Datasets:

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[ { "id": "7600639__text", "type": "abstract", "text": [ "Effect of estradiol on endotoxin-induced changes in steroid hormone levels and lethality in male rats. We examined the effect of exogenous estradiol on the changes in serum steroid hormone levels induced by a nonlethal dose of Escherichia coli endotoxin in male rats and the deaths due to nonlethal and lethal doses of endotoxin. Injection of estradiol 5 min before a nonlethal dose of endotoxin changed the serum sex steroid hormone response of male rats to endotoxin. The serum estrogen concentrations of estradiol + endotoxin-treated rats decreased by 50%, while those of the endotoxin-treated rats increased (2- to 5-fold). The serum androgen concentrations of estradiol + endotoxin-treated rats did not change significantly, while those of endotoxin-treated rats dropped to 30-40% 0.001. Exogenous estradiol also appeared to influence the percentage of endotoxin-induced deaths in a dose-dependent manner. It reduced the number of deaths induced by nonlethal (2 mg/kg) dose of endotoxin but increased the number of deaths induced by a highly lethal dose (8 mg/kg). These results, together with the known relationships between estrogen and the immune response, suggest that estrogens affect the course of septic shock in a complex fashion and may have either protective or deleterious effect." ], "offsets": [ [ 0, 1296 ] ] } ]

[ { "id": "7600639_T1", "type": "DRUG", "text": [ "estradiol" ], "offsets": [ [ 10, 19 ] ], "normalized": [] }, { "id": "7600639_T2", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 23, 32 ] ], "normalized": [] }, { "id": "7600639_T3", "type": "DRUG", "text": [ "estradiol" ], "offsets": [ [ 139, 148 ] ], "normalized": [] }, { "id": "7600639_T4", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 244, 253 ] ], "normalized": [] }, { "id": "7600639_T5", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 319, 328 ] ], "normalized": [] }, { "id": "7600639_T6", "type": "DRUG", "text": [ "estradiol" ], "offsets": [ [ 343, 352 ] ], "normalized": [] }, { "id": "7600639_T7", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 386, 395 ] ], "normalized": [] }, { "id": "7600639_T8", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 459, 468 ] ], "normalized": [] }, { "id": "7600639_T9", "type": "DRUG", "text": [ "estradiol" ], "offsets": [ [ 507, 516 ] ], "normalized": [] }, { "id": "7600639_T10", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 519, 528 ] ], "normalized": [] }, { "id": "7600639_T11", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 579, 588 ] ], "normalized": [] }, { "id": "7600639_T12", "type": "DRUG", "text": [ "estradiol" ], "offsets": [ [ 665, 674 ] ], "normalized": [] }, { "id": "7600639_T13", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 677, 686 ] ], "normalized": [] }, { "id": "7600639_T14", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 745, 754 ] ], "normalized": [] }, { "id": "7600639_T15", "type": "DRUG", "text": [ "estradiol" ], "offsets": [ [ 803, 812 ] ], "normalized": [] }, { "id": "7600639_T16", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 858, 867 ] ], "normalized": [] }, { "id": "7600639_T17", "type": "DRUG_N", "text": [ "endotoxin" ], "offsets": [ [ 982, 991 ] ], "normalized": [] }, { "id": "7600639_T18", "type": "GROUP", "text": [ "estrogen" ], "offsets": [ [ 1131, 1139 ] ], "normalized": [] }, { "id": "7600639_T19", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 1178, 1187 ] ], "normalized": [] } ]

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[ { "id": "7600639_R1", "type": "EFFECT", "arg1_id": "7600639_T6", "arg2_id": "7600639_T7", "normalized": [] }, { "id": "7600639_R2", "type": "MECHANISM", "arg1_id": "7600639_T9", "arg2_id": "7600639_T10", "normalized": [] }, { "id": "7600639_R3", "type": "EFFECT", "arg1_id": "7600639_T15", "arg2_id": "7600639_T16", "normalized": [] } ]

[ { "id": "1115340__text", "type": "abstract", "text": [ "Anaesthesia and the epileptic pateint. A review. A review is presented of some of the problems that may arise in association with anaesthesia for epileptic patients. There is the possibility of precipitating anticonvulsant drug toxicity. Numerous drug interactions are possible with some anticonvulsant agents, such as phenobarbitone and phenytoin, which affect hepatic microsomal enzyme systems. There is the risk of convulsions occurring in susceptible patients following the use of the new anaesthetic agents which are capable of inducing CNS excitability." ], "offsets": [ [ 0, 559 ] ] } ]

[ { "id": "1115340_T1", "type": "GROUP", "text": [ "anticonvulsant agents" ], "offsets": [ [ 288, 309 ] ], "normalized": [] }, { "id": "1115340_T2", "type": "DRUG", "text": [ "phenobarbitone" ], "offsets": [ [ 319, 333 ] ], "normalized": [] }, { "id": "1115340_T3", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 338, 347 ] ], "normalized": [] }, { "id": "1115340_T4", "type": "GROUP", "text": [ "anaesthetic agents" ], "offsets": [ [ 493, 511 ] ], "normalized": [] } ]

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[ { "id": "9120829__text", "type": "abstract", "text": [ "Acid-catalyzed ethanolysis of temazepam in anhydrous and aqueous ethanol solutions. The benzodiazepines are a family of anxiolytic and hypnotic drugs. When taken concurrently with ethanol, a pharmacological interaction may occur, potentiating the central nervous system depression produced by either drug. In addition to this pharmacological interaction, this report describes a novel chemical reaction between temazepam (a benzodiazepine) and ethanol under acidic conditions similar to those found in vivo, resulting in a 3-ethoxylated product. Optimal conditions, kinetics, equilibrium, and the mechanism of this acid-catalyzed ethanolysis are reported. The results raise the possibility that the ethanolysis reaction may occur in the stomach of people who consume alcohol and 3-hydroxy-1,4-benzodiazepine on a regular basis. The acid-catalyzed ethanol-drug reaction is a relatively unexplored area and may alter the pharmacological action of some drugs." ], "offsets": [ [ 0, 956 ] ] } ]

[ { "id": "9120829_T1", "type": "DRUG", "text": [ "temazepam" ], "offsets": [ [ 30, 39 ] ], "normalized": [] }, { "id": "9120829_T2", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 65, 72 ] ], "normalized": [] }, { "id": "9120829_T3", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 88, 103 ] ], "normalized": [] }, { "id": "9120829_T4", "type": "GROUP", "text": [ "anxiolytic" ], "offsets": [ [ 120, 130 ] ], "normalized": [] }, { "id": "9120829_T5", "type": "GROUP", "text": [ "hypnotic drugs" ], "offsets": [ [ 135, 149 ] ], "normalized": [] }, { "id": "9120829_T6", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 180, 187 ] ], "normalized": [] }, { "id": "9120829_T7", "type": "DRUG", "text": [ "temazepam" ], "offsets": [ [ 411, 420 ] ], "normalized": [] }, { "id": "9120829_T8", "type": "GROUP", "text": [ "benzodiazepine" ], "offsets": [ [ 424, 438 ] ], "normalized": [] }, { "id": "9120829_T9", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 444, 451 ] ], "normalized": [] }, { "id": "9120829_T10", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 767, 774 ] ], "normalized": [] }, { "id": "9120829_T11", "type": "GROUP", "text": [ "3-hydroxy-1,4-benzodiazepine" ], "offsets": [ [ 779, 807 ] ], "normalized": [] }, { "id": "9120829_T12", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 847, 854 ] ], "normalized": [] } ]

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[ { "id": "9120829_R1", "type": "MECHANISM", "arg1_id": "9120829_T1", "arg2_id": "9120829_T2", "normalized": [] }, { "id": "9120829_R2", "type": "MECHANISM", "arg1_id": "9120829_T7", "arg2_id": "9120829_T9", "normalized": [] }, { "id": "9120829_R3", "type": "MECHANISM", "arg1_id": "9120829_T10", "arg2_id": "9120829_T11", "normalized": [] } ]

[ { "id": "7746025__text", "type": "abstract", "text": [ "Effects of xanthine derivatives in a light/dark test in mice and the contribution of adenosine receptors. We investigated the effects of adenosine receptor antagonists, caffeine, theophylline, 8-phenyltheophylline, and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), in a light/dark test in mice. All antagonists decreased the time spent in the light zone in this test, which suggested that these compounds have anxiogenic effects. The anxiogenic effects of theophylline were reduced by pretreatment with CGS 21680, an A2-selective agonist, but not by N6-cyclopentyladenosine (CPA), an A1-selective agonist. However, the antagonism of the theophylline-induced anxiogenic effects by CGS21680 was only observed in the time spent in the light zone, and DPCPX-induced anxiogenic effects were neither reversed by CGS 21680 nor by CPA. Finally, it is notable that xanthine-derived adenosine antagonists tested here commonly showed anxiogenic effects in the light/dark test in mice. It is suggested that there is a minor contribution of adenosine receptors to these effects, although theophylline-induced anxiogenic effects were antagonized by an A2 receptor agonist." ], "offsets": [ [ 0, 1156 ] ] } ]

