs), salicylates, monoamine oxidase inhibitors, and non-selective beta-adrenergic-blocking agents may potentiate the hypoglycemic action of Starlix and other oral antidiabetic drugs. Certain drugs including thiazides, corticosteroids, thyroid products, and sympathomimetics may reduce the hypoglycemic action of Starlix and other oral antidiabetic drugs. When these drugs are administered to or withdrawn from patients receiving Starlix, the patient should be observed closely for changes in glycemic control." ], "offsets": [ [ 0, 2840 ] ] } ]

[ { "id": "Nateglinide_ddi_T1", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 47, 54 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T2", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 165, 172 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T3", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 296, 307 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T4", "type": "DRUG", "text": [ "Glyburide" ], "offsets": [ [ 392, 401 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T5", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 506, 513 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T6", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 575, 584 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T7", "type": "DRUG", "text": [ "Metformin" ], "offsets": [ [ 685, 694 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T8", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 701, 708 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T9", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 784, 793 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T10", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 936, 943 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T11", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 950, 957 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T12", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1037, 1044 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T13", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 1151, 1159 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T14", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 1201, 1208 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T15", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1298, 1306 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T16", "type": "DRUG", "text": [ "Diclofenac" ], "offsets": [ [ 1425, 1435 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T17", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 1482, 1489 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T18", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 1540, 1550 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T19", "type": "DRUG", "text": [ "Nateglinide" ], "offsets": [ [ 1649, 1660 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T20", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1789, 1799 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T21", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1801, 1812 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T22", "type": "DRUG", "text": [ "captopril" ], "offsets": [ [ 1814, 1823 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T23", "type": "DRUG", "text": [ "nicardipine" ], "offsets": [ [ 1825, 1836 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T24", "type": "DRUG", "text": [ "pravastatin" ], "offsets": [ [ 1838, 1849 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T25", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 1851, 1860 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T26", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1862, 1870 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T27", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1872, 1881 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T28", "type": "DRUG", "text": [ "acetylsalicylic acid" ], "offsets": [ [ 1883, 1903 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T29", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 1905, 1916 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T30", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 1922, 1931 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T31", "type": "DRUG", "text": [ "nateglinide" ], "offsets": [ [ 1969, 1980 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T32", "type": "DRUG", "text": [ "nateglinide" ], "offsets": [ [ 2009, 2020 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T33", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 2070, 2081 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T34", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 2083, 2092 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T35", "type": "DRUG", "text": [ "nicardipine" ], "offsets": [ [ 2094, 2105 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T36", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2107, 2115 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T37", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2117, 2126 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T38", "type": "DRUG", "text": [ "acetylsalicylic acid" ], "offsets": [ [ 2128, 2148 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T39", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 2154, 2165 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T40", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 2288, 2325 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T41", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2327, 2333 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T42", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 2336, 2347 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T43", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 2349, 2377 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T44", "type": "GROUP", "text": [ "non-selective beta-adrenergic-blocking agents" ], "offsets": [ [ 2383, 2428 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T45", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 2471, 2478 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T46", "type": "GROUP", "text": [ "antidiabetic drugs" ], "offsets": [ [ 2494, 2512 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T47", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 2538, 2547 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T48", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 2549, 2564 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T49", "type": "GROUP", "text": [ "thyroid products" ], "offsets": [ [ 2566, 2582 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T50", "type": "GROUP", "text": [ "sympathomimetics" ], "offsets": [ [ 2588, 2604 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T51", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 2643, 2650 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T52", "type": "GROUP", "text": [ "antidiabetic drugs" ], "offsets": [ [ 2666, 2684 ] ], "normalized": [] }, { "id": "Nateglinide_ddi_T53", "type": "BRAND", "text": [ "Starlix" ], "offsets": [ [ 2760, 2767 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Nateglinide_ddi_R1", "type": "MECHANISM", "arg1_id": "Nateglinide_ddi_T2", "arg2_id": "Nateglinide_ddi_T3", "normalized": [] }, { "id": "Nateglinide_ddi_R2", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T40", "arg2_id": "Nateglinide_ddi_T45", "normalized": [] }, { "id": "Nateglinide_ddi_R3", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T40", "arg2_id": "Nateglinide_ddi_T46", "normalized": [] }, { "id": "Nateglinide_ddi_R4", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T41", "arg2_id": "Nateglinide_ddi_T45", "normalized": [] }, { "id": "Nateglinide_ddi_R5", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T41", "arg2_id": "Nateglinide_ddi_T46", "normalized": [] }, { "id": "Nateglinide_ddi_R6", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T42", "arg2_id": "Nateglinide_ddi_T45", "normalized": [] }, { "id": "Nateglinide_ddi_R7", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T42", "arg2_id": "Nateglinide_ddi_T46", "normalized": [] }, { "id": "Nateglinide_ddi_R8", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T43", "arg2_id": "Nateglinide_ddi_T45", "normalized": [] }, { "id": "Nateglinide_ddi_R9", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T43", "arg2_id": "Nateglinide_ddi_T46", "normalized": [] }, { "id": "Nateglinide_ddi_R10", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T44", "arg2_id": "Nateglinide_ddi_T45", "normalized": [] }, { "id": "Nateglinide_ddi_R11", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T44", "arg2_id": "Nateglinide_ddi_T46", "normalized": [] }, { "id": "Nateglinide_ddi_R12", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T47", "arg2_id": "Nateglinide_ddi_T51", "normalized": [] }, { "id": "Nateglinide_ddi_R13", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T47", "arg2_id": "Nateglinide_ddi_T52", "normalized": [] }, { "id": "Nateglinide_ddi_R14", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T48", "arg2_id": "Nateglinide_ddi_T51", "normalized": [] }, { "id": "Nateglinide_ddi_R15", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T48", "arg2_id": "Nateglinide_ddi_T52", "normalized": [] }, { "id": "Nateglinide_ddi_R16", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T49", "arg2_id": "Nateglinide_ddi_T51", "normalized": [] }, { "id": "Nateglinide_ddi_R17", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T49", "arg2_id": "Nateglinide_ddi_T52", "normalized": [] }, { "id": "Nateglinide_ddi_R18", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T50", "arg2_id": "Nateglinide_ddi_T51", "normalized": [] }, { "id": "Nateglinide_ddi_R19", "type": "EFFECT", "arg1_id": "Nateglinide_ddi_T50", "arg2_id": "Nateglinide_ddi_T52", "normalized": [] } ]

[ { "id": "Cilostazol_ddi__text", "type": "abstract", "text": [ "Since PLETAL is extensively metabolized by cytochrome P-450 isoenzymes, caution should be exercised when PLETAL is coadministered with inhibitors of C.P.A. such as ketoconazole and erythromycin or inhibitors of CYP2C19 such as omeprazole. Pharmacokinetic studies have demonstrated that omeprazole and erythromycin significantly increased the systemic exposure of cilostazol and/or its major metabolites. Population pharmacokinetic studies showed higher concentrations of cilostazol among patients concurrently treated with diltiazem, an inhibitor of C.P.A.. Pletal does not, however, appear to cause increased blood levels of drugs metabolized by CYP3A4, as it had no effect on lovastatin, a drug with metabolism very sensitive to C.P.A. inhibition." ], "offsets": [ [ 0, 749 ] ] } ]

[ { "id": "Cilostazol_ddi_T1", "type": "BRAND", "text": [ "PLETAL" ], "offsets": [ [ 6, 12 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T2", "type": "BRAND", "text": [ "PLETAL" ], "offsets": [ [ 105, 111 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T3", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 164, 176 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T4", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 181, 193 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T5", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 227, 237 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T6", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 286, 296 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T7", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 301, 313 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T8", "type": "DRUG", "text": [ "cilostazol" ], "offsets": [ [ 363, 373 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T9", "type": "DRUG", "text": [ "cilostazol" ], "offsets": [ [ 471, 481 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T10", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 523, 532 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T11", "type": "BRAND", "text": [ "Pletal" ], "offsets": [ [ 558, 564 ] ], "normalized": [] }, { "id": "Cilostazol_ddi_T12", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 678, 688 ] ], "normalized": [] } ]

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[ { "id": "Cilostazol_ddi_R1", "type": "ADVISE", "arg1_id": "Cilostazol_ddi_T2", "arg2_id": "Cilostazol_ddi_T3", "normalized": [] }, { "id": "Cilostazol_ddi_R2", "type": "ADVISE", "arg1_id": "Cilostazol_ddi_T2", "arg2_id": "Cilostazol_ddi_T4", "normalized": [] }, { "id": "Cilostazol_ddi_R3", "type": "ADVISE", "arg1_id": "Cilostazol_ddi_T2", "arg2_id": "Cilostazol_ddi_T5", "normalized": [] }, { "id": "Cilostazol_ddi_R4", "type": "MECHANISM", "arg1_id": "Cilostazol_ddi_T6", "arg2_id": "Cilostazol_ddi_T8", "normalized": [] }, { "id": "Cilostazol_ddi_R5", "type": "MECHANISM", "arg1_id": "Cilostazol_ddi_T7", "arg2_id": "Cilostazol_ddi_T8", "normalized": [] }, { "id": "Cilostazol_ddi_R6", "type": "MECHANISM", "arg1_id": "Cilostazol_ddi_T9", "arg2_id": "Cilostazol_ddi_T10", "normalized": [] } ]

[ { "id": "Idoxuridine_ddi__text", "type": "abstract", "text": [ "Other medicines - Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are using idoxuridine, it is especially important that your health care professional know if you are using the following: Eye product containing boric acid. Boric acid may interact with the idoxuridine preparation causing a gritty substance to form or may interact with the preservative in the idoxuridine preparation causing a toxic effect in the eye." ], "offsets": [ [ 0, 634 ] ] } ]

[ { "id": "Idoxuridine_ddi_T1", "type": "DRUG", "text": [ "idoxuridine" ], "offsets": [ [ 292, 303 ] ], "normalized": [] }, { "id": "Idoxuridine_ddi_T2", "type": "DRUG", "text": [ "boric acid" ], "offsets": [ [ 427, 437 ] ], "normalized": [] }, { "id": "Idoxuridine_ddi_T3", "type": "DRUG", "text": [ "Boric acid" ], "offsets": [ [ 439, 449 ] ], "normalized": [] }, { "id": "Idoxuridine_ddi_T4", "type": "DRUG", "text": [ "idoxuridine" ], "offsets": [ [ 472, 483 ] ], "normalized": [] }, { "id": "Idoxuridine_ddi_T5", "type": "DRUG", "text": [ "idoxuridine" ], "offsets": [ [ 576, 587 ] ], "normalized": [] } ]

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[]

[ { "id": "Idoxuridine_ddi_R1", "type": "ADVISE", "arg1_id": "Idoxuridine_ddi_T1", "arg2_id": "Idoxuridine_ddi_T2", "normalized": [] }, { "id": "Idoxuridine_ddi_R2", "type": "MECHANISM", "arg1_id": "Idoxuridine_ddi_T3", "arg2_id": "Idoxuridine_ddi_T4", "normalized": [] } ]

[ { "id": "Ethinyl Estradiol_ddi__text", "type": "abstract", "text": [ "Certain endocrine and liver function tests may be affected by estrogen-containing oral contraceptives. The following similar changes may be expected with larger doses of estrogen: Increased sulfobromophthalein retention; increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platel et aggregation; increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by PBI, T4 by column, or T4 by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered: impaired glucose tolerance; decreased pregnanediol excretion; reduced response to metyrapone test; reduced serum folate concentration; increased serum triglyceride and phospholipid concentration." ], "offsets": [ [ 0, 812 ] ] } ]

[ { "id": "Ethinyl Estradiol_ddi_T1", "type": "GROUP", "text": [ "estrogen" ], "offsets": [ [ 62, 70 ] ], "normalized": [] }, { "id": "Ethinyl Estradiol_ddi_T2", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 87, 101 ] ], "normalized": [] }, { "id": "Ethinyl Estradiol_ddi_T3", "type": "GROUP", "text": [ "estrogen" ], "offsets": [ [ 170, 178 ] ], "normalized": [] } ]

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[ { "id": "Bicalutamide_ddi__text", "type": "abstract", "text": [ "In vitro studies have shown CASODEX can displace coumarin anticoagulants, such as warfarin, from their protein-binding sites. It is recommended that if CASODEX is started in patients already receiving coumarin anticoagulants, prothrombin times should be closely monitored and adjustment of the anticoagulant dose may be necessary." ], "offsets": [ [ 0, 330 ] ] } ]

[ { "id": "Bicalutamide_ddi_T1", "type": "BRAND", "text": [ "CASODEX" ], "offsets": [ [ 28, 35 ] ], "normalized": [] }, { "id": "Bicalutamide_ddi_T2", "type": "GROUP", "text": [ "coumarin anticoagulant" ], "offsets": [ [ 49, 71 ] ], "normalized": [] }, { "id": "Bicalutamide_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 82, 90 ] ], "normalized": [] }, { "id": "Bicalutamide_ddi_T4", "type": "BRAND", "text": [ "CASODEX" ], "offsets": [ [ 152, 159 ] ], "normalized": [] }, { "id": "Bicalutamide_ddi_T5", "type": "GROUP", "text": [ "coumarin anticoagulants" ], "offsets": [ [ 201, 224 ] ], "normalized": [] }, { "id": "Bicalutamide_ddi_T6", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 294, 307 ] ], "normalized": [] } ]

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[]

[ { "id": "Bicalutamide_ddi_R1", "type": "MECHANISM", "arg1_id": "Bicalutamide_ddi_T1", "arg2_id": "Bicalutamide_ddi_T2", "normalized": [] }, { "id": "Bicalutamide_ddi_R2", "type": "MECHANISM", "arg1_id": "Bicalutamide_ddi_T1", "arg2_id": "Bicalutamide_ddi_T3", "normalized": [] }, { "id": "Bicalutamide_ddi_R3", "type": "ADVISE", "arg1_id": "Bicalutamide_ddi_T4", "arg2_id": "Bicalutamide_ddi_T5", "normalized": [] }, { "id": "Bicalutamide_ddi_R4", "type": "ADVISE", "arg1_id": "Bicalutamide_ddi_T4", "arg2_id": "Bicalutamide_ddi_T6", "normalized": [] } ]

[ { "id": "Ketorolac_ddi__text", "type": "abstract", "text": [ "Ketorolac is highly bound to human plasma protein (mean 99.2%). Warfarin, Digoxin, Salicylate, and Heparin The in vitro binding of warfarin to plasma proteins is only slightly reduced by ketorolac tromethamine (99.5% control vs 99.3%) when ketorolac plasma concentrations reach 5 to10 m g/mL. Ketorolac does not alter digoxin protein binding. In vitro studies indicate that, at therapeutic concentrations of salicylate (300 m g/mL), the binding of ketorolac was reduced from approximately 99.2% to 97.5%, representing a potential twofold increase in unbound ketorolac plasma levels. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin andtolbutamide did not alter ketorolac tromethamine protein binding. In a study involving 12 adult volunteers, TORADOLORAL was coadministered with a single dose of 25 mg warfarin, causing no significant changes in pharmacokinetics or pharmacodynamics of warfarin. In another study, TORADOLIV/IM was given with two doses of 5000 U of heparin to 11 healthy volunteers, resulting in a mean template bleeding time of 6.4 minutes (3.2 to 11.4 min) compared to a mean of 6.0 minutes (3.4 to 7.5 min) for heparin alone and 5.1 minutes (3.5 to 8.5 min) for placebo. Although these results do not indicate a significant interaction between TORADOL and warfarin or heparin, the administration of TORADOL to patients taking anticoagulants should be done extremely cautiously, and patients should be closely monitored. Furosemide: TORADOL IV/IM reduced the diuretic response to furosemide in normovolemic healthy subjects by approximately 20% (mean sodium and urinary output decreased 17%). Probenecid: Concomitant administration of TORADOL ORAL and probenecid resulted in decreased clearance of ketorolac and significant increases in ketorolac plasma levels (total AUC increased approximately threefold from 5.4 to 17.8 m g/h/mL) and terminal half-life increased approximately twofold from 6.6 to 15.1 hours. Therefore, concomitant use of TORADOL and probenecid is contraindicated. Lithium: Inhibition of renal lithium clearance, leading to an increase in plasma lithium concentration, has been reported with some prostaglandin synthesis-inhibiting drugs. The effect of TORADOL on plasma lithium has not been studied, but cases of increased lithium plasma levels during TORADOL therapy have been reported. Methotrexate: Concomitant administration of methotrexate and some NSAIDs has been reported to reduce the clearance of methotrexate, enhancing the toxicity of methotrexate. The effect of TORADOL on methotrexate clearance has not been studied. Nondepolarizing Muscle Relaxants: In postmarketing experience there have been reports of a possible interaction between TORADOLIV/IM and nondepolarizing muscle relaxants that resulted in apnea. The concurrent use of TORADOL with muscle relaxants has not been formally studied. ACE Inhibitors: Concomitant use of ACE inhibitors may increase the risk of renal impairment, particularly in volume-depleted patients. Antiepileptic Drugs: Sporadic cases of seizures have been reported during concomitant use of TORADOL and antiepileptic drugs (phenytoin, carbamazepine). Psychoactive Drugs: Hallucinations have been reported when TORADOL was used in patients taking psychoactive drugs (fluoxetine, thiothixene, alprazolam). Morphine: TORADOLIV/IM has been administered concurrently with morphine in several clinical trials of postoperative pain without evidence of adverse interactions. Do not mix TORADOL and morphine in the same syringe. There is no evidence in animal or human studies that TORADOL induces or inhibits hepatic enzymes capable of metabolizing itself or other drugs ." ], "offsets": [ [ 0, 3704 ] ] } ]

[ { "id": "Ketorolac_ddi_T1", "type": "DRUG", "text": [ "Ketorolac" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T2", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 64, 72 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T3", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 74, 81 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T4", "type": "GROUP", "text": [ "Salicylate" ], "offsets": [ [ 83, 93 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T5", "type": "DRUG", "text": [ "Heparin" ], "offsets": [ [ 99, 106 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T6", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 131, 139 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T7", "type": "DRUG", "text": [ "ketorolac tromethamine" ], "offsets": [ [ 187, 209 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T8", "type": "DRUG", "text": [ "ketorolac" ], "offsets": [ [ 240, 249 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T9", "type": "DRUG", "text": [ "Ketorolac" ], "offsets": [ [ 293, 302 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T10", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 318, 325 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T11", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 408, 418 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T12", "type": "DRUG", "text": [ "ketorolac" ], "offsets": [ [ 448, 457 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T13", "type": "DRUG", "text": [ "ketorolac" ], "offsets": [ [ 558, 567 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T14", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 613, 620 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T15", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 622, 630 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T16", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 632, 641 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T17", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 643, 651 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T18", "type": "DRUG", "text": [ "piroxicam" ], "offsets": [ [ 653, 662 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T19", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 664, 677 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T20", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 679, 688 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T21", "type": "DRUG", "text": [ "ketorolac tromethamine" ], "offsets": [ [ 718, 740 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T22", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 859, 867 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T23", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 943, 951 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T24", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 1022, 1029 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T25", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 1187, 1194 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T26", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 1320, 1327 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T27", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1332, 1340 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T28", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 1344, 1351 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T29", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 1375, 1382 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T30", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1402, 1416 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T31", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 1496, 1506 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T32", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 1508, 1515 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T33", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 1534, 1542 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T34", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1555, 1565 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T35", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 1668, 1678 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T36", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 1710, 1717 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T37", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 1727, 1737 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T38", "type": "DRUG", "text": [ "ketorolac" ], "offsets": [ [ 1773, 1782 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T39", "type": "DRUG", "text": [ "ketorolac" ], "offsets": [ [ 1812, 1821 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T40", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 2017, 2024 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T41", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 2029, 2039 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T42", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 2060, 2067 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T43", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2089, 2096 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T44", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2141, 2148 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T45", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 2248, 2255 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T46", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2266, 2273 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T47", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2319, 2326 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T48", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 2348, 2355 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T49", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 2384, 2396 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T50", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2428, 2440 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T51", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2450, 2456 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T52", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2502, 2514 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T53", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2542, 2554 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T54", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 2570, 2577 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T55", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2581, 2593 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T56", "type": "GROUP", "text": [ "Nondepolarizing Muscle Relaxants" ], "offsets": [ [ 2626, 2658 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T57", "type": "GROUP", "text": [ "nondepolarizing muscle relaxants" ], "offsets": [ [ 2763, 2795 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T58", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 2842, 2849 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T59", "type": "GROUP", "text": [ "muscle relaxants" ], "offsets": [ [ 2855, 2871 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T60", "type": "GROUP", "text": [ "ACE Inhibitors" ], "offsets": [ [ 2903, 2917 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T61", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 2938, 2952 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T62", "type": "GROUP", "text": [ "Antiepileptic Drugs" ], "offsets": [ [ 3038, 3057 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T63", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 3131, 3138 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T64", "type": "GROUP", "text": [ "antiepileptic drugs" ], "offsets": [ [ 3143, 3162 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T65", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3164, 3173 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T66", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 3175, 3188 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T67", "type": "GROUP", "text": [ "Psychoactive Drugs" ], "offsets": [ [ 3191, 3209 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T68", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 3250, 3257 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T69", "type": "GROUP", "text": [ "psychoactive drugs" ], "offsets": [ [ 3286, 3304 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T70", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 3306, 3316 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T71", "type": "DRUG", "text": [ "thiothixene" ], "offsets": [ [ 3318, 3329 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T72", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 3331, 3341 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T73", "type": "DRUG", "text": [ "Morphine" ], "offsets": [ [ 3344, 3352 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T74", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 3407, 3415 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T75", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 3518, 3525 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T76", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 3530, 3538 ] ], "normalized": [] }, { "id": "Ketorolac_ddi_T77", "type": "BRAND", "text": [ "TORADOL" ], "offsets": [ [ 3613, 3620 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ketorolac_ddi_R1", "type": "MECHANISM", "arg1_id": "Ketorolac_ddi_T6", "arg2_id": "Ketorolac_ddi_T7", "normalized": [] }, { "id": "Ketorolac_ddi_R2", "type": "MECHANISM", "arg1_id": "Ketorolac_ddi_T11", "arg2_id": "Ketorolac_ddi_T12", "normalized": [] }, { "id": "Ketorolac_ddi_R3", "type": "ADVISE", "arg1_id": "Ketorolac_ddi_T29", "arg2_id": "Ketorolac_ddi_T30", "normalized": [] }, { "id": "Ketorolac_ddi_R4", "type": "EFFECT", "arg1_id": "Ketorolac_ddi_T32", "arg2_id": "Ketorolac_ddi_T34", "normalized": [] }, { "id": "Ketorolac_ddi_R5", "type": "MECHANISM", "arg1_id": "Ketorolac_ddi_T36", "arg2_id": "Ketorolac_ddi_T37", "normalized": [] }, { "id": "Ketorolac_ddi_R6", "type": "ADVISE", "arg1_id": "Ketorolac_ddi_T40", "arg2_id": "Ketorolac_ddi_T41", "normalized": [] }, { "id": "Ketorolac_ddi_R7", "type": "MECHANISM", "arg1_id": "Ketorolac_ddi_T47", "arg2_id": "Ketorolac_ddi_T48", "normalized": [] }, { "id": "Ketorolac_ddi_R8", "type": "MECHANISM", "arg1_id": "Ketorolac_ddi_T50", "arg2_id": "Ketorolac_ddi_T51", "normalized": [] }, { "id": "Ketorolac_ddi_R9", "type": "EFFECT", "arg1_id": "Ketorolac_ddi_T63", "arg2_id": "Ketorolac_ddi_T64", "normalized": [] }, { "id": "Ketorolac_ddi_R10", "type": "EFFECT", "arg1_id": "Ketorolac_ddi_T63", "arg2_id": "Ketorolac_ddi_T65", "normalized": [] }, { "id": "Ketorolac_ddi_R11", "type": "EFFECT", "arg1_id": "Ketorolac_ddi_T63", "arg2_id": "Ketorolac_ddi_T66", "normalized": [] }, { "id": "Ketorolac_ddi_R12", "type": "EFFECT", "arg1_id": "Ketorolac_ddi_T68", "arg2_id": "Ketorolac_ddi_T69", "normalized": [] }, { "id": "Ketorolac_ddi_R13", "type": "EFFECT", "arg1_id": "Ketorolac_ddi_T68", "arg2_id": "Ketorolac_ddi_T70", "normalized": [] }, { "id": "Ketorolac_ddi_R14", "type": "EFFECT", "arg1_id": "Ketorolac_ddi_T68", "arg2_id": "Ketorolac_ddi_T71", "normalized": [] }, { "id": "Ketorolac_ddi_R15", "type": "EFFECT", "arg1_id": "Ketorolac_ddi_T68", "arg2_id": "Ketorolac_ddi_T72", "normalized": [] } ]

[ { "id": "Flecainide_ddi__text", "type": "abstract", "text": [ "Drug Interactions. TAMBOCOR has been administered to patients receiving digitalis preparations or beta-adrenergic blocking agents without adverse effects. During administration of multiple oral doses of TAMBOCOR to healthy subjects stabilized on a maintenance dose of digoxin, a 13%-19% increase in plasma digoxin levels occurred at six hours postdose. In a study involving healthy subjects receiving TAMBOCOR and propranolol concurrently, plasma flecainide levels were increased about 20% and propranolol levels were increased about 30% compared to control values. In this formal interaction study, TAMBOCOR and propranolol were each found to have negative inotropic effects; when the drugs were administered together, the effects were additive. The effects of concomitant administration of TAMBOCOR and propranolol on the PR interval were less than additive. In TAMBOCOR clinical trials, patients who were receiving beta blockers concurrently did not experience an increased incidence of side effects. Nevertheless, the possibility of additive negative inotropic effects of beta blockers and flecainide should be recognized. Flecainide is not extensively bound to plasma proteins. In vitro studies with several drugs which may be administered concomitantly showed that the extent of flecainide binding to human plasma proteins is either unchanged or only slightly less. Consequently, interactions with other drugs which are highly protein bound (e.g., anticoagulants ) would not be expected. TAMBOCOR has been used in a large number of patients receiving diuretics without apparent interaction. Limited data in patients receiving known enzyme inducers ( phenytoin, phenobarbital, carbamazepine ) indicate only a 30% increase in the rate of flecainide elimination. In healthy subjects receiving cimetidine (1 gm daily) for one week, plasma flecainide levels increased by about 30% and half-life increased by about 10%. When amiodarone is added to flecainide therapy, plasma flecainide levels may increase two-fold or more in some patients, if flecainide dosage is not reduced. Drugs that inhibit cytochrome P450IID6, such as quinidine , might increase the plasma concentrations of flecainide in patients that are on chronic flecainide therapy; especially if these patients are extensive metabolizers. There has been little experience with the coadministration of TAMBOCOR and either disopyramide or verapamil. Because both of these drugs have negative inotropic properties and the effects of coadministration with TAMBOCOR are unknown, neither disopyramide nor verapamil should be administered concurrently with TAMBOCOR unless, in the judgment of the physician, the benefits of this combination outweigh the risks. There has been too little experience with the coadministration of TAMBOCOR with nifedipine or diltiazem to recommend concomitant use." ], "offsets": [ [ 0, 2850 ] ] } ]

[ { "id": "Flecainide_ddi_T1", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 19, 27 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T2", "type": "GROUP", "text": [ "digitalis preparations" ], "offsets": [ [ 72, 94 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T3", "type": "GROUP", "text": [ "beta-adrenergic blocking agents" ], "offsets": [ [ 98, 129 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T4", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 203, 211 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T5", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 268, 275 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T6", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 306, 313 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T7", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 401, 409 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T8", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 414, 425 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T9", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 447, 457 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T10", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 494, 505 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T11", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 600, 608 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T12", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 613, 624 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T13", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 792, 800 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T14", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 805, 816 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T15", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 864, 872 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T16", "type": "GROUP", "text": [ "beta blockers" ], "offsets": [ [ 918, 931 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T17", "type": "GROUP", "text": [ "beta blockers" ], "offsets": [ [ 1076, 1089 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T18", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1094, 1104 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T19", "type": "DRUG", "text": [ "Flecainide" ], "offsets": [ [ 1127, 1137 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T20", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1285, 1295 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T21", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1454, 1468 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T22", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 1494, 1502 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T23", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 1557, 1566 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T24", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1656, 1665 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T25", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1667, 1680 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T26", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1682, 1695 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T27", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1742, 1752 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T28", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1796, 1806 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T29", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1841, 1851 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T30", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 1925, 1935 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T31", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1948, 1958 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T32", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1975, 1985 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T33", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 2044, 2054 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T34", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 2126, 2135 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T35", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 2182, 2192 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T36", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 2225, 2235 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T37", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 2364, 2372 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T38", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 2384, 2396 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T39", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 2400, 2409 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T40", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 2515, 2523 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T41", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 2545, 2557 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T42", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 2562, 2571 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T43", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 2613, 2621 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T44", "type": "BRAND", "text": [ "TAMBOCOR" ], "offsets": [ [ 2783, 2791 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T45", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 2797, 2807 ] ], "normalized": [] }, { "id": "Flecainide_ddi_T46", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 2811, 2820 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Flecainide_ddi_R1", "type": "MECHANISM", "arg1_id": "Flecainide_ddi_T4", "arg2_id": "Flecainide_ddi_T5", "normalized": [] }, { "id": "Flecainide_ddi_R2", "type": "MECHANISM", "arg1_id": "Flecainide_ddi_T7", "arg2_id": "Flecainide_ddi_T8", "normalized": [] }, { "id": "Flecainide_ddi_R3", "type": "EFFECT", "arg1_id": "Flecainide_ddi_T13", "arg2_id": "Flecainide_ddi_T14", "normalized": [] }, { "id": "Flecainide_ddi_R4", "type": "EFFECT", "arg1_id": "Flecainide_ddi_T17", "arg2_id": "Flecainide_ddi_T18", "normalized": [] }, { "id": "Flecainide_ddi_R5", "type": "MECHANISM", "arg1_id": "Flecainide_ddi_T24", "arg2_id": "Flecainide_ddi_T27", "normalized": [] }, { "id": "Flecainide_ddi_R6", "type": "MECHANISM", "arg1_id": "Flecainide_ddi_T25", "arg2_id": "Flecainide_ddi_T27", "normalized": [] }, { "id": "Flecainide_ddi_R7", "type": "MECHANISM", "arg1_id": "Flecainide_ddi_T26", "arg2_id": "Flecainide_ddi_T27", "normalized": [] }, { "id": "Flecainide_ddi_R8", "type": "MECHANISM", "arg1_id": "Flecainide_ddi_T28", "arg2_id": "Flecainide_ddi_T29", "normalized": [] }, { "id": "Flecainide_ddi_R9", "type": "MECHANISM", "arg1_id": "Flecainide_ddi_T30", "arg2_id": "Flecainide_ddi_T31", "normalized": [] }, { "id": "Flecainide_ddi_R10", "type": "MECHANISM", "arg1_id": "Flecainide_ddi_T34", "arg2_id": "Flecainide_ddi_T35", "normalized": [] }, { "id": "Flecainide_ddi_R11", "type": "ADVISE", "arg1_id": "Flecainide_ddi_T41", "arg2_id": "Flecainide_ddi_T43", "normalized": [] }, { "id": "Flecainide_ddi_R12", "type": "ADVISE", "arg1_id": "Flecainide_ddi_T42", "arg2_id": "Flecainide_ddi_T43", "normalized": [] } ]

[ { "id": "Anileridine_ddi__text", "type": "abstract", "text": [ "Caution should be observed when anileridine is coadministered with other opioids, sedatives, phenothiazines, or anesthetics, as these agents may increase respiratory and circulatory depression." ], "offsets": [ [ 0, 193 ] ] } ]

[ { "id": "Anileridine_ddi_T1", "type": "DRUG", "text": [ "anileridine" ], "offsets": [ [ 32, 43 ] ], "normalized": [] }, { "id": "Anileridine_ddi_T2", "type": "GROUP", "text": [ "opioids" ], "offsets": [ [ 73, 80 ] ], "normalized": [] }, { "id": "Anileridine_ddi_T3", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 82, 91 ] ], "normalized": [] }, { "id": "Anileridine_ddi_T4", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 93, 107 ] ], "normalized": [] }, { "id": "Anileridine_ddi_T5", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 112, 123 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Anileridine_ddi_R1", "type": "ADVISE", "arg1_id": "Anileridine_ddi_T1", "arg2_id": "Anileridine_ddi_T2", "normalized": [] }, { "id": "Anileridine_ddi_R2", "type": "ADVISE", "arg1_id": "Anileridine_ddi_T1", "arg2_id": "Anileridine_ddi_T3", "normalized": [] }, { "id": "Anileridine_ddi_R3", "type": "ADVISE", "arg1_id": "Anileridine_ddi_T1", "arg2_id": "Anileridine_ddi_T4", "normalized": [] }, { "id": "Anileridine_ddi_R4", "type": "ADVISE", "arg1_id": "Anileridine_ddi_T1", "arg2_id": "Anileridine_ddi_T5", "normalized": [] } ]

[ { "id": "Tiagabine_ddi__text", "type": "abstract", "text": [ "In evaluating the potential for interactions among co-administered antiepilepsy drugs (AEDs), whether or not an AED induces or does not induce metabolic enzymes is an important consideration. Phenytoin, phenobarbital and carbamazepine are ge nerally classified as enzyme inducers; valproate and gabapentin are not. GABITRIL is considered to be a non-enzyme inducing AED. The drug interaction data described in this section were obtained from studies involving either healthy subjects or patients with epilepsy. Effects of GABITRIL on other Antiepilepsy Drugs (AEDs) : Phenytoin: Tiagabine had no effect on the steady-state plasma concentrations of phenytoin in patients with epilepsy. Carbamazepine: Tiagabine had no effect on the steady-state plasma concentrations of carbamazepine or its epoxide metabolite in patients with epilepsy. Valproate: Tiagabine causes a slight decrease (about 10%) in steady-state valproate concentrations. Phenobarbital or Primidone : No formal pharmacokinetic studies have been performed examining the addition of tiagabine to regimens containing phenobarbital or primidone. The addition of tiagabine in a limited number of patients in three well-controlled studies caused no systematic changes in phenobarbital or primidone concentrations when compared to placebo. Effects of other Antiepilepsy Drugs (AEDs) on GABITRIL : Carbamazepine: Population pharmacokinetic analyses indicate that tiagabine clearance is 60% greater in patients taking carbamazepine with or without other enzyme- inducing AEDs. Phenytoin: Population pharmacokinetic analyses indicate that tiagabine clearance is 60% greater in patients taking phenytoin with or without other enzyme- inducing AEDs. Phenobarbital (Primidone): Population pharmacokinetic analyses indicate that tiagabine clearance is 60% greater in patients taking phenobarbital (primidone) with or without other enzyme-inducing AEDs. Valproate: The addition of tiagabine to patients taking valproate chronically had no effect on tiagabine pharmacokinetics, but valproate significantly decreased tiagabine binding in vitro from 96.3 to 94.8%, which resulted in an increase of approximately 40% in the free tiagabine concentration. The clinical relevance of this in vitro finding is unknown. Interaction of GABITRIL with Other Drugs : Cimetidine : Co-administration of cimetidine (800 mg/day) to patients taking tiagabine chronically had no effect on tiagabine pharmacokinetics. Theophylline: A single 10 mg dose of tiagabine did not affect the pharmacokinetics of theophylline at steady state. Warfarin: No significant differences were observed in the steady-state pharmacokinetics of R-warfarin or S-warfarin with the addition of tiagabine given as a single dose. Prothrombin times were not affected by tiagabine. Digoxin: Concomitant administration of tiagabine did not affect the steady-state pharmacokinetics of digoxin or the mean daily trough serum level of digoxin. Ethanol or Triazolam: No significant differences were observed in the pharmacokinetics of triazolam (0.125 mg) and tiagabine (10 mg) when given together as a single dose. The pharmacokinetics of ethanol were not affected by multiple-dose administration of tiagabine. Tiagabine has shown no clinically important potentiation of the pharmacodynamic effects of triazo lam or alcohol. Because of the possible additive effects of drugs that may depress the nervous system, ethanol or triazolam should be used cautiously in combination with tiagabine. Oral Contraceptives: Multiple dose administration of tiagabine (8 mg/day monotherapy) did not alter the pharmacokinetics of oral contraceptives in healthy women of childbearing age. Antipyrine : Antipyrine pharmacokinetics were not significantly different before and after tiagabine multiple-dose regimens. This indicates that tiagabine does not cause induction or inhibition of the hepatic microsomal enzyme systems responsible for the metabolism of antipyrine. Interaction of GABITRIL with Highly Protein Bound Drugs: In vitro data showed that tiagabine is 96% bound to human plasma protein and therefore has the potential to interact with other highly protein bound compounds. Such an interaction can potentially lead to higher free fractions of either tiagabine or the competing drug." ], "offsets": [ [ 0, 4275 ] ] } ]