[ { "id": "7746025_T1", "type": "GROUP", "text": [ "xanthine derivatives" ], "offsets": [ [ 11, 31 ] ], "normalized": [] }, { "id": "7746025_T2", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 169, 177 ] ], "normalized": [] }, { "id": "7746025_T3", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 179, 191 ] ], "normalized": [] }, { "id": "7746025_T4", "type": "DRUG_N", "text": [ "8-phenyltheophylline" ], "offsets": [ [ 193, 213 ] ], "normalized": [] }, { "id": "7746025_T5", "type": "DRUG_N", "text": [ "8-cyclopentyl-1,3-dipropylxanthine" ], "offsets": [ [ 219, 253 ] ], "normalized": [] }, { "id": "7746025_T6", "type": "DRUG_N", "text": [ "DPCPX" ], "offsets": [ [ 255, 260 ] ], "normalized": [] }, { "id": "7746025_T7", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 454, 466 ] ], "normalized": [] }, { "id": "7746025_T8", "type": "DRUG_N", "text": [ "CGS 21680" ], "offsets": [ [ 501, 510 ] ], "normalized": [] }, { "id": "7746025_T9", "type": "DRUG_N", "text": [ "N6-cyclopentyladenosine" ], "offsets": [ [ 548, 571 ] ], "normalized": [] }, { "id": "7746025_T10", "type": "DRUG_N", "text": [ "CPA" ], "offsets": [ [ 573, 576 ] ], "normalized": [] }, { "id": "7746025_T11", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 635, 647 ] ], "normalized": [] }, { "id": "7746025_T12", "type": "DRUG_N", "text": [ "CGS21680" ], "offsets": [ [ 678, 686 ] ], "normalized": [] }, { "id": "7746025_T13", "type": "DRUG_N", "text": [ "DPCPX" ], "offsets": [ [ 746, 751 ] ], "normalized": [] }, { "id": "7746025_T14", "type": "DRUG", "text": [ "CGS 21680" ], "offsets": [ [ 804, 813 ] ], "normalized": [] }, { "id": "7746025_T15", "type": "DRUG_N", "text": [ "CPA" ], "offsets": [ [ 821, 824 ] ], "normalized": [] }, { "id": "7746025_T16", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1073, 1085 ] ], "normalized": [] } ]

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[ { "id": "7746025_R1", "type": "EFFECT", "arg1_id": "7746025_T7", "arg2_id": "7746025_T8", "normalized": [] }, { "id": "7746025_R2", "type": "EFFECT", "arg1_id": "7746025_T11", "arg2_id": "7746025_T12", "normalized": [] } ]

[ { "id": "10226677__text", "type": "abstract", "text": [ "Progestin-only oral contraception: a comprehensive review. In order to provide information for the appropriate package insert labeling of progestin-only oral contraceptives (POC) in the US, a comprehensive review was made of norgestrel (0.075 mg) and norethindrone (0.35 mg), with the clinical differences indicated where applicable. The goal of this review was to cite primary sources for virtually all research specific to POPs since 1975. Conclusions and the types of studies which support these conclusions are given for each major section. The introductory chapter discusses the advantages and disadvantages of POCs and the magnitude and prevalence of their use. Future trends are also predicted. Chapter 2 considers the mode of action, including ovulation prevention; suppression of midcycle gonadotropin peaks; changes in cervical mucus, the endometrium, and the fallopian tubes; and clinical implications. Chapter 3 covers pharmacology (pharmacokinetics, pharmacodynamics and potency, and clinical implications). The next chapter presents information on efficacy and pregnancy outcomes in terms of pregnancy rates, compliance and efficacy, ectopic pregnancies, the outcome of pregnancies conceived while using POCs, and fertility following discontinuation. Chapter 5 focuses on metabolic effects, specifically lipid metabolism, carbohydrate metabolism and diabetes, coagulation factors, and blood pressure. Cardiovascular disease is considered in the next chapter, and chapter 7 presents findings on endometrial, ovarian, cervical, breast, and other cancers. A host of other medical considerations are discussed in chapter 8, including persistent ovarian follicles; reproductive tract infections; abnormal vaginal bleeding; uterine fibroids; gestational trophoblastic disease; benign breast disease; diseases of the liver, gallbladder, and bowel; endocrine dysfunction; epilepsy; bone density; sickle cell disease; ocular effects; surgery; and overdose. The last 4 chapters cover interactions with drugs and laboratory tests, common side effects, breast feeding, and effective use of POCs. Information on precautions and contraindications, indications, use instructions, and instructions for appropriate actions after missing a pill is appended." ], "offsets": [ [ 0, 2253 ] ] } ]

[ { "id": "10226677_T1", "type": "GROUP", "text": [ "progestin-only oral contraceptives" ], "offsets": [ [ 138, 172 ] ], "normalized": [] }, { "id": "10226677_T2", "type": "GROUP", "text": [ "POC" ], "offsets": [ [ 174, 177 ] ], "normalized": [] }, { "id": "10226677_T3", "type": "DRUG", "text": [ "norgestrel" ], "offsets": [ [ 225, 235 ] ], "normalized": [] }, { "id": "10226677_T4", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 251, 264 ] ], "normalized": [] }, { "id": "10226677_T5", "type": "GROUP", "text": [ "POCs" ], "offsets": [ [ 616, 620 ] ], "normalized": [] }, { "id": "10226677_T6", "type": "GROUP", "text": [ "POCs" ], "offsets": [ [ 1218, 1222 ] ], "normalized": [] }, { "id": "10226677_T7", "type": "GROUP", "text": [ "POCs" ], "offsets": [ [ 2092, 2096 ] ], "normalized": [] } ]

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[ { "id": "19489169__text", "type": "abstract", "text": [ "Development and pharmacology of fluvastatin. Fluvastatin is the first synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitor to be approved for clinical use, and has been studied extensively in humans since 1986. It is structurally distinct from the other currently available HMGCoA reductase inhibitors (lovastatin, simvastatin, and pravastatin), leading to unique biopharmaceutical properties relative to the other agents of this class. Absorption of fluvastatin is virtually complete across all species, including man, and is not affected by the presence of food. Systemic exposure is limited, as fluvastatin is subject to first-pass metabolism, and the plasma half-life of the drug is approximately 30 minutes. Some 95% of a single dosage of fluvastatin is excreted via the biliary route, with less than 2% of this being the parent compound. Additionally, there is no evidence of circulating active metabolites or accumulation during chronic dosing. Studies of the effect of food on the pharmacokinetics of fluvastatin have demonstrated marked reductions in the rate of bioavailability--from 40% to 60%; however, a comparison of fluvastatin administration with the evening meal or at bedtime has revealed no significant differences in the extent of bioavailability (area under the curve) of these two regimens. Furthermore, no significant difference in pharmacodynamic effect (reduction in low-density lipoprotein cholesterol levels) could be ascertained between mealtime dosing and bedtime dosing. The pharmacokinetics of fluvastatin have also been assessed in various demographic groups. Relative to the general population, plasma concentrations of fluvastatin do not vary as a function of either age or gender. In addition, administration to a patient population with hepatic insufficiency resulted in a 2.5-fold increase in both the rate and extent of bioavailability relative to controls. Also, although minimal alterations of fluvastatin clearance in patients with renal insufficiency are anticipated due to limited renal excretion (5%), a study in this patient group is currently underway to examine this further. Interaction studies have been performed with fluvastatin and several drugs with which it might be coadministered. Cholestyramine, an anionic-binding resin, has a considerable effect in lowering the rate and extent of fluvastatin bioavailability. Although this effect was noted even when cholestyramine was given 4 hours prior to fluvastatin, this regimen did not result in diminished efficacy. Further, no effects on either warfarin levels or prothrombin times were observed in a study involving concomitant administration of warfarin and fluvastatin. Moreover, additional interaction studies with niacin and propranolol have not demonstrated any effect on fluvastatin plasma levels, and administration to a patient population chronically receiving digoxin resulted in no difference in the extent of bioavailability of digoxin relative to control data. The results generated to date in clinical pharmacokinetic studies with fluvastatin thus support its use in a broad population of hypercholesterolaemic patients." ], "offsets": [ [ 0, 3160 ] ] } ]