[ { "id": "Tiagabine_ddi_T1", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 87, 91 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T2", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 112, 115 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T3", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 192, 201 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T4", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 203, 216 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T5", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 221, 234 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T6", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 281, 290 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T7", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 295, 305 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T8", "type": "BRAND", "text": [ "GABITRIL" ], "offsets": [ [ 315, 323 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T9", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 366, 369 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T10", "type": "BRAND", "text": [ "GABITRIL" ], "offsets": [ [ 522, 530 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T11", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 560, 564 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T12", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 568, 577 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T13", "type": "DRUG", "text": [ "Tiagabine" ], "offsets": [ [ 579, 588 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T14", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 648, 657 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T15", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 685, 698 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T16", "type": "DRUG", "text": [ "Tiagabine" ], "offsets": [ [ 700, 709 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T17", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 769, 782 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T18", "type": "DRUG", "text": [ "Valproate" ], "offsets": [ [ 836, 845 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T19", "type": "DRUG", "text": [ "Tiagabine" ], "offsets": [ [ 847, 856 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T20", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 910, 919 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T21", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 936, 949 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T22", "type": "DRUG", "text": [ "Primidone" ], "offsets": [ [ 953, 962 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T23", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 1045, 1054 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T24", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1078, 1091 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T25", "type": "DRUG", "text": [ "primidone" ], "offsets": [ [ 1095, 1104 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T26", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 1122, 1131 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T27", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1229, 1242 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T28", "type": "DRUG", "text": [ "primidone" ], "offsets": [ [ 1246, 1255 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T29", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 1334, 1338 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T30", "type": "BRAND", "text": [ "GABITRIL" ], "offsets": [ [ 1343, 1351 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T31", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 1354, 1367 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T32", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 1419, 1428 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T33", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1473, 1486 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T34", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 1526, 1530 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T35", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 1532, 1541 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T36", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 1593, 1602 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T37", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1647, 1656 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T38", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 1696, 1700 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T39", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 1702, 1715 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T40", "type": "DRUG", "text": [ "Primidone" ], "offsets": [ [ 1717, 1726 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T41", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 1779, 1788 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T42", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1833, 1846 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T43", "type": "DRUG", "text": [ "primidone" ], "offsets": [ [ 1848, 1857 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T44", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 1897, 1901 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T45", "type": "DRUG", "text": [ "Valproate" ], "offsets": [ [ 1903, 1912 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T46", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 1930, 1939 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T47", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 1959, 1968 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T48", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 1998, 2007 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T49", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2030, 2039 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T50", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 2064, 2073 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T51", "type": "BRAND", "text": [ "GABITRIL" ], "offsets": [ [ 2274, 2282 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T52", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 2302, 2312 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T53", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2336, 2346 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T54", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 2379, 2388 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T55", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 2418, 2427 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T56", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 2446, 2458 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T57", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 2483, 2492 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T58", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2532, 2544 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T59", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 2562, 2570 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T60", "type": "DRUG", "text": [ "R-warfarin" ], "offsets": [ [ 2653, 2663 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T61", "type": "DRUG", "text": [ "S-warfarin" ], "offsets": [ [ 2667, 2677 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T62", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 2699, 2708 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T63", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 2772, 2781 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T64", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 2783, 2790 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T65", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 2822, 2831 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T66", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2884, 2891 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T67", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2932, 2939 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T68", "type": "DRUG", "text": [ "Ethanol" ], "offsets": [ [ 2941, 2948 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T69", "type": "DRUG", "text": [ "Triazolam" ], "offsets": [ [ 2952, 2961 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T70", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 3031, 3040 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T71", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 3056, 3065 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T72", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 3136, 3143 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T73", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 3197, 3206 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T74", "type": "DRUG", "text": [ "Tiagabine" ], "offsets": [ [ 3208, 3217 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T75", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 3313, 3320 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T76", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 3409, 3416 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T77", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 3420, 3429 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T78", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 3476, 3485 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T79", "type": "GROUP", "text": [ "Contraceptives" ], "offsets": [ [ 3492, 3506 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T80", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 3540, 3549 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T81", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 3616, 3630 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T82", "type": "DRUG", "text": [ "Antipyrine" ], "offsets": [ [ 3669, 3679 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T83", "type": "DRUG", "text": [ "Antipyrine" ], "offsets": [ [ 3682, 3692 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T84", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 3760, 3769 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T85", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 3814, 3823 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T86", "type": "DRUG", "text": [ "antipyrine" ], "offsets": [ [ 3938, 3948 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T87", "type": "BRAND", "text": [ "GABITRIL" ], "offsets": [ [ 3965, 3973 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T88", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 4033, 4042 ] ], "normalized": [] }, { "id": "Tiagabine_ddi_T89", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 4243, 4252 ] ], "normalized": [] } ]

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[ { "id": "Tiagabine_ddi_R1", "type": "MECHANISM", "arg1_id": "Tiagabine_ddi_T19", "arg2_id": "Tiagabine_ddi_T20", "normalized": [] }, { "id": "Tiagabine_ddi_R2", "type": "MECHANISM", "arg1_id": "Tiagabine_ddi_T32", "arg2_id": "Tiagabine_ddi_T33", "normalized": [] }, { "id": "Tiagabine_ddi_R3", "type": "MECHANISM", "arg1_id": "Tiagabine_ddi_T36", "arg2_id": "Tiagabine_ddi_T37", "normalized": [] }, { "id": "Tiagabine_ddi_R4", "type": "MECHANISM", "arg1_id": "Tiagabine_ddi_T41", "arg2_id": "Tiagabine_ddi_T42", "normalized": [] }, { "id": "Tiagabine_ddi_R5", "type": "MECHANISM", "arg1_id": "Tiagabine_ddi_T41", "arg2_id": "Tiagabine_ddi_T43", "normalized": [] }, { "id": "Tiagabine_ddi_R6", "type": "MECHANISM", "arg1_id": "Tiagabine_ddi_T49", "arg2_id": "Tiagabine_ddi_T50", "normalized": [] }, { "id": "Tiagabine_ddi_R7", "type": "ADVISE", "arg1_id": "Tiagabine_ddi_T76", "arg2_id": "Tiagabine_ddi_T78", "normalized": [] }, { "id": "Tiagabine_ddi_R8", "type": "ADVISE", "arg1_id": "Tiagabine_ddi_T77", "arg2_id": "Tiagabine_ddi_T78", "normalized": [] } ]

[ { "id": "Piperacillin_ddi__text", "type": "abstract", "text": [ "Aminoglycosides: The mixing of piperacillin with an aminoglycoside in vitro can result in substantial inactivation of the aminoglycoside. Vecuronium: When used in the perioperative period, piperacillin has been implicated in the prolongation of the neuromuscular blockade of vecuronium. Caution is indicated when piperacillin is used perioperatively. In one controlled clinical study, the ureidopenicillins, including piperacillin, were reported to prolong the action of vecuronium. Due to their similar mechanism of action, it is expected that the neuromuscular blockade produced by any of the non-depolarizing muscle relaxants could be prolonged in the presence of piperacillin. Probenecid: The oral combination of probenecid before intramuscular injection of PIPRACIL produces an increase in piperacillin peak serum level of about 30%. Anticoagulants: Coagulation parameters should be tested more frequently and monitored regularly during simultaneous administration of high doses of heparin, oral anticoagulants, or other drugs that may affect the blood coagulation system or the thrombocyte function. Methotrexate: Piperacillin sodium may reduce the excretion of methotrexate. Therefore, serum levels of methotrexate should be monitored in patients to avoid drug toxicity. Drug/Laboratory Test Interactions As with other penicillins, the administration of PIPRACIL may result in a false-positive reaction for glucose in the urine using a copper-reduction method. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used. There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving piperacillin/tazobactam injection who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with the Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving piperacillin should be interpreted cautiously and confirmed by other diagnostic methods." ], "offsets": [ [ 0, 2084 ] ] } ]

[ { "id": "Piperacillin_ddi_T1", "type": "GROUP", "text": [ "Aminoglycosides" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T2", "type": "DRUG", "text": [ "piperacillin" ], "offsets": [ [ 31, 43 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T3", "type": "GROUP", "text": [ "aminoglycoside" ], "offsets": [ [ 52, 66 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T4", "type": "GROUP", "text": [ "aminoglycoside" ], "offsets": [ [ 122, 136 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T5", "type": "DRUG", "text": [ "Vecuronium" ], "offsets": [ [ 138, 148 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T6", "type": "DRUG", "text": [ "piperacillin" ], "offsets": [ [ 189, 201 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T7", "type": "DRUG", "text": [ "vecuronium" ], "offsets": [ [ 275, 285 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T8", "type": "DRUG", "text": [ "piperacillin" ], "offsets": [ [ 313, 325 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T9", "type": "DRUG", "text": [ "piperacillin" ], "offsets": [ [ 418, 430 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T10", "type": "DRUG", "text": [ "vecuronium" ], "offsets": [ [ 471, 481 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T11", "type": "GROUP", "text": [ "non-depolarizing muscle relaxants" ], "offsets": [ [ 595, 628 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T12", "type": "DRUG", "text": [ "piperacillin" ], "offsets": [ [ 667, 679 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T13", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 681, 691 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T14", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 717, 727 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T15", "type": "BRAND", "text": [ "PIPRACIL" ], "offsets": [ [ 762, 770 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T16", "type": "DRUG", "text": [ "piperacillin" ], "offsets": [ [ 795, 807 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T17", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 839, 853 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T18", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 987, 994 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T19", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1001, 1015 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T20", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 1106, 1118 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T21", "type": "DRUG", "text": [ "Piperacillin sodium" ], "offsets": [ [ 1120, 1139 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T22", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1168, 1180 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T23", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1209, 1221 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T24", "type": "DRUG", "text": [ "penicillins" ], "offsets": [ [ 1326, 1337 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T25", "type": "BRAND", "text": [ "PIPRACIL" ], "offsets": [ [ 1361, 1369 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T26", "type": "DRUG", "text": [ "piperacillin" ], "offsets": [ [ 1691, 1703 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T27", "type": "DRUG", "text": [ "tazobactam" ], "offsets": [ [ 1704, 1714 ] ], "normalized": [] }, { "id": "Piperacillin_ddi_T28", "type": "DRUG", "text": [ "piperacillin" ], "offsets": [ [ 1996, 2008 ] ], "normalized": [] } ]

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[ { "id": "Piperacillin_ddi_R1", "type": "EFFECT", "arg1_id": "Piperacillin_ddi_T2", "arg2_id": "Piperacillin_ddi_T3", "normalized": [] }, { "id": "Piperacillin_ddi_R2", "type": "EFFECT", "arg1_id": "Piperacillin_ddi_T6", "arg2_id": "Piperacillin_ddi_T7", "normalized": [] }, { "id": "Piperacillin_ddi_R3", "type": "EFFECT", "arg1_id": "Piperacillin_ddi_T9", "arg2_id": "Piperacillin_ddi_T10", "normalized": [] }, { "id": "Piperacillin_ddi_R4", "type": "EFFECT", "arg1_id": "Piperacillin_ddi_T11", "arg2_id": "Piperacillin_ddi_T12", "normalized": [] }, { "id": "Piperacillin_ddi_R5", "type": "MECHANISM", "arg1_id": "Piperacillin_ddi_T14", "arg2_id": "Piperacillin_ddi_T15", "normalized": [] }, { "id": "Piperacillin_ddi_R6", "type": "MECHANISM", "arg1_id": "Piperacillin_ddi_T21", "arg2_id": "Piperacillin_ddi_T22", "normalized": [] } ]

[ { "id": "Nimodipine_ddi__text", "type": "abstract", "text": [ "It is possible that the cardiovascular action of other calcium channel blockers could be enhanced by the addition of Nimotop . In Europe, Nimotop was observed to occasionally intensify the effect of antihypertensive compounds taken concomitantly by patients suffering from hypertension; this phenomenon was not observed in North American clinical trials. A study in eight healthy volunteers has shown a 50% increase in mean peak nimodipine plasma concentrations and a 90% increase in mean area under the curve, after a one week course of cimetidine at 1,000 mg/day and nimodipine at 90 mg/day. This effect may be mediated by the known inhibition of hepatic cytochrome P- 450 by cimetidine, which could decrease first pass metabolism of nimodipine." ], "offsets": [ [ 0, 748 ] ] } ]

[ { "id": "Nimodipine_ddi_T1", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 55, 79 ] ], "normalized": [] }, { "id": "Nimodipine_ddi_T2", "type": "BRAND", "text": [ "Nimotop" ], "offsets": [ [ 117, 124 ] ], "normalized": [] }, { "id": "Nimodipine_ddi_T3", "type": "BRAND", "text": [ "Nimotop" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "Nimodipine_ddi_T4", "type": "GROUP", "text": [ "antihypertensive compounds" ], "offsets": [ [ 200, 226 ] ], "normalized": [] }, { "id": "Nimodipine_ddi_T5", "type": "DRUG", "text": [ "nimodipine" ], "offsets": [ [ 430, 440 ] ], "normalized": [] }, { "id": "Nimodipine_ddi_T6", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 539, 549 ] ], "normalized": [] }, { "id": "Nimodipine_ddi_T7", "type": "DRUG", "text": [ "nimodipine" ], "offsets": [ [ 570, 580 ] ], "normalized": [] }, { "id": "Nimodipine_ddi_T8", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 679, 689 ] ], "normalized": [] }, { "id": "Nimodipine_ddi_T9", "type": "DRUG", "text": [ "nimodipine" ], "offsets": [ [ 737, 747 ] ], "normalized": [] } ]

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[ { "id": "Nimodipine_ddi_R1", "type": "EFFECT", "arg1_id": "Nimodipine_ddi_T1", "arg2_id": "Nimodipine_ddi_T2", "normalized": [] }, { "id": "Nimodipine_ddi_R2", "type": "EFFECT", "arg1_id": "Nimodipine_ddi_T3", "arg2_id": "Nimodipine_ddi_T4", "normalized": [] }, { "id": "Nimodipine_ddi_R3", "type": "MECHANISM", "arg1_id": "Nimodipine_ddi_T6", "arg2_id": "Nimodipine_ddi_T7", "normalized": [] } ]

[ { "id": "Nedocromil_ddi__text", "type": "abstract", "text": [ "In clinical studies, Tilade has been co-administered with other anti-asthma medications, including inhaled and oral bronchodilators, and inhaled corticosteroids, with no evidence of increased frequency of adverse events or laboratory abnormalities. No formal drug-drug interaction studies, however, have been conducted." ], "offsets": [ [ 0, 319 ] ] } ]

[ { "id": "Nedocromil_ddi_T1", "type": "BRAND", "text": [ "Tilade" ], "offsets": [ [ 21, 27 ] ], "normalized": [] }, { "id": "Nedocromil_ddi_T2", "type": "GROUP", "text": [ "bronchodilators" ], "offsets": [ [ 116, 131 ] ], "normalized": [] }, { "id": "Nedocromil_ddi_T3", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 145, 160 ] ], "normalized": [] } ]

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[ { "id": "Etoposide_ddi__text", "type": "abstract", "text": [ "Caution should be exercised when administering ETOPOPHOS with drugs that are known to inhibit phosphatase activities (e.g., levamisole hydrochloride). High-dose cyclosporin A resulting in concentrations above 2000 ng/mL administered with oral etoposide has led to an 80% increase in etoposide exposure with a 38% decrease in total body clearance of etoposide compared to etoposide alone." ], "offsets": [ [ 0, 387 ] ] } ]

[ { "id": "Etoposide_ddi_T1", "type": "BRAND", "text": [ "ETOPOPHOS" ], "offsets": [ [ 47, 56 ] ], "normalized": [] }, { "id": "Etoposide_ddi_T2", "type": "DRUG", "text": [ "levamisole hydrochloride" ], "offsets": [ [ 124, 148 ] ], "normalized": [] }, { "id": "Etoposide_ddi_T3", "type": "DRUG", "text": [ "cyclosporin A" ], "offsets": [ [ 161, 174 ] ], "normalized": [] }, { "id": "Etoposide_ddi_T4", "type": "DRUG", "text": [ "etoposide" ], "offsets": [ [ 243, 252 ] ], "normalized": [] }, { "id": "Etoposide_ddi_T5", "type": "DRUG", "text": [ "etoposide" ], "offsets": [ [ 283, 292 ] ], "normalized": [] }, { "id": "Etoposide_ddi_T6", "type": "DRUG", "text": [ "etoposide" ], "offsets": [ [ 349, 358 ] ], "normalized": [] }, { "id": "Etoposide_ddi_T7", "type": "DRUG", "text": [ "etoposide" ], "offsets": [ [ 371, 380 ] ], "normalized": [] } ]

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[ { "id": "Etoposide_ddi_R1", "type": "ADVISE", "arg1_id": "Etoposide_ddi_T1", "arg2_id": "Etoposide_ddi_T2", "normalized": [] }, { "id": "Etoposide_ddi_R2", "type": "MECHANISM", "arg1_id": "Etoposide_ddi_T3", "arg2_id": "Etoposide_ddi_T4", "normalized": [] } ]

[ { "id": "Ipratropium_ddi__text", "type": "abstract", "text": [ "ATROVENT Inhalation Aerosol has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines, and steroids, commonly used in the treatment of chronic obstructive pulmonary disease. With the exception of albuterol, there are no formal studies fully evaluating the interaction effects of ATROVENT Inhalation Aerosol and these drugs with respect to effectiveness. Anticholinergic agents: Although ipratropium bromide is minimally absorbed into the systemic circulation, there is some potential for an additive interaction with concomitantly used anticholinergic medications. Caution is therefore advised in the coadministration of ATROVENT Inhalation Aerosol with other anticholinergic-containing drugs." ], "offsets": [ [ 0, 740 ] ] } ]

[ { "id": "Ipratropium_ddi_T1", "type": "BRAND", "text": [ "ATROVENT" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T2", "type": "GROUP", "text": [ "sympathomimetic bronchodilators" ], "offsets": [ [ 84, 115 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T3", "type": "GROUP", "text": [ "methylxanthines" ], "offsets": [ [ 117, 132 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T4", "type": "GROUP", "text": [ "steroids" ], "offsets": [ [ 138, 146 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T5", "type": "DRUG", "text": [ "albuterol" ], "offsets": [ [ 243, 252 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T6", "type": "BRAND", "text": [ "ATROVENT" ], "offsets": [ [ 326, 334 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T7", "type": "GROUP", "text": [ "Anticholinergic agents" ], "offsets": [ [ 401, 423 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T8", "type": "DRUG", "text": [ "ipratropium bromide" ], "offsets": [ [ 434, 453 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T9", "type": "GROUP", "text": [ "anticholinergic medications" ], "offsets": [ [ 583, 610 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T10", "type": "BRAND", "text": [ "ATROVENT" ], "offsets": [ [ 668, 676 ] ], "normalized": [] }, { "id": "Ipratropium_ddi_T11", "type": "GROUP", "text": [ "anticholinergic" ], "offsets": [ [ 707, 722 ] ], "normalized": [] } ]

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[ { "id": "Ipratropium_ddi_R1", "type": "EFFECT", "arg1_id": "Ipratropium_ddi_T8", "arg2_id": "Ipratropium_ddi_T9", "normalized": [] }, { "id": "Ipratropium_ddi_R2", "type": "ADVISE", "arg1_id": "Ipratropium_ddi_T10", "arg2_id": "Ipratropium_ddi_T11", "normalized": [] } ]

[ { "id": "Desmopressin_ddi__text", "type": "abstract", "text": [ "Although the pressor activity of Desmopressin is very low compared to its antidiuretic activity, large doses of Desmopressin Tablets should be used with other pressor agents only with careful patient monitoring." ], "offsets": [ [ 0, 211 ] ] } ]

[ { "id": "Desmopressin_ddi_T1", "type": "DRUG", "text": [ "Desmopressin" ], "offsets": [ [ 33, 45 ] ], "normalized": [] }, { "id": "Desmopressin_ddi_T2", "type": "DRUG", "text": [ "Desmopressin" ], "offsets": [ [ 112, 124 ] ], "normalized": [] } ]

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[ { "id": "Nilutamide_ddi__text", "type": "abstract", "text": [ "In vitro, nilutamide has been shown to inhibit the activity of liver cytochrome P-450 isoenzymes and therefore, may reduce the metabolism of compounds requiring these systems. Consequently, drugs with a low therapeutic margin, such as vitamin K antagonists, phenytoin, and theophylline, could have a delayed elimination and increases in their serum half-life leading to a toxic level. The dosage of these drugs or others with a similar metabolism may need to be modified if they are administered concomitantly with nilutamide. For example, when vitamin K antagonists are administered concomitantly with nilutamide, prothrombin time should be carefully monitored and if necessary, the dosage of vitamin K antagonists should be reduced." ], "offsets": [ [ 0, 734 ] ] } ]

[ { "id": "Nilutamide_ddi_T1", "type": "DRUG", "text": [ "nilutamide" ], "offsets": [ [ 10, 20 ] ], "normalized": [] }, { "id": "Nilutamide_ddi_T2", "type": "GROUP", "text": [ "vitamin K antagonists" ], "offsets": [ [ 235, 256 ] ], "normalized": [] }, { "id": "Nilutamide_ddi_T3", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 258, 267 ] ], "normalized": [] }, { "id": "Nilutamide_ddi_T4", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 273, 285 ] ], "normalized": [] }, { "id": "Nilutamide_ddi_T5", "type": "DRUG", "text": [ "nilutamide" ], "offsets": [ [ 515, 525 ] ], "normalized": [] }, { "id": "Nilutamide_ddi_T6", "type": "GROUP", "text": [ "vitamin K antagonists" ], "offsets": [ [ 545, 566 ] ], "normalized": [] }, { "id": "Nilutamide_ddi_T7", "type": "DRUG", "text": [ "nilutamide" ], "offsets": [ [ 603, 613 ] ], "normalized": [] }, { "id": "Nilutamide_ddi_T8", "type": "GROUP", "text": [ "vitamin K antagonists" ], "offsets": [ [ 694, 715 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Nilutamide_ddi_R1", "type": "ADVISE", "arg1_id": "Nilutamide_ddi_T6", "arg2_id": "Nilutamide_ddi_T7", "normalized": [] } ]

[ { "id": "Aciclovir_ddi__text", "type": "abstract", "text": [ "Co-administration of probenecid with acyclovir has been shown to increase the mean half-life and the area under the concentration-time curve. Urinary excretion and renal clearance were correspondingly reduced. The clinical effects of this combination have not been studied." ], "offsets": [ [ 0, 273 ] ] } ]

[ { "id": "Aciclovir_ddi_T1", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 21, 31 ] ], "normalized": [] }, { "id": "Aciclovir_ddi_T2", "type": "DRUG", "text": [ "acyclovir" ], "offsets": [ [ 37, 46 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Aciclovir_ddi_R1", "type": "MECHANISM", "arg1_id": "Aciclovir_ddi_T1", "arg2_id": "Aciclovir_ddi_T2", "normalized": [] } ]

[ { "id": "Cyclophosphamide_ddi__text", "type": "abstract", "text": [ "The rate of metabolism and the leukopenic activity of cyclophosphamide reportedly are increased by chronic administration of high doses of phenobarbital. The physician should be alert for possible combined drug actions, desirable or undesirable, involving cyclophosphamide even though cyclophosphamide has been used successfully concurrently with other drugs, including other cytotoxic drugs. Cyclophosphamide treatment, which causes a marked and persistent inhibition of cholinesterase activity, potentiates the effect of succinylcholine chloride. If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, the anesthesiologist should be alerted." ], "offsets": [ [ 0, 678 ] ] } ]

[ { "id": "Cyclophosphamide_ddi_T1", "type": "DRUG", "text": [ "cyclophosphamide" ], "offsets": [ [ 54, 70 ] ], "normalized": [] }, { "id": "Cyclophosphamide_ddi_T2", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 139, 152 ] ], "normalized": [] }, { "id": "Cyclophosphamide_ddi_T3", "type": "DRUG", "text": [ "cyclophosphamide" ], "offsets": [ [ 256, 272 ] ], "normalized": [] }, { "id": "Cyclophosphamide_ddi_T4", "type": "DRUG", "text": [ "cyclophosphamide" ], "offsets": [ [ 285, 301 ] ], "normalized": [] }, { "id": "Cyclophosphamide_ddi_T5", "type": "DRUG", "text": [ "Cyclophosphamide" ], "offsets": [ [ 393, 409 ] ], "normalized": [] }, { "id": "Cyclophosphamide_ddi_T6", "type": "DRUG", "text": [ "succinylcholine chloride" ], "offsets": [ [ 523, 547 ] ], "normalized": [] }, { "id": "Cyclophosphamide_ddi_T7", "type": "DRUG", "text": [ "cyclophosphamide" ], "offsets": [ [ 584, 600 ] ], "normalized": [] } ]

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[]

[ { "id": "Cyclophosphamide_ddi_R1", "type": "MECHANISM", "arg1_id": "Cyclophosphamide_ddi_T1", "arg2_id": "Cyclophosphamide_ddi_T2", "normalized": [] }, { "id": "Cyclophosphamide_ddi_R2", "type": "EFFECT", "arg1_id": "Cyclophosphamide_ddi_T5", "arg2_id": "Cyclophosphamide_ddi_T6", "normalized": [] } ]

[ { "id": "Arformoterol_ddi__text", "type": "abstract", "text": [ "If additional adrenergic drugs are to be administered by any route, they should be used with caution because the pharmacologically predictable sympathetic effects of BROVANA may be potentiated. When paroxetine, a potent inhibitor of CYP2D6, was co-administered with BROVANA at steady-state, exposure to either drug was not altered. Dosage adjustments of BROVANA are not necessary when the drug is given concomitantly with potent CYP2D6 inhibitors. Concomitant treatment with methylxanthines (aminophylline, theophylline), steroids, or diuretics may potentiate any hypokalemic effect of adrenergic agonists. The ECG changes and/or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the co-administration of beta-agonists with non-potassium sparing diuretics. BROVANA, as with other beta2-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval because the action of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias. The concurrent use of intravenously or orally administered methylxanthines (e.g., aminophylline, theophylline) by patients receiving BROVANA has not been completely evaluated. In two combined 12-week placebo controlled trials that included BROVANA doses of 15 mcg twice daily, 25 mcg twice daily, and 50 mcg once daily, 54 of 873 BROVANA -treated subjects received concomitant theophylline at study entry. In a 12-month controlled trial that included a 50 mcg once daily BROVANA dose, 30 of the 528 BROVANA -treated subjects received concomitant theophylline at study entry. In these trials, heart rate and systolic blood pressure were approximately 2-3 bpm and 6-8 mm Hg higher, respectively, in subjects on concomitant theophylline compared with the overall population. Beta-adrenergic receptor antagonists (beta-blockers) and BROVANA may interfere with the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in COPD patients. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution." ], "offsets": [ [ 0, 2868 ] ] } ]

[ { "id": "Arformoterol_ddi_T1", "type": "GROUP", "text": [ "adrenergic drugs" ], "offsets": [ [ 14, 30 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T2", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 166, 173 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T3", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 199, 209 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T4", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 266, 273 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T5", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 354, 361 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T6", "type": "GROUP", "text": [ "methylxanthines" ], "offsets": [ [ 475, 490 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T7", "type": "DRUG", "text": [ "aminophylline" ], "offsets": [ [ 492, 505 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T8", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 507, 519 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T9", "type": "GROUP", "text": [ "steroids" ], "offsets": [ [ 522, 530 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T10", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 535, 544 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T11", "type": "GROUP", "text": [ "adrenergic agonists" ], "offsets": [ [ 586, 605 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T12", "type": "GROUP", "text": [ "non-potassium sparing diuretics" ], "offsets": [ [ 685, 716 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T13", "type": "GROUP", "text": [ "loop", "diuretics" ], "offsets": [ [ 726, 730 ], [ 743, 752 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T14", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 734, 752 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T15", "type": "GROUP", "text": [ "beta-agonists" ], "offsets": [ [ 781, 794 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T16", "type": "GROUP", "text": [ "beta-agonist" ], "offsets": [ [ 840, 852 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T17", "type": "GROUP", "text": [ "beta-agonists" ], "offsets": [ [ 979, 992 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T18", "type": "GROUP", "text": [ "non-potassium sparing diuretics" ], "offsets": [ [ 998, 1029 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T19", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 1031, 1038 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T20", "type": "GROUP", "text": [ "beta2-agonists" ], "offsets": [ [ 1054, 1068 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T21", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 1145, 1173 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T22", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 1175, 1200 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T23", "type": "GROUP", "text": [ "adrenergic agonists" ], "offsets": [ [ 1267, 1286 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T24", "type": "GROUP", "text": [ "methylxanthines" ], "offsets": [ [ 1511, 1526 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T25", "type": "DRUG", "text": [ "aminophylline" ], "offsets": [ [ 1534, 1547 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T26", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1549, 1561 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T27", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 1585, 1592 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T28", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 1692, 1699 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T29", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 1782, 1789 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T30", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1829, 1841 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T31", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 1923, 1930 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T32", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 1951, 1958 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T33", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1998, 2010 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T34", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2173, 2185 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T35", "type": "GROUP", "text": [ "Beta-adrenergic receptor antagonists" ], "offsets": [ [ 2224, 2260 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T36", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 2262, 2275 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T37", "type": "BRAND", "text": [ "BROVANA" ], "offsets": [ [ 2281, 2288 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T38", "type": "GROUP", "text": [ "Beta-blockers" ], "offsets": [ [ 2365, 2378 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T39", "type": "GROUP", "text": [ "beta-agonists" ], "offsets": [ [ 2421, 2434 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T40", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 2556, 2569 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T41", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 2713, 2726 ] ], "normalized": [] }, { "id": "Arformoterol_ddi_T42", "type": "GROUP", "text": [ "cardioselective beta-blockers" ], "offsets": [ [ 2767, 2796 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Arformoterol_ddi_R1", "type": "ADVISE", "arg1_id": "Arformoterol_ddi_T1", "arg2_id": "Arformoterol_ddi_T2", "normalized": [] }, { "id": "Arformoterol_ddi_R2", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T6", "arg2_id": "Arformoterol_ddi_T11", "normalized": [] }, { "id": "Arformoterol_ddi_R3", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T7", "arg2_id": "Arformoterol_ddi_T11", "normalized": [] }, { "id": "Arformoterol_ddi_R4", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T8", "arg2_id": "Arformoterol_ddi_T11", "normalized": [] }, { "id": "Arformoterol_ddi_R5", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T9", "arg2_id": "Arformoterol_ddi_T11", "normalized": [] }, { "id": "Arformoterol_ddi_R6", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T10", "arg2_id": "Arformoterol_ddi_T11", "normalized": [] }, { "id": "Arformoterol_ddi_R7", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T12", "arg2_id": "Arformoterol_ddi_T15", "normalized": [] }, { "id": "Arformoterol_ddi_R8", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T13", "arg2_id": "Arformoterol_ddi_T15", "normalized": [] }, { "id": "Arformoterol_ddi_R9", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T14", "arg2_id": "Arformoterol_ddi_T15", "normalized": [] }, { "id": "Arformoterol_ddi_R10", "type": "ADVISE", "arg1_id": "Arformoterol_ddi_T17", "arg2_id": "Arformoterol_ddi_T18", "normalized": [] }, { "id": "Arformoterol_ddi_R11", "type": "ADVISE", "arg1_id": "Arformoterol_ddi_T19", "arg2_id": "Arformoterol_ddi_T21", "normalized": [] }, { "id": "Arformoterol_ddi_R12", "type": "ADVISE", "arg1_id": "Arformoterol_ddi_T19", "arg2_id": "Arformoterol_ddi_T22", "normalized": [] }, { "id": "Arformoterol_ddi_R13", "type": "ADVISE", "arg1_id": "Arformoterol_ddi_T20", "arg2_id": "Arformoterol_ddi_T21", "normalized": [] }, { "id": "Arformoterol_ddi_R14", "type": "ADVISE", "arg1_id": "Arformoterol_ddi_T20", "arg2_id": "Arformoterol_ddi_T22", "normalized": [] }, { "id": "Arformoterol_ddi_R15", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T21", "arg2_id": "Arformoterol_ddi_T23", "normalized": [] }, { "id": "Arformoterol_ddi_R16", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T22", "arg2_id": "Arformoterol_ddi_T23", "normalized": [] }, { "id": "Arformoterol_ddi_R17", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T35", "arg2_id": "Arformoterol_ddi_T37", "normalized": [] }, { "id": "Arformoterol_ddi_R18", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T36", "arg2_id": "Arformoterol_ddi_T37", "normalized": [] }, { "id": "Arformoterol_ddi_R19", "type": "EFFECT", "arg1_id": "Arformoterol_ddi_T38", "arg2_id": "Arformoterol_ddi_T39", "normalized": [] } ]

[ { "id": "Irinotecan_ddi__text", "type": "abstract", "text": [ "The adverse effects of CAMPTOSAR, such as myelosuppression and diarrhea, would be expected to be exacerbated by other antineoplastic agents having similar adverse effects. Patients who have previously received pelvic/ abdominal irradiation are at increased risk of severe myelosuppression following the administration of CAMPTOSAR. The concurrent administration of CAMPTOSAR with irradiation has not been adequately studied and is not recommended. Lymphocytopenia has been reported in patients receiving CAMPTOSAR, and it is possible that the administration of dexamethasone as antiemetic prophylaxis may have enhanced the likelihood of this effect. However, serious opportunistic infections have not been observed, and no complications have specifically been attributed to lymphocytopenia. Hyperglycemia has also been reported in patients receiving CAMPTOSAR. Usually, this has been observed in patients with a history of diabetes mellitus or evidence of glucose intolerance prior to administration of CAMPTOSAR. It is probable that dexamethasone, given as antiemetic prophylaxis, contributed to hyperglycemia in some patients. The incidence of akathisia in clinical trials of the weekly dosage schedule was greater (8.5%, 4/47 patients) when prochlorperazine was administered on the same day as CAMPTOSAR than when these drugs were given on separate days (1.3%, 1/80 patients). The 8.5% incidence of akathisia, however, is within the range reported for use of prochlorperazine when given as a premedication for other chemotherapies. It would be expected that laxative use during therapy with CAMPTOSAR would worsen the incidence or severity of diarrhea, but this has not been studied. In view of the potential risk of dehydration secondary to vomiting and/or diarrhea induced by CAMPTOSAR, the physician may wish to withhold diuretics during dosing with CAMPTOSAR and, certainly, during periods of active vomiting or diarrhea. Drug-Laboratory Test Interactions There are no known interactions between CAMPTOSAR and laboratory tests." ], "offsets": [ [ 0, 2034 ] ] } ]

[ { "id": "Irinotecan_ddi_T1", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 23, 32 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T2", "type": "GROUP", "text": [ "antineoplastic agents" ], "offsets": [ [ 118, 139 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T3", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 321, 330 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T4", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 365, 374 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T5", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 504, 513 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T6", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 561, 574 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T7", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 850, 859 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T8", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 1003, 1012 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T9", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1034, 1047 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T10", "type": "DRUG", "text": [ "prochlorperazine" ], "offsets": [ [ 1244, 1260 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T11", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 1297, 1306 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T12", "type": "DRUG", "text": [ "prochlorperazine" ], "offsets": [ [ 1462, 1478 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T13", "type": "GROUP", "text": [ "laxative" ], "offsets": [ [ 1561, 1569 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T14", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 1594, 1603 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T15", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 1781, 1790 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T16", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 1827, 1836 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T17", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 1856, 1865 ] ], "normalized": [] }, { "id": "Irinotecan_ddi_T18", "type": "BRAND", "text": [ "CAMPTOSAR" ], "offsets": [ [ 2003, 2012 ] ], "normalized": [] } ]

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[ { "id": "Irinotecan_ddi_R1", "type": "EFFECT", "arg1_id": "Irinotecan_ddi_T1", "arg2_id": "Irinotecan_ddi_T2", "normalized": [] }, { "id": "Irinotecan_ddi_R2", "type": "EFFECT", "arg1_id": "Irinotecan_ddi_T5", "arg2_id": "Irinotecan_ddi_T6", "normalized": [] }, { "id": "Irinotecan_ddi_R3", "type": "EFFECT", "arg1_id": "Irinotecan_ddi_T10", "arg2_id": "Irinotecan_ddi_T11", "normalized": [] }, { "id": "Irinotecan_ddi_R4", "type": "EFFECT", "arg1_id": "Irinotecan_ddi_T13", "arg2_id": "Irinotecan_ddi_T14", "normalized": [] }, { "id": "Irinotecan_ddi_R5", "type": "EFFECT", "arg1_id": "Irinotecan_ddi_T16", "arg2_id": "Irinotecan_ddi_T17", "normalized": [] } ]

[ { "id": "Benazepril_ddi__text", "type": "abstract", "text": [ "Diuretics: Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Lotensin. The possibility of hypotensive effects with Lotensin can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with Lotensin. If this is not possible, the starting dose should be reduced. Potassium Supplements and Potassium-Sparing Diuretics Lotensin can attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, they should be given with caution, and the patient's serum potassium should be monitored frequently. Oral Anticoagulants Interaction studies with warfarin and acenocoumarol failed to identify any clinically important effects on the serum concentrations or clinical effects of these anticoagulants. Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. These drugs should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased. Other No clinically important pharmacokinetic interactions occurred when Lotensin was administered concomitantly with hydrochlorothiazide, chlorthalidone, furosemide, digoxin, propranolol, atenolol, naproxen, or cimetidine. Lotensin has been used concomitantly with beta-adrenergic-blocking agents, calcium-channel-blocking agents, diuretics, digoxin, and hydralazine, without evidence of clinically important adverse interactions. Benazepril, like other ACE inhibitors, has had less than additive effects with beta-adrenergic blockers, presumably because both drugs lower blood pressure by inhibiting parts of the renin-angiotensin system ." ], "offsets": [ [ 0, 2073 ] ] } ]

[ { "id": "Benazepril_ddi_T1", "type": "GROUP", "text": [ "Diuretics" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T2", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 23, 32 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T3", "type": "BRAND", "text": [ "Lotensin" ], "offsets": [ [ 203, 211 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T4", "type": "BRAND", "text": [ "Lotensin" ], "offsets": [ [ 257, 265 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T5", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 311, 319 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T6", "type": "BRAND", "text": [ "Lotensin" ], "offsets": [ [ 388, 396 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T7", "type": "DRUG", "text": [ "Potassium" ], "offsets": [ [ 460, 469 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T8", "type": "GROUP", "text": [ "Potassium-Sparing Diuretics" ], "offsets": [ [ 486, 513 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T9", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 562, 580 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T10", "type": "GROUP", "text": [ "Potassium-sparing diuretics" ], "offsets": [ [ 582, 609 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T11", "type": "DRUG", "text": [ "spironolactone" ], "offsets": [ [ 611, 625 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T12", "type": "DRUG", "text": [ "amiloride" ], "offsets": [ [ 627, 636 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T13", "type": "DRUG", "text": [ "triamterene" ], "offsets": [ [ 638, 649 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T14", "type": "DRUG", "text": [ "potassium" ], "offsets": [ [ 666, 675 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T15", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 892, 906 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T16", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 932, 940 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T17", "type": "DRUG", "text": [ "acenocoumarol" ], "offsets": [ [ 945, 958 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T18", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1068, 1082 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T19", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 1084, 1091 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T20", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1109, 1116 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T21", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1140, 1147 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T22", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 1198, 1212 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T23", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1233, 1240 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T24", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1326, 1333 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T25", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 1362, 1370 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T26", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1397, 1404 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T27", "type": "BRAND", "text": [ "Lotensin" ], "offsets": [ [ 1505, 1513 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T28", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 1550, 1569 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T29", "type": "DRUG", "text": [ "chlorthalidone" ], "offsets": [ [ 1571, 1585 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T30", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1587, 1597 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T31", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1599, 1606 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T32", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1608, 1619 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T33", "type": "DRUG", "text": [ "atenolol" ], "offsets": [ [ 1621, 1629 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T34", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 1631, 1639 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T35", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1644, 1654 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T36", "type": "BRAND", "text": [ "Lotensin" ], "offsets": [ [ 1656, 1664 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T37", "type": "GROUP", "text": [ "beta-adrenergic-blocking agents" ], "offsets": [ [ 1698, 1729 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T38", "type": "GROUP", "text": [ "calcium-channel-blocking agents" ], "offsets": [ [ 1731, 1762 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T39", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 1764, 1773 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T40", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1775, 1782 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T41", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 1788, 1799 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T42", "type": "DRUG", "text": [ "Benazepril" ], "offsets": [ [ 1864, 1874 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T43", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 1887, 1901 ] ], "normalized": [] }, { "id": "Benazepril_ddi_T44", "type": "GROUP", "text": [ "beta-adrenergic blockers" ], "offsets": [ [ 1943, 1967 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Benazepril_ddi_R1", "type": "EFFECT", "arg1_id": "Benazepril_ddi_T2", "arg2_id": "Benazepril_ddi_T3", "normalized": [] }, { "id": "Benazepril_ddi_R2", "type": "ADVISE", "arg1_id": "Benazepril_ddi_T5", "arg2_id": "Benazepril_ddi_T6", "normalized": [] }, { "id": "Benazepril_ddi_R3", "type": "EFFECT", "arg1_id": "Benazepril_ddi_T8", "arg2_id": "Benazepril_ddi_T9", "normalized": [] }, { "id": "Benazepril_ddi_R4", "type": "MECHANISM", "arg1_id": "Benazepril_ddi_T22", "arg2_id": "Benazepril_ddi_T23", "normalized": [] }, { "id": "Benazepril_ddi_R5", "type": "EFFECT", "arg1_id": "Benazepril_ddi_T25", "arg2_id": "Benazepril_ddi_T26", "normalized": [] }, { "id": "Benazepril_ddi_R6", "type": "EFFECT", "arg1_id": "Benazepril_ddi_T42", "arg2_id": "Benazepril_ddi_T44", "normalized": [] }, { "id": "Benazepril_ddi_R7", "type": "EFFECT", "arg1_id": "Benazepril_ddi_T43", "arg2_id": "Benazepril_ddi_T44", "normalized": [] } ]