[ { "id": "19489169_T1", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 32, 43 ] ], "normalized": [] }, { "id": "19489169_T2", "type": "DRUG", "text": [ "Fluvastatin" ], "offsets": [ [ 45, 56 ] ], "normalized": [] }, { "id": "19489169_T3", "type": "GROUP", "text": [ "synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitor" ], "offsets": [ [ 70, 146 ] ], "normalized": [] }, { "id": "19489169_T4", "type": "GROUP", "text": [ "HMGCoA reductase inhibitors" ], "offsets": [ [ 298, 325 ] ], "normalized": [] }, { "id": "19489169_T5", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 327, 337 ] ], "normalized": [] }, { "id": "19489169_T6", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 339, 350 ] ], "normalized": [] }, { "id": "19489169_T7", "type": "DRUG", "text": [ "pravastatin" ], "offsets": [ [ 356, 367 ] ], "normalized": [] }, { "id": "19489169_T8", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 475, 486 ] ], "normalized": [] }, { "id": "19489169_T9", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 622, 633 ] ], "normalized": [] }, { "id": "19489169_T10", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 768, 779 ] ], "normalized": [] }, { "id": "19489169_T11", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 1033, 1044 ] ], "normalized": [] }, { "id": "19489169_T12", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 1155, 1166 ] ], "normalized": [] }, { "id": "19489169_T13", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 1549, 1560 ] ], "normalized": [] }, { "id": "19489169_T14", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 1677, 1688 ] ], "normalized": [] }, { "id": "19489169_T15", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 1958, 1969 ] ], "normalized": [] }, { "id": "19489169_T16", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 2192, 2203 ] ], "normalized": [] }, { "id": "19489169_T17", "type": "DRUG", "text": [ "Cholestyramine" ], "offsets": [ [ 2261, 2275 ] ], "normalized": [] }, { "id": "19489169_T18", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 2364, 2375 ] ], "normalized": [] }, { "id": "19489169_T19", "type": "DRUG", "text": [ "cholestyramine" ], "offsets": [ [ 2434, 2448 ] ], "normalized": [] }, { "id": "19489169_T20", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 2476, 2487 ] ], "normalized": [] }, { "id": "19489169_T21", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2571, 2579 ] ], "normalized": [] }, { "id": "19489169_T22", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 2673, 2681 ] ], "normalized": [] }, { "id": "19489169_T23", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 2686, 2697 ] ], "normalized": [] }, { "id": "19489169_T24", "type": "DRUG", "text": [ "niacin" ], "offsets": [ [ 2745, 2751 ] ], "normalized": [] }, { "id": "19489169_T25", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 2756, 2767 ] ], "normalized": [] }, { "id": "19489169_T26", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 2804, 2815 ] ], "normalized": [] }, { "id": "19489169_T27", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2896, 2903 ] ], "normalized": [] }, { "id": "19489169_T28", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2966, 2973 ] ], "normalized": [] }, { "id": "19489169_T29", "type": "DRUG", "text": [ "fluvastatin" ], "offsets": [ [ 3071, 3082 ] ], "normalized": [] } ]

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[ { "id": "19489169_R1", "type": "MECHANISM", "arg1_id": "19489169_T17", "arg2_id": "19489169_T18", "normalized": [] }, { "id": "19489169_R2", "type": "EFFECT", "arg1_id": "19489169_T19", "arg2_id": "19489169_T20", "normalized": [] } ]

[ { "id": "11180040__text", "type": "abstract", "text": [ "ADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia. ADL-8-2698 is a novel peripherally restricted opioid antagonist that may selectively prevent opioid-induced gastrointestinal effects without reversing analgesia. Gastrointestinal transit time (lactulose hydrogen breath test) was measured in 14 volunteers with oral and intravenous placebo, oral placebo and intravenous morphine (0.05 mg x kg(-1)), and oral ADL 8-2698 (4 mg) and intravenous morphine (0.05 mg x kg(-1)) in a double blind, cross-over study. Morphine prolonged gastrointestinal transit time from 69 to 103 minutes (P = .005); Morphine prolonged gastrointestinal transit time from 69 to 103 minutes (P = .005); this was prevented by ADL 8-2698 (P = .004). Postoperatively, 45 patients were randomly assigned in a double-blind fashion to receive ADL 8-2698 (4 mg) or placebo and intravenous morphine (0.15 mg/kg) or to receive oral and intravenous placebo. Analgesia and pupil constriction were measured. Morphine analgesia and pupil constriction were unaffected by ADL 8-2698 and differed from placebo (P < .002). We conclude that ADL 8-2698 prevents morphine-induced increases in gastrointestinal transit time by means of selective peripheral opioid anitagonism without affecting central opioid analgesia." ], "offsets": [ [ 0, 1371 ] ] } ]

[ { "id": "11180040_T1", "type": "DRUG", "text": [ "ADL 8-2698" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "11180040_T2", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 114, 122 ] ], "normalized": [] }, { "id": "11180040_T3", "type": "DRUG", "text": [ "ADL-8-2698" ], "offsets": [ [ 152, 162 ] ], "normalized": [] }, { "id": "11180040_T4", "type": "GROUP", "text": [ "peripherally restricted opioid antagonist" ], "offsets": [ [ 174, 215 ] ], "normalized": [] }, { "id": "11180040_T5", "type": "GROUP", "text": [ "opioid" ], "offsets": [ [ 245, 251 ] ], "normalized": [] }, { "id": "11180040_T6", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 471, 479 ] ], "normalized": [] }, { "id": "11180040_T7", "type": "DRUG", "text": [ "ADL 8-2698" ], "offsets": [ [ 509, 519 ] ], "normalized": [] }, { "id": "11180040_T8", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 543, 551 ] ], "normalized": [] }, { "id": "11180040_T9", "type": "DRUG", "text": [ "Morphine" ], "offsets": [ [ 608, 616 ] ], "normalized": [] }, { "id": "11180040_T10", "type": "DRUG", "text": [ "Morphine" ], "offsets": [ [ 692, 700 ] ], "normalized": [] }, { "id": "11180040_T11", "type": "DRUG", "text": [ "ADL 8-2698" ], "offsets": [ [ 798, 808 ] ], "normalized": [] }, { "id": "11180040_T12", "type": "DRUG", "text": [ "ADL 8-2698" ], "offsets": [ [ 910, 920 ] ], "normalized": [] }, { "id": "11180040_T13", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 955, 963 ] ], "normalized": [] }, { "id": "11180040_T14", "type": "DRUG", "text": [ "Morphine" ], "offsets": [ [ 1069, 1077 ] ], "normalized": [] }, { "id": "11180040_T15", "type": "DRUG", "text": [ "ADL 8-2698" ], "offsets": [ [ 1130, 1140 ] ], "normalized": [] }, { "id": "11180040_T16", "type": "DRUG", "text": [ "ADL 8-2698" ], "offsets": [ [ 1196, 1206 ] ], "normalized": [] }, { "id": "11180040_T17", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 1216, 1224 ] ], "normalized": [] } ]

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[ { "id": "11180040_R1", "type": "EFFECT", "arg1_id": "11180040_T1", "arg2_id": "11180040_T2", "normalized": [] }, { "id": "11180040_R2", "type": "EFFECT", "arg1_id": "11180040_T3", "arg2_id": "11180040_T5", "normalized": [] }, { "id": "11180040_R3", "type": "EFFECT", "arg1_id": "11180040_T10", "arg2_id": "11180040_T11", "normalized": [] }, { "id": "11180040_R4", "type": "EFFECT", "arg1_id": "11180040_T16", "arg2_id": "11180040_T17", "normalized": [] } ]

[ { "id": "2981704__text", "type": "abstract", "text": [ "Spermine promotes the translocation of phosphatidate phosphohydrolase from the cytosol to the microsomal fraction of rat liver and it enhances the effects of oleate in this respect. Spermine (0.5-2 mM) promoted the translocation of phosphatidate phosphohydrolase from the soluble to the microsomal fraction in a cell-free system derived from rat liver. By contrast, spermidine (1 mM) and putrescine (1 mM) had no significant effect on the translocation when added alone. Spermine, and to a lesser extent, spermidine, enhanced the translocating action of oleate and increased its effectiveness in transferring the phosphohydrolase from the soluble to the microsomal fraction. It is proposed that the phosphohydrolase becomes metabolically active when it combines with membranes and that polyamines might help to regulate this interaction. This could facilitate the action of fatty acids and enable cells to increase their capacity for triacylglycerol synthesis to match an increased availability of fatty acids." ], "offsets": [ [ 0, 1010 ] ] } ]

[ { "id": "2981704_T1", "type": "DRUG", "text": [ "Spermine" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "2981704_T2", "type": "DRUG", "text": [ "Spermine" ], "offsets": [ [ 182, 190 ] ], "normalized": [] }, { "id": "2981704_T3", "type": "DRUG_N", "text": [ "spermidine" ], "offsets": [ [ 366, 376 ] ], "normalized": [] }, { "id": "2981704_T4", "type": "DRUG_N", "text": [ "putrescine" ], "offsets": [ [ 388, 398 ] ], "normalized": [] }, { "id": "2981704_T5", "type": "DRUG", "text": [ "Spermine" ], "offsets": [ [ 471, 479 ] ], "normalized": [] }, { "id": "2981704_T6", "type": "DRUG_N", "text": [ "spermidine" ], "offsets": [ [ 505, 515 ] ], "normalized": [] } ]