[ { "id": "Cinoxacin_ddi__text", "type": "abstract", "text": [ "Elevated plasma levels of theophylline have been reported with concomitant use of some quinolones. There have been reports of theophylline-related side-effects in patients on concomitant theophylline-quinolone therapy. Therefore, monitoring of theophylline plasma levels should be considered and dosage of theophylline adjusted as required. 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. Although this interaction has not been reported with cinoxacin, caution should be exercised when cinoxacin is given concomitantly with caffeine-containing products. Antacids or sucralfate substantially interfere with the absorption of some quinolones, resulting in low urine levels. Also, concomitant administration of quinolones with products containing iron, multivitamins containing zinc, or Videx (didanosine) chewable/buffered tablets or the pediatric powder for oral solution may result in low urine levels. Quinolones, including cinoxacin, may enhance the effects of oral anticoagulants, such as warfarin or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be closely monitored. Seizures have been reported in patients taking another quinolone class antimicrobial and the nonsteroidal anti-inflammatory drug fenbufen concurrently. Animal studies also suggest an increased potential for seizures when these 2 drugs are given concomitantly. Fenbufen is not approved in the United States at this time. Physicians are provided this information to increase awareness of the potential for serious interactions when cinoxacin and certain nonsteroidal anti-inflammatory agents are administered concomitantly. Elevated cyclosporine serum levels have been reported with the concomitant use of quinolones and cyclosporine." ], "offsets": [ [ 0, 1908 ] ] } ]

[ { "id": "Cinoxacin_ddi_T1", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 26, 38 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T2", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 87, 97 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T3", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 126, 138 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T4", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 187, 199 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T5", "type": "GROUP", "text": [ "quinolone" ], "offsets": [ [ 200, 209 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T6", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 244, 256 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T7", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 306, 318 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T8", "type": "GROUP", "text": [ "Quinolones" ], "offsets": [ [ 341, 351 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T9", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 409, 417 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T10", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 457, 465 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T11", "type": "DRUG", "text": [ "cinoxacin" ], "offsets": [ [ 563, 572 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T12", "type": "DRUG", "text": [ "cinoxacin" ], "offsets": [ [ 607, 616 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T13", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 645, 653 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T14", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 675, 683 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T15", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 687, 697 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T16", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 750, 760 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T17", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 829, 839 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T18", "type": "DRUG", "text": [ "iron" ], "offsets": [ [ 865, 869 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T19", "type": "GROUP", "text": [ "multivitamins" ], "offsets": [ [ 871, 884 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T20", "type": "DRUG", "text": [ "zinc" ], "offsets": [ [ 896, 900 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T21", "type": "BRAND", "text": [ "Videx" ], "offsets": [ [ 905, 910 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T22", "type": "DRUG", "text": [ "didanosine" ], "offsets": [ [ 912, 922 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T23", "type": "GROUP", "text": [ "Quinolones" ], "offsets": [ [ 1024, 1034 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T24", "type": "DRUG", "text": [ "cinoxacin" ], "offsets": [ [ 1046, 1055 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T25", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1089, 1103 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T26", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1113, 1121 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T27", "type": "GROUP", "text": [ "quinolone class antimicrobial" ], "offsets": [ [ 1331, 1360 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T28", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory drug" ], "offsets": [ [ 1369, 1404 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T29", "type": "DRUG", "text": [ "fenbufen" ], "offsets": [ [ 1405, 1413 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T30", "type": "DRUG", "text": [ "Fenbufen" ], "offsets": [ [ 1536, 1544 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T31", "type": "DRUG", "text": [ "cinoxacin" ], "offsets": [ [ 1706, 1715 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T32", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 1728, 1765 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T33", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1807, 1819 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T34", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 1880, 1890 ] ], "normalized": [] }, { "id": "Cinoxacin_ddi_T35", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1895, 1907 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cinoxacin_ddi_R1", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T1", "arg2_id": "Cinoxacin_ddi_T2", "normalized": [] }, { "id": "Cinoxacin_ddi_R2", "type": "EFFECT", "arg1_id": "Cinoxacin_ddi_T4", "arg2_id": "Cinoxacin_ddi_T5", "normalized": [] }, { "id": "Cinoxacin_ddi_R3", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T8", "arg2_id": "Cinoxacin_ddi_T9", "normalized": [] }, { "id": "Cinoxacin_ddi_R4", "type": "ADVISE", "arg1_id": "Cinoxacin_ddi_T12", "arg2_id": "Cinoxacin_ddi_T13", "normalized": [] }, { "id": "Cinoxacin_ddi_R5", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T14", "arg2_id": "Cinoxacin_ddi_T16", "normalized": [] }, { "id": "Cinoxacin_ddi_R6", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T15", "arg2_id": "Cinoxacin_ddi_T16", "normalized": [] }, { "id": "Cinoxacin_ddi_R7", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T17", "arg2_id": "Cinoxacin_ddi_T18", "normalized": [] }, { "id": "Cinoxacin_ddi_R8", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T17", "arg2_id": "Cinoxacin_ddi_T20", "normalized": [] }, { "id": "Cinoxacin_ddi_R9", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T17", "arg2_id": "Cinoxacin_ddi_T21", "normalized": [] }, { "id": "Cinoxacin_ddi_R10", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T17", "arg2_id": "Cinoxacin_ddi_T22", "normalized": [] }, { "id": "Cinoxacin_ddi_R11", "type": "EFFECT", "arg1_id": "Cinoxacin_ddi_T23", "arg2_id": "Cinoxacin_ddi_T25", "normalized": [] }, { "id": "Cinoxacin_ddi_R12", "type": "EFFECT", "arg1_id": "Cinoxacin_ddi_T23", "arg2_id": "Cinoxacin_ddi_T26", "normalized": [] }, { "id": "Cinoxacin_ddi_R13", "type": "EFFECT", "arg1_id": "Cinoxacin_ddi_T24", "arg2_id": "Cinoxacin_ddi_T25", "normalized": [] }, { "id": "Cinoxacin_ddi_R14", "type": "EFFECT", "arg1_id": "Cinoxacin_ddi_T24", "arg2_id": "Cinoxacin_ddi_T26", "normalized": [] }, { "id": "Cinoxacin_ddi_R15", "type": "EFFECT", "arg1_id": "Cinoxacin_ddi_T27", "arg2_id": "Cinoxacin_ddi_T28", "normalized": [] }, { "id": "Cinoxacin_ddi_R16", "type": "EFFECT", "arg1_id": "Cinoxacin_ddi_T27", "arg2_id": "Cinoxacin_ddi_T29", "normalized": [] }, { "id": "Cinoxacin_ddi_R17", "type": "ADVISE", "arg1_id": "Cinoxacin_ddi_T31", "arg2_id": "Cinoxacin_ddi_T32", "normalized": [] }, { "id": "Cinoxacin_ddi_R18", "type": "MECHANISM", "arg1_id": "Cinoxacin_ddi_T34", "arg2_id": "Cinoxacin_ddi_T35", "normalized": [] } ]

[ { "id": "Peginterferon alfa-2a_ddi__text", "type": "abstract", "text": [ "Treatment with PEGASYS once weekly for 4 weeks in healthy subjects was associated with an inhibition of P450 1A2 and a 25% increase in theophylline AUC. Theophylline serum levels should be monitored and appropriate dose adjustments considered for patients given both theophylline and PEGASYS. There was no effect on the pharmacokinetics of representative drugs metabolized by CYP 2C9, CYP 2C19, CYP 2D6 or CYP 3A4. In patients with chronic hepatitis C treated with PEGASYS in combination with COPEGUS, PEGASYS treatment did not affect ribavirin distribution or clearance. Nucleoside Analogues Didanosine Co-administration of COPEGUS and didanosine is not recommended. Reports of fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in clinical trials. Stavudine and Zidovudine Ribavirin can antagonize the in vitro antiviral activity of stavudine and zidovudine against HIV. Therefore, concomitant use of ribavirin with either of these drugs should be avoided. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis PEGASYS has not been tested for its carcinogenic potential. Mutagenesis PEGASYS did not cause DNA damage when tested in the Ames bacterial mutagenicity assay and in the in vitro chromosomal aberration assay in human lymphocytes, either in the presence or absence of metabolic activation. Use With Ribavirin Ribavirin is genotoxic and mutagenic. The carcinogenic potential of ribavirin has not been fully determined. In a p53 (+/-) mouse carcinogenicity study at doses up to the maximum tolerated dose of 100 mg/kg/day ribavirin was not oncogenic. However, on a body surface area basis, this dose was 0.5 times maximum recommended human 24-hour dose of ribavirin. A study in rats to assess the carcinogenic potential of ribavirin is ongoing. Mutagenesis Impairment of Fertility PEGASYS may impair fertility in women. Prolonged menstrual cycles and/or amenorrhea were observed in female cynomolgus monkeys given sc injections of 600 m g/kg/dose (7200 m g/m2/dose) of PEGASYS every other day for one month, at approximately 180 times the recommended weekly human dose for a 60 kg person (based on body surface area). Menstrual cycle irregularities were accompanied by both a decrease and delay in the peak 17b -estradiol and progesterone levels following administration of PEGASYS to female monkeys. A return to normal menstrual rhythm followed cessation of treatment. Every other day dosing with 100m g/kg (1200m g/m2) PEGASYS (equivalent to approximately 30 times the recommended human dose) had no effects on cycle duration or reproductive hormone status. The effects of PEGASYS on male fertility have not been studied. However, no adverse effects on fertility were observed in male Rhesus monkeys treated with non-pegylated interferon alfa-2a for 5 months at doses up to 25 x 106 IU/kg/day. Pregnancy Pregnancy: Category C PEGASYS has not been studied for its teratogenic effect. Non-pegylated interferon alfa-2a treatment of pregnant Rhesus monkeys at approximately 20 to 500 times the human weekly dose resulted in a statistically significant increase in abortions. No teratogenic effects were seen in the offspring delivered at term. PEGASYS should be assumed to have abortifacient potential. There are no adequate and well-controlled studies of PEGASYS in pregnant women. PEGASYS is to be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. PEGASYS is recommended for use in women of childbearing potential only when they are using effective contraception during therapy. Pregnancy: Category X: Use With Ribavirin (see CONTRAINDICATIONS) Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. COPEGUS therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant . If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment cessation, such cases should be reported to the COPEGUS Pregnancy Registry at 1-800-526-6367. Nursing Mothers It is not known whether peginterferon or ribavirin or its components are excreted in human milk. The effect of orally ingested peginterferon or ribavirin from breast milk on the nursing infant has not been evaluated. Because of the potential for adverse reactions from the drugs in nursing infants, a decision must be made whether to discontinue nursing or discontinue PEGASYS and COPEGUS treatment. Pediatric Use The safety and effectiveness of PEGASYS, alone or in combination with COPEGUS in patients below the age of 18 years have not been established. PEGASYS contains benzyl alcohol. Benzyl alcohol has been reported to be associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. Geriatric Use Younger patients have higher virologic response rates than older patients. Clinical studies of PEGASYS alone or in combination with COPEGUS did not include sufficient numbers of subjects aged 65 or over to determine whether they respond differently from younger subjects. Adverse reactions related to alpha interferons, such as CNS, cardiac, and systemic (eg, flu-like) effects may be more severe in the elderly and caution should be exercised in the use of PEGASYS in this population. PEGASYS and COPEGUS are excreted by the kidney, and the risk of toxic reactions to this therapy may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. PEGASYS should be used with caution in patients with creatinine clearance 50 mL/min and COPEGUS should not be administered to patients with creatinine clearance 50 mL/min ." ], "offsets": [ [ 0, 5904 ] ] } ]

[ { "id": "Peginterferon alfa-2a_ddi_T1", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 15, 22 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T2", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 135, 147 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T3", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 153, 165 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T4", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 267, 279 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T5", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 284, 291 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T6", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 465, 472 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T7", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 493, 500 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T8", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 502, 509 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T9", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 535, 544 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T10", "type": "DRUG", "text": [ "Didanosine" ], "offsets": [ [ 593, 603 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T11", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 625, 632 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T12", "type": "DRUG", "text": [ "didanosine" ], "offsets": [ [ 637, 647 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T13", "type": "DRUG", "text": [ "Stavudine" ], "offsets": [ [ 837, 846 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T14", "type": "DRUG", "text": [ "Zidovudine" ], "offsets": [ [ 851, 861 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T15", "type": "DRUG", "text": [ "Ribavirin" ], "offsets": [ [ 862, 871 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T16", "type": "DRUG", "text": [ "stavudine" ], "offsets": [ [ 922, 931 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T17", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 936, 946 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T18", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 990, 999 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T19", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 1114, 1121 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T20", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 1186, 1193 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T21", "type": "DRUG", "text": [ "Ribavirin" ], "offsets": [ [ 1411, 1420 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T22", "type": "DRUG", "text": [ "Ribavirin" ], "offsets": [ [ 1421, 1430 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T23", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 1489, 1498 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T24", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 1632, 1641 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T25", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 1766, 1775 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T26", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 1833, 1842 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T27", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 1891, 1898 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T28", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 2079, 2086 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T29", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 2384, 2391 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T30", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 2531, 2538 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T31", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 2685, 2692 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T32", "type": "DRUG", "text": [ "pegylated interferon alfa-2a" ], "offsets": [ [ 2829, 2857 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T33", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 2938, 2945 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T34", "type": "DRUG", "text": [ "Non-pegylated interferon alfa-2a" ], "offsets": [ [ 2995, 3027 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T35", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 3252, 3259 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T36", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 3364, 3371 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T37", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 3391, 3398 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T38", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 3503, 3510 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T39", "type": "DRUG", "text": [ "Ribavirin" ], "offsets": [ [ 3666, 3675 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T40", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 3807, 3816 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T41", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 3818, 3825 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T42", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 4093, 4100 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T43", "type": "DRUG", "text": [ "peginterferon" ], "offsets": [ [ 4179, 4192 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T44", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 4196, 4205 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T45", "type": "DRUG", "text": [ "peginterferon" ], "offsets": [ [ 4282, 4295 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T46", "type": "DRUG", "text": [ "ribavirin" ], "offsets": [ [ 4299, 4308 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T47", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 4524, 4531 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T48", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 4536, 4543 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T49", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 4601, 4608 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T50", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 4639, 4646 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T51", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 4712, 4719 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T52", "type": "DRUG_N", "text": [ "benzyl alcohol" ], "offsets": [ [ 4729, 4743 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T53", "type": "DRUG_N", "text": [ "Benzyl alcohol" ], "offsets": [ [ 4745, 4759 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T54", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 5024, 5031 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T55", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 5061, 5068 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T56", "type": "DRUG", "text": [ "alpha interferon" ], "offsets": [ [ 5230, 5246 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T57", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 5387, 5394 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T58", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 5415, 5422 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T59", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 5427, 5434 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T60", "type": "BRAND", "text": [ "PEGASYS" ], "offsets": [ [ 5730, 5737 ] ], "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_T61", "type": "BRAND", "text": [ "COPEGUS" ], "offsets": [ [ 5819, 5826 ] ], "normalized": [] } ]

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[ { "id": "Peginterferon alfa-2a_ddi_R1", "type": "MECHANISM", "arg1_id": "Peginterferon alfa-2a_ddi_T1", "arg2_id": "Peginterferon alfa-2a_ddi_T2", "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_R2", "type": "ADVISE", "arg1_id": "Peginterferon alfa-2a_ddi_T4", "arg2_id": "Peginterferon alfa-2a_ddi_T5", "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_R3", "type": "ADVISE", "arg1_id": "Peginterferon alfa-2a_ddi_T11", "arg2_id": "Peginterferon alfa-2a_ddi_T12", "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_R4", "type": "EFFECT", "arg1_id": "Peginterferon alfa-2a_ddi_T15", "arg2_id": "Peginterferon alfa-2a_ddi_T16", "normalized": [] }, { "id": "Peginterferon alfa-2a_ddi_R5", "type": "EFFECT", "arg1_id": "Peginterferon alfa-2a_ddi_T15", "arg2_id": "Peginterferon alfa-2a_ddi_T17", "normalized": [] } ]

[ { "id": "Balsalazide_ddi__text", "type": "abstract", "text": [ "No drug interaction studies have been conducted for COLAZAL, however the use of orally administered antibiotics could, theoretically, interfere with the release of mesalamine in the colon." ], "offsets": [ [ 0, 188 ] ] } ]

[ { "id": "Balsalazide_ddi_T1", "type": "BRAND", "text": [ "COLAZAL" ], "offsets": [ [ 52, 59 ] ], "normalized": [] }, { "id": "Balsalazide_ddi_T2", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 100, 111 ] ], "normalized": [] }, { "id": "Balsalazide_ddi_T3", "type": "DRUG", "text": [ "mesalamine" ], "offsets": [ [ 164, 174 ] ], "normalized": [] } ]

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[ { "id": "Carboprost Tromethamine_ddi__text", "type": "abstract", "text": [ "HEMABATE may augment the activity of other oxytocic agents. Concomitant use with other oxytocic agents is not recommended ." ], "offsets": [ [ 0, 123 ] ] } ]

[ { "id": "Carboprost Tromethamine_ddi_T1", "type": "BRAND", "text": [ "HEMABATE" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Carboprost Tromethamine_ddi_T2", "type": "GROUP", "text": [ "oxytocic agents" ], "offsets": [ [ 43, 58 ] ], "normalized": [] }, { "id": "Carboprost Tromethamine_ddi_T3", "type": "GROUP", "text": [ "oxytocic agents" ], "offsets": [ [ 87, 102 ] ], "normalized": [] } ]

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[ { "id": "Carboprost Tromethamine_ddi_R1", "type": "EFFECT", "arg1_id": "Carboprost Tromethamine_ddi_T1", "arg2_id": "Carboprost Tromethamine_ddi_T2", "normalized": [] } ]

[ { "id": "Vardenafil_ddi__text", "type": "abstract", "text": [ "Effect of other drugs on Vardenafil In vitro studies: Studies in human liver microsomes showed that vardenafil is metabolized primarily by cytochrome P450 (CYP) isoforms 3A4/5, and to a lesser degree by CYP2C9. Therefore, inhibitors of these enzymes are expected to reduce vardenafil clearance. In vivo studies: Cytochrome P450 Inhibitors Cimetidine (400 mg b.i.d.) had no effect on vardenafil bioavailability (AUC) and maximum concentration (Cmax) of vardenafil when co-administered with 20 mg Vardenafil in healthy volunteers. Erythromycin (500 mg t.i.d) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in Cmax when co-administered with Vardenafil 5 mg in healthy volunteers. It is recommended not to exceed a single 5 mg dose of Vardenafil in a 24-hour period when used in combination with erythromycin. Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil AUC and a 4-fold increase in Cmax when co-administered with Vardenafil (5 mg) in healthy volunteers. A 5-mg Vardenafil dose should not be exceeded when used in combination with 200 mg once daily ketoconazole. Since higher doses of ketoconazole (400 mg daily) may result in higher increases in Cmax and AUC, a single 2.5 mg dose of Vardenafil should not be exceeded in a 24-hour period when used in combination with ketoconazole 400 mg daily. HIV Protease Inhibitors: Indinavir (800 mg t.i.d.) co-administered with Vardenafil 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil Cmax and a 2-fold increase in vardenafil half-life. It is recommended not to exceed a single 2.5 mg Vardenafil dose in a 24-hour period when used in combination with indinavir. Ritonavir (600 mg b.i.d.) co-administered with Vardenafil 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13-fold increase in vardenafil Cmax. The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a highly potent CYP3A4 inhibitor, which also inhibits CYP2C9. Ritonavir significantly prolonged the half-life of vardenafil to 26 hours. Consequently, it is recommended not to exceed a single 2.5 mg Vardenafil dose in a 72-hour period when used in combination with ritonavir. Other Drug Interactions: No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, Maalox, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters. Effects of Vardenafil on other drugs In vitro studies: Vardenafil and its metabolites had no effect on CYP1A2, 2A6, and 2E1 (Ki 100uM). Weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4) were found, but Ki values were in excess of plasma concentrations achieved following dosing. The most potent inhibitory activity was observed for vardenafil metabolite M1, which had a Ki of 1.4 uM toward CYP3A4, which is about 20 times higher than the M1 Cmax values after an 80 mg Vardenafil dose. In vivo studies: Nitrates: The blood pressure lowering effects of sublingual nitrates (0.4 mg) taken 1 and 4 hours after vardenafil and increases in heart rate when taken at 1, 4 and 8 hours were potentiated by a 20 mg dose of Vardenafil in healthy middle-aged subjects. These effects were not observed when Vardenafil 20 mg was taken 24 hours before the NTG. Potentiation of the hypotensive effects of nitrates for patients with ischemic heart disease has not been evaluated, and concomitant use of Vardenafil and nitrates is contraindicated. Nifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the relative bioavailability (AUC) or maximum concentration (Cmax) of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of Vardenafil when taken in combination. In these patients whose hypertension was controlled with nifedipine, Vardenafil 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mm Hg compared to placebo. Alpha-blockers: When Vardenafil 10 or 20 mg was given to healthy volunteers either simultaneously or 6 hours after a 10 mg dose of terazosin, significant hypotension developed in a substantial number of subjects. With simultaneous dosing of Vardenafil 10 mg and terazosin 10 mg, 6 of 8 subjects experienced a standing systolic blood pressure of less than 85 mm Hg. With simultaneous dosing of Vardenafil 20 mg and terazosin 10 mg, 2 of 9 subjects experienced a standing systolic blood pressure of less than 85 mm Hg. When Vardenafil dosing was separated from terazosin 10 mg by 6 hours, 7 of 28 subjects who received 20 mg of Vardenafil experienced a decrease in standing systolic blood pressure below 85 mm Hg. In a similar study with tamsulosin in healthy volunteers, 1 of 24 subjects dosed with Vardenafil 20 mg and tamsulosin 0.4 mg separated by 6 hours experienced a standing systolic blood pressure below 85 mm Hg. Two of 16 subjects dosed simultaneously with Vardenafil 10 mg and tamsulosin 0.4 mg experienced a standing systolic blood pressure below 85 mm Hg. The administration of lower doses of Vardenafil with alpha-blockers has not been completely evaluated to determine if they can be safely administered together. Based on these data, Vardenafil should not be used in patients on alpha-blocker therapy. Ritonavir and indinavir: Upon concomitant administration of 5 mg of Vardenafil with 600 mg BID ritonavir, the Cmax and AUC of ritonavir were reduced by approximately 20%. Upon administration of 10 mg of Vardenafil with 800 mg TID indinavir, the Cmax and AUC of indinavir were reduced by 40% and 30%, respectively. Alcohol: Alcohol (0.5 g/kg body weight: approximately 40 mL of absolute alcohol in a 70 kg person) and vardenafil plasma levels were not altered when dosed simultaneously. Vardenafil (20 mg) did not potentiate the hypotensive effects of alcohol during the 4-hour observation period in healthy volunteers when administered with alcohol (0.5 g/kg body weight). Aspirin: Vardenafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by aspirin (two 81 mg tablets). Other interactions: Vardenafil had no effect on the pharmacodynamics of glyburide (glucose and insulin concentrations) and warfarin (prothrombin time or other pharmacodynamic parameters)." ], "offsets": [ [ 0, 6376 ] ] } ]

[ { "id": "Vardenafil_ddi_T1", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 25, 35 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T2", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 100, 110 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T3", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 273, 283 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T4", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 339, 349 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T5", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 383, 393 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T6", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 452, 462 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T7", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 495, 505 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T8", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 529, 541 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T9", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 587, 597 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T10", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 658, 668 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T11", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 751, 761 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T12", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 812, 824 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T13", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 826, 838 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T14", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 890, 900 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T15", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 961, 971 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T16", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 1009, 1019 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T17", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1096, 1108 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T18", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1132, 1144 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T19", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 1232, 1242 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T20", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1316, 1328 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T21", "type": "GROUP", "text": [ "HIV Protease Inhibitors" ], "offsets": [ [ 1343, 1366 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T22", "type": "DRUG", "text": [ "Indinavir" ], "offsets": [ [ 1368, 1377 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T23", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 1415, 1425 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T24", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 1466, 1476 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T25", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 1503, 1513 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T26", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 1544, 1554 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T27", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 1614, 1624 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T28", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 1680, 1689 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T29", "type": "DRUG", "text": [ "Ritonavir" ], "offsets": [ [ 1691, 1700 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T30", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 1738, 1748 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T31", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 1788, 1798 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T32", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 1829, 1839 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T33", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 1913, 1923 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T34", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 1927, 1936 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T35", "type": "DRUG", "text": [ "Ritonavir" ], "offsets": [ [ 2000, 2009 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T36", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 2051, 2061 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T37", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 2137, 2147 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T38", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 2203, 2212 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T39", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 2293, 2303 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T40", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 2329, 2338 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T41", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2340, 2348 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T42", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2350, 2357 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T43", "type": "BRAND", "text": [ "Maalox" ], "offsets": [ [ 2359, 2365 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T44", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 2371, 2381 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T45", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2390, 2398 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T46", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 2406, 2416 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T47", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 2503, 2513 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T48", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 2547, 2557 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T49", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 2988, 2998 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T50", "type": "GROUP", "text": [ "Nitrates" ], "offsets": [ [ 3022, 3030 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T51", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 3082, 3090 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T52", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 3126, 3136 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T53", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 3232, 3242 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T54", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 3313, 3323 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T55", "type": "DRUG", "text": [ "NTG" ], "offsets": [ [ 3360, 3363 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T56", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 3408, 3416 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T57", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 3505, 3515 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T58", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 3520, 3528 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T59", "type": "DRUG", "text": [ "Nifedipine" ], "offsets": [ [ 3549, 3559 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T60", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 3561, 3571 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T61", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 3618, 3628 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T62", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 3741, 3751 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T63", "type": "DRUG", "text": [ "Nifedipine" ], "offsets": [ [ 3792, 3802 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T64", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 3838, 3848 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T65", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 3933, 3943 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T66", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 3945, 3955 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T67", "type": "GROUP", "text": [ "Alpha-blockers" ], "offsets": [ [ 4073, 4087 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T68", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 4094, 4104 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T69", "type": "DRUG", "text": [ "terazosin" ], "offsets": [ [ 4204, 4213 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T70", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 4314, 4324 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T71", "type": "DRUG", "text": [ "terazosin" ], "offsets": [ [ 4335, 4344 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T72", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 4466, 4476 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T73", "type": "DRUG", "text": [ "terazosin" ], "offsets": [ [ 4487, 4496 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T74", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 4595, 4605 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T75", "type": "DRUG", "text": [ "terazosin" ], "offsets": [ [ 4632, 4641 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T76", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 4699, 4709 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T77", "type": "DRUG", "text": [ "tamsulosin" ], "offsets": [ [ 4809, 4819 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T78", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 4871, 4881 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T79", "type": "DRUG", "text": [ "tamsulosin" ], "offsets": [ [ 4892, 4902 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T80", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 5039, 5049 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T81", "type": "DRUG", "text": [ "tamsulosin" ], "offsets": [ [ 5060, 5070 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T82", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 5178, 5188 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T83", "type": "GROUP", "text": [ "alpha-blockers" ], "offsets": [ [ 5194, 5208 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T84", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 5322, 5332 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T85", "type": "GROUP", "text": [ "alpha-blocker" ], "offsets": [ [ 5367, 5380 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T86", "type": "DRUG", "text": [ "Ritonavir" ], "offsets": [ [ 5390, 5399 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T87", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 5404, 5413 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T88", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 5458, 5468 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T89", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 5485, 5494 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T90", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 5516, 5525 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T91", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 5593, 5603 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T92", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 5620, 5629 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T93", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 5651, 5660 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T94", "type": "DRUG", "text": [ "Alcohol" ], "offsets": [ [ 5704, 5711 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T95", "type": "DRUG", "text": [ "Alcohol" ], "offsets": [ [ 5713, 5720 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T96", "type": "DRUG", "text": [ "vardenafil" ], "offsets": [ [ 5807, 5817 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T97", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 5876, 5886 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T98", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 5941, 5948 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T99", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 6031, 6038 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T100", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 6063, 6070 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T101", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 6072, 6082 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T102", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 6160, 6167 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T103", "type": "DRUG", "text": [ "Vardenafil" ], "offsets": [ [ 6209, 6219 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T104", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 6261, 6270 ] ], "normalized": [] }, { "id": "Vardenafil_ddi_T105", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 6312, 6320 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Vardenafil_ddi_R1", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T8", "arg2_id": "Vardenafil_ddi_T9", "normalized": [] }, { "id": "Vardenafil_ddi_R2", "type": "ADVISE", "arg1_id": "Vardenafil_ddi_T11", "arg2_id": "Vardenafil_ddi_T12", "normalized": [] }, { "id": "Vardenafil_ddi_R3", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T13", "arg2_id": "Vardenafil_ddi_T14", "normalized": [] }, { "id": "Vardenafil_ddi_R4", "type": "ADVISE", "arg1_id": "Vardenafil_ddi_T16", "arg2_id": "Vardenafil_ddi_T17", "normalized": [] }, { "id": "Vardenafil_ddi_R5", "type": "ADVISE", "arg1_id": "Vardenafil_ddi_T19", "arg2_id": "Vardenafil_ddi_T20", "normalized": [] }, { "id": "Vardenafil_ddi_R6", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T22", "arg2_id": "Vardenafil_ddi_T23", "normalized": [] }, { "id": "Vardenafil_ddi_R7", "type": "ADVISE", "arg1_id": "Vardenafil_ddi_T27", "arg2_id": "Vardenafil_ddi_T28", "normalized": [] }, { "id": "Vardenafil_ddi_R8", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T29", "arg2_id": "Vardenafil_ddi_T30", "normalized": [] }, { "id": "Vardenafil_ddi_R9", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T33", "arg2_id": "Vardenafil_ddi_T34", "normalized": [] }, { "id": "Vardenafil_ddi_R10", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T35", "arg2_id": "Vardenafil_ddi_T36", "normalized": [] }, { "id": "Vardenafil_ddi_R11", "type": "ADVISE", "arg1_id": "Vardenafil_ddi_T37", "arg2_id": "Vardenafil_ddi_T38", "normalized": [] }, { "id": "Vardenafil_ddi_R12", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T51", "arg2_id": "Vardenafil_ddi_T52", "normalized": [] }, { "id": "Vardenafil_ddi_R13", "type": "ADVISE", "arg1_id": "Vardenafil_ddi_T57", "arg2_id": "Vardenafil_ddi_T58", "normalized": [] }, { "id": "Vardenafil_ddi_R14", "type": "EFFECT", "arg1_id": "Vardenafil_ddi_T65", "arg2_id": "Vardenafil_ddi_T66", "normalized": [] }, { "id": "Vardenafil_ddi_R15", "type": "EFFECT", "arg1_id": "Vardenafil_ddi_T68", "arg2_id": "Vardenafil_ddi_T69", "normalized": [] }, { "id": "Vardenafil_ddi_R16", "type": "EFFECT", "arg1_id": "Vardenafil_ddi_T70", "arg2_id": "Vardenafil_ddi_T71", "normalized": [] }, { "id": "Vardenafil_ddi_R17", "type": "EFFECT", "arg1_id": "Vardenafil_ddi_T72", "arg2_id": "Vardenafil_ddi_T73", "normalized": [] }, { "id": "Vardenafil_ddi_R18", "type": "EFFECT", "arg1_id": "Vardenafil_ddi_T74", "arg2_id": "Vardenafil_ddi_T75", "normalized": [] }, { "id": "Vardenafil_ddi_R19", "type": "EFFECT", "arg1_id": "Vardenafil_ddi_T78", "arg2_id": "Vardenafil_ddi_T79", "normalized": [] }, { "id": "Vardenafil_ddi_R20", "type": "EFFECT", "arg1_id": "Vardenafil_ddi_T80", "arg2_id": "Vardenafil_ddi_T81", "normalized": [] }, { "id": "Vardenafil_ddi_R21", "type": "ADVISE", "arg1_id": "Vardenafil_ddi_T84", "arg2_id": "Vardenafil_ddi_T85", "normalized": [] }, { "id": "Vardenafil_ddi_R22", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T88", "arg2_id": "Vardenafil_ddi_T89", "normalized": [] }, { "id": "Vardenafil_ddi_R23", "type": "MECHANISM", "arg1_id": "Vardenafil_ddi_T91", "arg2_id": "Vardenafil_ddi_T92", "normalized": [] } ]

[ { "id": "Lactulose_ddi__text", "type": "abstract", "text": [ "Results of preliminary studies in humans and rats suggest that nonabsorbable antacids given concurrently with lactulose may inhibit the desired lactulose-induced drop in colonic pH. Therefore, a possible lack of desired effect of treatment should be taken into consideration before such drugs are given concomitantly with lactulose." ], "offsets": [ [ 0, 332 ] ] } ]

[ { "id": "Lactulose_ddi_T1", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 77, 85 ] ], "normalized": [] }, { "id": "Lactulose_ddi_T2", "type": "DRUG", "text": [ "lactulose" ], "offsets": [ [ 110, 119 ] ], "normalized": [] }, { "id": "Lactulose_ddi_T3", "type": "DRUG", "text": [ "lactulose" ], "offsets": [ [ 144, 153 ] ], "normalized": [] }, { "id": "Lactulose_ddi_T4", "type": "DRUG", "text": [ "lactulose" ], "offsets": [ [ 322, 331 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Lactulose_ddi_R1", "type": "MECHANISM", "arg1_id": "Lactulose_ddi_T1", "arg2_id": "Lactulose_ddi_T2", "normalized": [] } ]

[ { "id": "Anagrelide_ddi__text", "type": "abstract", "text": [ "Limited PK and/or PD studies investigating possible interactions between anagrelide and other medicinal products have been conducted. In vivo interaction studies in humans have demonstrated that digoxin and warfarin do not affect the PK properties of anagrelide, nor does anagrelide affect the PK properties of digoxin or warfarin. Although additional drug interaction studies have not been conducted, the most common medications used concomitantly with anagrelide in clinical trials were aspirin, acetaminophen, furosemide, iron, ranitidine, hydroxyurea, and allopurinol. There is no clinical evidence to suggest that anagrelide interacts with any of these compounds. An in vivo interaction study in humans demonstrated that a single 1mg dose of anagrelide administered concomitantly with a single 900 mg dose of aspirin was generally well tolerated. There was no effect on bleeding time, PT or aPTT. No clinically relevant pharmacokinetic interactions between anagrelide and acetylsalicylic acid were observed. In that same study, aspirin alone produced a marked inhibition in platelet aggregation ex vivo. Anagrelide alone had no effect on platelet aggregation, but did slightly enhance the inhibition of platelet aggregation by aspirin. Anagrelide is metabolized at least in part by CYP1A2. It is known that CYP1A2 is inhibited by several medicinal products, including fluvoxamine, and such medicinal products could theoretically adversely influence the clearance of anagrelide. Anagrelide demonstrates some limited inhibitory activity towards CYP1A2 which may present a theoretical potential for interaction with other coadministered medicinal products sharing that clearance mechanism e.g. Anagrelide demonstrates some limited inhibitory activity towards CYP1A2 which may present a theoretical potential for interaction with other coadministered medicinal products sharing that clearance mechanism e.g. theophylline. Anagrelide is an inhibitor of cyclic AMP PDE III. The effects of medicinal products with similar properties such as inotropes milrinone, enoximone, amrinone, olprinone and cilostazol may be exacerbated by anagrelide. There is a single case report, which suggests that sucralfate may interfere with anagrelide absorption. Food has no clinically significant effect on the bioavailability of anagrelide." ], "offsets": [ [ 0, 2323 ] ] } ]

[ { "id": "Anagrelide_ddi_T1", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 73, 83 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T2", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 195, 202 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 207, 215 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T4", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 251, 261 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T5", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 272, 282 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T6", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 311, 318 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T7", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 322, 330 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T8", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 454, 464 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T9", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 489, 496 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T10", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 498, 511 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T11", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 513, 523 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T12", "type": "DRUG", "text": [ "iron" ], "offsets": [ [ 525, 529 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T13", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 531, 541 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T14", "type": "DRUG", "text": [ "hydroxyurea" ], "offsets": [ [ 543, 554 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T15", "type": "DRUG", "text": [ "allopurinol" ], "offsets": [ [ 560, 571 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T16", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 619, 629 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T17", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 747, 757 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T18", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 814, 821 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T19", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 962, 972 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T20", "type": "DRUG", "text": [ "acetylsalicylic acid" ], "offsets": [ [ 977, 997 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T21", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 1033, 1040 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T22", "type": "DRUG", "text": [ "Anagrelide" ], "offsets": [ [ 1109, 1119 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T23", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 1232, 1239 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T24", "type": "DRUG", "text": [ "Anagrelide" ], "offsets": [ [ 1241, 1251 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T25", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 1373, 1384 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T26", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 1471, 1481 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T27", "type": "DRUG", "text": [ "Anagrelide" ], "offsets": [ [ 1483, 1493 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T28", "type": "DRUG", "text": [ "Anagrelide" ], "offsets": [ [ 1696, 1706 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T29", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1909, 1921 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T30", "type": "DRUG", "text": [ "Anagrelide" ], "offsets": [ [ 1923, 1933 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T31", "type": "DRUG", "text": [ "milrinone" ], "offsets": [ [ 2049, 2058 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T32", "type": "DRUG", "text": [ "enoximone" ], "offsets": [ [ 2060, 2069 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T33", "type": "DRUG", "text": [ "amrinone" ], "offsets": [ [ 2071, 2079 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T34", "type": "DRUG_N", "text": [ "olprinone" ], "offsets": [ [ 2081, 2090 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T35", "type": "DRUG", "text": [ "cilostazol" ], "offsets": [ [ 2095, 2105 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T36", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 2128, 2138 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T37", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 2191, 2201 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T38", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 2221, 2231 ] ], "normalized": [] }, { "id": "Anagrelide_ddi_T39", "type": "DRUG", "text": [ "anagrelide" ], "offsets": [ [ 2312, 2322 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Anagrelide_ddi_R1", "type": "EFFECT", "arg1_id": "Anagrelide_ddi_T22", "arg2_id": "Anagrelide_ddi_T23", "normalized": [] }, { "id": "Anagrelide_ddi_R2", "type": "MECHANISM", "arg1_id": "Anagrelide_ddi_T25", "arg2_id": "Anagrelide_ddi_T26", "normalized": [] }, { "id": "Anagrelide_ddi_R3", "type": "MECHANISM", "arg1_id": "Anagrelide_ddi_T28", "arg2_id": "Anagrelide_ddi_T29", "normalized": [] }, { "id": "Anagrelide_ddi_R4", "type": "EFFECT", "arg1_id": "Anagrelide_ddi_T31", "arg2_id": "Anagrelide_ddi_T36", "normalized": [] }, { "id": "Anagrelide_ddi_R5", "type": "EFFECT", "arg1_id": "Anagrelide_ddi_T32", "arg2_id": "Anagrelide_ddi_T36", "normalized": [] }, { "id": "Anagrelide_ddi_R6", "type": "EFFECT", "arg1_id": "Anagrelide_ddi_T33", "arg2_id": "Anagrelide_ddi_T36", "normalized": [] }, { "id": "Anagrelide_ddi_R7", "type": "EFFECT", "arg1_id": "Anagrelide_ddi_T34", "arg2_id": "Anagrelide_ddi_T36", "normalized": [] }, { "id": "Anagrelide_ddi_R8", "type": "EFFECT", "arg1_id": "Anagrelide_ddi_T35", "arg2_id": "Anagrelide_ddi_T36", "normalized": [] }, { "id": "Anagrelide_ddi_R9", "type": "MECHANISM", "arg1_id": "Anagrelide_ddi_T37", "arg2_id": "Anagrelide_ddi_T38", "normalized": [] } ]