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[ { "id": "11154900__text", "type": "abstract", "text": [ "Thiolated carboxymethylcellulose: in vitro evaluation of its permeation enhancing effect on peptide drugs. The purpose of this study was to evaluate the effect of sodium carboxymethylcellulose (NaCMC) and carboxymethylcellulose-cysteine (CMC-Cys) conjugates on the intestinal permeation of sodium fluorescein (NaFlu) and model peptide drugs, bacitracin and insulin. Cysteine was covalently linked to carbodiimide activated NaCMC. Iodometric titration of the polymer conjugates was used to determine the extent of immobilised cysteine. Permeation studies were performed on guinea pig small intestinal mucosa mounted in Ussing-type chamber. Unmodified NaCMC (1% m/v) significantly improved the transport ratio (R= P(app) polymer/ P(app) control) of NaFlu to 1.3 and 1% (m/v) NaCMC conjugated with cysteine further enhanced the permeation. Cysteine conjugation at 3.6, 5.3 and 7.3% (m/m) resulted in R-values of 1.4, 1.7 and 1.8, respectively. Decreasing the concentration of CMC-Cys, exhibiting 7.3% (m/m) of immobilised cysteine (CMC-Cys7.3) from 1% (m/v) to 0.5% (m/v) decreased the R-value of NaFlu from 1.8 to 1.2. NaCMC at 1% (m/v) in the presence of free cysteine had no significant effect on the R-value of NaFlu compared to NaCMC alone. Formulation of fluorescence labelled bacitracin and insulin in unconjugated NaCMC (1% m/v) did not significantly improve the permeation, however in the presence of 1% (m/v) CMC-Cys7.3 a significantly improved permeation was observed (R= 1.3). Conjugation at NaCMC with cysteine moieties significantly improves the intestinal permeation of the hydrophilic molecule NaFlu and the model peptide drugs bacitracin and insulin in vitro, therefore this conjugated system maybe useful for peroral administration of peptide drugs in the future." ], "offsets": [ [ 0, 1778 ] ] } ]

[ { "id": "11154900_T1", "type": "DRUG_N", "text": [ "Thiolated carboxymethylcellulose" ], "offsets": [ [ 0, 32 ] ], "normalized": [] }, { "id": "11154900_T2", "type": "DRUG_N", "text": [ "sodium carboxymethylcellulose" ], "offsets": [ [ 163, 192 ] ], "normalized": [] }, { "id": "11154900_T3", "type": "DRUG_N", "text": [ "NaCMC" ], "offsets": [ [ 194, 199 ] ], "normalized": [] }, { "id": "11154900_T4", "type": "DRUG_N", "text": [ "carboxymethylcellulose-cysteine" ], "offsets": [ [ 205, 236 ] ], "normalized": [] }, { "id": "11154900_T5", "type": "DRUG_N", "text": [ "CMC-Cys" ], "offsets": [ [ 238, 245 ] ], "normalized": [] }, { "id": "11154900_T6", "type": "DRUG", "text": [ "sodium fluorescein" ], "offsets": [ [ 290, 308 ] ], "normalized": [] }, { "id": "11154900_T7", "type": "DRUG", "text": [ "NaFlu" ], "offsets": [ [ 310, 315 ] ], "normalized": [] }, { "id": "11154900_T8", "type": "DRUG", "text": [ "bacitracin" ], "offsets": [ [ 342, 352 ] ], "normalized": [] }, { "id": "11154900_T9", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 357, 364 ] ], "normalized": [] }, { "id": "11154900_T10", "type": "DRUG", "text": [ "Cysteine" ], "offsets": [ [ 366, 374 ] ], "normalized": [] }, { "id": "11154900_T11", "type": "DRUG_N", "text": [ "NaCMC" ], "offsets": [ [ 423, 428 ] ], "normalized": [] }, { "id": "11154900_T12", "type": "DRUG", "text": [ "cysteine" ], "offsets": [ [ 525, 533 ] ], "normalized": [] }, { "id": "11154900_T13", "type": "DRUG_N", "text": [ "NaCMC" ], "offsets": [ [ 650, 655 ] ], "normalized": [] }, { "id": "11154900_T14", "type": "DRUG", "text": [ "NaFlu" ], "offsets": [ [ 747, 752 ] ], "normalized": [] }, { "id": "11154900_T15", "type": "DRUG_N", "text": [ "NaCMC" ], "offsets": [ [ 773, 778 ] ], "normalized": [] }, { "id": "11154900_T16", "type": "DRUG", "text": [ "cysteine" ], "offsets": [ [ 795, 803 ] ], "normalized": [] }, { "id": "11154900_T17", "type": "DRUG", "text": [ "Cysteine" ], "offsets": [ [ 837, 845 ] ], "normalized": [] }, { "id": "11154900_T18", "type": "DRUG_N", "text": [ "CMC-Cys" ], "offsets": [ [ 973, 980 ] ], "normalized": [] }, { "id": "11154900_T19", "type": "DRUG", "text": [ "cysteine" ], "offsets": [ [ 1019, 1027 ] ], "normalized": [] }, { "id": "11154900_T20", "type": "DRUG", "text": [ "NaFlu" ], "offsets": [ [ 1094, 1099 ] ], "normalized": [] }, { "id": "11154900_T21", "type": "DRUG_N", "text": [ "NaCMC" ], "offsets": [ [ 1117, 1122 ] ], "normalized": [] }, { "id": "11154900_T22", "type": "DRUG", "text": [ "cysteine" ], "offsets": [ [ 1159, 1167 ] ], "normalized": [] }, { "id": "11154900_T23", "type": "DRUG", "text": [ "NaFlu" ], "offsets": [ [ 1212, 1217 ] ], "normalized": [] }, { "id": "11154900_T24", "type": "DRUG_N", "text": [ "NaCMC" ], "offsets": [ [ 1230, 1235 ] ], "normalized": [] }, { "id": "11154900_T25", "type": "DRUG", "text": [ "bacitracin" ], "offsets": [ [ 1280, 1290 ] ], "normalized": [] }, { "id": "11154900_T26", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 1295, 1302 ] ], "normalized": [] }, { "id": "11154900_T27", "type": "DRUG_N", "text": [ "NaCMC" ], "offsets": [ [ 1319, 1324 ] ], "normalized": [] }, { "id": "11154900_T28", "type": "DRUG_N", "text": [ "CMC-Cys" ], "offsets": [ [ 1416, 1423 ] ], "normalized": [] }, { "id": "11154900_T29", "type": "DRUG_N", "text": [ "NaCMC" ], "offsets": [ [ 1501, 1506 ] ], "normalized": [] }, { "id": "11154900_T30", "type": "DRUG", "text": [ "cysteine" ], "offsets": [ [ 1512, 1520 ] ], "normalized": [] }, { "id": "11154900_T31", "type": "DRUG", "text": [ "NaFlu" ], "offsets": [ [ 1607, 1612 ] ], "normalized": [] }, { "id": "11154900_T32", "type": "DRUG", "text": [ "bacitracin" ], "offsets": [ [ 1641, 1651 ] ], "normalized": [] }, { "id": "11154900_T33", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 1656, 1663 ] ], "normalized": [] } ]

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[ { "id": "3871459__text", "type": "abstract", "text": [ "Jacalin: an IgA-binding lectin. We previously reported that seeds of Artocarpus integrifolia (jackfruit) contain a lectin, which we call jacalin, that is both a potent T cell mitogen and an apparently T cell-independent activator of human B cells for the secretion of immunoglobulins. During the above experiments we noted a massive precipitation in cell cultures stimulated with greater than or equal to 100 micrograms of lectin. In this paper, we show that the precipitate is formed after the interaction of jacalin and the serum protein added to the culture medium. More importantly, we demonstrate that IgA is probably the major serum constituent precipitated by the lectin and that no IgG or IgM can be detected in the precipitates. In secretions such as colostrum, IgA is the only protein precipitated by jacalin. On the basis of this specificity we describe a simple and reliable affinity chromatography procedure for the purification of both human serum and colostrum IgA. Jacalin is a D-Gal binding lectin and should be a useful tool for studying of serum and secretory IgA." ], "offsets": [ [ 0, 1083 ] ] } ]

[ { "id": "3871459_T1", "type": "DRUG_N", "text": [ "Jacalin" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "3871459_T2", "type": "DRUG_N", "text": [ "jacalin" ], "offsets": [ [ 137, 144 ] ], "normalized": [] }, { "id": "3871459_T3", "type": "DRUG_N", "text": [ "jacalin" ], "offsets": [ [ 510, 517 ] ], "normalized": [] }, { "id": "3871459_T4", "type": "DRUG_N", "text": [ "jacalin" ], "offsets": [ [ 811, 818 ] ], "normalized": [] }, { "id": "3871459_T5", "type": "DRUG_N", "text": [ "Jacalin" ], "offsets": [ [ 981, 988 ] ], "normalized": [] } ]

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[ { "id": "4038510__text", "type": "abstract", "text": [ "High-dose cisplatin with sodium thiosulfate protection. Nephrotoxicity frequently limits the dose of cisplatin to less than 120 mg/m2 per injection. Sodium thiosulfate is a neutralizing agent for cisplatin that protects against renal damage. To determine whether injection of thiosulfate would permit larger doses of cisplatin to be administered, a fixed 9.9-g/m2 dose of thiosulfate was given intravenously over three hours concurrently with escalating doses of cisplatin. Cisplatin was administered over the last two hours of the thiosulfate infusion. Using this technique, it was possible to escalate the cisplatin dose to 225 mg/m2 before dose-limiting toxicities were encountered. Comparison of cisplatin pharmacokinetics in patients treated with 202.5 mg/m2 plus thiosulfate to those in patients treated with 100 mg/m2 without thiosulfate indicated that there were no changes in the elimination rate constant, volume of distribution, or total body clearance of cisplatin. The total drug exposure for the plasma was approximately twofold at the higher cisplatin dose. This study demonstrates that concurrent administration of thiosulfate permits at least a twofold increase in dose and total exposure to cisplatin." ], "offsets": [ [ 0, 1219 ] ] } ]

[ { "id": "4038510_T1", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 10, 19 ] ], "normalized": [] }, { "id": "4038510_T2", "type": "DRUG", "text": [ "sodium thiosulfate" ], "offsets": [ [ 25, 43 ] ], "normalized": [] }, { "id": "4038510_T3", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 101, 110 ] ], "normalized": [] }, { "id": "4038510_T4", "type": "DRUG", "text": [ "Sodium thiosulfate" ], "offsets": [ [ 149, 167 ] ], "normalized": [] }, { "id": "4038510_T5", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 196, 205 ] ], "normalized": [] }, { "id": "4038510_T6", "type": "DRUG", "text": [ "thiosulfate" ], "offsets": [ [ 276, 287 ] ], "normalized": [] }, { "id": "4038510_T7", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 317, 326 ] ], "normalized": [] }, { "id": "4038510_T8", "type": "DRUG", "text": [ "thiosulfate" ], "offsets": [ [ 372, 383 ] ], "normalized": [] }, { "id": "4038510_T9", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 463, 472 ] ], "normalized": [] }, { "id": "4038510_T10", "type": "DRUG", "text": [ "Cisplatin" ], "offsets": [ [ 474, 483 ] ], "normalized": [] }, { "id": "4038510_T11", "type": "DRUG", "text": [ "thiosulfate" ], "offsets": [ [ 532, 543 ] ], "normalized": [] }, { "id": "4038510_T12", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 608, 617 ] ], "normalized": [] }, { "id": "4038510_T13", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 700, 709 ] ], "normalized": [] }, { "id": "4038510_T14", "type": "DRUG", "text": [ "thiosulfate" ], "offsets": [ [ 769, 780 ] ], "normalized": [] }, { "id": "4038510_T15", "type": "DRUG", "text": [ "thiosulfate" ], "offsets": [ [ 833, 844 ] ], "normalized": [] }, { "id": "4038510_T16", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 967, 976 ] ], "normalized": [] }, { "id": "4038510_T17", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 1057, 1066 ] ], "normalized": [] }, { "id": "4038510_T18", "type": "DRUG", "text": [ "thiosulfate" ], "offsets": [ [ 1131, 1142 ] ], "normalized": [] }, { "id": "4038510_T19", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 1209, 1218 ] ], "normalized": [] } ]

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[ { "id": "4038510_R1", "type": "EFFECT", "arg1_id": "4038510_T1", "arg2_id": "4038510_T2", "normalized": [] }, { "id": "4038510_R2", "type": "EFFECT", "arg1_id": "4038510_T4", "arg2_id": "4038510_T5", "normalized": [] }, { "id": "4038510_R3", "type": "MECHANISM", "arg1_id": "4038510_T18", "arg2_id": "4038510_T19", "normalized": [] } ]

[ { "id": "8521984__text", "type": "abstract", "text": [ "[A pharmacological analysis of the effect of angiotensin on stimulated gastric secretion] Chronic experiments on dogs with gastric fistulas were carried out to study the influence of angiotensin 1 and angiotensin 2 on pentagastrin- and histamine-induced gastric acid secretion. It was established that both angiotensins inhibited gastric acid secretion stimulated by pentagastrin but not by histamine. Comparative analysis of the effects of stimulation and inhibition of cholino- and adrenoreceptors on this inhibitory action of angiotensins suggested the mediation of angiotensin influence through the modulation of cholinergic reactions of parietal cells in the stomach." ], "offsets": [ [ 0, 672 ] ] } ]

[ { "id": "8521984_T1", "type": "DRUG_N", "text": [ "angiotensin" ], "offsets": [ [ 45, 56 ] ], "normalized": [] }, { "id": "8521984_T2", "type": "DRUG_N", "text": [ "angiotensin 1" ], "offsets": [ [ 183, 196 ] ], "normalized": [] }, { "id": "8521984_T3", "type": "DRUG_N", "text": [ "angiotensin 2" ], "offsets": [ [ 201, 214 ] ], "normalized": [] }, { "id": "8521984_T4", "type": "DRUG", "text": [ "pentagastrin" ], "offsets": [ [ 218, 230 ] ], "normalized": [] }, { "id": "8521984_T5", "type": "DRUG", "text": [ "histamine" ], "offsets": [ [ 236, 245 ] ], "normalized": [] }, { "id": "8521984_T6", "type": "DRUG", "text": [ "pentagastrin" ], "offsets": [ [ 367, 379 ] ], "normalized": [] }, { "id": "8521984_T7", "type": "DRUG", "text": [ "histamine" ], "offsets": [ [ 391, 400 ] ], "normalized": [] }, { "id": "8521984_T8", "type": "DRUG_N", "text": [ "angiotensins" ], "offsets": [ [ 529, 541 ] ], "normalized": [] }, { "id": "8521984_T9", "type": "DRUG_N", "text": [ "angiotensin" ], "offsets": [ [ 569, 580 ] ], "normalized": [] } ]

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[ { "id": "3881917__text", "type": "abstract", "text": [ "Pharmacokinetics of calcium-entry blockers. Effective use of drugs in therapy depends not only on clinical acumen but also on the availability of relevant pharmacokinetic and pharmacodynamic data. Such information assists in development of safe dosing regimens, prediction of abnormal handling of drugs in states of disease and disorder and anticipation of drug interactions. For the calcium-entry blocking agents now available in the United States (verapamil, nifedipine and diltiazem), these data appeared well after clinical patterns of use evolved. Nonetheless, their relevance continues to be demonstrated by the dependence of each agent on intact liver blood flow and function for normal rates of elimination; by the nonlinear kinetic characteristics for verapamil and diltiazem (and probably for nifedipine, as well) and the derivative implications for decreased dosing frequency requirements; and by observations now appearing on the relation between plasma drug levels and drug effects, both therapeutic and toxic. Such data are discussed herein, with emphasis on those aspects that impact on the clinical use of the calcium-entry antagonists." ], "offsets": [ [ 0, 1152 ] ] } ]

[ { "id": "3881917_T1", "type": "GROUP", "text": [ "calcium-entry blockers" ], "offsets": [ [ 20, 42 ] ], "normalized": [] }, { "id": "3881917_T2", "type": "GROUP", "text": [ "calcium-entry blocking agents" ], "offsets": [ [ 384, 413 ] ], "normalized": [] }, { "id": "3881917_T3", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 450, 459 ] ], "normalized": [] }, { "id": "3881917_T4", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 461, 471 ] ], "normalized": [] }, { "id": "3881917_T5", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 476, 485 ] ], "normalized": [] }, { "id": "3881917_T6", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 761, 770 ] ], "normalized": [] }, { "id": "3881917_T7", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 775, 784 ] ], "normalized": [] }, { "id": "3881917_T8", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 803, 813 ] ], "normalized": [] }, { "id": "3881917_T9", "type": "GROUP", "text": [ "calcium-entry antagonists" ], "offsets": [ [ 1126, 1151 ] ], "normalized": [] } ]

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[ { "id": "11213850__text", "type": "abstract", "text": [ "Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers. STUDY OBJECTIVE: To evaluate the effect of fluoxetine on the pharmacokinetics and cardiovascular safety of cisapride at steady state in healthy men. DESIGN: Open-label, three-phase, sequential study. SETTING: Clinical research center. SUBJECTS:Twelve healthy male volunteers. INTERVENTIONS: Each subject was treated according to the following sequence: baseline; phase 1 (days 1-6): cisapride 10 mg 4 times/day; washout (days 7-13); phase 2 (days 14-44): fluoxetine 20 mg/day; and phase 3 (days 45-52): cisapride 10 mg 4 times/day (days 45-51) plus fluoxetine 20 mg/day (days 45-52). MEASUREMENTS and MAIN RESULTS: Blood samples were drawn and 12-lead electrocardiograms performed at specified time points after the last morning dose of cisapride in phases 1 and 3. Blood samples also were taken before morning doses on the 3rd, 4th, and 5th days of phases 1 and 3. Electrocardiograms were done at baseline and on the last day of the washout period and phase 2. Coadministration of fluoxetine significantly decreased cisapride plasma concentrations. There were no clinically significant changes in corrected QT intervals during administration of cisapride alone or with fluoxetine. Cisapride was well tolerated when administered alone or with fluoxetine. CONCLUSION: Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine." ], "offsets": [ [ 0, 1479 ] ] } ]