[ { "id": "Dantrolene_ddi__text", "type": "abstract", "text": [ "Dantrium is metabolized by the liver, and it is theoretically possible that its metabolism may be enhanced by drugs known to induce hepatic microsomal enzymes. However, neither phenobarbital nor diazepam appears to affect Dantrium metabolism. Binding to plasma protein is not significantly altered by diazepam, diphenylhydantoin, or phenylbutazone. Binding to plasma proteins is reduced by warfarin and clotibrate and increased by tolbutamide. Cardiovascular collapse in patients treated simultaneously with varapamil and dantrolene sodium is rare. The combination of therapeutic doses of intravenous dantrolene sodium and verapamil in halothane a-chloralose anesthetized swine has resulted in ventricular fibrillation and cardiovascular collapse in association with marked hyperkalemia. It is recommended that the combination of intravenous dantrolene sodium and calcium channel blockers, such as verapamil, not be used together during the management of malignant hyperthermia crisis until the relevance of these findings to humans is established. Administration of dantrolene may potentiate vecuronium-induced neuromuscular block." ], "offsets": [ [ 0, 1132 ] ] } ]

[ { "id": "Dantrolene_ddi_T1", "type": "BRAND", "text": [ "Dantrium" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T2", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 177, 190 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T3", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 195, 203 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T4", "type": "BRAND", "text": [ "Dantrium" ], "offsets": [ [ 222, 230 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T5", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 301, 309 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T6", "type": "DRUG", "text": [ "diphenylhydantoin" ], "offsets": [ [ 311, 328 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T7", "type": "DRUG", "text": [ "phenylbutazone" ], "offsets": [ [ 333, 347 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T8", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 390, 398 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T9", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 431, 442 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T10", "type": "DRUG", "text": [ "dantrolene sodium" ], "offsets": [ [ 522, 539 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T11", "type": "DRUG", "text": [ "dantrolene sodium" ], "offsets": [ [ 601, 618 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T12", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 623, 632 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T13", "type": "DRUG", "text": [ "halothane" ], "offsets": [ [ 636, 645 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T14", "type": "DRUG", "text": [ "dantrolene sodium" ], "offsets": [ [ 842, 859 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T15", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 864, 888 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T16", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 898, 907 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T17", "type": "DRUG", "text": [ "dantrolene" ], "offsets": [ [ 1067, 1077 ] ], "normalized": [] }, { "id": "Dantrolene_ddi_T18", "type": "DRUG", "text": [ "vecuronium" ], "offsets": [ [ 1093, 1103 ] ], "normalized": [] } ]

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[]

[ { "id": "Dantrolene_ddi_R1", "type": "ADVISE", "arg1_id": "Dantrolene_ddi_T14", "arg2_id": "Dantrolene_ddi_T15", "normalized": [] }, { "id": "Dantrolene_ddi_R2", "type": "ADVISE", "arg1_id": "Dantrolene_ddi_T14", "arg2_id": "Dantrolene_ddi_T16", "normalized": [] }, { "id": "Dantrolene_ddi_R3", "type": "EFFECT", "arg1_id": "Dantrolene_ddi_T17", "arg2_id": "Dantrolene_ddi_T18", "normalized": [] } ]

[ { "id": "Iloprost_ddi__text", "type": "abstract", "text": [ "In studies in normal volunteers, there was no pharmacodynamic interaction between intravenous iloprost and either nifedipine, diltiazem, or captopril. However, iloprost has the potential to increase the hypotensive effect of vasodilators and antihypertensive agents. Since iloprost inhibits platelet function, there is a potential for increased risk of bleeding, particularly in patients maintained on anticoagulants. During clinical trials, iloprost was used concurrently with anticoagulants, diuretics, cardiac glycosides, calcium channel blockers, analgesics, antipyretics, nonsteroidal antiinflammatories, corticosteroids, and other medications. Intravenous infusion of iloprost had no effect on the pharmacokinetics of digoxin. Acetylsalicylic acid did not alter the clearance (pharmacokinetics) of iloprost. Although clinical studies have not been conducted, in vitro studies of iloprost indicate that no relevant inhibition of cytochrome P450 drug metabolism would be expected." ], "offsets": [ [ 0, 984 ] ] } ]

[ { "id": "Iloprost_ddi_T1", "type": "DRUG", "text": [ "iloprost" ], "offsets": [ [ 94, 102 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T2", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 114, 124 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T3", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 126, 135 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T4", "type": "DRUG", "text": [ "captopril" ], "offsets": [ [ 140, 149 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T5", "type": "DRUG", "text": [ "iloprost" ], "offsets": [ [ 160, 168 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T6", "type": "GROUP", "text": [ "vasodilators" ], "offsets": [ [ 225, 237 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T7", "type": "GROUP", "text": [ "antihypertensive agents" ], "offsets": [ [ 242, 265 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T8", "type": "DRUG", "text": [ "iloprost" ], "offsets": [ [ 273, 281 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T9", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 402, 416 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T10", "type": "DRUG", "text": [ "iloprost" ], "offsets": [ [ 442, 450 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T11", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 478, 492 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T12", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 494, 503 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T13", "type": "GROUP", "text": [ "cardiac glycosides" ], "offsets": [ [ 505, 523 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T14", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 525, 549 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T15", "type": "GROUP", "text": [ "analgesics" ], "offsets": [ [ 551, 561 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T16", "type": "GROUP", "text": [ "antipyretics" ], "offsets": [ [ 563, 575 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T17", "type": "GROUP", "text": [ "nonsteroidal antiinflammatories" ], "offsets": [ [ 577, 608 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T18", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 610, 625 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T19", "type": "DRUG", "text": [ "iloprost" ], "offsets": [ [ 674, 682 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T20", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 724, 731 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T21", "type": "DRUG", "text": [ "Acetylsalicylic acid" ], "offsets": [ [ 733, 753 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T22", "type": "DRUG", "text": [ "iloprost" ], "offsets": [ [ 804, 812 ] ], "normalized": [] }, { "id": "Iloprost_ddi_T23", "type": "DRUG", "text": [ "iloprost" ], "offsets": [ [ 885, 893 ] ], "normalized": [] } ]

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[]

[ { "id": "Iloprost_ddi_R1", "type": "EFFECT", "arg1_id": "Iloprost_ddi_T5", "arg2_id": "Iloprost_ddi_T6", "normalized": [] }, { "id": "Iloprost_ddi_R2", "type": "EFFECT", "arg1_id": "Iloprost_ddi_T5", "arg2_id": "Iloprost_ddi_T7", "normalized": [] }, { "id": "Iloprost_ddi_R3", "type": "EFFECT", "arg1_id": "Iloprost_ddi_T8", "arg2_id": "Iloprost_ddi_T9", "normalized": [] } ]

[ { "id": "Calcium Gluceptate_ddi__text", "type": "abstract", "text": [ "May interact with cefamandole naftate, cephalothin sodium, magnesium sulfate, prednisolone sodium succinate, and prochlorperazine edisylate." ], "offsets": [ [ 0, 140 ] ] } ]

[ { "id": "Calcium Gluceptate_ddi_T1", "type": "DRUG", "text": [ "cefamandole naftate" ], "offsets": [ [ 18, 37 ] ], "normalized": [] }, { "id": "Calcium Gluceptate_ddi_T2", "type": "DRUG", "text": [ "cephalothin sodium" ], "offsets": [ [ 39, 57 ] ], "normalized": [] }, { "id": "Calcium Gluceptate_ddi_T3", "type": "DRUG", "text": [ "magnesium sulfate" ], "offsets": [ [ 59, 76 ] ], "normalized": [] }, { "id": "Calcium Gluceptate_ddi_T4", "type": "DRUG", "text": [ "prednisolone sodium succinate" ], "offsets": [ [ 78, 107 ] ], "normalized": [] }, { "id": "Calcium Gluceptate_ddi_T5", "type": "DRUG", "text": [ "prochlorperazine edisylate" ], "offsets": [ [ 113, 139 ] ], "normalized": [] } ]

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[ { "id": "Etomidate_ddi__text", "type": "abstract", "text": [ "The following drug interactions have been reported with etomidate. Drug Effect Probenecid Prolonged action of etomidate Diazoxide Hypotension Zimelidine etomidate antagonism Opioid analgesics Decreased antinociceptive action Aminophylline Etomidate antagonism Midazolam Synergism" ], "offsets": [ [ 0, 298 ] ] } ]

[ { "id": "Etomidate_ddi_T1", "type": "DRUG", "text": [ "etomidate" ], "offsets": [ [ 56, 65 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T2", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 79, 89 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T3", "type": "DRUG", "text": [ "etomidate" ], "offsets": [ [ 113, 122 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T4", "type": "DRUG", "text": [ "Diazoxide" ], "offsets": [ [ 123, 132 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T5", "type": "DRUG_N", "text": [ "Zimelidine" ], "offsets": [ [ 148, 158 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T6", "type": "DRUG", "text": [ "etomidate" ], "offsets": [ [ 162, 171 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T7", "type": "GROUP", "text": [ "Opioid analgesics" ], "offsets": [ [ 183, 200 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T8", "type": "DRUG", "text": [ "Aminophylline" ], "offsets": [ [ 237, 250 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T9", "type": "DRUG", "text": [ "Etomidate" ], "offsets": [ [ 255, 264 ] ], "normalized": [] }, { "id": "Etomidate_ddi_T10", "type": "DRUG", "text": [ "Midazolam" ], "offsets": [ [ 276, 285 ] ], "normalized": [] } ]

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[ { "id": "Fexofenadine_ddi__text", "type": "abstract", "text": [ "Drug Interaction with Erythromycin and Ketoconazole Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, co administration of fexofenadine hydrochloride with either ketoconazole or erythromycin led to increased plasma concentrations of fexofenadine. Fexofenadine had no effect on the pharmacokinetics of either erythromycin or ketoconazole. In 2 separate studies, fexofenadine hydrochloride 120 mg twice daily (240 mg total daily dose) was co-administered with either erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady-state conditions to healthy volunteers (n=24, each study). No differences in adverse events or QTc interval were observed when subjects were administered fexofenadine hydrochloride alone or in combination with either erythromycin or ketoconazole. The findings of these studies are summarized in the following table: Effects on steady-state fexofenadine pharmacokinetics after 7 days of co-administration with fexofenadine hydrochloride 120 mg every 12 hours (two times the recommended twice daily dose) in healthy volunteers (n=24) Concomitant Drug cmaxSS (Peak plasma concentration) AUCss(0-12h) (Extent of systemic exposure) Erythromycin (500 mg every 8 hrs) +82% +109% Ketoconazole (400 mg once daily) +135% +164% The changes in plasma levels were within the range of plasma levels achieved in adequate and well-controlled clinical trials. The mechanism of these interactions has been evaluated in in vitro, in situ, and in vivo animal models. These studies indicate that ketoconazole or erythromycin co-administration enhances fexofenadine gastrointestinal absorption. This observed increase in the bioavailability of fexofenadine may be due to transport-related effects, such as p-glycoprotein. in vivo animal studies also suggest that in addition to enhancing absorption, ketoconazole decreases fexofenadine gastrointestinal secretion, while erythromycin may also decrease biliary excretion. Drug Interactions with Antacids Administration of 120 mg of fexofenadine hydrochloride (2 x 60 mg capsule) within 15 minutes of an aluminum and magnesium containing antacid (Maalox ) decreased fexofenadine AUC by 41% and cmax by 43%. ALLEGRA should not be taken closely in time with aluminum and magnesium containing antacids. Interactions with Fruit Juices Fruit juices such as grapefruit, orange and apple may reduce the bioavailability and exposure of fexofenadine. This is based on the results from 3 clinical studies using histamine induced skin wheals and flares coupled with population pharmacokinetic analysis. The size of wheal and flare were significantly larger when fexofenadine hydrochloride was administered with either grapefruit or orange juices compared to water. Based on the literature reports, the same effects may be extrapolated to other fruit juices such as apple juice. The clinical significance of these observations is unknown. In addition, based on the population pharmacokinetics analysis of the combined data from grapefruit and orange juices studies with the data from a bioequivalence study, the bioavailability of fexofenadine was reduced by 36%. Therefore, to maximize the effects of fexofenadine, it is recommended that ALLEGRA should be taken with water ." ], "offsets": [ [ 0, 3262 ] ] } ]

[ { "id": "Fexofenadine_ddi_T1", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 22, 34 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T2", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 39, 51 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T3", "type": "DRUG", "text": [ "Fexofenadine" ], "offsets": [ [ 52, 64 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T4", "type": "DRUG", "text": [ "fexofenadine hydrochloride" ], "offsets": [ [ 151, 177 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T5", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 190, 202 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T6", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 206, 218 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T7", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 261, 273 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T8", "type": "DRUG", "text": [ "Fexofenadine" ], "offsets": [ [ 275, 287 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T9", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 336, 348 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T10", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 352, 364 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T11", "type": "DRUG", "text": [ "fexofenadine hydrochloride" ], "offsets": [ [ 389, 415 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T12", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 493, 505 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T13", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 530, 542 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T14", "type": "DRUG", "text": [ "fexofenadine hydrochloride" ], "offsets": [ [ 728, 754 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T15", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 791, 803 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T16", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 807, 819 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T17", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 914, 926 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T18", "type": "DRUG", "text": [ "fexofenadine hydrochloride" ], "offsets": [ [ 983, 1009 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T19", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 1201, 1213 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T20", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 1246, 1258 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T21", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1549, 1561 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T22", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1565, 1577 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T23", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 1605, 1617 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T24", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 1696, 1708 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T25", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1852, 1864 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T26", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 1875, 1887 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T27", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1922, 1934 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T28", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 1995, 2003 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T29", "type": "DRUG", "text": [ "fexofenadine hydrochloride" ], "offsets": [ [ 2032, 2058 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T30", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 2103, 2111 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T31", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 2116, 2125 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T32", "type": "GROUP", "text": [ "antacid" ], "offsets": [ [ 2137, 2144 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T33", "type": "BRAND", "text": [ "Maalox" ], "offsets": [ [ 2146, 2152 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T34", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 2165, 2177 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T35", "type": "BRAND", "text": [ "ALLEGRA" ], "offsets": [ [ 2206, 2213 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T36", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 2255, 2263 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T37", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 2268, 2277 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T38", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 2289, 2297 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T39", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 2427, 2439 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T40", "type": "DRUG", "text": [ "histamine" ], "offsets": [ [ 2500, 2509 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T41", "type": "DRUG", "text": [ "fexofenadine hydrochloride" ], "offsets": [ [ 2650, 2676 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T42", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 3118, 3130 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T43", "type": "DRUG", "text": [ "fexofenadine" ], "offsets": [ [ 3189, 3201 ] ], "normalized": [] }, { "id": "Fexofenadine_ddi_T44", "type": "BRAND", "text": [ "ALLEGRA" ], "offsets": [ [ 3226, 3233 ] ], "normalized": [] } ]

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[ { "id": "Fexofenadine_ddi_R1", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T4", "arg2_id": "Fexofenadine_ddi_T5", "normalized": [] }, { "id": "Fexofenadine_ddi_R2", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T4", "arg2_id": "Fexofenadine_ddi_T6", "normalized": [] }, { "id": "Fexofenadine_ddi_R3", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T21", "arg2_id": "Fexofenadine_ddi_T23", "normalized": [] }, { "id": "Fexofenadine_ddi_R4", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T22", "arg2_id": "Fexofenadine_ddi_T23", "normalized": [] }, { "id": "Fexofenadine_ddi_R5", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T25", "arg2_id": "Fexofenadine_ddi_T26", "normalized": [] }, { "id": "Fexofenadine_ddi_R6", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T29", "arg2_id": "Fexofenadine_ddi_T30", "normalized": [] }, { "id": "Fexofenadine_ddi_R7", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T29", "arg2_id": "Fexofenadine_ddi_T31", "normalized": [] }, { "id": "Fexofenadine_ddi_R8", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T29", "arg2_id": "Fexofenadine_ddi_T32", "normalized": [] }, { "id": "Fexofenadine_ddi_R9", "type": "MECHANISM", "arg1_id": "Fexofenadine_ddi_T29", "arg2_id": "Fexofenadine_ddi_T33", "normalized": [] }, { "id": "Fexofenadine_ddi_R10", "type": "ADVISE", "arg1_id": "Fexofenadine_ddi_T35", "arg2_id": "Fexofenadine_ddi_T36", "normalized": [] }, { "id": "Fexofenadine_ddi_R11", "type": "ADVISE", "arg1_id": "Fexofenadine_ddi_T35", "arg2_id": "Fexofenadine_ddi_T37", "normalized": [] } ]

[ { "id": "Fenfluramine_ddi__text", "type": "abstract", "text": [ "Fenfluramine may increase slightly the effect of antihypertensive drugs, e.g., guanethidine, methyldopa, reserpine. Other CNS depressant drugs should be used with caution in patients taking fenfluramine, since the effects may be additive." ], "offsets": [ [ 0, 238 ] ] } ]

[ { "id": "Fenfluramine_ddi_T1", "type": "DRUG", "text": [ "Fenfluramine" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Fenfluramine_ddi_T2", "type": "GROUP", "text": [ "antihypertensive drugs" ], "offsets": [ [ 49, 71 ] ], "normalized": [] }, { "id": "Fenfluramine_ddi_T3", "type": "DRUG", "text": [ "guanethidine" ], "offsets": [ [ 79, 91 ] ], "normalized": [] }, { "id": "Fenfluramine_ddi_T4", "type": "DRUG", "text": [ "methyldopa" ], "offsets": [ [ 93, 103 ] ], "normalized": [] }, { "id": "Fenfluramine_ddi_T5", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 105, 114 ] ], "normalized": [] }, { "id": "Fenfluramine_ddi_T6", "type": "GROUP", "text": [ "CNS depressant drugs" ], "offsets": [ [ 122, 142 ] ], "normalized": [] }, { "id": "Fenfluramine_ddi_T7", "type": "DRUG", "text": [ "fenfluramine" ], "offsets": [ [ 190, 202 ] ], "normalized": [] } ]

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[ { "id": "Fenfluramine_ddi_R1", "type": "EFFECT", "arg1_id": "Fenfluramine_ddi_T1", "arg2_id": "Fenfluramine_ddi_T2", "normalized": [] }, { "id": "Fenfluramine_ddi_R2", "type": "EFFECT", "arg1_id": "Fenfluramine_ddi_T1", "arg2_id": "Fenfluramine_ddi_T3", "normalized": [] }, { "id": "Fenfluramine_ddi_R3", "type": "EFFECT", "arg1_id": "Fenfluramine_ddi_T1", "arg2_id": "Fenfluramine_ddi_T4", "normalized": [] }, { "id": "Fenfluramine_ddi_R4", "type": "EFFECT", "arg1_id": "Fenfluramine_ddi_T1", "arg2_id": "Fenfluramine_ddi_T5", "normalized": [] }, { "id": "Fenfluramine_ddi_R5", "type": "ADVISE", "arg1_id": "Fenfluramine_ddi_T6", "arg2_id": "Fenfluramine_ddi_T7", "normalized": [] } ]

[ { "id": "Netilmicin_ddi__text", "type": "abstract", "text": [ "Netilmicin should not be administered concomitantly with potent loop diuretics such as furosemide and ethacrynic acid as the potential for ototoxicity is enhanced by the combination." ], "offsets": [ [ 0, 182 ] ] } ]

[ { "id": "Netilmicin_ddi_T1", "type": "DRUG", "text": [ "Netilmicin" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Netilmicin_ddi_T2", "type": "GROUP", "text": [ "loop diuretics" ], "offsets": [ [ 64, 78 ] ], "normalized": [] }, { "id": "Netilmicin_ddi_T3", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 87, 97 ] ], "normalized": [] }, { "id": "Netilmicin_ddi_T4", "type": "DRUG", "text": [ "ethacrynic acid" ], "offsets": [ [ 102, 117 ] ], "normalized": [] } ]

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[ { "id": "Netilmicin_ddi_R1", "type": "ADVISE", "arg1_id": "Netilmicin_ddi_T1", "arg2_id": "Netilmicin_ddi_T2", "normalized": [] }, { "id": "Netilmicin_ddi_R2", "type": "ADVISE", "arg1_id": "Netilmicin_ddi_T1", "arg2_id": "Netilmicin_ddi_T3", "normalized": [] }, { "id": "Netilmicin_ddi_R3", "type": "ADVISE", "arg1_id": "Netilmicin_ddi_T1", "arg2_id": "Netilmicin_ddi_T4", "normalized": [] } ]

[ { "id": "Citalopram_ddi__text", "type": "abstract", "text": [ "Central nervous system depressant (CNS) drugs including alcohol, antidepressants, antihistamines, antipsychotics, blood pressure medications (reserpine, methyldopa, beta-blockers), motion sickness medications, muscle relaxants, narcotics, sedatives, sleeping pills and tranquilizers" ], "offsets": [ [ 0, 282 ] ] } ]

[ { "id": "Citalopram_ddi_T1", "type": "GROUP", "text": [ "Central nervous system depressant" ], "offsets": [ [ 0, 33 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 56, 63 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T3", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 65, 80 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T4", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 82, 96 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T5", "type": "GROUP", "text": [ "antipsychotics" ], "offsets": [ [ 98, 112 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T6", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 142, 151 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T7", "type": "DRUG", "text": [ "methyldopa" ], "offsets": [ [ 153, 163 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T8", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 165, 178 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T9", "type": "GROUP", "text": [ "muscle relaxants" ], "offsets": [ [ 210, 226 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T10", "type": "GROUP", "text": [ "narcotics" ], "offsets": [ [ 228, 237 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T11", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 239, 248 ] ], "normalized": [] }, { "id": "Citalopram_ddi_T12", "type": "GROUP", "text": [ "tranquilizers" ], "offsets": [ [ 269, 282 ] ], "normalized": [] } ]

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[ { "id": "Hydrocortisone_ddi__text", "type": "abstract", "text": [ "No information available." ], "offsets": [ [ 0, 25 ] ] } ]

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[ { "id": "Deserpidine_ddi__text", "type": "abstract", "text": [ "Taking a rauwolfia alkaloid while you are taking or within 2 weeks of taking MAO inhibitors may increase the risk of central nervous system depression or may cause a severe high blood pressure reaction." ], "offsets": [ [ 0, 202 ] ] } ]

[ { "id": "Deserpidine_ddi_T1", "type": "GROUP", "text": [ "rauwolfia alkaloid" ], "offsets": [ [ 9, 27 ] ], "normalized": [] }, { "id": "Deserpidine_ddi_T2", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 77, 91 ] ], "normalized": [] } ]

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[ { "id": "Deserpidine_ddi_R1", "type": "EFFECT", "arg1_id": "Deserpidine_ddi_T1", "arg2_id": "Deserpidine_ddi_T2", "normalized": [] } ]

[ { "id": "Lepirudin_ddi__text", "type": "abstract", "text": [ "Concomitant treatment with thrombolytics (eg, rt-PA or streptokinase) may: - increase the risk of bleeding complications - considerably enhance the effect of REFLUDAN on aPTT prolongation Concomitant treatment with coumarin derivatives (vitamin K antagonists) and drugs that affect platelet function may also increase the risk of bleeding." ], "offsets": [ [ 0, 339 ] ] } ]

[ { "id": "Lepirudin_ddi_T1", "type": "GROUP", "text": [ "thrombolytics" ], "offsets": [ [ 27, 40 ] ], "normalized": [] }, { "id": "Lepirudin_ddi_T2", "type": "DRUG", "text": [ "streptokinase" ], "offsets": [ [ 55, 68 ] ], "normalized": [] }, { "id": "Lepirudin_ddi_T3", "type": "BRAND", "text": [ "REFLUDAN" ], "offsets": [ [ 158, 166 ] ], "normalized": [] }, { "id": "Lepirudin_ddi_T4", "type": "GROUP", "text": [ "coumarin derivatives" ], "offsets": [ [ 215, 235 ] ], "normalized": [] }, { "id": "Lepirudin_ddi_T5", "type": "GROUP", "text": [ "vitamin K antagonists" ], "offsets": [ [ 237, 258 ] ], "normalized": [] } ]

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[ { "id": "Deferasirox_ddi__text", "type": "abstract", "text": [ "The concomitant administration of Exjade and aluminum-containing antacid preparations has not been formally studied. Although deferasirox has a lower affinity for aluminum than for iron, Exjade should not be taken with aluminum-containing antacid preparations. In healthy volunteers, Exjade had no effect on the pharmacokinetics of digoxin. The effect of digoxin on Exjade pharmacokinetics has not been studied. The concomitant administration of Exjade and vitamin C has not been formally studied. Doses of vitamin C up to 200 mg were allowed in clinical studies without negative consequences. The interaction of Exjade with hydroxyurea has not been formally studied. No inhibition of deferasirox metabolism by hydroxyurea is expected based on the results of an in vitro study. Exjade should not be combined with other iron chelator therapies, as safety of such combinations has not been established. Drug/Food Interactions The bioavailability (AUC) of deferasirox was variably increased when taken with a meal. Deferasirox should be taken on an empty stomach 30 minutes before eating. Exjade tablets for oral suspension can be dispersed in water, orange juice, or apple juice." ], "offsets": [ [ 0, 1177 ] ] } ]

[ { "id": "Deferasirox_ddi_T1", "type": "BRAND", "text": [ "Exjade" ], "offsets": [ [ 34, 40 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T2", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 45, 53 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T3", "type": "GROUP", "text": [ "antacid preparations" ], "offsets": [ [ 65, 85 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T4", "type": "DRUG", "text": [ "deferasirox" ], "offsets": [ [ 126, 137 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T5", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 163, 171 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T6", "type": "DRUG", "text": [ "iron" ], "offsets": [ [ 181, 185 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T7", "type": "BRAND", "text": [ "Exjade" ], "offsets": [ [ 187, 193 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T8", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 219, 227 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T9", "type": "GROUP", "text": [ "antacid preparations" ], "offsets": [ [ 239, 259 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T10", "type": "BRAND", "text": [ "Exjade" ], "offsets": [ [ 284, 290 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T11", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 332, 339 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T12", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 355, 362 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T13", "type": "BRAND", "text": [ "Exjade" ], "offsets": [ [ 366, 372 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T14", "type": "BRAND", "text": [ "Exjade" ], "offsets": [ [ 446, 452 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T15", "type": "DRUG", "text": [ "vitamin C" ], "offsets": [ [ 457, 466 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T16", "type": "DRUG", "text": [ "vitamin C" ], "offsets": [ [ 507, 516 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T17", "type": "BRAND", "text": [ "Exjade" ], "offsets": [ [ 613, 619 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T18", "type": "DRUG", "text": [ "hydroxyurea" ], "offsets": [ [ 625, 636 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T19", "type": "DRUG", "text": [ "deferasirox" ], "offsets": [ [ 685, 696 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T20", "type": "DRUG", "text": [ "hydroxyurea" ], "offsets": [ [ 711, 722 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T21", "type": "BRAND", "text": [ "Exjade" ], "offsets": [ [ 778, 784 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T22", "type": "DRUG", "text": [ "deferasirox" ], "offsets": [ [ 953, 964 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T23", "type": "DRUG", "text": [ "Deferasirox" ], "offsets": [ [ 1012, 1023 ] ], "normalized": [] }, { "id": "Deferasirox_ddi_T24", "type": "BRAND", "text": [ "Exjade" ], "offsets": [ [ 1086, 1092 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Deferasirox_ddi_R1", "type": "ADVISE", "arg1_id": "Deferasirox_ddi_T7", "arg2_id": "Deferasirox_ddi_T8", "normalized": [] } ]

[ { "id": "Doxapram_ddi__text", "type": "abstract", "text": [ "Administration of doxapram to patients who are receiving sympathomimetic or monoamine oxidase inhibiting drugs may result in an additive pressor effect . In patients who have received muscle relaxants, doxapram may temporarily mask the residual effects of muscle relaxant drugs. In patients who have received general anesthesia utilizing a volatile agent known to sensitize the myocardium to catecholamines, administration of doxapram should be delayed until the volatile agent has been excreted in order to lessen the potential for arrhythmias, including ventricular tachycardia and ventricular fibrillation." ], "offsets": [ [ 0, 609 ] ] } ]

[ { "id": "Doxapram_ddi_T1", "type": "DRUG", "text": [ "doxapram" ], "offsets": [ [ 18, 26 ] ], "normalized": [] }, { "id": "Doxapram_ddi_T2", "type": "GROUP", "text": [ "sympathomimetic" ], "offsets": [ [ 57, 72 ] ], "normalized": [] }, { "id": "Doxapram_ddi_T3", "type": "GROUP", "text": [ "monoamine oxidase inhibiting drugs" ], "offsets": [ [ 76, 110 ] ], "normalized": [] }, { "id": "Doxapram_ddi_T4", "type": "GROUP", "text": [ "muscle relaxants" ], "offsets": [ [ 184, 200 ] ], "normalized": [] }, { "id": "Doxapram_ddi_T5", "type": "DRUG", "text": [ "doxapram" ], "offsets": [ [ 202, 210 ] ], "normalized": [] }, { "id": "Doxapram_ddi_T6", "type": "GROUP", "text": [ "muscle relaxant drugs" ], "offsets": [ [ 256, 277 ] ], "normalized": [] }, { "id": "Doxapram_ddi_T7", "type": "DRUG", "text": [ "doxapram" ], "offsets": [ [ 426, 434 ] ], "normalized": [] } ]

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[]

[ { "id": "Doxapram_ddi_R1", "type": "EFFECT", "arg1_id": "Doxapram_ddi_T1", "arg2_id": "Doxapram_ddi_T2", "normalized": [] }, { "id": "Doxapram_ddi_R2", "type": "EFFECT", "arg1_id": "Doxapram_ddi_T1", "arg2_id": "Doxapram_ddi_T3", "normalized": [] }, { "id": "Doxapram_ddi_R3", "type": "EFFECT", "arg1_id": "Doxapram_ddi_T5", "arg2_id": "Doxapram_ddi_T6", "normalized": [] } ]

[ { "id": "Interferon beta-1b_ddi__text", "type": "abstract", "text": [ "Interactions between Betaseron and other drugs have not been fully evaluated. Although studies designed to examine drug interactions have not been done, it was noted that corticosteroid or ACTH treatment of relapses for periods of up to 28 days has been administered to patients (N=180) receiving Betaseron. Betaseron administration to three cancer patients over a dose range of 0.025 mg to 2.2 mg led to a dose-dependent inhibition of antipyrine elimination.14 The effect of alternate-day administration of 0.25 mg of Betaseron on drug metabolism in MS patients is unknown." ], "offsets": [ [ 0, 574 ] ] } ]

[ { "id": "Interferon beta-1b_ddi_T1", "type": "BRAND", "text": [ "Betaseron" ], "offsets": [ [ 21, 30 ] ], "normalized": [] }, { "id": "Interferon beta-1b_ddi_T2", "type": "GROUP", "text": [ "corticosteroid" ], "offsets": [ [ 171, 185 ] ], "normalized": [] }, { "id": "Interferon beta-1b_ddi_T3", "type": "DRUG", "text": [ "ACTH" ], "offsets": [ [ 189, 193 ] ], "normalized": [] }, { "id": "Interferon beta-1b_ddi_T4", "type": "BRAND", "text": [ "Betaseron" ], "offsets": [ [ 297, 306 ] ], "normalized": [] }, { "id": "Interferon beta-1b_ddi_T5", "type": "BRAND", "text": [ "Betaseron" ], "offsets": [ [ 308, 317 ] ], "normalized": [] }, { "id": "Interferon beta-1b_ddi_T6", "type": "DRUG", "text": [ "antipyrine" ], "offsets": [ [ 436, 446 ] ], "normalized": [] }, { "id": "Interferon beta-1b_ddi_T7", "type": "BRAND", "text": [ "Betaseron" ], "offsets": [ [ 519, 528 ] ], "normalized": [] } ]

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[]

[ { "id": "Interferon beta-1b_ddi_R1", "type": "MECHANISM", "arg1_id": "Interferon beta-1b_ddi_T5", "arg2_id": "Interferon beta-1b_ddi_T6", "normalized": [] } ]

[ { "id": "Erlotinib_ddi__text", "type": "abstract", "text": [ "Co-treatment with the potent CYP3A4 inhibitor ketoconazole increases erlotinib AUC by 2/3. Caution should be used when administering or taking TARCEVA with ketoconazole and other strong CYP3A4 inhibitors such as, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), and voriconazole . Pre-treatment with the CYP3A4 inducer rifampicin decreased erlotinib AUC by about 2/3. Alternate treatments lacking CYP3A4 inducing activity should be considered. If an alternative treatment is unavailable, a TARCEVA dose greater than 150 mg should be considered for NSCLC patients, and greater than 100 mg considered for pancreatic cancer patients. If the TARCEVA dose is adjusted upward, the dose will need to be reduced upon discontinuation of rifampicin or other inducers. Other CYP3A4 inducers include, but are not limited to, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. Johns Wort. Hepatotoxicity Asymptomatic increases in liver transaminases have been observed in TARCEVA treated patients; therefore, periodic liver function testing (transaminases, bilirubin, and alkaline phosphatase) should be considered. Dose reduction or interruption of TARCEVA should be considered if changes in liver function are severe. Patients with Hepatic Impairment In vitro and in vivo evidence suggest that erlotinib is cleared primarily by the liver. Therefore, erlotinib exposure may be increased in patients with hepatic dysfunction. Elevated International Normalized Ratio and Potential Bleeding International Normalized Ratio (INR) elevations and infrequent reports of bleeding events including gastrointestinal and non-gastrointestinal bleedings have been reported in clinical studies, some associated with concomitant warfarin administration. Patients taking warfarin or other coumarin-derivative anticoagulants should be monitored regularly for changes in prothrombin time or INR ." ], "offsets": [ [ 0, 1994 ] ] } ]

[ { "id": "Erlotinib_ddi_T1", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 46, 58 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T2", "type": "DRUG", "text": [ "erlotinib" ], "offsets": [ [ 69, 78 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T3", "type": "BRAND", "text": [ "TARCEVA" ], "offsets": [ [ 143, 150 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T4", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 156, 168 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T5", "type": "DRUG", "text": [ "atazanavir" ], "offsets": [ [ 233, 243 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T6", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 245, 259 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T7", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 261, 270 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T8", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 272, 284 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T9", "type": "DRUG", "text": [ "nefazodone" ], "offsets": [ [ 286, 296 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T10", "type": "DRUG", "text": [ "nelfinavir" ], "offsets": [ [ 298, 308 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T11", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 310, 319 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T12", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 321, 331 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T13", "type": "DRUG", "text": [ "telithromycin" ], "offsets": [ [ 333, 346 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T14", "type": "DRUG", "text": [ "troleandomycin" ], "offsets": [ [ 348, 362 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T15", "type": "DRUG", "text": [ "TAO" ], "offsets": [ [ 364, 367 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T16", "type": "DRUG", "text": [ "voriconazole" ], "offsets": [ [ 374, 386 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T17", "type": "DRUG", "text": [ "rifampicin" ], "offsets": [ [ 427, 437 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T18", "type": "DRUG", "text": [ "erlotinib" ], "offsets": [ [ 448, 457 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T19", "type": "BRAND", "text": [ "TARCEVA" ], "offsets": [ [ 598, 605 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T20", "type": "BRAND", "text": [ "TARCEVA" ], "offsets": [ [ 746, 753 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T21", "type": "DRUG", "text": [ "rifampicin" ], "offsets": [ [ 836, 846 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T22", "type": "DRUG", "text": [ "rifabutin" ], "offsets": [ [ 921, 930 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T23", "type": "DRUG", "text": [ "rifapentine" ], "offsets": [ [ 932, 943 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T24", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 945, 954 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T25", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 956, 969 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T26", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 971, 984 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T27", "type": "BRAND", "text": [ "TARCEVA" ], "offsets": [ [ 1088, 1095 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T28", "type": "BRAND", "text": [ "TARCEVA" ], "offsets": [ [ 1266, 1273 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T29", "type": "DRUG", "text": [ "erlotinib" ], "offsets": [ [ 1412, 1421 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T30", "type": "DRUG", "text": [ "erlotinib" ], "offsets": [ [ 1468, 1477 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T31", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1830, 1838 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T32", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1871, 1879 ] ], "normalized": [] }, { "id": "Erlotinib_ddi_T33", "type": "GROUP", "text": [ "coumarin-derivative anticoagulants" ], "offsets": [ [ 1889, 1923 ] ], "normalized": [] } ]

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[ { "id": "Erlotinib_ddi_R1", "type": "MECHANISM", "arg1_id": "Erlotinib_ddi_T1", "arg2_id": "Erlotinib_ddi_T2", "normalized": [] }, { "id": "Erlotinib_ddi_R2", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T4", "normalized": [] }, { "id": "Erlotinib_ddi_R3", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T5", "normalized": [] }, { "id": "Erlotinib_ddi_R4", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T6", "normalized": [] }, { "id": "Erlotinib_ddi_R5", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T7", "normalized": [] }, { "id": "Erlotinib_ddi_R6", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T8", "normalized": [] }, { "id": "Erlotinib_ddi_R7", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T9", "normalized": [] }, { "id": "Erlotinib_ddi_R8", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T10", "normalized": [] }, { "id": "Erlotinib_ddi_R9", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T11", "normalized": [] }, { "id": "Erlotinib_ddi_R10", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T12", "normalized": [] }, { "id": "Erlotinib_ddi_R11", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T13", "normalized": [] }, { "id": "Erlotinib_ddi_R12", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T14", "normalized": [] }, { "id": "Erlotinib_ddi_R13", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T15", "normalized": [] }, { "id": "Erlotinib_ddi_R14", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T3", "arg2_id": "Erlotinib_ddi_T16", "normalized": [] }, { "id": "Erlotinib_ddi_R15", "type": "MECHANISM", "arg1_id": "Erlotinib_ddi_T17", "arg2_id": "Erlotinib_ddi_T18", "normalized": [] }, { "id": "Erlotinib_ddi_R16", "type": "ADVISE", "arg1_id": "Erlotinib_ddi_T20", "arg2_id": "Erlotinib_ddi_T21", "normalized": [] } ]

[ { "id": "Decitabine_ddi__text", "type": "abstract", "text": [ "Drug interaction studies with decitabine have not been conducted. In vitro studies in human liver microsomes suggest that decitabine is unlikely to inhibit or induce cytochrome P450 enzymes. In vitro metabolism studies have suggested that decitabine is not a substrate for the human liver cytochrome P450 enzymes. As plasma protein binding of decitabine is negligible ( 1%), interactions due to displacement of more highly protein bound drugs from plasma proteins are not expected." ], "offsets": [ [ 0, 481 ] ] } ]

[ { "id": "Decitabine_ddi_T1", "type": "DRUG", "text": [ "decitabine" ], "offsets": [ [ 30, 40 ] ], "normalized": [] }, { "id": "Decitabine_ddi_T2", "type": "DRUG", "text": [ "decitabine" ], "offsets": [ [ 122, 132 ] ], "normalized": [] }, { "id": "Decitabine_ddi_T3", "type": "DRUG", "text": [ "decitabine" ], "offsets": [ [ 239, 249 ] ], "normalized": [] }, { "id": "Decitabine_ddi_T4", "type": "DRUG", "text": [ "decitabine" ], "offsets": [ [ 343, 353 ] ], "normalized": [] } ]

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[ { "id": "Ethopropazine_ddi__text", "type": "abstract", "text": [ "Ethopropazine may interact with alcohol or other CNS depressants, causing increased sedative effects. It may also interact with amantadine or other anticholinergic drugs or MAOIs, which may intensify the anticholinergic action. Ethopropazine can interact with chlorpromazine, increasing the metabolism of chlorpromazine." ], "offsets": [ [ 0, 320 ] ] } ]

[ { "id": "Ethopropazine_ddi_T1", "type": "DRUG", "text": [ "Ethopropazine" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "Ethopropazine_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 32, 39 ] ], "normalized": [] }, { "id": "Ethopropazine_ddi_T3", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 49, 64 ] ], "normalized": [] }, { "id": "Ethopropazine_ddi_T4", "type": "DRUG", "text": [ "amantadine" ], "offsets": [ [ 128, 138 ] ], "normalized": [] }, { "id": "Ethopropazine_ddi_T5", "type": "GROUP", "text": [ "anticholinergic drugs" ], "offsets": [ [ 148, 169 ] ], "normalized": [] }, { "id": "Ethopropazine_ddi_T6", "type": "GROUP", "text": [ "MAOIs" ], "offsets": [ [ 173, 178 ] ], "normalized": [] }, { "id": "Ethopropazine_ddi_T7", "type": "DRUG", "text": [ "Ethopropazine" ], "offsets": [ [ 228, 241 ] ], "normalized": [] }, { "id": "Ethopropazine_ddi_T8", "type": "DRUG", "text": [ "chlorpromazine" ], "offsets": [ [ 260, 274 ] ], "normalized": [] }, { "id": "Ethopropazine_ddi_T9", "type": "DRUG", "text": [ "chlorpromazine" ], "offsets": [ [ 305, 319 ] ], "normalized": [] } ]

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[]

[ { "id": "Ethopropazine_ddi_R1", "type": "EFFECT", "arg1_id": "Ethopropazine_ddi_T1", "arg2_id": "Ethopropazine_ddi_T2", "normalized": [] }, { "id": "Ethopropazine_ddi_R2", "type": "EFFECT", "arg1_id": "Ethopropazine_ddi_T1", "arg2_id": "Ethopropazine_ddi_T3", "normalized": [] }, { "id": "Ethopropazine_ddi_R3", "type": "MECHANISM", "arg1_id": "Ethopropazine_ddi_T7", "arg2_id": "Ethopropazine_ddi_T8", "normalized": [] } ]

[ { "id": "Capecitabine_ddi__text", "type": "abstract", "text": [ "Antacid: The effect of an aluminum hydroxide- and magnesium hydroxide-containing antacid (Maalox)* on the pharmacokinetics of capecitabine was investigated in 12 cancer patients. There was a small increase in plasma concentrations of capecitabine and one metabolite (5-DFCR); there was no effect on the 3 major metabolites (5-DFUR, 5-FU and FBAL). Coumarin Anticoagulants Altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. Patients taking coumarin-derivative anticoagulants concomitantly with capecitabine should be monitored regularly for alterations in their coagulation parameters (PT or INR). Leucovorin: The concentration of 5-fluorouracil is increased and its toxicity may be enhanced by leucovorin. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil." ], "offsets": [ [ 0, 987 ] ] } ]

[ { "id": "Capecitabine_ddi_T1", "type": "GROUP", "text": [ "Antacid" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T2", "type": "DRUG", "text": [ "aluminum hydroxide" ], "offsets": [ [ 26, 44 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T3", "type": "DRUG", "text": [ "magnesium hydroxide" ], "offsets": [ [ 50, 69 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T4", "type": "GROUP", "text": [ "antacid" ], "offsets": [ [ 81, 88 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T5", "type": "BRAND", "text": [ "Maalox" ], "offsets": [ [ 90, 96 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T6", "type": "DRUG", "text": [ "capecitabine" ], "offsets": [ [ 126, 138 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T7", "type": "DRUG", "text": [ "capecitabine" ], "offsets": [ [ 234, 246 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T8", "type": "DRUG_N", "text": [ "5-DFCR" ], "offsets": [ [ 267, 273 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T9", "type": "DRUG_N", "text": [ "5-DFUR" ], "offsets": [ [ 324, 330 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T10", "type": "DRUG_N", "text": [ "5-FU" ], "offsets": [ [ 332, 336 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T11", "type": "DRUG_N", "text": [ "FBAL" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T12", "type": "GROUP", "text": [ "Coumarin Anticoagulants" ], "offsets": [ [ 348, 371 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T13", "type": "DRUG", "text": [ "capecitabine" ], "offsets": [ [ 457, 469 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T14", "type": "GROUP", "text": [ "coumarin-derivative anticoagulants" ], "offsets": [ [ 489, 523 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T15", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 532, 540 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T16", "type": "DRUG", "text": [ "phenprocoumon" ], "offsets": [ [ 545, 558 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T17", "type": "GROUP", "text": [ "coumarin-derivative anticoagulants" ], "offsets": [ [ 576, 610 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T18", "type": "DRUG", "text": [ "capecitabine" ], "offsets": [ [ 630, 642 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T19", "type": "DRUG", "text": [ "Leucovorin" ], "offsets": [ [ 734, 744 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T20", "type": "DRUG", "text": [ "5-fluorouracil" ], "offsets": [ [ 767, 781 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T21", "type": "DRUG", "text": [ "leucovorin" ], "offsets": [ [ 831, 841 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T22", "type": "DRUG", "text": [ "leucovorin" ], "offsets": [ [ 959, 969 ] ], "normalized": [] }, { "id": "Capecitabine_ddi_T23", "type": "DRUG", "text": [ "fluorouracil" ], "offsets": [ [ 974, 986 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Capecitabine_ddi_R1", "type": "EFFECT", "arg1_id": "Capecitabine_ddi_T13", "arg2_id": "Capecitabine_ddi_T14", "normalized": [] }, { "id": "Capecitabine_ddi_R2", "type": "EFFECT", "arg1_id": "Capecitabine_ddi_T13", "arg2_id": "Capecitabine_ddi_T16", "normalized": [] }, { "id": "Capecitabine_ddi_R3", "type": "ADVISE", "arg1_id": "Capecitabine_ddi_T17", "arg2_id": "Capecitabine_ddi_T18", "normalized": [] }, { "id": "Capecitabine_ddi_R4", "type": "MECHANISM", "arg1_id": "Capecitabine_ddi_T20", "arg2_id": "Capecitabine_ddi_T21", "normalized": [] }, { "id": "Capecitabine_ddi_R5", "type": "EFFECT", "arg1_id": "Capecitabine_ddi_T22", "arg2_id": "Capecitabine_ddi_T23", "normalized": [] } ]

[ { "id": "Dobutamine_ddi__text", "type": "abstract", "text": [ "Animal studies indicate that dobutamine may be ineffective if the patient has recently received a b-blocking drug. In such a case, the peripheral vascular resistance may increase. Preliminary studies indicate that the concomitant use of dobutamine and nitroprusside results in a higher cardiac output and, usually, a lower pulmonary wedge pressure than when either drug is used alone. There was no evidence of drug interactions in clinical studies in which dobutamine was administered concurrently with other drugs, including digitalis preparations, furosemide, spironolactone, lidocaine, glyceryl trinitrate, isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid, and acetaminophen." ], "offsets": [ [ 0, 722 ] ] } ]

[ { "id": "Dobutamine_ddi_T1", "type": "DRUG", "text": [ "dobutamine" ], "offsets": [ [ 29, 39 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T2", "type": "GROUP", "text": [ "b-blocking drug" ], "offsets": [ [ 98, 113 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T3", "type": "DRUG", "text": [ "dobutamine" ], "offsets": [ [ 237, 247 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T4", "type": "DRUG", "text": [ "nitroprusside" ], "offsets": [ [ 252, 265 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T5", "type": "DRUG", "text": [ "dobutamine" ], "offsets": [ [ 457, 467 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T6", "type": "GROUP", "text": [ "digitalis preparations" ], "offsets": [ [ 526, 548 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T7", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 550, 560 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T8", "type": "DRUG", "text": [ "spironolactone" ], "offsets": [ [ 562, 576 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T9", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 578, 587 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T10", "type": "DRUG", "text": [ "glyceryl trinitrate" ], "offsets": [ [ 589, 608 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T11", "type": "DRUG", "text": [ "isosorbide dinitrate" ], "offsets": [ [ 610, 630 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T12", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 632, 640 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T13", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 642, 650 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T14", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 652, 659 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T15", "type": "DRUG", "text": [ "protamine" ], "offsets": [ [ 661, 670 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T16", "type": "DRUG", "text": [ "potassium chloride" ], "offsets": [ [ 672, 690 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T17", "type": "DRUG", "text": [ "folic acid" ], "offsets": [ [ 692, 702 ] ], "normalized": [] }, { "id": "Dobutamine_ddi_T18", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 708, 721 ] ], "normalized": [] } ]

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[]

[ { "id": "Dobutamine_ddi_R1", "type": "EFFECT", "arg1_id": "Dobutamine_ddi_T1", "arg2_id": "Dobutamine_ddi_T2", "normalized": [] }, { "id": "Dobutamine_ddi_R2", "type": "EFFECT", "arg1_id": "Dobutamine_ddi_T3", "arg2_id": "Dobutamine_ddi_T4", "normalized": [] } ]

[ { "id": "Epoetin alfa_ddi__text", "type": "abstract", "text": [ "No evidence of interaction of PROCRIT with other drugs was observed in the course of clinical trials." ], "offsets": [ [ 0, 101 ] ] } ]

[ { "id": "Epoetin alfa_ddi_T1", "type": "BRAND", "text": [ "PROCRIT" ], "offsets": [ [ 30, 37 ] ], "normalized": [] } ]

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[ { "id": "Isoflurane_ddi__text", "type": "abstract", "text": [ "Isoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably nondepolarizing muscle relaxants, and MAC (minimum alveolar concentration) is reduced by concomitant administration of N 2O. See CLINICAL PHARMACOLOGY." ], "offsets": [ [ 0, 239 ] ] } ]

[ { "id": "Isoflurane_ddi_T1", "type": "DRUG", "text": [ "Isoflurane" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Isoflurane_ddi_T2", "type": "GROUP", "text": [ "muscle relaxants" ], "offsets": [ [ 57, 73 ] ], "normalized": [] }, { "id": "Isoflurane_ddi_T3", "type": "GROUP", "text": [ "nondepolarizing muscle relaxants" ], "offsets": [ [ 88, 120 ] ], "normalized": [] } ]

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[]

[ { "id": "Isoflurane_ddi_R1", "type": "EFFECT", "arg1_id": "Isoflurane_ddi_T1", "arg2_id": "Isoflurane_ddi_T2", "normalized": [] }, { "id": "Isoflurane_ddi_R2", "type": "EFFECT", "arg1_id": "Isoflurane_ddi_T1", "arg2_id": "Isoflurane_ddi_T3", "normalized": [] } ]

[ { "id": "Isradipine_ddi__text", "type": "abstract", "text": [ "Nitroglycerin: DynaCirc (isradipine) has been safely coadministered with nitroglycerin. Hydrochlorothiazide: A study in normal healthy volunteers has shown that concomitant administration of DynaCirc (isradipine) and hydrochlorothiazide does not result in altered pharmacoktnetics of either drug. In a study in hypertensive patients, addition of isradipine to existing hydrochlorothiazide therapy did not result in any unexpected adverse effects, and isradipine had an additional antihypertensive effect. Propranolol: In a single dose study in normal volunteers, coadministration of propranolol had a small effect on the rate but no effect on the extent of isradipine bioavailability. Significant increases In AUC (27%) and Cmax (58%) and decreases in tmax (23%) of propranolol were noted in this study. However, concomitant administration of 5 mg b.i.d. isradipine and 40 mg b.i.d. propranolol to healthy volunteers under steady-state conditions had no relevant effect on either drug s bioavailability, AUC and Cmax, differences were 20% between isradipine given singly and in combination with propranolol, and between propranolol given singly and in combination with isradipine. Cimetidine: In a study in healthy volunteers, a one-week course of cimetidine at 400 mg b.i.d. with a single 5 mg dose of isradipine on the sixth day showed an increase in isradipine mean peak plasma concentrations (36%) and significant increase in area under the curve (50%). If isradipine therapy is initiated in a patient currently receiving cimetidine careful monitoring for adverse reactions is advised and downward dose adjustment may be required. Rifampicin: In a study in healthy volunteers, a six-day course of rifampicin at 600 mg/day followed by a single 5 mg dose of isradipine resulted in a reduction in isradipine levels to below detectable limits. If rifampicin therapy is required, isradipine concentrations and therapeutic effects are likely to be markedly reduced or abolished as a consequence of increased metabolism and higher clearance of isradipine. Warfarin: In a study in healthy volunteers, no clinically relevant pharmacokinetic or pharmacodynamic interaction between isradipine and racemic warfarin was seen when two single oral doses of warfarin (0.7 mg/kg body weight) were administered during 11 days of multipledose treatment with 5 mg b.i.d. isradipine. Neither racemic warfarin nor isradipine binding to plasma proteins in vitro was altered by the addition of the other drug. Digoxin: The concomitant administration of DynaCirc (isradipine) and digoxin in a single-dose pharmacokinetic study did not affect renal, nonrenal and total body clearance of digoxin. Fentanyl Anesthesia: Severe hypotension has been reported during fentanyl anesthesia with concomitant use of a beta blocker and a calcium channel blocker. Even though such interactions have not been seen in clinical studies with DynaCirc (isradipine), an increased volume of circulating fluids might be required if such an interaction were to occur." ], "offsets": [ [ 0, 3028 ] ] } ]

[ { "id": "Isradipine_ddi_T1", "type": "DRUG", "text": [ "Nitroglycerin" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T2", "type": "BRAND", "text": [ "DynaCirc" ], "offsets": [ [ 15, 23 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T3", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 26, 36 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T4", "type": "DRUG", "text": [ "nitroglycerin" ], "offsets": [ [ 74, 87 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T5", "type": "DRUG", "text": [ "Hydrochlorothiazide" ], "offsets": [ [ 89, 108 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T6", "type": "BRAND", "text": [ "DynaCirc" ], "offsets": [ [ 192, 200 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T7", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 203, 213 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T8", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 219, 238 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T9", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 348, 358 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T10", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 371, 390 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T11", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 453, 463 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T12", "type": "DRUG", "text": [ "Propranolol" ], "offsets": [ [ 507, 518 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T13", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 585, 596 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T14", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 659, 669 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T15", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 768, 779 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T16", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 857, 867 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T17", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 885, 896 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T18", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 1050, 1060 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T19", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1098, 1109 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T20", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1123, 1134 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T21", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 1172, 1182 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T22", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 1184, 1194 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T23", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1251, 1261 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T24", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 1306, 1316 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T25", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 1356, 1366 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T26", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 1464, 1474 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T27", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1529, 1539 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T28", "type": "DRUG", "text": [ "Rifampicin" ], "offsets": [ [ 1638, 1648 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T29", "type": "DRUG", "text": [ "rifampicin" ], "offsets": [ [ 1704, 1714 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T30", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 1763, 1773 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T31", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 1801, 1811 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T32", "type": "DRUG", "text": [ "rifampicin" ], "offsets": [ [ 1850, 1860 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T33", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 1882, 1892 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T34", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 2044, 2054 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T35", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 2056, 2064 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T36", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 2178, 2188 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T37", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2201, 2209 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T38", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2249, 2257 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T39", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 2358, 2368 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T40", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2386, 2394 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T41", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 2399, 2409 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T42", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 2493, 2500 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T43", "type": "BRAND", "text": [ "DynaCirc" ], "offsets": [ [ 2536, 2544 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T44", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 2547, 2557 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T45", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2563, 2570 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T46", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2669, 2676 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T47", "type": "DRUG", "text": [ "Fentanyl" ], "offsets": [ [ 2678, 2686 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T48", "type": "DRUG", "text": [ "fentanyl" ], "offsets": [ [ 2743, 2751 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T49", "type": "GROUP", "text": [ "beta blocker" ], "offsets": [ [ 2789, 2801 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T50", "type": "GROUP", "text": [ "calcium channel blocker" ], "offsets": [ [ 2808, 2831 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T51", "type": "BRAND", "text": [ "DynaCirc" ], "offsets": [ [ 2907, 2915 ] ], "normalized": [] }, { "id": "Isradipine_ddi_T52", "type": "DRUG", "text": [ "isradipine" ], "offsets": [ [ 2918, 2928 ] ], "normalized": [] } ]

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[ { "id": "Isradipine_ddi_R1", "type": "MECHANISM", "arg1_id": "Isradipine_ddi_T23", "arg2_id": "Isradipine_ddi_T24", "normalized": [] }, { "id": "Isradipine_ddi_R2", "type": "ADVISE", "arg1_id": "Isradipine_ddi_T26", "arg2_id": "Isradipine_ddi_T27", "normalized": [] }, { "id": "Isradipine_ddi_R3", "type": "MECHANISM", "arg1_id": "Isradipine_ddi_T29", "arg2_id": "Isradipine_ddi_T30", "normalized": [] }, { "id": "Isradipine_ddi_R4", "type": "MECHANISM", "arg1_id": "Isradipine_ddi_T32", "arg2_id": "Isradipine_ddi_T33", "normalized": [] }, { "id": "Isradipine_ddi_R5", "type": "EFFECT", "arg1_id": "Isradipine_ddi_T48", "arg2_id": "Isradipine_ddi_T49", "normalized": [] }, { "id": "Isradipine_ddi_R6", "type": "EFFECT", "arg1_id": "Isradipine_ddi_T48", "arg2_id": "Isradipine_ddi_T50", "normalized": [] } ]

[ { "id": "Clobetasol_ddi__text", "type": "abstract", "text": [ "No separate information available" ], "offsets": [ [ 0, 33 ] ] } ]

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[]

[ { "id": "Lidocaine_ddi__text", "type": "abstract", "text": [ "The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents." ], "offsets": [ [ 0, 669 ] ] } ]

[ { "id": "Lidocaine_ddi_T1", "type": "GROUP", "text": [ "anesthetic solutions" ], "offsets": [ [ 28, 48 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T2", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 60, 71 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T3", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 75, 89 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T4", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 112, 140 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T5", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 144, 169 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T6", "type": "GROUP", "text": [ "Phenothiazines" ], "offsets": [ [ 214, 228 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T7", "type": "GROUP", "text": [ "butyrophenones" ], "offsets": [ [ 233, 247 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T8", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 292, 303 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T9", "type": "GROUP", "text": [ "vasopressor drugs" ], "offsets": [ [ 487, 504 ] ], "normalized": [] }, { "id": "Lidocaine_ddi_T10", "type": "GROUP", "text": [ "ergot-type oxytocic drugs" ], "offsets": [ [ 572, 597 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Lidocaine_ddi_R1", "type": "EFFECT", "arg1_id": "Lidocaine_ddi_T2", "arg2_id": "Lidocaine_ddi_T4", "normalized": [] }, { "id": "Lidocaine_ddi_R2", "type": "EFFECT", "arg1_id": "Lidocaine_ddi_T2", "arg2_id": "Lidocaine_ddi_T5", "normalized": [] }, { "id": "Lidocaine_ddi_R3", "type": "EFFECT", "arg1_id": "Lidocaine_ddi_T3", "arg2_id": "Lidocaine_ddi_T4", "normalized": [] }, { "id": "Lidocaine_ddi_R4", "type": "EFFECT", "arg1_id": "Lidocaine_ddi_T3", "arg2_id": "Lidocaine_ddi_T5", "normalized": [] }, { "id": "Lidocaine_ddi_R5", "type": "EFFECT", "arg1_id": "Lidocaine_ddi_T6", "arg2_id": "Lidocaine_ddi_T8", "normalized": [] }, { "id": "Lidocaine_ddi_R6", "type": "EFFECT", "arg1_id": "Lidocaine_ddi_T7", "arg2_id": "Lidocaine_ddi_T8", "normalized": [] } ]

[ { "id": "19-norandrostenedione_ddi__text", "type": "abstract", "text": [ "No drug, nutritional supplement, food or herb interactions have yet been reported." ], "offsets": [ [ 0, 82 ] ] } ]

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[ { "id": "Gemcitabine_ddi__text", "type": "abstract", "text": [ "No specific drug interaction studies have been conducted. For information on the pharmacokinetics of Gemzar and cisplatin in combination, see Drug Interactions under CLINICAL PHARMACOLOGY section." ], "offsets": [ [ 0, 196 ] ] } ]

[ { "id": "Gemcitabine_ddi_T1", "type": "BRAND", "text": [ "Gemzar" ], "offsets": [ [ 101, 107 ] ], "normalized": [] }, { "id": "Gemcitabine_ddi_T2", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 112, 121 ] ], "normalized": [] } ]

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[ { "id": "Desoximetasone_ddi__text", "type": "abstract", "text": [ "No specific information available ." ], "offsets": [ [ 0, 35 ] ] } ]

[]

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[ { "id": "Adefovir Dipivoxil_ddi__text", "type": "abstract", "text": [ "Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription products you may use, especially of: aminoglycosides (e.g., gentamicin, amikacin), amphotericin B, cyclosporine, non-steroidal anti-inflammatory drugs (e.g., ibuprofen), tacrolimus, vancomycin. Do not start or stop any medicine without doctor or pharmacist approval." ], "offsets": [ [ 0, 367 ] ] } ]

[ { "id": "Adefovir Dipivoxil_ddi_T1", "type": "GROUP", "text": [ "aminoglycosides" ], "offsets": [ [ 138, 153 ] ], "normalized": [] }, { "id": "Adefovir Dipivoxil_ddi_T2", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 161, 171 ] ], "normalized": [] }, { "id": "Adefovir Dipivoxil_ddi_T3", "type": "DRUG", "text": [ "amikacin" ], "offsets": [ [ 173, 181 ] ], "normalized": [] }, { "id": "Adefovir Dipivoxil_ddi_T4", "type": "DRUG", "text": [ "amphotericin B" ], "offsets": [ [ 184, 198 ] ], "normalized": [] }, { "id": "Adefovir Dipivoxil_ddi_T5", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 200, 212 ] ], "normalized": [] }, { "id": "Adefovir Dipivoxil_ddi_T6", "type": "GROUP", "text": [ "non-steroidal anti-inflammatory" ], "offsets": [ [ 214, 245 ] ], "normalized": [] }, { "id": "Adefovir Dipivoxil_ddi_T7", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 259, 268 ] ], "normalized": [] }, { "id": "Adefovir Dipivoxil_ddi_T8", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 271, 281 ] ], "normalized": [] }, { "id": "Adefovir Dipivoxil_ddi_T9", "type": "DRUG", "text": [ "vancomycin" ], "offsets": [ [ 283, 293 ] ], "normalized": [] } ]

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[ { "id": "Cosyntropin_ddi__text", "type": "abstract", "text": [ "Corticotropin may accentuate the electrolyte loss associated with diuretic therapy." ], "offsets": [ [ 0, 83 ] ] } ]

[ { "id": "Cosyntropin_ddi_T1", "type": "DRUG", "text": [ "Corticotropin" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "Cosyntropin_ddi_T2", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 66, 74 ] ], "normalized": [] } ]

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[ { "id": "Cosyntropin_ddi_R1", "type": "EFFECT", "arg1_id": "Cosyntropin_ddi_T1", "arg2_id": "Cosyntropin_ddi_T2", "normalized": [] } ]

[ { "id": "Chloroprocaine_ddi__text", "type": "abstract", "text": [ "The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors, tricyclic antidepressants or phenothiazines may produce severe, prolonged hypotension or hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. The para-aminobenzoic acid metabolite of chloroprocaine inhibits the action of sulfonamides. Therefore, chloroprocaine should not be used in any condition in which a sulfonamide drug is being employed." ], "offsets": [ [ 0, 811 ] ] } ]

[ { "id": "Chloroprocaine_ddi_T1", "type": "GROUP", "text": [ "anesthetic solutions" ], "offsets": [ [ 28, 48 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T2", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 60, 71 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T3", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 75, 89 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T4", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 112, 140 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T5", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 142, 167 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T6", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 171, 185 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T7", "type": "GROUP", "text": [ "vasopressor drugs" ], "offsets": [ [ 427, 444 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T8", "type": "GROUP", "text": [ "ergot-type oxytocic drugs" ], "offsets": [ [ 512, 537 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T9", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 689, 701 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T10", "type": "DRUG", "text": [ "chloroprocaine" ], "offsets": [ [ 714, 728 ] ], "normalized": [] }, { "id": "Chloroprocaine_ddi_T11", "type": "GROUP", "text": [ "sulfonamide drug" ], "offsets": [ [ 776, 792 ] ], "normalized": [] } ]

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[ { "id": "Chloroprocaine_ddi_R1", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T1", "arg2_id": "Chloroprocaine_ddi_T5", "normalized": [] }, { "id": "Chloroprocaine_ddi_R2", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T1", "arg2_id": "Chloroprocaine_ddi_T6", "normalized": [] }, { "id": "Chloroprocaine_ddi_R3", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T2", "arg2_id": "Chloroprocaine_ddi_T4", "normalized": [] }, { "id": "Chloroprocaine_ddi_R4", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T2", "arg2_id": "Chloroprocaine_ddi_T5", "normalized": [] }, { "id": "Chloroprocaine_ddi_R5", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T2", "arg2_id": "Chloroprocaine_ddi_T6", "normalized": [] }, { "id": "Chloroprocaine_ddi_R6", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T3", "arg2_id": "Chloroprocaine_ddi_T4", "normalized": [] }, { "id": "Chloroprocaine_ddi_R7", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T3", "arg2_id": "Chloroprocaine_ddi_T5", "normalized": [] }, { "id": "Chloroprocaine_ddi_R8", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T3", "arg2_id": "Chloroprocaine_ddi_T6", "normalized": [] }, { "id": "Chloroprocaine_ddi_R9", "type": "EFFECT", "arg1_id": "Chloroprocaine_ddi_T7", "arg2_id": "Chloroprocaine_ddi_T8", "normalized": [] }, { "id": "Chloroprocaine_ddi_R10", "type": "ADVISE", "arg1_id": "Chloroprocaine_ddi_T10", "arg2_id": "Chloroprocaine_ddi_T11", "normalized": [] } ]

[ { "id": "Arbutamine_ddi__text", "type": "abstract", "text": [ "Beta-adrenergic blocking agents: concurrent use may blunt the response to arbutamine. Beta-adrenergic blocking agents should be withdrawn at least 48 hours before conducting an arbutamine-mediated stress test. Antiarrhythmic agents, class I (such as flecainide, lidocaine, or quinidine): concurrent use with arbutamine may have a proarrhythmic effect. Antidepressants (tricyclic), atropine or other anticholinergic agents, or digitalis glycosides: concurrent use with arbutamine may produce additive inotropic and/or chronotropic effects." ], "offsets": [ [ 0, 538 ] ] } ]

[ { "id": "Arbutamine_ddi_T1", "type": "GROUP", "text": [ "Beta-adrenergic blocking agents" ], "offsets": [ [ 0, 31 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T2", "type": "DRUG", "text": [ "arbutamine" ], "offsets": [ [ 74, 84 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T3", "type": "GROUP", "text": [ "Beta-adrenergic blocking agents" ], "offsets": [ [ 86, 117 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T4", "type": "DRUG", "text": [ "arbutamine" ], "offsets": [ [ 177, 187 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T5", "type": "DRUG", "text": [ "Antiarrhythmic agents, class I" ], "offsets": [ [ 210, 240 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T6", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 250, 260 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T7", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 262, 271 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T8", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 276, 285 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T9", "type": "DRUG", "text": [ "arbutamine" ], "offsets": [ [ 308, 318 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T10", "type": "GROUP", "text": [ "Antidepressants" ], "offsets": [ [ 352, 367 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T11", "type": "GROUP", "text": [ "tricyclic" ], "offsets": [ [ 369, 378 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T12", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 381, 389 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T13", "type": "GROUP", "text": [ "anticholinergic agents" ], "offsets": [ [ 399, 421 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T14", "type": "GROUP", "text": [ "digitalis glycosides" ], "offsets": [ [ 426, 446 ] ], "normalized": [] }, { "id": "Arbutamine_ddi_T15", "type": "DRUG", "text": [ "arbutamine" ], "offsets": [ [ 468, 478 ] ], "normalized": [] } ]

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[ { "id": "Arbutamine_ddi_R1", "type": "ADVISE", "arg1_id": "Arbutamine_ddi_T3", "arg2_id": "Arbutamine_ddi_T4", "normalized": [] } ]

[ { "id": "Nabilone_ddi__text", "type": "abstract", "text": [ "Nabilone should be administered with caution to patients who are taking other psychoactive drugs or CNS depressants, including alcohol, barbiturates and narcotic analgesics, or to those with a history of psychiatric disorder (including manic-depressive illness and schizophrenia). Nabilone has been shown to have an additive CNS depressant effect when given with either diazepam, secobarbitone sodium, alcohol or codeine." ], "offsets": [ [ 0, 421 ] ] } ]

[ { "id": "Nabilone_ddi_T1", "type": "DRUG", "text": [ "Nabilone" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T2", "type": "GROUP", "text": [ "psychoactive drugs" ], "offsets": [ [ 78, 96 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T3", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 100, 115 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T4", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 127, 134 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T5", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 136, 148 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T6", "type": "GROUP", "text": [ "narcotic analgesics" ], "offsets": [ [ 153, 172 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T7", "type": "DRUG", "text": [ "Nabilone" ], "offsets": [ [ 281, 289 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T8", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 370, 378 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T9", "type": "BRAND", "text": [ "secobarbitone sodium" ], "offsets": [ [ 380, 400 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T10", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 402, 409 ] ], "normalized": [] }, { "id": "Nabilone_ddi_T11", "type": "DRUG", "text": [ "codeine" ], "offsets": [ [ 413, 420 ] ], "normalized": [] } ]

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[ { "id": "Nabilone_ddi_R1", "type": "ADVISE", "arg1_id": "Nabilone_ddi_T1", "arg2_id": "Nabilone_ddi_T2", "normalized": [] }, { "id": "Nabilone_ddi_R2", "type": "ADVISE", "arg1_id": "Nabilone_ddi_T1", "arg2_id": "Nabilone_ddi_T3", "normalized": [] }, { "id": "Nabilone_ddi_R3", "type": "ADVISE", "arg1_id": "Nabilone_ddi_T1", "arg2_id": "Nabilone_ddi_T4", "normalized": [] }, { "id": "Nabilone_ddi_R4", "type": "ADVISE", "arg1_id": "Nabilone_ddi_T1", "arg2_id": "Nabilone_ddi_T5", "normalized": [] }, { "id": "Nabilone_ddi_R5", "type": "ADVISE", "arg1_id": "Nabilone_ddi_T1", "arg2_id": "Nabilone_ddi_T6", "normalized": [] }, { "id": "Nabilone_ddi_R6", "type": "EFFECT", "arg1_id": "Nabilone_ddi_T7", "arg2_id": "Nabilone_ddi_T8", "normalized": [] }, { "id": "Nabilone_ddi_R7", "type": "EFFECT", "arg1_id": "Nabilone_ddi_T7", "arg2_id": "Nabilone_ddi_T9", "normalized": [] }, { "id": "Nabilone_ddi_R8", "type": "EFFECT", "arg1_id": "Nabilone_ddi_T7", "arg2_id": "Nabilone_ddi_T10", "normalized": [] }, { "id": "Nabilone_ddi_R9", "type": "EFFECT", "arg1_id": "Nabilone_ddi_T7", "arg2_id": "Nabilone_ddi_T11", "normalized": [] } ]

[ { "id": "Chlorpheniramine_ddi__text", "type": "abstract", "text": [ "Substrate of CYP2D6 (minor), 3A4 (major); Inhibits CYP2D6 (weak). Increased toxicity (CNS depression): CNS depressants, MAO inhibitors, tricyclic antidepressants, phenothiazines. CYP3A4 inhibitors: May increase the levels/effects of chlorpheniramine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil." ], "offsets": [ [ 0, 469 ] ] } ]

[ { "id": "Chlorpheniramine_ddi_T1", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 103, 118 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T2", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 120, 134 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T3", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 136, 161 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T4", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 163, 177 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T5", "type": "DRUG", "text": [ "chlorpheniramine" ], "offsets": [ [ 233, 249 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T6", "type": "GROUP", "text": [ "azole antifungals" ], "offsets": [ [ 278, 295 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T7", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 297, 310 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T8", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 312, 326 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T9", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 328, 338 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T10", "type": "DRUG", "text": [ "doxycycline" ], "offsets": [ [ 340, 351 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T11", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 353, 365 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T12", "type": "DRUG", "text": [ "imatinib" ], "offsets": [ [ 367, 375 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T13", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 377, 386 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T14", "type": "DRUG", "text": [ "nefazodone" ], "offsets": [ [ 388, 398 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T15", "type": "DRUG", "text": [ "nicardipine" ], "offsets": [ [ 400, 411 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T16", "type": "DRUG", "text": [ "propofol" ], "offsets": [ [ 413, 421 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T17", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 423, 442 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T18", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 444, 453 ] ], "normalized": [] }, { "id": "Chlorpheniramine_ddi_T19", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 459, 468 ] ], "normalized": [] } ]

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[ { "id": "Goserelin_ddi__text", "type": "abstract", "text": [ "No formal drug-drug interaction studies have been performed. No confirmed interactions have been reported between ZOLADEX and other drugs" ], "offsets": [ [ 0, 137 ] ] } ]

[ { "id": "Goserelin_ddi_T1", "type": "BRAND", "text": [ "ZOLADEX" ], "offsets": [ [ 114, 121 ] ], "normalized": [] } ]

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[ { "id": "Daptomycin_ddi__text", "type": "abstract", "text": [ "Warfarin: Concomitant administration of daptomycin (6 mg/kg once every 24 hours for 5 days) and warfarin (25 mg single oral dose) had no significant effect on the pharmacokinetics of either drug, and the INR was not significantly altered. HMG-CoA Reductase Inhibitors: Inhibitors of HMG-CoA reductase may cause myopathy, which is manifested as muscle pain or weakness associated with elevated levels of CPK. There were no reports of skeletal myopathy in a placebo-controlled Phase I trial in which 10 healthy subjects on stable simvastatin therapy were treated concurrently with daptomycin (4 mg/kg once every 24 hours) for 14 days. Experience with co-administration of HMG-CoA reductase inhibitors and Fentanyl in patients is limited,therefore,consideration should be given to temporarily suspending use of HMG-CoA reductase inhibitors in patients receiving Fentanyl. Drug-Laboratory Test Interactions: There are no reported drug-laboratory test interactions." ], "offsets": [ [ 0, 960 ] ] } ]

[ { "id": "Daptomycin_ddi_T1", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T2", "type": "DRUG", "text": [ "daptomycin" ], "offsets": [ [ 40, 50 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 96, 104 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T4", "type": "GROUP", "text": [ "HMG-CoA Reductase Inhibitors" ], "offsets": [ [ 239, 267 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T5", "type": "GROUP", "text": [ "Inhibitors of HMG-CoA reductase" ], "offsets": [ [ 269, 300 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T6", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 528, 539 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T7", "type": "DRUG", "text": [ "daptomycin" ], "offsets": [ [ 579, 589 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T8", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 670, 698 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T9", "type": "DRUG", "text": [ "Fentanyl" ], "offsets": [ [ 703, 711 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T10", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 808, 836 ] ], "normalized": [] }, { "id": "Daptomycin_ddi_T11", "type": "DRUG", "text": [ "Fentanyl" ], "offsets": [ [ 859, 867 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Daptomycin_ddi_R1", "type": "ADVISE", "arg1_id": "Daptomycin_ddi_T10", "arg2_id": "Daptomycin_ddi_T11", "normalized": [] } ]

[ { "id": "Enalapril_ddi__text", "type": "abstract", "text": [ "Hypotension: Patients on Diuretic Therapy: Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with enalapril or enalaprilat. The possibility of hypotensive effects with enalapril or enalaprilat can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril or enalaprilat. If it is necessary to continue the diuretic, provide close medical supervision after the initial dose for at least two hours and until blood pressure has stabilized for at least an additional hour.. Agents Causing Renin Release: The antihypertensive effect of enalapril and enalapril IV is augmented by antihypertensive agents that cause renin release (e.g., diuretics). Non-steroidal Anti-inflammatory Agents: In some patients with compromised renal function who are being treated with nonsteroidal anti-inflammatory drugs, the co-administration of enalapril may result in a further deterioration of renal function. These effects are usually reversible. In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving VASOTEC. In this study there was no evidence of a blunting of the antihypertensive action of VASOTEC. However, 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. Other Cardiovascular Agents: Enalapril and enalapril IV have been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine, prazosin and digoxin without evidence of clinically significant adverse interactions. Enalapril IV has been used concomitantly with digitalis without evidence of clinically significant adverse reactions. Agents Increasing Serum Potassium: Enalapril and enalapril IV attenuate potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium. Potassium sparing agents should generally not be used in patients with heart failure receiving enalapril. Lithium: Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. It is recommended that serum lithium levels be monitored frequently if enalapril is administered concomitantly with lithium." ], "offsets": [ [ 0, 2828 ] ] } ]