[ { "id": "11213850_T1", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 33, 43 ] ], "normalized": [] }, { "id": "11213850_T2", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 47, 56 ] ], "normalized": [] }, { "id": "11213850_T3", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 158, 168 ] ], "normalized": [] }, { "id": "11213850_T4", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 222, 231 ] ], "normalized": [] }, { "id": "11213850_T5", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 498, 507 ] ], "normalized": [] }, { "id": "11213850_T6", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 570, 580 ] ], "normalized": [] }, { "id": "11213850_T7", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 618, 627 ] ], "normalized": [] }, { "id": "11213850_T8", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 664, 674 ] ], "normalized": [] }, { "id": "11213850_T9", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 852, 861 ] ], "normalized": [] }, { "id": "11213850_T10", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1097, 1107 ] ], "normalized": [] }, { "id": "11213850_T11", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1132, 1141 ] ], "normalized": [] }, { "id": "11213850_T12", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1261, 1270 ] ], "normalized": [] }, { "id": "11213850_T13", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1285, 1295 ] ], "normalized": [] }, { "id": "11213850_T14", "type": "DRUG", "text": [ "Cisapride" ], "offsets": [ [ 1297, 1306 ] ], "normalized": [] }, { "id": "11213850_T15", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1358, 1368 ] ], "normalized": [] }, { "id": "11213850_T16", "type": "DRUG", "text": [ "Cisapride" ], "offsets": [ [ 1382, 1391 ] ], "normalized": [] }, { "id": "11213850_T17", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1468, 1478 ] ], "normalized": [] } ]

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[ { "id": "11213850_R1", "type": "MECHANISM", "arg1_id": "11213850_T10", "arg2_id": "11213850_T11", "normalized": [] } ]

[ { "id": "11180037__text", "type": "abstract", "text": [ "Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide. OBJECTIVE: Our objective was to examine the interaction between fluvoxamine and tolbutamide to confirm that fluvoxamine inhibits CYP2C9. METHODS: The study was carried out as an open, randomized, crossover design with 14 healthy participants. In period A, all volunteers took 500 mg of tolbutamide orally. In period B, the volunteers were randomly assigned to one of two groups. Each group took either 150 mg or 75 mg of fluvoxamine a day for 5 days (day -3 to day 2). The groups then took 500 mg of tolbutamide as a single dose (day 0). In both periods, blood and urine were sampled at regular intervals. Plasma was analyzed for tolbutamide, and urine was analyzed for tolbutamide and its two metabolites, 4-hydroxytolbutamide and carboxytolbutamide by means of HPLC. RESULTS: During treatment with fluvoxamine, there was a statistically significant decrease in the median of the total clearance of tolbutamide, from 845 mL/h to 688 mL/h, among the volunteers who received 75 mg/d. There was a reduction that reached borderline statistical significance in the group that received 150 mg/d of tolbutamide. The clearance by means of 4-hydroxytolbutamide and carboxytolbutamide was significantly reduced in both groups (ie, from 901 mL/h to 318 mL/h in the group that received 150 mg of tolbutamide per day and from 723 mL/h to 457 mL/h in the group that received 75 mg of tolbutamide per day). Thus there was a tendency toward a more pronounced inhibition of the 4-hydroxylation during treatment with 150 mg/d of fluvoxamine compared with 75 mg/d, but the difference was not statistically significant. CONCLUSION: Fluvoxamine is a moderate inhibitor of CYP2C9 in vivo." ], "offsets": [ [ 0, 1743 ] ] } ]

[ { "id": "11180037_T1", "type": "DRUG", "text": [ "Fluvoxamine" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "11180037_T2", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 63, 74 ] ], "normalized": [] }, { "id": "11180037_T3", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 140, 151 ] ], "normalized": [] }, { "id": "11180037_T4", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 156, 167 ] ], "normalized": [] }, { "id": "11180037_T5", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 184, 195 ] ], "normalized": [] }, { "id": "11180037_T6", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 362, 373 ] ], "normalized": [] }, { "id": "11180037_T7", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 497, 508 ] ], "normalized": [] }, { "id": "11180037_T8", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 576, 587 ] ], "normalized": [] }, { "id": "11180037_T9", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 706, 717 ] ], "normalized": [] }, { "id": "11180037_T10", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 746, 757 ] ], "normalized": [] }, { "id": "11180037_T11", "type": "DRUG_N", "text": [ "4-hydroxytolbutamide" ], "offsets": [ [ 783, 803 ] ], "normalized": [] }, { "id": "11180037_T12", "type": "DRUG_N", "text": [ "carboxytolbutamide" ], "offsets": [ [ 808, 826 ] ], "normalized": [] }, { "id": "11180037_T13", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 876, 887 ] ], "normalized": [] }, { "id": "11180037_T14", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 976, 987 ] ], "normalized": [] }, { "id": "11180037_T15", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 1169, 1180 ] ], "normalized": [] }, { "id": "11180037_T16", "type": "DRUG_N", "text": [ "4-hydroxytolbutamide" ], "offsets": [ [ 1208, 1228 ] ], "normalized": [] }, { "id": "11180037_T17", "type": "DRUG_N", "text": [ "carboxytolbutamide" ], "offsets": [ [ 1233, 1251 ] ], "normalized": [] }, { "id": "11180037_T18", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 1361, 1372 ] ], "normalized": [] }, { "id": "11180037_T19", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 1447, 1458 ] ], "normalized": [] }, { "id": "11180037_T20", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 1588, 1599 ] ], "normalized": [] }, { "id": "11180037_T21", "type": "DRUG", "text": [ "Fluvoxamine" ], "offsets": [ [ 1689, 1700 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11180037_R1", "type": "MECHANISM", "arg1_id": "11180037_T1", "arg2_id": "11180037_T2", "normalized": [] }, { "id": "11180037_R2", "type": "MECHANISM", "arg1_id": "11180037_T13", "arg2_id": "11180037_T14", "normalized": [] } ]

[ { "id": "11206047__text", "type": "abstract", "text": [ "Effect of coadministered drugs and ethanol on the binding of therapeutic drugs to human serum in vitro. The effects of coadministered drugs and ethanol on the binding of therapeutic drugs to human serum in vitro was investigated. Acetaminophen, lidocaine, phenobarbital, quinidine, theophylline, and valproic acid were added to pooled human serum at therapeutic concentrations. To each preparation was added one additional drug at three concentrations ranging from therapeutic to toxic. The following eight target drug/added drug combinations were studied: acetaminophen/phenobarbital. acetaminophen/theophylline, lidocaine/quinidine, phenobarbital/acetaminophen, phenobarbital/valproic acid, quinidine/lidocaine, theophylline/acetaminophen, and valproic acid/phenobarbital. Each serum without the other added drug as well as the serum supplemented with the other drug at the three concentrations was dialyzed against phosphate buffer. Similarly dialyzed were phenobarbital, quinidine, and theophylline, both alone at therapeutic concentrations in serum and with ethanol at three different concentrations in serum. The percentage of drug binding in each preparation was calculated. Acetaminophen diminished the binding of theophylline to human serum by a net change of 5.7% (percentage increase in free drug fraction [FDF], 11.0%) at 662 micromol/L and by a net change of 7.1% (percentage increase in FDF, 13.7%) at 1324 micromol/L. Theophylline decreased the binding of acetaminophen by a net change of 6.8% (percentage increase in FDF, 8.8%) at 277.5 micromol/L; phenobarbital reduced it by a net change of 6.6% (percentage increase in FDF, 8.5%) at 431 micromol/L. Valproic acid diminished binding of phenobarbital by a net change of 9.9% (percentage increase in FDF, 21.2%) at 1732 micromol/L. No significant effects were noted with other drug combinations or with the addition of ethanol. Coingestion of acetaminophen with theophylline, phenobarbital with acetaminophen, and valproic acid with phenobarbital at high to toxic concentrations decreases the binding of the target drug. The resulting increase in free drug concentration may lead to enhanced drug effect in vivo." ], "offsets": [ [ 0, 2178 ] ] } ]