[ { "id": "Enalapril_ddi_T1", "type": "DRUG", "text": [ "diuretics" ], "offsets": [ [ 55, 64 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T2", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 238, 247 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T3", "type": "DRUG", "text": [ "enalaprilat" ], "offsets": [ [ 251, 262 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T4", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 308, 317 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T5", "type": "DRUG", "text": [ "enalaprilat" ], "offsets": [ [ 321, 332 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T6", "type": "DRUG", "text": [ "diuretic" ], "offsets": [ [ 378, 386 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T7", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 455, 464 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T8", "type": "DRUG", "text": [ "enalaprilat" ], "offsets": [ [ 468, 479 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T9", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 516, 524 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T10", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 741, 750 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T11", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 755, 764 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T12", "type": "GROUP", "text": [ "antihypertensive agents" ], "offsets": [ [ 784, 807 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T13", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 840, 849 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T14", "type": "GROUP", "text": [ "Non-steroidal Anti-inflammatory Agents" ], "offsets": [ [ 852, 890 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T15", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory drugs" ], "offsets": [ [ 968, 1004 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T16", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 1031, 1040 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T17", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 1170, 1182 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T18", "type": "DRUG", "text": [ "sulindac" ], "offsets": [ [ 1186, 1194 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T19", "type": "BRAND", "text": [ "VASOTEC" ], "offsets": [ [ 1247, 1254 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T20", "type": "BRAND", "text": [ "VASOTEC" ], "offsets": [ [ 1340, 1347 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T21", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1379, 1385 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T22", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 1430, 1444 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T23", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1512, 1518 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T24", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 1538, 1552 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T25", "type": "DRUG", "text": [ "Enalapril" ], "offsets": [ [ 1583, 1592 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T26", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 1597, 1606 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T27", "type": "GROUP", "text": [ "beta adrenergic-blocking agents" ], "offsets": [ [ 1644, 1675 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T28", "type": "DRUG", "text": [ "methyldopa" ], "offsets": [ [ 1677, 1687 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T29", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 1689, 1697 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T30", "type": "GROUP", "text": [ "calcium-blocking agents" ], "offsets": [ [ 1699, 1722 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T31", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 1724, 1735 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T32", "type": "DRUG", "text": [ "prazosin" ], "offsets": [ [ 1737, 1745 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T33", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1750, 1757 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T34", "type": "DRUG", "text": [ "Enalapril" ], "offsets": [ [ 1823, 1832 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T35", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 1869, 1878 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T36", "type": "DRUG", "text": [ "Enalapril" ], "offsets": [ [ 1976, 1985 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T37", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 1990, 1999 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T38", "type": "GROUP", "text": [ "thiazide-type diuretics" ], "offsets": [ [ 2038, 2061 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T39", "type": "GROUP", "text": [ "Potassium-sparing diuretics" ], "offsets": [ [ 2063, 2090 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T40", "type": "DRUG", "text": [ "spironolactone" ], "offsets": [ [ 2098, 2112 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T41", "type": "DRUG", "text": [ "triamterene" ], "offsets": [ [ 2114, 2125 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T42", "type": "DRUG", "text": [ "amiloride" ], "offsets": [ [ 2130, 2139 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T43", "type": "DRUG", "text": [ "potassium" ], "offsets": [ [ 2142, 2151 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T44", "type": "DRUG", "text": [ "potassium" ], "offsets": [ [ 2168, 2177 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T45", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 2533, 2542 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T46", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 2544, 2551 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T47", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 2553, 2560 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T48", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2610, 2617 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T49", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 2688, 2702 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T50", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2733, 2740 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T51", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 2775, 2784 ] ], "normalized": [] }, { "id": "Enalapril_ddi_T52", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2820, 2827 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Enalapril_ddi_R1", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T1", "arg2_id": "Enalapril_ddi_T2", "normalized": [] }, { "id": "Enalapril_ddi_R2", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T1", "arg2_id": "Enalapril_ddi_T3", "normalized": [] }, { "id": "Enalapril_ddi_R3", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T4", "arg2_id": "Enalapril_ddi_T6", "normalized": [] }, { "id": "Enalapril_ddi_R4", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T5", "arg2_id": "Enalapril_ddi_T6", "normalized": [] }, { "id": "Enalapril_ddi_R5", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T10", "arg2_id": "Enalapril_ddi_T12", "normalized": [] }, { "id": "Enalapril_ddi_R6", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T10", "arg2_id": "Enalapril_ddi_T13", "normalized": [] }, { "id": "Enalapril_ddi_R7", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T11", "arg2_id": "Enalapril_ddi_T12", "normalized": [] }, { "id": "Enalapril_ddi_R8", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T11", "arg2_id": "Enalapril_ddi_T13", "normalized": [] }, { "id": "Enalapril_ddi_R9", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T15", "arg2_id": "Enalapril_ddi_T16", "normalized": [] }, { "id": "Enalapril_ddi_R10", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T21", "arg2_id": "Enalapril_ddi_T22", "normalized": [] }, { "id": "Enalapril_ddi_R11", "type": "ADVISE", "arg1_id": "Enalapril_ddi_T23", "arg2_id": "Enalapril_ddi_T24", "normalized": [] }, { "id": "Enalapril_ddi_R12", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T36", "arg2_id": "Enalapril_ddi_T38", "normalized": [] }, { "id": "Enalapril_ddi_R13", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T37", "arg2_id": "Enalapril_ddi_T38", "normalized": [] }, { "id": "Enalapril_ddi_R14", "type": "EFFECT", "arg1_id": "Enalapril_ddi_T48", "arg2_id": "Enalapril_ddi_T49", "normalized": [] }, { "id": "Enalapril_ddi_R15", "type": "ADVISE", "arg1_id": "Enalapril_ddi_T51", "arg2_id": "Enalapril_ddi_T52", "normalized": [] } ]

[ { "id": "Diclofenac_ddi__text", "type": "abstract", "text": [ "Aspirin: Concomitant administration of diclofenac and aspirin is not recommended because diclofenac is displaced from its binding sites during the concomitant administration of aspirin, resulting in lower plasma concentrations, peak plasma levels, and AUC values. Anticoagulants: While studies have not shown diclofenac to interact with anticoagulants of the warfarin type, caution should be exercised, nonetheless, since interactions have been seen with other NSAIDs. Because prostaglandins play an important role in hemostasis, and NSAIDs affect platelet function as well, concurrent therapy with all NSAIDs, including diclofenac, and warfarin requires close monitoring of patients to be certain that no change in their anticoagulant dosage is required. Digoxin, Methotrexate, Cyclosporine: Diclofenac, like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Ingestion of diclofenac may increase serum concentrations of digoxin and methotrexate and increase cyclosporine s nephrotoxicity. Patients who begin taking diclofenac or who increase their diclofenac dose or any other NSAID while taking digoxin, methotrexate, or cyclosporine may develop toxicity characteristics for these drugs. They should be observed closely, particularly if renal function is impaired. In the case of digoxin, serum levels should be monitored. Lithium: Diclofenac decreases lithium renal clearance and increases lithium plasma levels. In patients taking diclofenac and lithium concomitantly, lithium toxicity may develop. Oral Hypoglycemics: Diclofenac does not alter glucose metabolism in normal subjects nor does it alter the effects of oral hypoglycemic agents. There are rare reports, however, from marketing experiences, of changes in effects of insulin or oral hypoglycemic agents in the presence of diclofenac that necessitated changes in the doses of such agents. Both hypo- and hyperglycemic effects have been reported. A direct causal relationship has not been established, but physicians should consider the possibility that diclofenac may alter a diabetic patient s response to insulin or oral hypoglycemic agents. Diuretics: Diclofenac and other NSAIDs can inhibit the activity of diuretics. Concomitant treatment with potassium-sparing diuretics may be associated with increased serum potassium levels. Other Drugs: In small groups of patients (7-10/interaction study), the concomitant administration of azathioprine, gold, chloroquine, D-penicillamine, prednisolone, doxycycline, or digitoxin did not significantly affect the peak levels and AUC values of diclofenac. Phenobarbital toxicity has been reported to have occurred in a patient on chronic phenobarbital treatment following the initiation of diclofenac therapy. Protein Binding In vitro, diclofenac interferes minimally or not at all with the protein binding of salicylic acid (20% decrease in binding), tolbutamide, prednisolone (10% decrease in binding), or warfarin. Benzylpenicillin, ampicillin, oxacillin, chlortetracycline, doxycycline, cephalothin, erythromycin, and sulfamethoxazole have no influence in vitro on the protein binding of diclofenac in human serum. Drug/Laboratory Test Interactions Effect on Blood Coagulation: Diclofenac increases platelet aggregation time but does not affect bleeding time, plasma thrombin clotting time, plasma fibrinogen, or factors V and VII to XII. Statistically significant changes in prothrombin and partial thromboplastin times have been reported in normal volunteers. The mean changes were observed to be less than 1 second in both instances, however, and are unlikely to be clinically important. Diclofenac is a prostaglandin synthetase inhibitor, however, and all drugs that inhibit prostaglandin synthesis interfere with platelet function to some degree; therefore, patients who may be adversely affected by such an action should be carefully observed." ], "offsets": [ [ 0, 3901 ] ] } ]

[ { "id": "Diclofenac_ddi_T1", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T2", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 39, 49 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T3", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 54, 61 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T4", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 89, 99 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T5", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 177, 184 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T6", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 264, 278 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T7", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 309, 319 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T8", "type": "GROUP", "text": [ "anticoagulants of the warfarin type" ], "offsets": [ [ 337, 372 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T9", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 461, 467 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T10", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 534, 540 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T11", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 603, 609 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T12", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 621, 631 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T13", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 637, 645 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T14", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 722, 735 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T15", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 756, 763 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T16", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 765, 777 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T17", "type": "DRUG", "text": [ "Cyclosporine" ], "offsets": [ [ 779, 791 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T18", "type": "DRUG", "text": [ "Diclofenac" ], "offsets": [ [ 793, 803 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T19", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 816, 822 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T20", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 913, 923 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T21", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 961, 968 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T22", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 973, 985 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T23", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 999, 1011 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T24", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 1056, 1066 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T25", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 1089, 1099 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T26", "type": "GROUP", "text": [ "NSAID" ], "offsets": [ [ 1118, 1123 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T27", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1137, 1144 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T28", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1146, 1158 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T29", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1163, 1175 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T30", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1322, 1329 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T31", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 1365, 1372 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T32", "type": "DRUG", "text": [ "Diclofenac" ], "offsets": [ [ 1374, 1384 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T33", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1395, 1402 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T34", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1433, 1440 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T35", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 1475, 1485 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T36", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1490, 1497 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T37", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1513, 1520 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T38", "type": "GROUP", "text": [ "Hypoglycemics" ], "offsets": [ [ 1548, 1561 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T39", "type": "DRUG", "text": [ "Diclofenac" ], "offsets": [ [ 1563, 1573 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T40", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 1665, 1684 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T41", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 1772, 1779 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T42", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 1788, 1807 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T43", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 1827, 1837 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T44", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 2057, 2067 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T45", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 2111, 2118 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T46", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 2127, 2146 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T47", "type": "GROUP", "text": [ "Diuretics" ], "offsets": [ [ 2148, 2157 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T48", "type": "DRUG", "text": [ "Diclofenac" ], "offsets": [ [ 2159, 2169 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T49", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2180, 2186 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T50", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 2215, 2224 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T51", "type": "GROUP", "text": [ "potassium-sparing diuretics" ], "offsets": [ [ 2253, 2280 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T52", "type": "DRUG", "text": [ "azathioprine" ], "offsets": [ [ 2439, 2451 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T53", "type": "GROUP", "text": [ "gold" ], "offsets": [ [ 2453, 2457 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T54", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 2459, 2470 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T55", "type": "DRUG", "text": [ "D-penicillamine" ], "offsets": [ [ 2472, 2487 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T56", "type": "DRUG", "text": [ "prednisolone" ], "offsets": [ [ 2489, 2501 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T57", "type": "DRUG", "text": [ "doxycycline" ], "offsets": [ [ 2503, 2514 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T58", "type": "DRUG", "text": [ "digitoxin" ], "offsets": [ [ 2519, 2528 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T59", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 2592, 2602 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T60", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 2604, 2617 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T61", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 2686, 2699 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T62", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 2738, 2748 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T63", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 2784, 2794 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T64", "type": "DRUG", "text": [ "salicylic acid" ], "offsets": [ [ 2858, 2872 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T65", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 2900, 2911 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T66", "type": "DRUG", "text": [ "prednisolone" ], "offsets": [ [ 2913, 2925 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T67", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2956, 2964 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T68", "type": "DRUG", "text": [ "Benzylpenicillin" ], "offsets": [ [ 2966, 2982 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T69", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 2984, 2994 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T70", "type": "DRUG", "text": [ "oxacillin" ], "offsets": [ [ 2996, 3005 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T71", "type": "DRUG", "text": [ "chlortetracycline" ], "offsets": [ [ 3007, 3024 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T72", "type": "DRUG", "text": [ "doxycycline" ], "offsets": [ [ 3026, 3037 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T73", "type": "DRUG", "text": [ "cephalothin" ], "offsets": [ [ 3039, 3050 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T74", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 3052, 3064 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T75", "type": "DRUG", "text": [ "sulfamethoxazole" ], "offsets": [ [ 3070, 3086 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T76", "type": "DRUG", "text": [ "diclofenac" ], "offsets": [ [ 3140, 3150 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T77", "type": "DRUG", "text": [ "Diclofenac" ], "offsets": [ [ 3230, 3240 ] ], "normalized": [] }, { "id": "Diclofenac_ddi_T78", "type": "DRUG", "text": [ "Diclofenac" ], "offsets": [ [ 3643, 3653 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Diclofenac_ddi_R1", "type": "ADVISE", "arg1_id": "Diclofenac_ddi_T2", "arg2_id": "Diclofenac_ddi_T3", "normalized": [] }, { "id": "Diclofenac_ddi_R2", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T4", "arg2_id": "Diclofenac_ddi_T5", "normalized": [] }, { "id": "Diclofenac_ddi_R3", "type": "ADVISE", "arg1_id": "Diclofenac_ddi_T7", "arg2_id": "Diclofenac_ddi_T9", "normalized": [] }, { "id": "Diclofenac_ddi_R4", "type": "ADVISE", "arg1_id": "Diclofenac_ddi_T11", "arg2_id": "Diclofenac_ddi_T13", "normalized": [] }, { "id": "Diclofenac_ddi_R5", "type": "ADVISE", "arg1_id": "Diclofenac_ddi_T12", "arg2_id": "Diclofenac_ddi_T13", "normalized": [] }, { "id": "Diclofenac_ddi_R6", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T20", "arg2_id": "Diclofenac_ddi_T21", "normalized": [] }, { "id": "Diclofenac_ddi_R7", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T20", "arg2_id": "Diclofenac_ddi_T22", "normalized": [] }, { "id": "Diclofenac_ddi_R8", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T20", "arg2_id": "Diclofenac_ddi_T23", "normalized": [] }, { "id": "Diclofenac_ddi_R9", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T24", "arg2_id": "Diclofenac_ddi_T27", "normalized": [] }, { "id": "Diclofenac_ddi_R10", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T24", "arg2_id": "Diclofenac_ddi_T28", "normalized": [] }, { "id": "Diclofenac_ddi_R11", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T24", "arg2_id": "Diclofenac_ddi_T29", "normalized": [] }, { "id": "Diclofenac_ddi_R12", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T26", "arg2_id": "Diclofenac_ddi_T27", "normalized": [] }, { "id": "Diclofenac_ddi_R13", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T26", "arg2_id": "Diclofenac_ddi_T28", "normalized": [] }, { "id": "Diclofenac_ddi_R14", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T26", "arg2_id": "Diclofenac_ddi_T29", "normalized": [] }, { "id": "Diclofenac_ddi_R15", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T32", "arg2_id": "Diclofenac_ddi_T33", "normalized": [] }, { "id": "Diclofenac_ddi_R16", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T32", "arg2_id": "Diclofenac_ddi_T34", "normalized": [] }, { "id": "Diclofenac_ddi_R17", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T35", "arg2_id": "Diclofenac_ddi_T36", "normalized": [] }, { "id": "Diclofenac_ddi_R18", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T41", "arg2_id": "Diclofenac_ddi_T43", "normalized": [] }, { "id": "Diclofenac_ddi_R19", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T42", "arg2_id": "Diclofenac_ddi_T43", "normalized": [] }, { "id": "Diclofenac_ddi_R20", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T44", "arg2_id": "Diclofenac_ddi_T45", "normalized": [] }, { "id": "Diclofenac_ddi_R21", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T44", "arg2_id": "Diclofenac_ddi_T46", "normalized": [] }, { "id": "Diclofenac_ddi_R22", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T48", "arg2_id": "Diclofenac_ddi_T50", "normalized": [] }, { "id": "Diclofenac_ddi_R23", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T49", "arg2_id": "Diclofenac_ddi_T50", "normalized": [] }, { "id": "Diclofenac_ddi_R24", "type": "EFFECT", "arg1_id": "Diclofenac_ddi_T61", "arg2_id": "Diclofenac_ddi_T62", "normalized": [] }, { "id": "Diclofenac_ddi_R25", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T63", "arg2_id": "Diclofenac_ddi_T64", "normalized": [] }, { "id": "Diclofenac_ddi_R26", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T63", "arg2_id": "Diclofenac_ddi_T65", "normalized": [] }, { "id": "Diclofenac_ddi_R27", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T63", "arg2_id": "Diclofenac_ddi_T66", "normalized": [] }, { "id": "Diclofenac_ddi_R28", "type": "MECHANISM", "arg1_id": "Diclofenac_ddi_T63", "arg2_id": "Diclofenac_ddi_T67", "normalized": [] } ]

[ { "id": "Aprepitant_ddi__text", "type": "abstract", "text": [ "Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. Effect of aprepitant on the pharmacokinetics of other agents As a moderate inhibitor of CYP3A4, aprepitant can increase plasma concentrations of coadministered medicinal products that are metabolized through CYP3A4. Aprepitant has been shown to induce the metabolism of S(-) warfarin and tolbutamide, which are metabolized through CYP2C9. Coadministration of Aprepitant with these drugs or other drugs that are known to be metabolized by CYP2C9, such as phenytoin, may result in lower plasma concentrations of these drugs. Aprepitant is unlikely to interact with drugs that are substrates for the P-glycoprotein transporter, as demonstrated by the lack of interaction of Aprepitant with digoxin in a clinical drug interaction study. 5-HT3 antagonists: In clinical drug interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron or granisetron. No clinical or drug interaction study was conducted with dolasetron. Corticosteroids: Dexamethasone: Aprepitant, when given as a regimen of 125mg with dexamethasone coadministered orally as 20 mg on Day 1, and Aprepitant when given as 80 mg/day with dexamethasone coadministered orally as 8 mg on Days 2 through 5, increased the AUC of dexamethasone, a CYP3A4 substrate by 2.2-fold, on Days 1 and 5. The oral dexamethasone doses should be reduced by approximately 50% when coadministered with Aprepitant, to achieve exposures of dexamethasone similar to those obtained when it is given without Aprepitant. The daily dose of dexamethasone administered in clinical studies with Aprepitant reflects an approximate 50% reduction of the dose of dexamethasone. Methylprednisolone Aprepitant, when given as a regimen of 125 mg on Day 1 and 80 mg/day on Days 2 and 3, increased the AUC of methylprednisolone, a CYP3A4 substrate, by 1.34-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was coadministered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3. The IV methylprednisolone dose should be reduced by approximately 25%, and the oral methylprednisolone dose should be reduced by approximately 50% when coadministered with Aprepitant to achieve exposures of methylprednisolone similar to those obtained when it is given without Aprepitant. Warfarin: A single 125-mg dose of Aprepitant was administered on Day 1 and 80 mg/day on Days 2 and 3 to healthy subjects who were stabilized on chronic warfarin therapy. Although there was no effect of Aprepitant on the plasma AUC of R(+) or S(-) warfarin determined on Day 3, there was a 34% decrease in S(-)warfarin (a CYP2C9 substrate) trough concentration accompanied by a 14% decrease in the prothrombin time (reported as International Normalized Ratio or INR) 5 days after completion of dosing with Aprepitant. In patients on chronic warfarin therapy, the prothrombin time (INR) should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of Aprepitant with each chemotherapy cycle. Tolbutamide: Aprepitant, when given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 23% on Day 4, 28% on Day 8, and 15% on Day 15, when a single dose of tolbutamide 500 mg was admini,stered orally prior to the administration of the 3-day regimen of Aprepitant and on Days 4,8, and 15. Oral contraceptives: Aprepitant, when given once daily for 14 days as a 100-mg capsule with an oral contraceptive containing 35 mcg of ethinyl estradiol and 1 mg of norethindrone, decreased the AUC of ethinyl estradiol by 43%, and decreased the AUC of norethindrone by 8%; therefore, the efficacy of oral contraceptives during administration of Aprepitant may be reduced. Although a 3-day regimen of Aprepitant given concomitantly with oral contraceptives has not been studied, alternative or back-up methods of contraception should be used. Midazolam: Aprepitant increased the AUC of midazolam, a sensitive CYP3A4 substrate, by 2.3-fold on Day 1 and 3.3-fold on Day 5, when a single oral dose of midazolam 2 mg was coadministered on Day 1 and Day 5 of a regimen of Aprepitant 125 mg on Day 1 and 80 mg/day on Days 2 through 5. The potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) should be considered when coadministering these agents with Aprepitant. In another study with intravenous administration of midazolam, Aprepitant was given as 125 mg on Day 1 and 80 mg/day on Days 2 and 3, and midazolam 2 mg IV was given prior to the administration of the 3-day regimen of Aprepitant and on Days 4, 8, and 15. Aprepitant increased the AUC of midazolam by 25% on Day 4 and decreased the AUC of midazolam by 19% on Day 8 relative to the dosing of Aprepitant on Days 1 through 3. These effects were not considered clinically important. The AUC of midazolam on Day 15 was similar to that observed at baseline. Effect of other agents on the pharmacokinefics of aprepitant Aprepitant is a substrate for CYP3A4; therefore, coadministration of Aprepitant with drugs that inhibit CYP3A4 activity may result in increased plasma concentrations of aprepitant. Consequently, concomitant administration of Aprepitant with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) should be approached with caution. Because moderate CYP3A4 inhibitors (e.g., diltiazem) result in 2-fold increase in plasma concentrations of aprepitant, concomitant administration should also be approached with caution. Aprepitant is a substrate for CYP3A4; therefore, coadministration of Aprepitant with drugs that strongly induce CYP3A4 activity (e.g., rifampin, carbamazepine, phenytoin) may result in reduced plasma concentrations of aprepitant that may result in decreased efficacy of Aprepitant. Ketoconazole: When a single 125-mg dose of Aprepitant was administered on Day5 of a Ketoconazole: When a single 125-mg dose of Aprepitant was administered on Day5 of a 10-day regimen of 400 mg/day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold. Concomitant administration of Aprepitant with strong CYP3A4 inhibitors should be approached cautiously. Rifampin: When a single 375-mg dose of Aprepitant was administered on Day9 of a 14-day regimen of 600 mg/day of rifampin, a strong CYP3A4 inducer, the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased approximately 3-fold. Coadministration of Aprepitant with drugs that induce CYP3A4 activity may result in reduced plasma concentrations and decreased efficacy of Aprepitant. Additional interactions Diltiazem: In patients with mild to moderate hypertension, administration of aprepitant once daily, as a tablet formulation comparable to 230 mg of the capsule formulation, with diltiazem 120 mg 3 times daily for 5 days, resulted in a 2-fold increase of aprepitant AUC and a simultaneous 1.7-fold increase of diltiazem AUC. These pharmacokinetic effects did not result in clinically meaningful changes in ECG, heart rate or blood pressure beyond those changes induced by diltiazem alone. Paroxetine: Coadministration of once daily doses of aprepitant, as a tablet formulation comparable to 85 mg or 170 mg of the capsule formulation, with paroxetine 20 mg once daily, resulted in a decrease in AUC by approximately 25% and Cmax, by approximately 20% of both aprepitant and paroxetine." ], "offsets": [ [ 0, 7706 ] ] } ]

[ { "id": "Aprepitant_ddi_T1", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T2", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 75, 85 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T3", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 126, 136 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T4", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 212, 222 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T5", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 332, 342 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T6", "type": "DRUG", "text": [ "S(-) warfarin" ], "offsets": [ [ 386, 399 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T7", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 404, 415 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T8", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 475, 485 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T9", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 570, 579 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T10", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 639, 649 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T11", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 787, 797 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T12", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 803, 810 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T13", "type": "GROUP", "text": [ "5-HT3 antagonists" ], "offsets": [ [ 849, 866 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T14", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 906, 916 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T15", "type": "DRUG", "text": [ "ondansetron" ], "offsets": [ [ 986, 997 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T16", "type": "DRUG", "text": [ "granisetron" ], "offsets": [ [ 1001, 1012 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T17", "type": "DRUG", "text": [ "dolasetron" ], "offsets": [ [ 1071, 1081 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T18", "type": "GROUP", "text": [ "Corticosteroids" ], "offsets": [ [ 1083, 1098 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T19", "type": "DRUG", "text": [ "Dexamethasone" ], "offsets": [ [ 1100, 1113 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T20", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 1115, 1125 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T21", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1165, 1178 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T22", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 1224, 1234 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T23", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1264, 1277 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T24", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1350, 1363 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T25", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1423, 1436 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T26", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 1507, 1517 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T27", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1543, 1556 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T28", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 1608, 1618 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T29", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1638, 1651 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T30", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 1690, 1700 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T31", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1754, 1767 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T32", "type": "DRUG", "text": [ "Methylprednisolone" ], "offsets": [ [ 1769, 1787 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T33", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 1788, 1798 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T34", "type": "DRUG", "text": [ "methylprednisolone" ], "offsets": [ [ 1895, 1913 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T35", "type": "DRUG", "text": [ "methylprednisolone" ], "offsets": [ [ 1988, 2006 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T36", "type": "DRUG", "text": [ "methylprednisolone" ], "offsets": [ [ 2103, 2121 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T37", "type": "DRUG", "text": [ "methylprednisolone" ], "offsets": [ [ 2180, 2198 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T38", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 2268, 2278 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T39", "type": "DRUG", "text": [ "methylprednisolone" ], "offsets": [ [ 2303, 2321 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T40", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 2373, 2383 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T41", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 2385, 2393 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T42", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 2419, 2429 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T43", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2537, 2545 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T44", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 2587, 2597 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T45", "type": "DRUG", "text": [ "R(+)", "warfarin" ], "offsets": [ [ 2619, 2623 ], [ 2632, 2640 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T46", "type": "DRUG", "text": [ "S(-) warfarin" ], "offsets": [ [ 2627, 2640 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T47", "type": "DRUG", "text": [ "S(-)warfarin" ], "offsets": [ [ 2690, 2702 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T48", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 2890, 2900 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T49", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2925, 2933 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T50", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 3095, 3105 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T51", "type": "DRUG", "text": [ "Tolbutamide" ], "offsets": [ [ 3136, 3147 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T52", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 3149, 3159 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T53", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 3243, 3254 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T54", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 3348, 3359 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T55", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 3444, 3454 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T56", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 3485, 3499 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T57", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 3501, 3511 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T58", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 3580, 3593 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T59", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 3615, 3632 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T60", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 3645, 3658 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T61", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 3681, 3698 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T62", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 3732, 3745 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T63", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 3785, 3799 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T64", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 3825, 3835 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T65", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 3880, 3890 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T66", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 3921, 3935 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T67", "type": "DRUG", "text": [ "Midazolam" ], "offsets": [ [ 4022, 4031 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T68", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 4033, 4043 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T69", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4065, 4074 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T70", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4177, 4186 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T71", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 4246, 4256 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T72", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4368, 4377 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T73", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 4387, 4402 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T74", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 4427, 4437 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T75", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 4439, 4448 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T76", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 4510, 4520 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T77", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4574, 4583 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T78", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 4585, 4595 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T79", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4660, 4669 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T80", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 4740, 4750 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T81", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 4777, 4787 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T82", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4809, 4818 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T83", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 4860, 4869 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T84", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 4912, 4922 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T85", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 5011, 5020 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T86", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 5123, 5133 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T87", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 5134, 5144 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T88", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 5203, 5213 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T89", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 5303, 5313 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T90", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 5359, 5369 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T91", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 5407, 5419 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T92", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 5421, 5433 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T93", "type": "DRUG", "text": [ "nefazodone" ], "offsets": [ [ 5435, 5445 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T94", "type": "DRUG", "text": [ "troleandomycin" ], "offsets": [ [ 5447, 5461 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T95", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 5463, 5477 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T96", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 5479, 5488 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T97", "type": "DRUG", "text": [ "nelfinavir" ], "offsets": [ [ 5490, 5500 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T98", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 5579, 5588 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T99", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 5644, 5654 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T100", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 5723, 5733 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T101", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 5792, 5802 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T102", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 5858, 5866 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T103", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 5868, 5881 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T104", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 5883, 5892 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T105", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 5941, 5951 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T106", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 5993, 6003 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T107", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 6005, 6017 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T108", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 6048, 6058 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T109", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 6089, 6101 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T110", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 6132, 6142 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T111", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 6205, 6217 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T112", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 6257, 6267 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T113", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 6334, 6344 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T114", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 6407, 6417 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T115", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 6481, 6489 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T116", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 6520, 6530 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T117", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 6593, 6601 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T118", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 6639, 6649 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T119", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 6766, 6776 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T120", "type": "DRUG", "text": [ "Aprepitant" ], "offsets": [ [ 6886, 6896 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T121", "type": "DRUG", "text": [ "Diltiazem" ], "offsets": [ [ 6922, 6931 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T122", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 6999, 7009 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T123", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 7100, 7109 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T124", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 7176, 7186 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T125", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 7231, 7240 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T126", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 7393, 7402 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T127", "type": "DRUG", "text": [ "Paroxetine" ], "offsets": [ [ 7410, 7420 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T128", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 7462, 7472 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T129", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 7561, 7571 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T130", "type": "DRUG", "text": [ "aprepitant" ], "offsets": [ [ 7680, 7690 ] ], "normalized": [] }, { "id": "Aprepitant_ddi_T131", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 7695, 7705 ] ], "normalized": [] } ]

[]

[]

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"arg1_id": "Aprepitant_ddi_T33", "arg2_id": "Aprepitant_ddi_T34", "normalized": [] }, { "id": "Aprepitant_ddi_R9", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T36", "arg2_id": "Aprepitant_ddi_T38", "normalized": [] }, { "id": "Aprepitant_ddi_R10", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T37", "arg2_id": "Aprepitant_ddi_T38", "normalized": [] }, { "id": "Aprepitant_ddi_R11", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T47", "arg2_id": "Aprepitant_ddi_T48", "normalized": [] }, { "id": "Aprepitant_ddi_R12", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T49", "arg2_id": "Aprepitant_ddi_T50", "normalized": [] }, { "id": "Aprepitant_ddi_R13", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T54", "arg2_id": "Aprepitant_ddi_T55", "normalized": [] }, { "id": "Aprepitant_ddi_R14", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T57", "arg2_id": "Aprepitant_ddi_T59", "normalized": [] }, { "id": "Aprepitant_ddi_R15", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T57", "arg2_id": "Aprepitant_ddi_T60", "normalized": [] }, { "id": "Aprepitant_ddi_R16", "type": "EFFECT", "arg1_id": "Aprepitant_ddi_T63", "arg2_id": "Aprepitant_ddi_T64", "normalized": [] }, { "id": "Aprepitant_ddi_R17", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T65", "arg2_id": "Aprepitant_ddi_T66", "normalized": [] }, { "id": "Aprepitant_ddi_R18", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T68", "arg2_id": "Aprepitant_ddi_T69", "normalized": [] }, { "id": "Aprepitant_ddi_R19", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T72", "arg2_id": "Aprepitant_ddi_T76", "normalized": [] }, { "id": "Aprepitant_ddi_R20", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T73", "arg2_id": "Aprepitant_ddi_T76", "normalized": [] }, { "id": "Aprepitant_ddi_R21", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T74", "arg2_id": "Aprepitant_ddi_T76", "normalized": [] }, { "id": "Aprepitant_ddi_R22", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T75", "arg2_id": "Aprepitant_ddi_T76", "normalized": [] }, { "id": "Aprepitant_ddi_R23", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T81", "arg2_id": "Aprepitant_ddi_T82", "normalized": [] }, { "id": "Aprepitant_ddi_R24", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T81", "arg2_id": "Aprepitant_ddi_T83", "normalized": [] }, { "id": "Aprepitant_ddi_R25", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T90", "arg2_id": "Aprepitant_ddi_T91", "normalized": [] }, { "id": "Aprepitant_ddi_R26", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T90", "arg2_id": "Aprepitant_ddi_T92", "normalized": [] }, { "id": "Aprepitant_ddi_R27", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T90", "arg2_id": "Aprepitant_ddi_T93", "normalized": [] }, { "id": "Aprepitant_ddi_R28", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T90", "arg2_id": "Aprepitant_ddi_T94", "normalized": [] }, { "id": "Aprepitant_ddi_R29", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T90", "arg2_id": "Aprepitant_ddi_T95", "normalized": [] }, { "id": "Aprepitant_ddi_R30", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T90", "arg2_id": "Aprepitant_ddi_T96", "normalized": [] }, { "id": "Aprepitant_ddi_R31", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T90", "arg2_id": "Aprepitant_ddi_T97", "normalized": [] }, { "id": "Aprepitant_ddi_R32", "type": "ADVISE", "arg1_id": "Aprepitant_ddi_T98", "arg2_id": "Aprepitant_ddi_T99", "normalized": [] }, { "id": "Aprepitant_ddi_R33", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T101", "arg2_id": "Aprepitant_ddi_T102", "normalized": [] }, { "id": "Aprepitant_ddi_R34", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T101", "arg2_id": "Aprepitant_ddi_T104", "normalized": [] }, { "id": "Aprepitant_ddi_R35", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T101", "arg2_id": "Aprepitant_ddi_T105", "normalized": [] }, { "id": "Aprepitant_ddi_R36", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T110", "arg2_id": "Aprepitant_ddi_T111", "normalized": [] }, { "id": "Aprepitant_ddi_R37", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T116", "arg2_id": "Aprepitant_ddi_T117", "normalized": [] }, { "id": "Aprepitant_ddi_R38", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T122", "arg2_id": "Aprepitant_ddi_T123", "normalized": [] }, { "id": "Aprepitant_ddi_R39", "type": "MECHANISM", "arg1_id": "Aprepitant_ddi_T128", "arg2_id": "Aprepitant_ddi_T129", "normalized": [] } ]

[ { "id": "Cyclobenzaprine_ddi__text", "type": "abstract", "text": [ "FLEXERIL may have life-threatening interactions with MAO inhibitors. FLEXERIL may enhance the effects of alcohol, barbiturates, and other CNS depressants. Tricyclic antidepressants may block the antihypertensive action of guanethidine and similarly acting compounds. Tricyclic antidepressants may enhance the seizure risk in patients taking tramadol ." ], "offsets": [ [ 0, 351 ] ] } ]

[ { "id": "Cyclobenzaprine_ddi_T1", "type": "BRAND", "text": [ "FLEXERIL" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T2", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 53, 67 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T3", "type": "BRAND", "text": [ "FLEXERIL" ], "offsets": [ [ 69, 77 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T4", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 105, 112 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T5", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 114, 126 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T6", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 138, 153 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T7", "type": "GROUP", "text": [ "Tricyclic antidepressants" ], "offsets": [ [ 155, 180 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T8", "type": "DRUG", "text": [ "guanethidine" ], "offsets": [ [ 222, 234 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T9", "type": "GROUP", "text": [ "Tricyclic antidepressants" ], "offsets": [ [ 267, 292 ] ], "normalized": [] }, { "id": "Cyclobenzaprine_ddi_T10", "type": "DRUG", "text": [ "tramadol" ], "offsets": [ [ 341, 349 ] ], "normalized": [] } ]

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[ { "id": "Cyclobenzaprine_ddi_R1", "type": "INT", "arg1_id": "Cyclobenzaprine_ddi_T1", "arg2_id": "Cyclobenzaprine_ddi_T2", "normalized": [] }, { "id": "Cyclobenzaprine_ddi_R2", "type": "EFFECT", "arg1_id": "Cyclobenzaprine_ddi_T3", "arg2_id": "Cyclobenzaprine_ddi_T4", "normalized": [] }, { "id": "Cyclobenzaprine_ddi_R3", "type": "EFFECT", "arg1_id": "Cyclobenzaprine_ddi_T3", "arg2_id": "Cyclobenzaprine_ddi_T5", "normalized": [] }, { "id": "Cyclobenzaprine_ddi_R4", "type": "EFFECT", "arg1_id": "Cyclobenzaprine_ddi_T3", "arg2_id": "Cyclobenzaprine_ddi_T6", "normalized": [] }, { "id": "Cyclobenzaprine_ddi_R5", "type": "EFFECT", "arg1_id": "Cyclobenzaprine_ddi_T7", "arg2_id": "Cyclobenzaprine_ddi_T8", "normalized": [] }, { "id": "Cyclobenzaprine_ddi_R6", "type": "EFFECT", "arg1_id": "Cyclobenzaprine_ddi_T9", "arg2_id": "Cyclobenzaprine_ddi_T10", "normalized": [] } ]

[ { "id": "Abarelix_ddi__text", "type": "abstract", "text": [ "No formal drug/drug interaction studies with Plenaxis were performed. Cytochrome P-450 is not known to be involved in the metabolism of Plenaxis. Plenaxis is highly bound to plasma proteins (96 to 99%). Laboratory Tests Response to Plenaxis should be monitored by measuring serum total testosterone concentrations just prior to administration on Day 29 and every 8 weeks thereafter. Serum transaminase levels should be obtained before starting treatment with Plenaxis and periodically during treatment. Periodic measurement of serum PSA levels may also be considered." ], "offsets": [ [ 0, 567 ] ] } ]