[ { "id": "11206047_T1", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 35, 42 ] ], "normalized": [] }, { "id": "11206047_T2", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 144, 151 ] ], "normalized": [] }, { "id": "11206047_T3", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 230, 243 ] ], "normalized": [] }, { "id": "11206047_T4", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 245, 254 ] ], "normalized": [] }, { "id": "11206047_T5", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 256, 269 ] ], "normalized": [] }, { "id": "11206047_T6", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 271, 280 ] ], "normalized": [] }, { "id": "11206047_T7", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 282, 294 ] ], "normalized": [] }, { "id": "11206047_T8", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 300, 313 ] ], "normalized": [] }, { "id": "11206047_T9", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 557, 570 ] ], "normalized": [] }, { "id": "11206047_T10", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 571, 584 ] ], "normalized": [] }, { "id": "11206047_T11", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 586, 599 ] ], "normalized": [] }, { "id": "11206047_T12", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 600, 612 ] ], "normalized": [] }, { "id": "11206047_T13", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 614, 623 ] ], "normalized": [] }, { "id": "11206047_T14", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 624, 633 ] ], "normalized": [] }, { "id": "11206047_T15", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 635, 648 ] ], "normalized": [] }, { "id": "11206047_T16", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 649, 662 ] ], "normalized": [] }, { "id": "11206047_T17", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 664, 677 ] ], "normalized": [] }, { "id": "11206047_T18", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 678, 691 ] ], "normalized": [] }, { "id": "11206047_T19", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 693, 702 ] ], "normalized": [] }, { "id": "11206047_T20", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 703, 712 ] ], "normalized": [] }, { "id": "11206047_T21", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 714, 726 ] ], "normalized": [] }, { "id": "11206047_T22", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 727, 740 ] ], "normalized": [] }, { "id": "11206047_T23", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 746, 759 ] ], "normalized": [] }, { "id": "11206047_T24", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 760, 773 ] ], "normalized": [] }, { "id": "11206047_T25", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 960, 973 ] ], "normalized": [] }, { "id": "11206047_T26", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 975, 984 ] ], "normalized": [] }, { "id": "11206047_T27", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 990, 1002 ] ], "normalized": [] }, { "id": "11206047_T28", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 1063, 1070 ] ], "normalized": [] }, { "id": "11206047_T29", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 1182, 1195 ] ], "normalized": [] }, { "id": "11206047_T30", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1222, 1234 ] ], "normalized": [] }, { "id": "11206047_T31", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 1433, 1445 ] ], "normalized": [] }, { "id": "11206047_T32", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 1471, 1484 ] ], "normalized": [] }, { "id": "11206047_T33", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1565, 1578 ] ], "normalized": [] }, { "id": "11206047_T34", "type": "DRUG", "text": [ "Valproic acid" ], "offsets": [ [ 1668, 1681 ] ], "normalized": [] }, { "id": "11206047_T35", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1704, 1717 ] ], "normalized": [] }, { "id": "11206047_T36", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 1885, 1892 ] ], "normalized": [] }, { "id": "11206047_T37", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 1909, 1922 ] ], "normalized": [] }, { "id": "11206047_T38", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1928, 1940 ] ], "normalized": [] }, { "id": "11206047_T39", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1942, 1955 ] ], "normalized": [] }, { "id": "11206047_T40", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 1961, 1974 ] ], "normalized": [] }, { "id": "11206047_T41", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 1980, 1993 ] ], "normalized": [] }, { "id": "11206047_T42", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1999, 2012 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11206047_R1", "type": "MECHANISM", "arg1_id": "11206047_T29", "arg2_id": "11206047_T30", "normalized": [] }, { "id": "11206047_R2", "type": "MECHANISM", "arg1_id": "11206047_T31", "arg2_id": "11206047_T32", "normalized": [] }, { "id": "11206047_R3", "type": "MECHANISM", "arg1_id": "11206047_T34", "arg2_id": "11206047_T35", "normalized": [] }, { "id": "11206047_R4", "type": "EFFECT", "arg1_id": "11206047_T37", "arg2_id": "11206047_T38", "normalized": [] }, { "id": "11206047_R5", "type": "EFFECT", "arg1_id": "11206047_T39", "arg2_id": "11206047_T40", "normalized": [] }, { "id": "11206047_R6", "type": "EFFECT", "arg1_id": "11206047_T41", "arg2_id": "11206047_T42", "normalized": [] } ]

[ { "id": "7632757__text", "type": "abstract", "text": [ "Therapeutic drug monitoring can avoid iatrogenic alterations caused by 99mTc-methylene diphosphonate (MDP)-gentamicin interaction. Gentamicin is an aminoglycoside antibiotic used to treat a wide variety of infections caused by gram-negative organisms, but it is potentially toxic to the kidneys. Due to its nephrotoxicity, gentamicin may cause abnormal renal uptake to be seen on 99mTc-MDP bone scintigraphy. The presence of the radiopharmaceutical in the kidneys, along with an increase in renal retention, tend to produce scintigraphic results that falsely identify characteristics related to diseases such as renal vascular, or urinary tract obstruction, and even renal cancer. An altered biodistribution may provide misleading information that can either mask or mimic certain disease symptoms. A method to maximize the therapeutic benefit of gentamicin while minimizing the risk of nephrotoxicity and the appearance of a hot kidney on scintigraphy is desirable. Serial pharmacokinetic dosing has been proposed as a method to accomplish this goal. Therapeutic drug monitoring (TDM) of gentamicin therapy, and bone scintigraphy employing 99mTc-MDP as the radiopharmaceutical was carried out in 22 patients. The data presented here demonstrate that with serial pharmacokinetic dosing of gentamicin, the iatrogenic alteration caused by gentamicin therapy can be avoided." ], "offsets": [ [ 0, 1371 ] ] } ]

[ { "id": "7632757_T1", "type": "DRUG", "text": [ "99mTc-methylene diphosphonate" ], "offsets": [ [ 71, 100 ] ], "normalized": [] }, { "id": "7632757_T2", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 107, 117 ] ], "normalized": [] }, { "id": "7632757_T3", "type": "DRUG", "text": [ "Gentamicin" ], "offsets": [ [ 131, 141 ] ], "normalized": [] }, { "id": "7632757_T4", "type": "GROUP", "text": [ "aminoglycoside antibiotic" ], "offsets": [ [ 148, 173 ] ], "normalized": [] }, { "id": "7632757_T5", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 323, 333 ] ], "normalized": [] }, { "id": "7632757_T6", "type": "DRUG", "text": [ "99mTc-MDP" ], "offsets": [ [ 380, 389 ] ], "normalized": [] }, { "id": "7632757_T7", "type": "GROUP", "text": [ "radiopharmaceutical" ], "offsets": [ [ 429, 448 ] ], "normalized": [] }, { "id": "7632757_T8", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 847, 857 ] ], "normalized": [] }, { "id": "7632757_T9", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 1089, 1099 ] ], "normalized": [] }, { "id": "7632757_T10", "type": "DRUG", "text": [ "99mTc-MDP" ], "offsets": [ [ 1141, 1150 ] ], "normalized": [] }, { "id": "7632757_T11", "type": "GROUP", "text": [ "radiopharmaceutical" ], "offsets": [ [ 1158, 1177 ] ], "normalized": [] }, { "id": "7632757_T12", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 1289, 1299 ] ], "normalized": [] }, { "id": "7632757_T13", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 1337, 1347 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7632757_R1", "type": "EFFECT", "arg1_id": "7632757_T1", "arg2_id": "7632757_T2", "normalized": [] }, { "id": "7632757_R2", "type": "MECHANISM", "arg1_id": "7632757_T5", "arg2_id": "7632757_T6", "normalized": [] } ]

[ { "id": "1115445__text", "type": "abstract", "text": [ "Rifampin and warfarin: a drug interaction. The drug interaction between warfarin and rifampin is not well known. Rifampin has been reported to increase the warfarin requirements in human subjects ingesting these agents simultaneously. The concomitant administration of rifampin and warfarin resulted in the need for an unusually high maintenance dose of warfarin (20 mg per day) in order to produce a therapeutic effect. Withdrawal of rifampin decreased the warfarin requirement by 50%. This effect may be mediated by the ability of rifampin to induce microsomal enzymes and, thus, the catabolism of warfarin. The effect of rifampin on the warfarin requirement of our patient appeared to be maximal 5 to 7 days after the initiation of rifampin and extended a similar length of time after rifampin withdrawal. This interaction appears to be clinically significant." ], "offsets": [ [ 0, 863 ] ] } ]