[ { "id": "Abarelix_ddi_T1", "type": "BRAND", "text": [ "Plenaxis" ], "offsets": [ [ 45, 53 ] ], "normalized": [] }, { "id": "Abarelix_ddi_T2", "type": "BRAND", "text": [ "Plenaxis" ], "offsets": [ [ 136, 144 ] ], "normalized": [] }, { "id": "Abarelix_ddi_T3", "type": "BRAND", "text": [ "Plenaxis" ], "offsets": [ [ 146, 154 ] ], "normalized": [] }, { "id": "Abarelix_ddi_T4", "type": "BRAND", "text": [ "Plenaxis" ], "offsets": [ [ 232, 240 ] ], "normalized": [] }, { "id": "Abarelix_ddi_T5", "type": "DRUG", "text": [ "testosterone" ], "offsets": [ [ 286, 298 ] ], "normalized": [] }, { "id": "Abarelix_ddi_T6", "type": "BRAND", "text": [ "Plenaxis" ], "offsets": [ [ 459, 467 ] ], "normalized": [] } ]

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[ { "id": "Gadodiamide_ddi__text", "type": "abstract", "text": [ "LABORATORY TEST FINDINGS Asymptomatic, transitory changes in serum iron have been observed. The clinical significance is unknown. Omniscan interferes with serum calcium measurements with some colorimetric (complexometric) methods commonly used in hospitals, resulting in serum calcium concentrations lower than the true values. Thus, it is recommended not to use such methods for 12-24 hours after administration of Omniscan. If such measurements are necessary, the use of other methods is recommended. All patients in whom this effect was observed remained asymptomatic." ], "offsets": [ [ 0, 571 ] ] } ]

[ { "id": "Gadodiamide_ddi_T1", "type": "BRAND", "text": [ "Omniscan" ], "offsets": [ [ 130, 138 ] ], "normalized": [] }, { "id": "Gadodiamide_ddi_T2", "type": "BRAND", "text": [ "Omniscan" ], "offsets": [ [ 416, 424 ] ], "normalized": [] } ]

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[ { "id": "Ethosuximide_ddi__text", "type": "abstract", "text": [ "Since Zarontin (ethosuximide) may interact with concurrently administered antiepileptic drugs, periodic serum level determinations of these drugs may be necessary (eg, ethosuximide may elevate phenytoin serum levels and valproic acid has been reported to both increase and decrease ethosuximide levels)." ], "offsets": [ [ 0, 303 ] ] } ]

[ { "id": "Ethosuximide_ddi_T1", "type": "BRAND", "text": [ "Zarontin" ], "offsets": [ [ 6, 14 ] ], "normalized": [] }, { "id": "Ethosuximide_ddi_T2", "type": "DRUG", "text": [ "ethosuximide" ], "offsets": [ [ 16, 28 ] ], "normalized": [] }, { "id": "Ethosuximide_ddi_T3", "type": "GROUP", "text": [ "antiepileptic drugs" ], "offsets": [ [ 74, 93 ] ], "normalized": [] }, { "id": "Ethosuximide_ddi_T4", "type": "DRUG", "text": [ "ethosuximide" ], "offsets": [ [ 168, 180 ] ], "normalized": [] }, { "id": "Ethosuximide_ddi_T5", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 193, 202 ] ], "normalized": [] }, { "id": "Ethosuximide_ddi_T6", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 220, 233 ] ], "normalized": [] }, { "id": "Ethosuximide_ddi_T7", "type": "DRUG", "text": [ "ethosuximide" ], "offsets": [ [ 282, 294 ] ], "normalized": [] } ]

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[ { "id": "Ethosuximide_ddi_R1", "type": "INT", "arg1_id": "Ethosuximide_ddi_T1", "arg2_id": "Ethosuximide_ddi_T3", "normalized": [] }, { "id": "Ethosuximide_ddi_R2", "type": "INT", "arg1_id": "Ethosuximide_ddi_T2", "arg2_id": "Ethosuximide_ddi_T3", "normalized": [] }, { "id": "Ethosuximide_ddi_R3", "type": "MECHANISM", "arg1_id": "Ethosuximide_ddi_T4", "arg2_id": "Ethosuximide_ddi_T5", "normalized": [] }, { "id": "Ethosuximide_ddi_R4", "type": "MECHANISM", "arg1_id": "Ethosuximide_ddi_T6", "arg2_id": "Ethosuximide_ddi_T7", "normalized": [] } ]

[ { "id": "Natalizumab_ddi__text", "type": "abstract", "text": [ "After multiple dosing, interferon beta-1a (AVONEX 30 mcg IM once weekly) reduced TYSABRI clearance by approximately 30%. The similarity of the TYSABRI -associated adverse event profile between Study 1 (without co-administered AVONEX ) and Study 2 (with co-administered AVONEX ) indicates that this alteration in clearance does not necessitate reduction of the TYSABRI dose to maintain safety, General). Results of studies in multiple sclerosis patients taking TYSABRI and concomitant interferon beta-1a (AVONEX 30 mcg IM once weekly) or glatiramer acetate were inconclusive with regard to the need for dose adjustment of the beta-interferon or glatiramer acetate." ], "offsets": [ [ 0, 668 ] ] } ]

[ { "id": "Natalizumab_ddi_T1", "type": "DRUG", "text": [ "interferon beta-1a" ], "offsets": [ [ 23, 41 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T2", "type": "BRAND", "text": [ "AVONEX" ], "offsets": [ [ 43, 49 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T3", "type": "BRAND", "text": [ "TYSABRI" ], "offsets": [ [ 82, 89 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T4", "type": "BRAND", "text": [ "TYSABRI" ], "offsets": [ [ 145, 152 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T5", "type": "BRAND", "text": [ "AVONEX" ], "offsets": [ [ 228, 234 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T6", "type": "BRAND", "text": [ "AVONEX" ], "offsets": [ [ 271, 277 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T7", "type": "BRAND", "text": [ "TYSABRI" ], "offsets": [ [ 362, 369 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T8", "type": "BRAND", "text": [ "TYSABRI" ], "offsets": [ [ 463, 470 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T9", "type": "DRUG", "text": [ "interferon beta-1a" ], "offsets": [ [ 488, 506 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T10", "type": "BRAND", "text": [ "AVONEX" ], "offsets": [ [ 508, 514 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T11", "type": "DRUG", "text": [ "glatiramer acetate" ], "offsets": [ [ 542, 560 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T12", "type": "DRUG", "text": [ "beta-interferon" ], "offsets": [ [ 630, 645 ] ], "normalized": [] }, { "id": "Natalizumab_ddi_T13", "type": "DRUG", "text": [ "glatiramer acetate" ], "offsets": [ [ 649, 667 ] ], "normalized": [] } ]

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[ { "id": "Natalizumab_ddi_R1", "type": "MECHANISM", "arg1_id": "Natalizumab_ddi_T1", "arg2_id": "Natalizumab_ddi_T3", "normalized": [] }, { "id": "Natalizumab_ddi_R2", "type": "MECHANISM", "arg1_id": "Natalizumab_ddi_T2", "arg2_id": "Natalizumab_ddi_T3", "normalized": [] } ]

[ { "id": "Glycopyrrolate_ddi__text", "type": "abstract", "text": [ "The concurrent use of Robinul Injection with other anticholinergics or medications with anticholinergic activity, such as phenothiazines, antiparkinson drugs, or tricyclic antidepressants, may intensify the antimuscarinic effects and may result in an increase in anticholinergic side effects. Concomitant administration of Robinul Injection and potassium chloride in a wax matrix may increase the severity of potassium chloride-induced gastrointestinal lesions as a result of a slower gastrointestinal transit time." ], "offsets": [ [ 0, 515 ] ] } ]

[ { "id": "Glycopyrrolate_ddi_T1", "type": "BRAND", "text": [ "Robinul" ], "offsets": [ [ 22, 29 ] ], "normalized": [] }, { "id": "Glycopyrrolate_ddi_T2", "type": "GROUP", "text": [ "anticholinergics" ], "offsets": [ [ 51, 67 ] ], "normalized": [] }, { "id": "Glycopyrrolate_ddi_T3", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 122, 136 ] ], "normalized": [] }, { "id": "Glycopyrrolate_ddi_T4", "type": "GROUP", "text": [ "antiparkinson drugs" ], "offsets": [ [ 138, 157 ] ], "normalized": [] }, { "id": "Glycopyrrolate_ddi_T5", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 162, 187 ] ], "normalized": [] }, { "id": "Glycopyrrolate_ddi_T6", "type": "BRAND", "text": [ "Robinul" ], "offsets": [ [ 323, 330 ] ], "normalized": [] }, { "id": "Glycopyrrolate_ddi_T7", "type": "DRUG", "text": [ "potassium chloride" ], "offsets": [ [ 345, 363 ] ], "normalized": [] } ]

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[ { "id": "Glycopyrrolate_ddi_R1", "type": "EFFECT", "arg1_id": "Glycopyrrolate_ddi_T1", "arg2_id": "Glycopyrrolate_ddi_T2", "normalized": [] }, { "id": "Glycopyrrolate_ddi_R2", "type": "EFFECT", "arg1_id": "Glycopyrrolate_ddi_T1", "arg2_id": "Glycopyrrolate_ddi_T3", "normalized": [] }, { "id": "Glycopyrrolate_ddi_R3", "type": "EFFECT", "arg1_id": "Glycopyrrolate_ddi_T1", "arg2_id": "Glycopyrrolate_ddi_T4", "normalized": [] }, { "id": "Glycopyrrolate_ddi_R4", "type": "EFFECT", "arg1_id": "Glycopyrrolate_ddi_T1", "arg2_id": "Glycopyrrolate_ddi_T5", "normalized": [] }, { "id": "Glycopyrrolate_ddi_R5", "type": "MECHANISM", "arg1_id": "Glycopyrrolate_ddi_T6", "arg2_id": "Glycopyrrolate_ddi_T7", "normalized": [] } ]

[ { "id": "Nafcillin_ddi__text", "type": "abstract", "text": [ "Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided." ], "offsets": [ [ 0, 148 ] ] } ]

[ { "id": "Nafcillin_ddi_T1", "type": "DRUG", "text": [ "Tetracycline" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Nafcillin_ddi_T2", "type": "GROUP", "text": [ "bacteriostatic antibiotic" ], "offsets": [ [ 16, 41 ] ], "normalized": [] }, { "id": "Nafcillin_ddi_T3", "type": "DRUG", "text": [ "penicillin" ], "offsets": [ [ 85, 95 ] ], "normalized": [] } ]

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[ { "id": "Nafcillin_ddi_R1", "type": "EFFECT", "arg1_id": "Nafcillin_ddi_T1", "arg2_id": "Nafcillin_ddi_T3", "normalized": [] } ]

[ { "id": "Busulfan_ddi__text", "type": "abstract", "text": [ "Itraconazole decreases busulfan clearance by up to 25%, and may produce AUCs 1500 M min in some patients. Fluconazole, and the 5-HT3 antiemetics ondansetron (Zofran) and granisetron (Kytril) have all been used with BUSULFEX. Phenytoin increases the clearance of busulfan by 15% or more, possibly due to the induction of glutathione-S-transferase. Since the pharmacokinetics of BUSULFEX were studied in patients treated with phenytoin, the clearance of BUSULFEX at the recommended dose may be lower and exposure (AUC) higher in patients not treated with phenytoin. Because busulfan is eliminated from the body via conjugation with glutathione, use of acetaminophen prior to ( 72 hours) or concurrent with BUSULFEX may result in reduced busulfan clearance based upon the known property of acetaminophen to decrease glutathione levels in the blood and tissues." ], "offsets": [ [ 0, 860 ] ] } ]

[ { "id": "Busulfan_ddi_T1", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T2", "type": "DRUG", "text": [ "busulfan" ], "offsets": [ [ 23, 31 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T3", "type": "DRUG", "text": [ "Fluconazole" ], "offsets": [ [ 109, 120 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T4", "type": "GROUP", "text": [ "5-HT3 antiemetics" ], "offsets": [ [ 130, 147 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T5", "type": "DRUG", "text": [ "ondansetron" ], "offsets": [ [ 148, 159 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T6", "type": "BRAND", "text": [ "Zofran" ], "offsets": [ [ 161, 167 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T7", "type": "DRUG", "text": [ "granisetron" ], "offsets": [ [ 173, 184 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T8", "type": "BRAND", "text": [ "Kytril" ], "offsets": [ [ 186, 192 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T9", "type": "BRAND", "text": [ "BUSULFEX" ], "offsets": [ [ 218, 226 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T10", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 228, 237 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T11", "type": "DRUG", "text": [ "busulfan" ], "offsets": [ [ 265, 273 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T12", "type": "BRAND", "text": [ "BUSULFEX" ], "offsets": [ [ 380, 388 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T13", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 427, 436 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T14", "type": "BRAND", "text": [ "BUSULFEX" ], "offsets": [ [ 455, 463 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T15", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 556, 565 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T16", "type": "DRUG", "text": [ "busulfan" ], "offsets": [ [ 575, 583 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T17", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 653, 666 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T18", "type": "BRAND", "text": [ "BUSULFEX" ], "offsets": [ [ 707, 715 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T19", "type": "DRUG", "text": [ "busulfan" ], "offsets": [ [ 738, 746 ] ], "normalized": [] }, { "id": "Busulfan_ddi_T20", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 790, 803 ] ], "normalized": [] } ]

[]

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[ { "id": "Busulfan_ddi_R1", "type": "MECHANISM", "arg1_id": "Busulfan_ddi_T1", "arg2_id": "Busulfan_ddi_T2", "normalized": [] }, { "id": "Busulfan_ddi_R2", "type": "MECHANISM", "arg1_id": "Busulfan_ddi_T10", "arg2_id": "Busulfan_ddi_T11", "normalized": [] }, { "id": "Busulfan_ddi_R3", "type": "MECHANISM", "arg1_id": "Busulfan_ddi_T12", "arg2_id": "Busulfan_ddi_T13", "normalized": [] }, { "id": "Busulfan_ddi_R4", "type": "MECHANISM", "arg1_id": "Busulfan_ddi_T17", "arg2_id": "Busulfan_ddi_T18", "normalized": [] } ]

[ { "id": "Disulfiram_ddi__text", "type": "abstract", "text": [ "Disulfiram appears to decrease the rate at which certain drugs are metabolized and therefore may increase the blood levels and the possibility of clinical toxicity of drugs given concomitantly. DISULFIRAM SHOULD BE USED WITH CAUTION IN THOSE PATIENTS REVEIVING PHENYTOIN AND ITS CONGENERS. SINCE THE CONCOMITANT ADMINISTRATION OF THESE TWO DRUGS CAN LEAD TO PHENYTOIN INTOXICATION, PRIOR TO ADMINISTERING DISULFIRAM TO A PATIENT ON PHENYTOIN THERAPY, A BASELINE PHENYTOIN SERUM LEVEL SHOULD BE OBTAINED. SUBSEQUENT TO INITIATION OF DISULFIRAM THERAPY. SERUM LEVELS OF PHENYTOIN SHOULD BE DETERMINED ON DIFFERENT DAYS FOR EVIDENCE OF AN INCREASE OR FOR A CONTINUING RISE IN LEVELS. INCREASED PHENYTOIN LEVELS SHOULD BE TREATED WITH APPROPRIATE DOSAGE ADJUSTMENT. It may be necessary to adjust the dosage of oral anticoagulants upon beginning or stopping disulfiram. since disulfiram may prolong prothrombin time. Patients taking isoniazid when disulfiram is given should be observed for the appearance of unsteady gait or marked changes in mental status; the disulfiram should be discontinued if such signs appear. In rats, simultaneous ingestion of disulfiram and nitrite in the diet for 78 weeks has been reported to cause tumors, and it has been suggested that disulfiram may react with nitrites in the rat stomach to form a nitrosamine, which is tumorigenic. Disulfiram alone in the rat s diet did not lead to such tumors. The relevance of this finding to humans is not known at this time." ], "offsets": [ [ 0, 1492 ] ] } ]

[ { "id": "Disulfiram_ddi_T1", "type": "DRUG", "text": [ "Disulfiram" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T2", "type": "DRUG", "text": [ "DISULFIRAM" ], "offsets": [ [ 194, 204 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T3", "type": "DRUG", "text": [ "PHENYTOIN" ], "offsets": [ [ 261, 270 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T4", "type": "DRUG", "text": [ "PHENYTOIN" ], "offsets": [ [ 358, 367 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T5", "type": "DRUG", "text": [ "DISULFIRAM" ], "offsets": [ [ 405, 415 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T6", "type": "DRUG", "text": [ "PHENYTOIN" ], "offsets": [ [ 432, 441 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T7", "type": "DRUG", "text": [ "PHENYTOIN" ], "offsets": [ [ 462, 471 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T8", "type": "DRUG", "text": [ "DISULFIRAM" ], "offsets": [ [ 532, 542 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T9", "type": "DRUG", "text": [ "PHENYTOIN" ], "offsets": [ [ 568, 577 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T10", "type": "DRUG", "text": [ "PHENYTOIN" ], "offsets": [ [ 691, 700 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T11", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 811, 825 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T12", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 853, 863 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T13", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 871, 881 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T14", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 928, 937 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T15", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 943, 953 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T16", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 1058, 1068 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T17", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 1149, 1159 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T18", "type": "DRUG", "text": [ "nitrite" ], "offsets": [ [ 1164, 1171 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T19", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 1263, 1273 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T20", "type": "GROUP", "text": [ "nitrites" ], "offsets": [ [ 1289, 1297 ] ], "normalized": [] }, { "id": "Disulfiram_ddi_T21", "type": "DRUG", "text": [ "Disulfiram" ], "offsets": [ [ 1362, 1372 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Disulfiram_ddi_R1", "type": "ADVISE", "arg1_id": "Disulfiram_ddi_T2", "arg2_id": "Disulfiram_ddi_T3", "normalized": [] }, { "id": "Disulfiram_ddi_R2", "type": "EFFECT", "arg1_id": "Disulfiram_ddi_T5", "arg2_id": "Disulfiram_ddi_T6", "normalized": [] }, { "id": "Disulfiram_ddi_R3", "type": "ADVISE", "arg1_id": "Disulfiram_ddi_T11", "arg2_id": "Disulfiram_ddi_T12", "normalized": [] }, { "id": "Disulfiram_ddi_R4", "type": "ADVISE", "arg1_id": "Disulfiram_ddi_T14", "arg2_id": "Disulfiram_ddi_T15", "normalized": [] }, { "id": "Disulfiram_ddi_R5", "type": "EFFECT", "arg1_id": "Disulfiram_ddi_T17", "arg2_id": "Disulfiram_ddi_T18", "normalized": [] }, { "id": "Disulfiram_ddi_R6", "type": "EFFECT", "arg1_id": "Disulfiram_ddi_T19", "arg2_id": "Disulfiram_ddi_T20", "normalized": [] } ]

[ { "id": "Acamprosate_ddi__text", "type": "abstract", "text": [ "The concomitant intake of alcohol and Acamprosate does not affect the pharmacokinetics of either alcohol or acamprosate. Pharmacokinetic studies indicate that administration of disulfiram or diazepam does not affect the pharmacokinetics of acamprosate. Co-administration of naltrexone with Acamprosate produced a 25% increase in AUC and a 33% increase in the Cmax of acamprosate. No adjustment of dosage is recommended in such patients. The pharmacokinetics of naltrexone and its major metabolite 6-beta-naltrexol were unaffected following co-administration with Acamprosate. Other concomitant therapies: In clinical trials, the safety profile in subjects treated with Acamprosate concomitantly with anxiolytics, hypnotics and sedatives (including benzodiazepines), or non-opioid analgesics was similar to that of subjects taking placebo with these concomitant medications. Patients taking Acamprosate concomitantly with antidepressants more commonly reported both weight gain and weight loss, compared with patients taking either medication alone." ], "offsets": [ [ 0, 1048 ] ] } ]

[ { "id": "Acamprosate_ddi_T1", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 26, 33 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T2", "type": "DRUG", "text": [ "Acamprosate" ], "offsets": [ [ 38, 49 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T3", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 97, 104 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T4", "type": "DRUG", "text": [ "acamprosate" ], "offsets": [ [ 108, 119 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T5", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 177, 187 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T6", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 191, 199 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T7", "type": "DRUG", "text": [ "acamprosate" ], "offsets": [ [ 240, 251 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T8", "type": "DRUG", "text": [ "naltrexone" ], "offsets": [ [ 274, 284 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T9", "type": "DRUG", "text": [ "Acamprosate" ], "offsets": [ [ 290, 301 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T10", "type": "DRUG", "text": [ "acamprosate" ], "offsets": [ [ 367, 378 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T11", "type": "DRUG", "text": [ "naltrexone" ], "offsets": [ [ 461, 471 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T12", "type": "DRUG_N", "text": [ "6-beta-naltrexol" ], "offsets": [ [ 497, 513 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T13", "type": "DRUG", "text": [ "Acamprosate" ], "offsets": [ [ 563, 574 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T14", "type": "DRUG", "text": [ "Acamprosate" ], "offsets": [ [ 669, 680 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T15", "type": "GROUP", "text": [ "anxiolytics" ], "offsets": [ [ 700, 711 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T16", "type": "GROUP", "text": [ "hypnotics" ], "offsets": [ [ 713, 722 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T17", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 727, 736 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T18", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 748, 763 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T19", "type": "GROUP", "text": [ "non-opioid analgesics" ], "offsets": [ [ 769, 790 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T20", "type": "DRUG", "text": [ "Acamprosate" ], "offsets": [ [ 890, 901 ] ], "normalized": [] }, { "id": "Acamprosate_ddi_T21", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 921, 936 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Acamprosate_ddi_R1", "type": "MECHANISM", "arg1_id": "Acamprosate_ddi_T8", "arg2_id": "Acamprosate_ddi_T9", "normalized": [] }, { "id": "Acamprosate_ddi_R2", "type": "EFFECT", "arg1_id": "Acamprosate_ddi_T20", "arg2_id": "Acamprosate_ddi_T21", "normalized": [] } ]

[ { "id": "Chlorthalidone_ddi__text", "type": "abstract", "text": [ "Chlorthalidone may add to or potentiate the action of other antihypertensive drugs. Potentiation occurs with ganglionic peripheral adrenergic blocking drugs. Medication such as digitalis may also influence serum electrolytes. Warning signs, irrespective of cause, are: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Insulin requirements in diabetic patients may be increased, decreased, or unchanged. Higher dosage of oral hypoglycemic agents may be required. Latent diabetes mellitus may become manifest during chlorthalidone administration. Chlorthalidone and related drugs may increase the responsiveness to tubocurarine. Chlorthalidone and related drugs may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use." ], "offsets": [ [ 0, 981 ] ] } ]

[ { "id": "Chlorthalidone_ddi_T1", "type": "DRUG", "text": [ "Chlorthalidone" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T2", "type": "GROUP", "text": [ "antihypertensive drugs" ], "offsets": [ [ 60, 82 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T3", "type": "GROUP", "text": [ "ganglionic peripheral adrenergic blocking drugs" ], "offsets": [ [ 109, 156 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T4", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 177, 186 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T5", "type": "DRUG", "text": [ "Insulin" ], "offsets": [ [ 482, 489 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T6", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 589, 608 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T7", "type": "DRUG", "text": [ "chlorthalidone" ], "offsets": [ [ 678, 692 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T8", "type": "DRUG", "text": [ "Chlorthalidone" ], "offsets": [ [ 709, 723 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T9", "type": "DRUG", "text": [ "tubocurarine" ], "offsets": [ [ 777, 789 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T10", "type": "DRUG", "text": [ "Chlorthalidone" ], "offsets": [ [ 791, 805 ] ], "normalized": [] }, { "id": "Chlorthalidone_ddi_T11", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 864, 878 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Chlorthalidone_ddi_R1", "type": "EFFECT", "arg1_id": "Chlorthalidone_ddi_T1", "arg2_id": "Chlorthalidone_ddi_T2", "normalized": [] }, { "id": "Chlorthalidone_ddi_R2", "type": "EFFECT", "arg1_id": "Chlorthalidone_ddi_T8", "arg2_id": "Chlorthalidone_ddi_T9", "normalized": [] }, { "id": "Chlorthalidone_ddi_R3", "type": "EFFECT", "arg1_id": "Chlorthalidone_ddi_T10", "arg2_id": "Chlorthalidone_ddi_T11", "normalized": [] } ]

[ { "id": "Menadione_ddi__text", "type": "abstract", "text": [ "Broad-Spectrum Antibiotics-Broad-spectrum antibiotics may sterilize the bowel and decrease the vitamin K contribution to the body by the intestinal microflora. Cephalosporins-Cephalosporins containing side chains of N-methylthiotetrazole (cefmenoxime, cefoperazone, cefotetan, cefamandole, latamoxef) or methylthiadiazole (cefazolin) can cause vitamin K deficiency and hypoprothrombinemia. These cephalosporins are inhibitors of hepatic vitamin K epoxide reductase. Cholestyramine-Concomitant intake of cholestyramine and vitamin K may reduce the absorption of vitamin K. Colestipol-Concomitant intake of colestipol and vitamin K may reduce the absorption of vitamin K. Mineral Oil-Concomitant intake of mineral oil and vitamin K may reduce the absorption of vitamin K. Orlistat-Orlistat may decrease the absorption of vitamin K. Salicylates-Salicylates in large doses may inhibit vitamin K epoxide reductase resulting in vitamin K deficiency. Warfarin-Vitamin K can antagonize the effect of warfarin" ], "offsets": [ [ 0, 1000 ] ] } ]

[ { "id": "Menadione_ddi_T1", "type": "GROUP", "text": [ "Broad-Spectrum Antibiotics" ], "offsets": [ [ 0, 26 ] ], "normalized": [] }, { "id": "Menadione_ddi_T2", "type": "GROUP", "text": [ "Broad-spectrum antibiotics" ], "offsets": [ [ 27, 53 ] ], "normalized": [] }, { "id": "Menadione_ddi_T3", "type": "GROUP", "text": [ "vitamin K" ], "offsets": [ [ 95, 104 ] ], "normalized": [] }, { "id": "Menadione_ddi_T4", "type": "GROUP", "text": [ "Cephalosporins" ], "offsets": [ [ 160, 174 ] ], "normalized": [] }, { "id": "Menadione_ddi_T5", "type": "GROUP", "text": [ "Cephalosporins" ], "offsets": [ [ 175, 189 ] ], "normalized": [] }, { "id": "Menadione_ddi_T6", "type": "DRUG", "text": [ "cefmenoxime" ], "offsets": [ [ 239, 250 ] ], "normalized": [] }, { "id": "Menadione_ddi_T7", "type": "DRUG", "text": [ "cefoperazone" ], "offsets": [ [ 252, 264 ] ], "normalized": [] }, { "id": "Menadione_ddi_T8", "type": "DRUG", "text": [ "cefotetan" ], "offsets": [ [ 266, 275 ] ], "normalized": [] }, { "id": "Menadione_ddi_T9", "type": "DRUG", "text": [ "cefamandole" ], "offsets": [ [ 277, 288 ] ], "normalized": [] }, { "id": "Menadione_ddi_T10", "type": "DRUG", "text": [ "latamoxef" ], "offsets": [ [ 290, 299 ] ], "normalized": [] }, { "id": "Menadione_ddi_T11", "type": "DRUG", "text": [ "cefazolin" ], "offsets": [ [ 323, 332 ] ], "normalized": [] }, { "id": "Menadione_ddi_T12", "type": "GROUP", "text": [ "cephalosporins" ], "offsets": [ [ 396, 410 ] ], "normalized": [] }, { "id": "Menadione_ddi_T13", "type": "DRUG", "text": [ "Cholestyramine" ], "offsets": [ [ 466, 480 ] ], "normalized": [] }, { "id": "Menadione_ddi_T14", "type": "DRUG", "text": [ "cholestyramine" ], "offsets": [ [ 503, 517 ] ], "normalized": [] }, { "id": "Menadione_ddi_T15", "type": "GROUP", "text": [ "vitamin K" ], "offsets": [ [ 522, 531 ] ], "normalized": [] }, { "id": "Menadione_ddi_T16", "type": "GROUP", "text": [ "vitamin K" ], "offsets": [ [ 561, 570 ] ], "normalized": [] }, { "id": "Menadione_ddi_T17", "type": "DRUG", "text": [ "Colestipol" ], "offsets": [ [ 572, 582 ] ], "normalized": [] }, { "id": "Menadione_ddi_T18", "type": "DRUG", "text": [ "colestipol" ], "offsets": [ [ 605, 615 ] ], "normalized": [] }, { "id": "Menadione_ddi_T19", "type": "GROUP", "text": [ "vitamin K" ], "offsets": [ [ 620, 629 ] ], "normalized": [] }, { "id": "Menadione_ddi_T20", "type": "GROUP", "text": [ "vitamin K" ], "offsets": [ [ 659, 668 ] ], "normalized": [] }, { "id": "Menadione_ddi_T21", "type": "DRUG_N", "text": [ "Mineral Oil" ], "offsets": [ [ 670, 681 ] ], "normalized": [] }, { "id": "Menadione_ddi_T22", "type": "DRUG_N", "text": [ "mineral oil" ], "offsets": [ [ 704, 715 ] ], "normalized": [] }, { "id": "Menadione_ddi_T23", "type": "GROUP", "text": [ "vitamin K" ], "offsets": [ [ 720, 729 ] ], "normalized": [] }, { "id": "Menadione_ddi_T24", "type": "GROUP", "text": [ "vitamin K" ], "offsets": [ [ 759, 768 ] ], "normalized": [] }, { "id": "Menadione_ddi_T25", "type": "DRUG", "text": [ "Orlistat" ], "offsets": [ [ 770, 778 ] ], "normalized": [] }, { "id": "Menadione_ddi_T26", "type": "DRUG", "text": [ "Orlistat" ], "offsets": [ [ 779, 787 ] ], "normalized": [] }, { "id": "Menadione_ddi_T27", "type": "GROUP", "text": [ "vitamin K" ], "offsets": [ [ 819, 828 ] ], "normalized": [] }, { "id": "Menadione_ddi_T28", "type": "GROUP", "text": [ "Salicylates" ], "offsets": [ [ 830, 841 ] ], "normalized": [] }, { "id": "Menadione_ddi_T29", "type": "GROUP", "text": [ "Salicylates" ], "offsets": [ [ 842, 853 ] ], "normalized": [] }, { "id": "Menadione_ddi_T30", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 944, 952 ] ], "normalized": [] }, { "id": "Menadione_ddi_T31", "type": "GROUP", "text": [ "Vitamin K" ], "offsets": [ [ 953, 962 ] ], "normalized": [] }, { "id": "Menadione_ddi_T32", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 992, 1000 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Menadione_ddi_R1", "type": "MECHANISM", "arg1_id": "Menadione_ddi_T14", "arg2_id": "Menadione_ddi_T15", "normalized": [] }, { "id": "Menadione_ddi_R2", "type": "MECHANISM", "arg1_id": "Menadione_ddi_T18", "arg2_id": "Menadione_ddi_T19", "normalized": [] }, { "id": "Menadione_ddi_R3", "type": "MECHANISM", "arg1_id": "Menadione_ddi_T22", "arg2_id": "Menadione_ddi_T23", "normalized": [] }, { "id": "Menadione_ddi_R4", "type": "MECHANISM", "arg1_id": "Menadione_ddi_T26", "arg2_id": "Menadione_ddi_T27", "normalized": [] }, { "id": "Menadione_ddi_R5", "type": "EFFECT", "arg1_id": "Menadione_ddi_T31", "arg2_id": "Menadione_ddi_T32", "normalized": [] } ]

[ { "id": "Bitolterol_ddi__text", "type": "abstract", "text": [ "Use of MAO inhibitors may cause an excessive increase in blood pressure and heart stimulation. If you are also using a steroid inhaler, take bitolterol first and then wait about 15 minutes before using the steroid inhaler. This allows bitolterol to open air passages, increasing the effectiveness of the steroid." ], "offsets": [ [ 0, 312 ] ] } ]

[ { "id": "Bitolterol_ddi_T1", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 7, 21 ] ], "normalized": [] }, { "id": "Bitolterol_ddi_T2", "type": "GROUP", "text": [ "steroid" ], "offsets": [ [ 119, 126 ] ], "normalized": [] }, { "id": "Bitolterol_ddi_T3", "type": "DRUG", "text": [ "bitolterol" ], "offsets": [ [ 141, 151 ] ], "normalized": [] }, { "id": "Bitolterol_ddi_T4", "type": "GROUP", "text": [ "steroid" ], "offsets": [ [ 206, 213 ] ], "normalized": [] }, { "id": "Bitolterol_ddi_T5", "type": "DRUG", "text": [ "bitolterol" ], "offsets": [ [ 235, 245 ] ], "normalized": [] }, { "id": "Bitolterol_ddi_T6", "type": "GROUP", "text": [ "steroid" ], "offsets": [ [ 304, 311 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Bitolterol_ddi_R1", "type": "ADVISE", "arg1_id": "Bitolterol_ddi_T2", "arg2_id": "Bitolterol_ddi_T3", "normalized": [] }, { "id": "Bitolterol_ddi_R2", "type": "ADVISE", "arg1_id": "Bitolterol_ddi_T3", "arg2_id": "Bitolterol_ddi_T4", "normalized": [] }, { "id": "Bitolterol_ddi_R3", "type": "EFFECT", "arg1_id": "Bitolterol_ddi_T5", "arg2_id": "Bitolterol_ddi_T6", "normalized": [] } ]

[ { "id": "Carbinoxamine_ddi__text", "type": "abstract", "text": [ "Antihistamines may enhance the effects of tricyclic antidepressants, barbiturates, alcohol, and other CNS depressants. MAO inhibitors prolong and intensify the anticholinergic effects of antihistamines. Sympathomimetic amines may reduce the antihypertensive effects of reserpine, veratrum alkaloids, methyldopa and mecamylamine. Effects of sympathomimetics are increased with MAO inhibitors and beta adrenergic blockers." ], "offsets": [ [ 0, 420 ] ] } ]

[ { "id": "Carbinoxamine_ddi_T1", "type": "GROUP", "text": [ "Antihistamines" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T2", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 42, 67 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T3", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 69, 81 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T4", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 83, 90 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T5", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 102, 117 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T6", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 119, 133 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T7", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 187, 201 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T8", "type": "GROUP", "text": [ "Sympathomimetic amines" ], "offsets": [ [ 203, 225 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T9", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 269, 278 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T10", "type": "GROUP", "text": [ "veratrum alkaloids" ], "offsets": [ [ 280, 298 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T11", "type": "DRUG", "text": [ "methyldopa" ], "offsets": [ [ 300, 310 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T12", "type": "DRUG", "text": [ "mecamylamine" ], "offsets": [ [ 315, 327 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T13", "type": "GROUP", "text": [ "sympathomimetics" ], "offsets": [ [ 340, 356 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T14", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 376, 390 ] ], "normalized": [] }, { "id": "Carbinoxamine_ddi_T15", "type": "GROUP", "text": [ "beta adrenergic blockers" ], "offsets": [ [ 395, 419 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Carbinoxamine_ddi_R1", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T1", "arg2_id": "Carbinoxamine_ddi_T2", "normalized": [] }, { "id": "Carbinoxamine_ddi_R2", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T1", "arg2_id": "Carbinoxamine_ddi_T3", "normalized": [] }, { "id": "Carbinoxamine_ddi_R3", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T1", "arg2_id": "Carbinoxamine_ddi_T4", "normalized": [] }, { "id": "Carbinoxamine_ddi_R4", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T1", "arg2_id": "Carbinoxamine_ddi_T5", "normalized": [] }, { "id": "Carbinoxamine_ddi_R5", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T6", "arg2_id": "Carbinoxamine_ddi_T7", "normalized": [] }, { "id": "Carbinoxamine_ddi_R6", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T8", "arg2_id": "Carbinoxamine_ddi_T9", "normalized": [] }, { "id": "Carbinoxamine_ddi_R7", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T8", "arg2_id": "Carbinoxamine_ddi_T10", "normalized": [] }, { "id": "Carbinoxamine_ddi_R8", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T8", "arg2_id": "Carbinoxamine_ddi_T11", "normalized": [] }, { "id": "Carbinoxamine_ddi_R9", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T8", "arg2_id": "Carbinoxamine_ddi_T12", "normalized": [] }, { "id": "Carbinoxamine_ddi_R10", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T13", "arg2_id": "Carbinoxamine_ddi_T14", "normalized": [] }, { "id": "Carbinoxamine_ddi_R11", "type": "EFFECT", "arg1_id": "Carbinoxamine_ddi_T13", "arg2_id": "Carbinoxamine_ddi_T15", "normalized": [] } ]

[ { "id": "Brimonidine_ddi__text", "type": "abstract", "text": [ "Although specific drug interaction studies have not been conducted with ALPHAGAN P, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered. Alpha-agonists, as a class, may reduce pulse and blood pressure. Caution in using concomitant drugs such as beta-blockers (ophthalmic and systemic), anti-hypertensives and/or cardiac glycosides is advised. Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine.It is not known whether the concurrent use of these agents with ALPHAGAN P in humans can lead to resulting interference with the IOP lowering effect. No data on the level of circulating catecholamines after ALPHAGAN P administration are available. Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines." ], "offsets": [ [ 0, 933 ] ] } ]

[ { "id": "Brimonidine_ddi_T1", "type": "BRAND", "text": [ "ALPHAGAN P" ], "offsets": [ [ 72, 82 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T2", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 143, 158 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T3", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 160, 167 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T4", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 169, 181 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T5", "type": "GROUP", "text": [ "opiates" ], "offsets": [ [ 183, 190 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T6", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 192, 201 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T7", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 206, 217 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T8", "type": "GROUP", "text": [ "Alpha-agonists" ], "offsets": [ [ 241, 255 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T9", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 349, 362 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T10", "type": "GROUP", "text": [ "anti-hypertensives" ], "offsets": [ [ 390, 408 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T11", "type": "GROUP", "text": [ "cardiac glycosides" ], "offsets": [ [ 416, 434 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T12", "type": "GROUP", "text": [ "Tricyclic antidepressants" ], "offsets": [ [ 447, 472 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T13", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 536, 545 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T14", "type": "BRAND", "text": [ "ALPHAGAN P" ], "offsets": [ [ 610, 620 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T15", "type": "BRAND", "text": [ "ALPHAGAN P" ], "offsets": [ [ 753, 763 ] ], "normalized": [] }, { "id": "Brimonidine_ddi_T16", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 842, 867 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Brimonidine_ddi_R1", "type": "ADVISE", "arg1_id": "Brimonidine_ddi_T1", "arg2_id": "Brimonidine_ddi_T2", "normalized": [] }, { "id": "Brimonidine_ddi_R2", "type": "ADVISE", "arg1_id": "Brimonidine_ddi_T1", "arg2_id": "Brimonidine_ddi_T3", "normalized": [] }, { "id": "Brimonidine_ddi_R3", "type": "ADVISE", "arg1_id": "Brimonidine_ddi_T1", "arg2_id": "Brimonidine_ddi_T4", "normalized": [] }, { "id": "Brimonidine_ddi_R4", "type": "ADVISE", "arg1_id": "Brimonidine_ddi_T1", "arg2_id": "Brimonidine_ddi_T5", "normalized": [] }, { "id": "Brimonidine_ddi_R5", "type": "ADVISE", "arg1_id": "Brimonidine_ddi_T1", "arg2_id": "Brimonidine_ddi_T6", "normalized": [] }, { "id": "Brimonidine_ddi_R6", "type": "ADVISE", "arg1_id": "Brimonidine_ddi_T1", "arg2_id": "Brimonidine_ddi_T7", "normalized": [] }, { "id": "Brimonidine_ddi_R7", "type": "EFFECT", "arg1_id": "Brimonidine_ddi_T12", "arg2_id": "Brimonidine_ddi_T13", "normalized": [] } ]

[ { "id": "Lisdexamfetamine_ddi__text", "type": "abstract", "text": [ "Urinary acidifying agents These agents (ammonium chloride, sodium acid phosphate, etc.) increase the concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines. Adrenergic blockers Adrenergic blockers are inhibited by amphetamines. Antidepressants, tricyclic Amphetamines may enhance the activity of tricyclic antidepressants or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. MAO inhibitors MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Antihistamines: Amphetamines may counteract the sedative effect of antihistamines. Antihypertensives: Amphetamines may antagonize the hypotensive effects of antihypertensives. Chlorpromazine: Chlorpromazine blocks dopamine and norepinephrine receptors, thus inhibiting the central stimulant effects of amphetamines and can be used to treat amphetamine poisoning. Ethosuximide: Amphetamines may delay intestinal absorption of ethosuximide. Haloperidol: Haloperidol blocks dopamine receptors, thus inhibiting the central stimulant effects of amphetamines. Lithium carbonate: The anorectic and stimulatory effects of amphetamines may be inhibited by lithium carbonate. Meperidine: Amphetamines potentiate the analgesic effect of meperidine. Methenamine therapy Urinary excretion of amphetamines is increased, and efficacy is reduced by acidifying agents used in methenamine therapy. Norepinephrine: Amphetamines enhance the adrenergic effect of norepinephrine. Phenobarbital: Amphetamines may delay intestinal absorption of phenobarbital; co-administration of phenobarbital may produce a synergistic anticonvulsant action. Phenytoin: Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action. Propoxyphene: In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur. Veratrum alkaloids: Amphetamines inhibit the hypotensive effect of veratrum alkaloids. Drug/Laboratory Test Interactions: Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations." ], "offsets": [ [ 0, 2812 ] ] } ]

[ { "id": "Lisdexamfetamine_ddi_T1", "type": "DRUG", "text": [ "ammonium chloride" ], "offsets": [ [ 40, 57 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T2", "type": "DRUG", "text": [ "sodium acid phosphate" ], "offsets": [ [ 59, 80 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T3", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 145, 156 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T4", "type": "GROUP", "text": [ "amphetamines" ], "offsets": [ [ 262, 274 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T5", "type": "GROUP", "text": [ "Adrenergic blockers" ], "offsets": [ [ 276, 295 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T6", "type": "GROUP", "text": [ "Adrenergic blockers" ], "offsets": [ [ 296, 315 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T7", "type": "GROUP", "text": [ "amphetamines" ], "offsets": [ [ 333, 345 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T8", "type": "GROUP", "text": [ "Antidepressants" ], "offsets": [ [ 347, 362 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T9", "type": "GROUP", "text": [ "tricyclic" ], "offsets": [ [ 364, 373 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T10", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 374, 386 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T11", "type": "DRUG", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 415, 440 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T12", "type": "GROUP", "text": [ "sympathomimetic agents" ], "offsets": [ [ 444, 466 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T13", "type": "DRUG", "text": [ "d-amphetamine" ], "offsets": [ [ 468, 481 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T14", "type": "DRUG", "text": [ "desipramine" ], "offsets": [ [ 487, 498 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T15", "type": "DRUG", "text": [ "protriptyline" ], "offsets": [ [ 502, 515 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T16", "type": "GROUP", "text": [ "tricyclics" ], "offsets": [ [ 535, 545 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T17", "type": "DRUG", "text": [ "d-amphetamine" ], "offsets": [ [ 609, 622 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T18", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 680, 694 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T19", "type": "GROUP", "text": [ "MAOI antidepressants" ], "offsets": [ [ 695, 715 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T20", "type": "DRUG", "text": [ "furazolidone" ], "offsets": [ [ 744, 756 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T21", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 763, 774 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T22", "type": "GROUP", "text": [ "amphetamines" ], "offsets": [ [ 812, 824 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T23", "type": "GROUP", "text": [ "Antihistamines" ], "offsets": [ [ 1108, 1122 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T24", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 1124, 1136 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T25", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 1175, 1189 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T26", "type": "GROUP", "text": [ "Antihypertensives" ], "offsets": [ [ 1191, 1208 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T27", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 1210, 1222 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T28", "type": "DRUG", "text": [ "antihypertensives" ], "offsets": [ [ 1265, 1282 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T29", "type": "DRUG", "text": [ "Chlorpromazine" ], "offsets": [ [ 1284, 1298 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T30", "type": "DRUG", "text": [ "Chlorpromazine" ], "offsets": [ [ 1300, 1314 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T31", "type": "GROUP", "text": [ "amphetamines" ], "offsets": [ [ 1410, 1422 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T32", "type": "GROUP", "text": [ "amphetamine" ], "offsets": [ [ 1448, 1459 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T33", "type": "DRUG", "text": [ "Ethosuximide" ], "offsets": [ [ 1471, 1483 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T34", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 1485, 1497 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T35", "type": "DRUG", "text": [ "ethosuximide" ], "offsets": [ [ 1533, 1545 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T36", "type": "DRUG", "text": [ "Haloperidol" ], "offsets": [ [ 1547, 1558 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T37", "type": "DRUG", "text": [ "Haloperidol" ], "offsets": [ [ 1560, 1571 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T38", "type": "GROUP", "text": [ "amphetamines" ], "offsets": [ [ 1648, 1660 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T39", "type": "DRUG", "text": [ "Lithium carbonate" ], "offsets": [ [ 1662, 1679 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T40", "type": "GROUP", "text": [ "amphetamines" ], "offsets": [ [ 1722, 1734 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T41", "type": "DRUG", "text": [ "lithium carbonate" ], "offsets": [ [ 1755, 1772 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T42", "type": "DRUG", "text": [ "Meperidine" ], "offsets": [ [ 1774, 1784 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T43", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 1786, 1798 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T44", "type": "DRUG", "text": [ "meperidine" ], "offsets": [ [ 1834, 1844 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T45", "type": "DRUG", "text": [ "Methenamine" ], "offsets": [ [ 1846, 1857 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T46", "type": "GROUP", "text": [ "amphetamines" ], "offsets": [ [ 1887, 1899 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T47", "type": "DRUG", "text": [ "methenamine" ], "offsets": [ [ 1967, 1978 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T48", "type": "DRUG", "text": [ "Norepinephrine" ], "offsets": [ [ 1988, 2002 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T49", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 2004, 2016 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T50", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 2050, 2064 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T51", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 2066, 2079 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T52", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 2081, 2093 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T53", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 2129, 2142 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T54", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 2165, 2178 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T55", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 2228, 2237 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T56", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 2239, 2251 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T57", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2287, 2296 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T58", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2319, 2328 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T59", "type": "DRUG", "text": [ "Propoxyphene" ], "offsets": [ [ 2378, 2390 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T60", "type": "DRUG", "text": [ "propoxyphene" ], "offsets": [ [ 2404, 2416 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T61", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 2429, 2440 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T62", "type": "GROUP", "text": [ "Veratrum alkaloids" ], "offsets": [ [ 2505, 2523 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T63", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 2525, 2537 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T64", "type": "GROUP", "text": [ "veratrum alkaloids" ], "offsets": [ [ 2572, 2590 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T65", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 2627, 2639 ] ], "normalized": [] }, { "id": "Lisdexamfetamine_ddi_T66", "type": "GROUP", "text": [ "Amphetamines" ], "offsets": [ [ 2749, 2761 ] ], "normalized": [] } ]

[]

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[ { "id": "Lisdexamfetamine_ddi_R1", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T1", "arg2_id": "Lisdexamfetamine_ddi_T3", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R2", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T2", "arg2_id": "Lisdexamfetamine_ddi_T3", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R3", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T6", "arg2_id": "Lisdexamfetamine_ddi_T7", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R4", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T10", "arg2_id": "Lisdexamfetamine_ddi_T11", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R5", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T10", "arg2_id": "Lisdexamfetamine_ddi_T12", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R6", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T13", "arg2_id": "Lisdexamfetamine_ddi_T14", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R7", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T13", "arg2_id": "Lisdexamfetamine_ddi_T15", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R8", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T13", "arg2_id": "Lisdexamfetamine_ddi_T16", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R9", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T19", "arg2_id": "Lisdexamfetamine_ddi_T21", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R10", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T20", "arg2_id": "Lisdexamfetamine_ddi_T21", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R11", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T24", "arg2_id": "Lisdexamfetamine_ddi_T25", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R12", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T27", "arg2_id": "Lisdexamfetamine_ddi_T28", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R13", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T30", "arg2_id": "Lisdexamfetamine_ddi_T31", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R14", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T34", "arg2_id": "Lisdexamfetamine_ddi_T35", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R15", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T37", "arg2_id": "Lisdexamfetamine_ddi_T38", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R16", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T40", "arg2_id": "Lisdexamfetamine_ddi_T41", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R17", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T43", "arg2_id": "Lisdexamfetamine_ddi_T44", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R18", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T46", "arg2_id": "Lisdexamfetamine_ddi_T47", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R19", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T49", "arg2_id": "Lisdexamfetamine_ddi_T50", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R20", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T52", "arg2_id": "Lisdexamfetamine_ddi_T53", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R21", "type": "MECHANISM", "arg1_id": "Lisdexamfetamine_ddi_T56", "arg2_id": "Lisdexamfetamine_ddi_T57", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R22", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T60", "arg2_id": "Lisdexamfetamine_ddi_T61", "normalized": [] }, { "id": "Lisdexamfetamine_ddi_R23", "type": "EFFECT", "arg1_id": "Lisdexamfetamine_ddi_T63", "arg2_id": "Lisdexamfetamine_ddi_T64", "normalized": [] } ]

[ { "id": "Dicyclomine_ddi__text", "type": "abstract", "text": [ "The following agents may increase certain actions or side effects of anticholinergic drugs. amantadine antiarrhythmic agents of class (e.g. quinidine), antihistamines antipsychotic agents (e.g. phenothiazines), benzodiazepines. MAO inhibitors, narcotic analgesics (e.g., meperidine), nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants, and other drugs having anticholinergic activity. Anticholinergics antagonize the effects of antiglaucoma agents. Anticholinergic drugs in the presence of increased intraocular pressure may be hazardous when taken concurrently with agents such as corti costeroids.. Anticholinergic agents may affect gastrointestinal absorption of various drugs, such as slowly dissolving dosage forms of digoxin; increased serum digoxin concentrations may result. Anticholinergic drugs may antagonize the effects of the drugs that alter gastrointestinal motility, such as metoclopramide. Because antacids may interfere with the absorption of anticholinergic agents, simultaneous use of these drugs should be avoided. The inhibiting effects of anticholinergic drugs on gastric hydrochloric acid secretion are antagonized by agents used to treat achlorhydria and those used to test gastric secretion." ], "offsets": [ [ 0, 1239 ] ] } ]

[ { "id": "Dicyclomine_ddi_T1", "type": "GROUP", "text": [ "anticholinergic drugs" ], "offsets": [ [ 69, 90 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T2", "type": "DRUG", "text": [ "amantadine" ], "offsets": [ [ 92, 102 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T3", "type": "GROUP", "text": [ "antiarrhythmic agents" ], "offsets": [ [ 103, 124 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T4", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 140, 149 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T5", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 152, 166 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T6", "type": "GROUP", "text": [ "antipsychotic agents" ], "offsets": [ [ 167, 187 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T7", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 194, 208 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T8", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 211, 226 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T9", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 228, 242 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T10", "type": "GROUP", "text": [ "narcotic analgesics" ], "offsets": [ [ 244, 263 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T11", "type": "DRUG", "text": [ "meperidine" ], "offsets": [ [ 271, 281 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T12", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 284, 292 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T13", "type": "GROUP", "text": [ "nitrites" ], "offsets": [ [ 297, 305 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T14", "type": "GROUP", "text": [ "sympathomimetic agents" ], "offsets": [ [ 307, 329 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T15", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 331, 356 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T16", "type": "GROUP", "text": [ "Anticholinergics" ], "offsets": [ [ 407, 423 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T17", "type": "GROUP", "text": [ "antiglaucoma agents" ], "offsets": [ [ 450, 469 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T18", "type": "GROUP", "text": [ "Anticholinergic drugs" ], "offsets": [ [ 471, 492 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T19", "type": "GROUP", "text": [ "Anticholinergic agents" ], "offsets": [ [ 623, 645 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T20", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 745, 752 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T21", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 770, 777 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T22", "type": "GROUP", "text": [ "Anticholinergic drugs" ], "offsets": [ [ 805, 826 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T23", "type": "DRUG", "text": [ "metoclopramide" ], "offsets": [ [ 913, 927 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T24", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 937, 945 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T25", "type": "GROUP", "text": [ "anticholinergic agents" ], "offsets": [ [ 983, 1005 ] ], "normalized": [] }, { "id": "Dicyclomine_ddi_T26", "type": "GROUP", "text": [ "anticholinergic drugs" ], "offsets": [ [ 1084, 1105 ] ], "normalized": [] } ]

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[ { "id": "Dicyclomine_ddi_R1", "type": "MECHANISM", "arg1_id": "Dicyclomine_ddi_T19", "arg2_id": "Dicyclomine_ddi_T20", "normalized": [] }, { "id": "Dicyclomine_ddi_R2", "type": "MECHANISM", "arg1_id": "Dicyclomine_ddi_T22", "arg2_id": "Dicyclomine_ddi_T23", "normalized": [] }, { "id": "Dicyclomine_ddi_R3", "type": "MECHANISM", "arg1_id": "Dicyclomine_ddi_T24", "arg2_id": "Dicyclomine_ddi_T25", "normalized": [] } ]

[ { "id": "Brompheniramine_ddi__text", "type": "abstract", "text": [ "Dexbrompheniramine can interact with alcohol or other CNS depressants (may potentiate the CNS depressant effects of either these medications or antihistamines), anticholinergics or other medications with anticholinergic activity (anticholinergic effects may be potentiated when these medications are used concurrently with antihistamines), and monoamine oxidase (MAO) inhibitors (concurrent use with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines)." ], "offsets": [ [ 0, 507 ] ] } ]

[ { "id": "Brompheniramine_ddi_T1", "type": "DRUG", "text": [ "Dexbrompheniramine" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "Brompheniramine_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 37, 44 ] ], "normalized": [] }, { "id": "Brompheniramine_ddi_T3", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 54, 69 ] ], "normalized": [] }, { "id": "Brompheniramine_ddi_T4", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 144, 158 ] ], "normalized": [] }, { "id": "Brompheniramine_ddi_T5", "type": "GROUP", "text": [ "anticholinergics" ], "offsets": [ [ 161, 177 ] ], "normalized": [] }, { "id": "Brompheniramine_ddi_T6", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 323, 337 ] ], "normalized": [] }, { "id": "Brompheniramine_ddi_T7", "type": "GROUP", "text": [ "monoamine oxidase (MAO) inhibitors" ], "offsets": [ [ 344, 378 ] ], "normalized": [] }, { "id": "Brompheniramine_ddi_T8", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 400, 414 ] ], "normalized": [] }, { "id": "Brompheniramine_ddi_T9", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 491, 505 ] ], "normalized": [] } ]

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[ { "id": "Brompheniramine_ddi_R1", "type": "EFFECT", "arg1_id": "Brompheniramine_ddi_T1", "arg2_id": "Brompheniramine_ddi_T2", "normalized": [] }, { "id": "Brompheniramine_ddi_R2", "type": "EFFECT", "arg1_id": "Brompheniramine_ddi_T1", "arg2_id": "Brompheniramine_ddi_T3", "normalized": [] }, { "id": "Brompheniramine_ddi_R3", "type": "EFFECT", "arg1_id": "Brompheniramine_ddi_T1", "arg2_id": "Brompheniramine_ddi_T5", "normalized": [] }, { "id": "Brompheniramine_ddi_R4", "type": "EFFECT", "arg1_id": "Brompheniramine_ddi_T1", "arg2_id": "Brompheniramine_ddi_T7", "normalized": [] } ]

[ { "id": "Betamethasone_ddi__text", "type": "abstract", "text": [ "APRD00513_IN,txt" ], "offsets": [ [ 0, 16 ] ] } ]

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[ { "id": "Epinastine_ddi__text", "type": "abstract", "text": [ "None Reported" ], "offsets": [ [ 0, 13 ] ] } ]

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[ { "id": "Enflurane_ddi__text", "type": "abstract", "text": [ "The action of nondepolarizing relaxants is augmented by Enflurane. Less than the usual amounts of these medicines should be used. If the usual amounts of nondepolarizing relaxants are given, the time for recovery from neuromuscular blockade will be longer in the presence of Enflurane than when halothane or nitrous oxide with a balanced technique are used." ], "offsets": [ [ 0, 357 ] ] } ]

[ { "id": "Enflurane_ddi_T1", "type": "DRUG", "text": [ "Enflurane" ], "offsets": [ [ 56, 65 ] ], "normalized": [] }, { "id": "Enflurane_ddi_T2", "type": "DRUG", "text": [ "Enflurane" ], "offsets": [ [ 275, 284 ] ], "normalized": [] }, { "id": "Enflurane_ddi_T3", "type": "DRUG", "text": [ "halothane" ], "offsets": [ [ 295, 304 ] ], "normalized": [] }, { "id": "Enflurane_ddi_T4", "type": "DRUG", "text": [ "nitrous oxide" ], "offsets": [ [ 308, 321 ] ], "normalized": [] } ]

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[ { "id": "Loxapine_ddi__text", "type": "abstract", "text": [ "There have been rare reports of significant respiratory depression, stupor and/or hypotension with the concomitant use of loxapine and lorazepam. The risk of using loxapine in combination with CNS-active drugs has not been systematically evaluated. Therefore, caution is advised if the concomitant administration of loxapine and CNS-active drugs is required." ], "offsets": [ [ 0, 358 ] ] } ]

[ { "id": "Loxapine_ddi_T1", "type": "DRUG", "text": [ "loxapine" ], "offsets": [ [ 122, 130 ] ], "normalized": [] }, { "id": "Loxapine_ddi_T2", "type": "DRUG", "text": [ "lorazepam" ], "offsets": [ [ 135, 144 ] ], "normalized": [] }, { "id": "Loxapine_ddi_T3", "type": "DRUG", "text": [ "loxapine" ], "offsets": [ [ 164, 172 ] ], "normalized": [] }, { "id": "Loxapine_ddi_T4", "type": "DRUG", "text": [ "loxapine" ], "offsets": [ [ 316, 324 ] ], "normalized": [] } ]

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[ { "id": "Loxapine_ddi_R1", "type": "EFFECT", "arg1_id": "Loxapine_ddi_T1", "arg2_id": "Loxapine_ddi_T2", "normalized": [] } ]

[ { "id": "Demeclocycline_ddi__text", "type": "abstract", "text": [ "Because the 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, such as the tetracycline class of antibiotics, may interfere with the bactericidal action of penicillins, it is not advisable to administer these drugs concomitantly. Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective. Breakthrough bleeding has been reported" ], "offsets": [ [ 0, 525 ] ] } ]

[ { "id": "Demeclocycline_ddi_T1", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 12, 25 ] ], "normalized": [] }, { "id": "Demeclocycline_ddi_T2", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 102, 115 ] ], "normalized": [] }, { "id": "Demeclocycline_ddi_T3", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 165, 178 ] ], "normalized": [] }, { "id": "Demeclocycline_ddi_T4", "type": "GROUP", "text": [ "tetracycline class" ], "offsets": [ [ 227, 245 ] ], "normalized": [] }, { "id": "Demeclocycline_ddi_T5", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 249, 260 ] ], "normalized": [] }, { "id": "Demeclocycline_ddi_T6", "type": "GROUP", "text": [ "penicillins" ], "offsets": [ [ 308, 319 ] ], "normalized": [] }, { "id": "Demeclocycline_ddi_T7", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 400, 413 ] ], "normalized": [] }, { "id": "Demeclocycline_ddi_T8", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 424, 438 ] ], "normalized": [] }, { "id": "Demeclocycline_ddi_T9", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 455, 469 ] ], "normalized": [] } ]

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[ { "id": "Demeclocycline_ddi_R1", "type": "ADVISE", "arg1_id": "Demeclocycline_ddi_T1", "arg2_id": "Demeclocycline_ddi_T2", "normalized": [] }, { "id": "Demeclocycline_ddi_R2", "type": "EFFECT", "arg1_id": "Demeclocycline_ddi_T4", "arg2_id": "Demeclocycline_ddi_T6", "normalized": [] }, { "id": "Demeclocycline_ddi_R3", "type": "EFFECT", "arg1_id": "Demeclocycline_ddi_T7", "arg2_id": "Demeclocycline_ddi_T8", "normalized": [] } ]

[ { "id": "Levothyroxine_ddi__text", "type": "abstract", "text": [ "The magnitude and relative importance of the effects noted below are likely to be patient specific and may vary by such factors as age, gender, race, intercurrent illnesses, dose of either agent, additional concomitant medications, and timing of drug administration. Any agent that alters thyroid hormone synthesis, secretion, distribution, effect on target tissues, metabolism, or elimination may alter the optimal therapeutic dose of levothyroxine sodium. Levothyroxine Sodium Absorption: The following agents may bind and decrease absorption of levothyroxine sodium from the gastrointestinal tract: aluminum hydoxide, cholestyramine resin, colestipol hydrochloride, ferrous sulfate, sodium polystyrene sulfonate, soybean flour (e.g., infant formula), sucralfate. Binding to Serum Proteins: The following agents may either inhibit levothyroxine sodium binding to serum proteins or alter the concentrations of serum binding proteins: androgens and related anabolic hormones, asparaginase, clofibrate, estrogens and estrogen-containing compounds, 5-fluorouracil, furosemide, glucocorticoids, meclofenamic acid, mefenamic acid, methadone, perphenazine, phenylbutazone, phenytoin, salicylates, tamoxifen. Thyroid Physiology: The following agents may alter thyroid hormone or TSH levels, generally by effects on thyroid hormone synthesis, secretion, distribution, metabolism, hormone action, or elimination, or altered TSH secretion: aminoglutethimide, p-aminosalicylic acid, amiodarone, androgens and related anabolic hormones, complex anions (thiocyanate, perchlorate, pertechnetate), antithyroid drugs, b-adrenergic blocking agents, carbamazepine, chloral hydrate, diazepam, dopamine and dopamine agonists, ethionamide, glucocorticoids, heparin, hepatic enzyme inducers, insulin, iodinated cholestographic agents, iodine-containing compounds, levodopa, lovastatin, lithium, 6-mercaptopurine, metoclopramide, mitotane, nitroprusside, phenobarbital, phenytoin, resorcinol, rifampin, somatostatin analogs, sulfonamides, sulfonylureas, thiazide diuretics. Adrenocorticoids: Metabolic clearance of adrenocorticoids is decreased in hypothyroid patients and increased in hyperthyroid patients, and may therefore change with changing thyroid status. Amiodarone: Amiodarone therapy alone can cause hypothyroidism or hyperthyroidism. Anticoagulants (Oral): The hypoprothrombinemic effect of anticoagulants may be potentiated, apparently by increased catabloism of vitamin K-dependent clotting factors. Antidiabetic Agents (Insulin, Sulfonylureas): Requirements for insulin or oral antidiabetic agents may be reduced in hypothyroid patients with diabetes mellitus and may subsequently increase with the initiation of thyroid hormone replacement therapy. b-Adrenergic Blocking Agents: Actions of some of beta-blocking agents may be impaired when hypothyroid patients become euthyroid. Cytokines (interferon, interleukin): Cytokines have been reported to induce both hyperthyroidism and hypothyroidism. Digitalis Glycosides: Therapeutic effects of digitalis glycosides may be reduced. Serum digitalis levels may be decreased in hyperthyroidism or when a hypothyroid patient becomes euthyroid. Ketamine: Marked hypertension and tachycardia have been reported in association with concomitant administration of levothyroxine sodium and ketamine. Maprotiline: Risk of cardiac arrhythmias may increase. Sodium Iodide (123I and 131I), Sodium Pertechnetate Tc99m: Uptake of radiolabeled ions may be decreased. Somatrem/Somatropin: Excessive concurrent use of thyroid hormone may accelerate epiphyseal closure. Untreated hypothyroidism may interfere with the growth response to somatrem or somatropin. Theophylline: Theophylline clearance may decrease in hypothyroid patients and return toward normal when a euthyroid state is achieved. Tricyclic Antidepressants: Concurrent use may increase the therapeutic and toxic effects of both drugs, possibly due to increased catecholamine sensitivity. Onset of action of tricyclics may be accelerated. Sympathomimetic Agents: Possible increased risk of coronary insufficiency in patients with coronary artery disease." ], "offsets": [ [ 0, 4138 ] ] } ]

[ { "id": "Levothyroxine_ddi_T1", "type": "DRUG", "text": [ "levothyroxine" ], "offsets": [ [ 436, 449 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T2", "type": "DRUG", "text": [ "Levothyroxine Sodium" ], "offsets": [ [ 458, 478 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T3", "type": "DRUG", "text": [ "levothyroxine sodium" ], "offsets": [ [ 548, 568 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T4", "type": "DRUG", "text": [ "aluminum hydoxide" ], "offsets": [ [ 602, 619 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T5", "type": "DRUG", "text": [ "cholestyramine" ], "offsets": [ [ 621, 635 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T6", "type": "DRUG", "text": [ "colestipol hydrochloride" ], "offsets": [ [ 643, 667 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T7", "type": "DRUG", "text": [ "ferrous sulfate" ], "offsets": [ [ 669, 684 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T8", "type": "DRUG", "text": [ "sodium polystyrene sulfonate" ], "offsets": [ [ 686, 714 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T9", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 754, 764 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T10", "type": "DRUG", "text": [ "levothyroxine sodium" ], "offsets": [ [ 833, 853 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T11", "type": "GROUP", "text": [ "androgens" ], "offsets": [ [ 935, 944 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T12", "type": "GROUP", "text": [ "anabolic hormones" ], "offsets": [ [ 957, 974 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T13", "type": "DRUG", "text": [ "asparaginase" ], "offsets": [ [ 976, 988 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T14", "type": "DRUG", "text": [ "clofibrate" ], "offsets": [ [ 990, 1000 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T15", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 1002, 1011 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T16", "type": "GROUP", "text": [ "estrogen-containing compounds" ], "offsets": [ [ 1016, 1045 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T17", "type": "DRUG", "text": [ "5-fluorouracil" ], "offsets": [ [ 1047, 1061 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T18", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1063, 1073 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T19", "type": "GROUP", "text": [ "glucocorticoids" ], "offsets": [ [ 1075, 1090 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T20", "type": "DRUG", "text": [ "meclofenamic acid" ], "offsets": [ [ 1092, 1109 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T21", "type": "DRUG", "text": [ "mefenamic acid" ], "offsets": [ [ 1111, 1125 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T22", "type": "DRUG", "text": [ "methadone" ], "offsets": [ [ 1127, 1136 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T23", "type": "DRUG", "text": [ "perphenazine" ], "offsets": [ [ 1138, 1150 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T24", "type": "DRUG", "text": [ "phenylbutazone" ], "offsets": [ [ 1152, 1166 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T25", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1168, 1177 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T26", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 1179, 1190 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T27", "type": "DRUG", "text": [ "tamoxifen" ], "offsets": [ [ 1192, 1201 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T28", "type": "DRUG", "text": [ "aminoglutethimide" ], "offsets": [ [ 1431, 1448 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T29", "type": "DRUG", "text": [ "p-aminosalicylic acid" ], "offsets": [ [ 1450, 1471 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T30", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 1473, 1483 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T31", "type": "GROUP", "text": [ "androgens" ], "offsets": [ [ 1485, 1494 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T32", "type": "DRUG", "text": [ "thiocyanate" ], "offsets": [ [ 1542, 1553 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T33", "type": "DRUG", "text": [ "perchlorate" ], "offsets": [ [ 1555, 1566 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T34", "type": "DRUG", "text": [ "pertechnetate" ], "offsets": [ [ 1568, 1581 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T35", "type": "GROUP", "text": [ "antithyroid drugs" ], "offsets": [ [ 1584, 1601 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T36", "type": "GROUP", "text": [ "b-adrenergic blocking agents" ], "offsets": [ [ 1603, 1631 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T37", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1633, 1646 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T38", "type": "DRUG", "text": [ "chloral hydrate" ], "offsets": [ [ 1648, 1663 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T39", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 1665, 1673 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T40", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 1675, 1683 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T41", "type": "GROUP", "text": [ "dopamine agonists" ], "offsets": [ [ 1688, 1705 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T42", "type": "DRUG", "text": [ "ethionamide" ], "offsets": [ [ 1707, 1718 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T43", "type": "GROUP", "text": [ "glucocorticoids" ], "offsets": [ [ 1720, 1735 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T44", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 1737, 1744 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T45", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 1771, 1778 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T46", "type": "GROUP", "text": [ "iodine-containing compounds" ], "offsets": [ [ 1814, 1841 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T47", "type": "DRUG", "text": [ "levodopa" ], "offsets": [ [ 1843, 1851 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T48", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 1853, 1863 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T49", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1865, 1872 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T50", "type": "DRUG", "text": [ "6-mercaptopurine" ], "offsets": [ [ 1874, 1890 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T51", "type": "DRUG", "text": [ "metoclopramide" ], "offsets": [ [ 1892, 1906 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T52", "type": "DRUG", "text": [ "mitotane" ], "offsets": [ [ 1908, 1916 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T53", "type": "DRUG", "text": [ "nitroprusside" ], "offsets": [ [ 1918, 1931 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T54", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1933, 1946 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T55", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1948, 1957 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T56", "type": "DRUG", "text": [ "resorcinol" ], "offsets": [ [ 1959, 1969 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T57", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1971, 1979 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T58", "type": "GROUP", "text": [ "somatostatin analogs" ], "offsets": [ [ 1981, 2001 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T59", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 2003, 2015 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T60", "type": "GROUP", "text": [ "sulfonylureas" ], "offsets": [ [ 2017, 2030 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T61", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 2032, 2050 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T62", "type": "DRUG", "text": [ "Amiodarone" ], "offsets": [ [ 2242, 2252 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T63", "type": "DRUG", "text": [ "Amiodarone" ], "offsets": [ [ 2254, 2264 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T64", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 2324, 2338 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T65", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 2381, 2395 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T66", "type": "GROUP", "text": [ "Antidiabetic Agents" ], "offsets": [ [ 2492, 2511 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T67", "type": "DRUG", "text": [ "Insulin" ], "offsets": [ [ 2513, 2520 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T68", "type": "GROUP", "text": [ "Sulfonylureas" ], "offsets": [ [ 2522, 2535 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T69", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 2555, 2562 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T70", "type": "GROUP", "text": [ "antidiabetic agents" ], "offsets": [ [ 2571, 2590 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T71", "type": "GROUP", "text": [ "b-Adrenergic Blocking Agents" ], "offsets": [ [ 2743, 2771 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T72", "type": "GROUP", "text": [ "beta-blocking agents" ], "offsets": [ [ 2792, 2812 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T73", "type": "GROUP", "text": [ "Cytokines" ], "offsets": [ [ 2873, 2882 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T74", "type": "GROUP", "text": [ "interferon" ], "offsets": [ [ 2884, 2894 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T75", "type": "GROUP", "text": [ "interleukin" ], "offsets": [ [ 2896, 2907 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T76", "type": "GROUP", "text": [ "Cytokines" ], "offsets": [ [ 2910, 2919 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T77", "type": "GROUP", "text": [ "Digitalis Glycosides" ], "offsets": [ [ 2990, 3010 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T78", "type": "GROUP", "text": [ "digitalis glycosides" ], "offsets": [ [ 3035, 3055 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T79", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 3078, 3087 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T80", "type": "DRUG", "text": [ "Ketamine" ], "offsets": [ [ 3180, 3188 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T81", "type": "DRUG", "text": [ "levothyroxine sodium" ], "offsets": [ [ 3295, 3315 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T82", "type": "DRUG", "text": [ "ketamine" ], "offsets": [ [ 3320, 3328 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T83", "type": "DRUG", "text": [ "Maprotiline" ], "offsets": [ [ 3330, 3341 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T84", "type": "DRUG", "text": [ "Sodium Iodide" ], "offsets": [ [ 3385, 3398 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T85", "type": "DRUG", "text": [ "Sodium Pertechnetate Tc99m" ], "offsets": [ [ 3416, 3442 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T86", "type": "DRUG", "text": [ "Somatrem" ], "offsets": [ [ 3490, 3498 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T87", "type": "DRUG", "text": [ "Somatropin" ], "offsets": [ [ 3499, 3509 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T88", "type": "GROUP", "text": [ "thyroid hormone" ], "offsets": [ [ 3539, 3554 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T89", "type": "DRUG", "text": [ "somatrem" ], "offsets": [ [ 3657, 3665 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T90", "type": "DRUG", "text": [ "somatropin" ], "offsets": [ [ 3669, 3679 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T91", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 3681, 3693 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T92", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 3695, 3707 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T93", "type": "GROUP", "text": [ "Tricyclic Antidepressants" ], "offsets": [ [ 3816, 3841 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T94", "type": "GROUP", "text": [ "tricyclics" ], "offsets": [ [ 3992, 4002 ] ], "normalized": [] }, { "id": "Levothyroxine_ddi_T95", "type": "GROUP", "text": [ "Sympathomimetic Agents" ], "offsets": [ [ 4023, 4045 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Levothyroxine_ddi_R1", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T3", "arg2_id": "Levothyroxine_ddi_T4", "normalized": [] }, { "id": "Levothyroxine_ddi_R2", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T3", "arg2_id": "Levothyroxine_ddi_T5", "normalized": [] }, { "id": "Levothyroxine_ddi_R3", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T3", "arg2_id": "Levothyroxine_ddi_T6", "normalized": [] }, { "id": "Levothyroxine_ddi_R4", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T3", "arg2_id": "Levothyroxine_ddi_T7", "normalized": [] }, { "id": "Levothyroxine_ddi_R5", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T3", "arg2_id": "Levothyroxine_ddi_T8", "normalized": [] }, { "id": "Levothyroxine_ddi_R6", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T3", "arg2_id": "Levothyroxine_ddi_T9", "normalized": [] }, { "id": "Levothyroxine_ddi_R7", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T11", "normalized": [] }, { "id": "Levothyroxine_ddi_R8", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T12", "normalized": [] }, { "id": "Levothyroxine_ddi_R9", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T13", "normalized": [] }, { "id": "Levothyroxine_ddi_R10", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T14", "normalized": [] }, { "id": "Levothyroxine_ddi_R11", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T15", "normalized": [] }, { "id": "Levothyroxine_ddi_R12", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T16", "normalized": [] }, { "id": "Levothyroxine_ddi_R13", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T17", "normalized": [] }, { "id": "Levothyroxine_ddi_R14", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T18", "normalized": [] }, { "id": "Levothyroxine_ddi_R15", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T19", "normalized": [] }, { "id": "Levothyroxine_ddi_R16", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T20", "normalized": [] }, { "id": "Levothyroxine_ddi_R17", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T21", "normalized": [] }, { "id": "Levothyroxine_ddi_R18", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T22", "normalized": [] }, { "id": "Levothyroxine_ddi_R19", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T23", "normalized": [] }, { "id": "Levothyroxine_ddi_R20", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T24", "normalized": [] }, { "id": "Levothyroxine_ddi_R21", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T25", "normalized": [] }, { "id": "Levothyroxine_ddi_R22", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T26", "normalized": [] }, { "id": "Levothyroxine_ddi_R23", "type": "MECHANISM", "arg1_id": "Levothyroxine_ddi_T10", "arg2_id": "Levothyroxine_ddi_T27", "normalized": [] }, { "id": "Levothyroxine_ddi_R24", "type": "EFFECT", "arg1_id": "Levothyroxine_ddi_T81", "arg2_id": "Levothyroxine_ddi_T82", "normalized": [] } ]

[ { "id": "Benztropine_ddi__text", "type": "abstract", "text": [ "Antipsychotic drugs such as phenothiazines or haloperidol; tricyclic antidepressants." ], "offsets": [ [ 0, 85 ] ] } ]

[ { "id": "Benztropine_ddi_T1", "type": "GROUP", "text": [ "Antipsychotic drugs" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "Benztropine_ddi_T2", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 28, 42 ] ], "normalized": [] }, { "id": "Benztropine_ddi_T3", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 46, 57 ] ], "normalized": [] }, { "id": "Benztropine_ddi_T4", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 59, 84 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Brinzolamide_ddi__text", "type": "abstract", "text": [ "AZOPT (brinzolamide ophthalmic suspension) 1% contains a carbonic anhydrase inhibitor. Acid-base and electrolyte alterations were not reported in the clinical trials with brinzolamide. However, in patients treated with oral carbonic anhydrase inhibitors, rare instances of drug interactions have occurred with high-dose salicylate therapy. Therefore, the potential for such drug interaction should be considered in patients receiving AZOPT (brinzolamide ophthalmic suspension) 1%." ], "offsets": [ [ 0, 480 ] ] } ]

[ { "id": "Brinzolamide_ddi_T1", "type": "BRAND", "text": [ "AZOPT" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "Brinzolamide_ddi_T2", "type": "DRUG", "text": [ "brinzolamide" ], "offsets": [ [ 7, 19 ] ], "normalized": [] }, { "id": "Brinzolamide_ddi_T3", "type": "GROUP", "text": [ "carbonic anhydrase inhibitor" ], "offsets": [ [ 57, 85 ] ], "normalized": [] }, { "id": "Brinzolamide_ddi_T4", "type": "DRUG", "text": [ "brinzolamide" ], "offsets": [ [ 171, 183 ] ], "normalized": [] }, { "id": "Brinzolamide_ddi_T5", "type": "GROUP", "text": [ "carbonic anhydrase inhibitors" ], "offsets": [ [ 224, 253 ] ], "normalized": [] }, { "id": "Brinzolamide_ddi_T6", "type": "DRUG", "text": [ "salicylate" ], "offsets": [ [ 320, 330 ] ], "normalized": [] }, { "id": "Brinzolamide_ddi_T7", "type": "BRAND", "text": [ "AZOPT" ], "offsets": [ [ 434, 439 ] ], "normalized": [] }, { "id": "Brinzolamide_ddi_T8", "type": "DRUG", "text": [ "brinzolamide" ], "offsets": [ [ 441, 453 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Brinzolamide_ddi_R1", "type": "INT", "arg1_id": "Brinzolamide_ddi_T5", "arg2_id": "Brinzolamide_ddi_T6", "normalized": [] } ]