[ { "id": "1115445_T1", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "1115445_T2", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 13, 21 ] ], "normalized": [] }, { "id": "1115445_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 72, 80 ] ], "normalized": [] }, { "id": "1115445_T4", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 85, 93 ] ], "normalized": [] }, { "id": "1115445_T5", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 113, 121 ] ], "normalized": [] }, { "id": "1115445_T6", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 156, 164 ] ], "normalized": [] }, { "id": "1115445_T7", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 269, 277 ] ], "normalized": [] }, { "id": "1115445_T8", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 282, 290 ] ], "normalized": [] }, { "id": "1115445_T9", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 354, 362 ] ], "normalized": [] }, { "id": "1115445_T10", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 435, 443 ] ], "normalized": [] }, { "id": "1115445_T11", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 458, 466 ] ], "normalized": [] }, { "id": "1115445_T12", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 533, 541 ] ], "normalized": [] }, { "id": "1115445_T13", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 600, 608 ] ], "normalized": [] }, { "id": "1115445_T14", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 624, 632 ] ], "normalized": [] }, { "id": "1115445_T15", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 640, 648 ] ], "normalized": [] }, { "id": "1115445_T16", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 735, 743 ] ], "normalized": [] }, { "id": "1115445_T17", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 788, 796 ] ], "normalized": [] } ]

[]

[]

[ { "id": "1115445_R1", "type": "INT", "arg1_id": "1115445_T1", "arg2_id": "1115445_T2", "normalized": [] }, { "id": "1115445_R2", "type": "INT", "arg1_id": "1115445_T3", "arg2_id": "1115445_T4", "normalized": [] }, { "id": "1115445_R3", "type": "MECHANISM", "arg1_id": "1115445_T5", "arg2_id": "1115445_T6", "normalized": [] }, { "id": "1115445_R4", "type": "MECHANISM", "arg1_id": "1115445_T7", "arg2_id": "1115445_T8", "normalized": [] }, { "id": "1115445_R5", "type": "MECHANISM", "arg1_id": "1115445_T10", "arg2_id": "1115445_T11", "normalized": [] }, { "id": "1115445_R6", "type": "MECHANISM", "arg1_id": "1115445_T12", "arg2_id": "1115445_T13", "normalized": [] }, { "id": "1115445_R7", "type": "EFFECT", "arg1_id": "1115445_T14", "arg2_id": "1115445_T15", "normalized": [] } ]

[ { "id": "163470__text", "type": "abstract", "text": [ "[Dose-time effects of competitive displacement of radiopertechnetate by sodium perchlorate following oral and intravenous administration] The effect of various doses of sodium perchlorate in several dose fractions on the extent and the time scale of displacement of radiopertechnetate, in dependence on application mode, was studied. An intravenous dose of 50 mg perchlorate was in respect of competitive suppression of organs actively concentrating pertechnetate as effective as intravenous 1000 mg ClO-4- simultaneously or 1000 mg orally 30 min before the injection of radiopertechnetate. An intravenous injection of perchlorate given later also produces a complete and immediately beginning depletion of pertechnetate already accumulated in the thyroid, within a period of 195 min after 99m-TcO-4-injection with a corresponding increase in blood levels. 20 mg result in incomplete depletion which becomes complete after a second additional dose. The intravenous application of perchlorate offers advantages in clinical use." ], "offsets": [ [ 0, 1026 ] ] } ]

[ { "id": "163470_T1", "type": "DRUG", "text": [ "radiopertechnetate" ], "offsets": [ [ 50, 68 ] ], "normalized": [] }, { "id": "163470_T2", "type": "DRUG_N", "text": [ "sodium perchlorate" ], "offsets": [ [ 72, 90 ] ], "normalized": [] }, { "id": "163470_T3", "type": "DRUG_N", "text": [ "sodium perchlorate" ], "offsets": [ [ 169, 187 ] ], "normalized": [] }, { "id": "163470_T4", "type": "DRUG", "text": [ "radiopertechnetate" ], "offsets": [ [ 266, 284 ] ], "normalized": [] }, { "id": "163470_T5", "type": "DRUG_N", "text": [ "perchlorate" ], "offsets": [ [ 363, 374 ] ], "normalized": [] }, { "id": "163470_T6", "type": "DRUG", "text": [ "pertechnetate" ], "offsets": [ [ 450, 463 ] ], "normalized": [] }, { "id": "163470_T7", "type": "DRUG", "text": [ "radiopertechnetate" ], "offsets": [ [ 571, 589 ] ], "normalized": [] }, { "id": "163470_T8", "type": "DRUG_N", "text": [ "perchlorate" ], "offsets": [ [ 619, 630 ] ], "normalized": [] }, { "id": "163470_T9", "type": "DRUG", "text": [ "pertechnetate" ], "offsets": [ [ 707, 720 ] ], "normalized": [] }, { "id": "163470_T10", "type": "DRUG_N", "text": [ "perchlorate" ], "offsets": [ [ 980, 991 ] ], "normalized": [] } ]

[]

[]

[ { "id": "163470_R1", "type": "MECHANISM", "arg1_id": "163470_T8", "arg2_id": "163470_T9", "normalized": [] } ]

[ { "id": "16649344__text", "type": "abstract", "text": [ "Sirolimus: mammalian target of rapamycin inhibitor to prevent kidney rejection. Current immunosuppressive therapies are effective but can be associated with significant adverse reactions. Sirolimus works differently from the immunosuppressants currently available, and except for increased lipid levels, the adverse reaction profile of sirolimus does not appear to overlap to any great extent with that associated with cyclosporine or tacrolimus. While additional research is needed, the initial clinical data in kidney recipients suggest that sirolimus, in combination with cyclosporine or tacrolimus, might have the potential to reduce the frequency of rejection episodes, permit reductions in cyclosporine or tacrolimus dosage, and permit steroid withdrawal (Kelly, 1999)." ], "offsets": [ [ 0, 775 ] ] } ]

[ { "id": "16649344_T1", "type": "DRUG", "text": [ "Sirolimus" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "16649344_T2", "type": "DRUG", "text": [ "rapamycin" ], "offsets": [ [ 31, 40 ] ], "normalized": [] }, { "id": "16649344_T3", "type": "DRUG", "text": [ "Sirolimus" ], "offsets": [ [ 188, 197 ] ], "normalized": [] }, { "id": "16649344_T4", "type": "GROUP", "text": [ "immunosuppressants" ], "offsets": [ [ 225, 243 ] ], "normalized": [] }, { "id": "16649344_T5", "type": "DRUG", "text": [ "sirolimus" ], "offsets": [ [ 336, 345 ] ], "normalized": [] }, { "id": "16649344_T6", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 419, 431 ] ], "normalized": [] }, { "id": "16649344_T7", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 435, 445 ] ], "normalized": [] }, { "id": "16649344_T8", "type": "DRUG", "text": [ "sirolimus" ], "offsets": [ [ 544, 553 ] ], "normalized": [] }, { "id": "16649344_T9", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 575, 587 ] ], "normalized": [] }, { "id": "16649344_T10", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 591, 601 ] ], "normalized": [] }, { "id": "16649344_T11", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 696, 708 ] ], "normalized": [] }, { "id": "16649344_T12", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 712, 722 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "3964797__text", "type": "abstract", "text": [ "Pharmacokinetic evaluation of the digoxin-amiodarone interaction. Amiodarone is known to raise serum digoxin levels. This study was designed to evaluate the pharmacokinetic basis of this interaction in 10 normal subjects. The pharmacokinetic variables for digoxin were determined after a 1.0 mg intravenous dose of digoxin in each subject, before and after oral amiodarone, 400 mg daily for 3 weeks. During amiodarone administration, systemic clearance of digoxin was reduced from 234 +/- 72 ml/min (mean +/- standard deviation) to 172 +/- 33 ml/min (p less than 0.01). This was due to reductions in both renal clearance (from 105 +/- 39 to 84 +/- 15 ml/min) (p less than 0.05) and nonrenal clearance (from 130 +/- 38 to 88 +/- 20 ml/min) (p less than 0.01). Digoxin half-life of elimination was prolonged from 34 +/- 13 to 40 +/- 16 hours (p less than 0.05). Digoxin volume of distribution was not significantly changed. Amiodarone caused a three- to fivefold increase in serum reverse triiodothyronine levels, but changes in thyroid function were not quantitatively related to the changes in digoxin pharmacokinetics. These alterations in digoxin pharmacokinetics produced by amiodarone explain the increase in serum digoxin level that has been observed when this drug combination has been used clinically." ], "offsets": [ [ 0, 1308 ] ] } ]

[ { "id": "3964797_T1", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 34, 41 ] ], "normalized": [] }, { "id": "3964797_T2", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 42, 52 ] ], "normalized": [] }, { "id": "3964797_T3", "type": "DRUG", "text": [ "Amiodarone" ], "offsets": [ [ 66, 76 ] ], "normalized": [] }, { "id": "3964797_T4", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 101, 108 ] ], "normalized": [] }, { "id": "3964797_T5", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 256, 263 ] ], "normalized": [] }, { "id": "3964797_T6", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 315, 322 ] ], "normalized": [] }, { "id": "3964797_T7", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 362, 372 ] ], "normalized": [] }, { "id": "3964797_T8", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 407, 417 ] ], "normalized": [] }, { "id": "3964797_T9", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 456, 463 ] ], "normalized": [] }, { "id": "3964797_T10", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 759, 766 ] ], "normalized": [] }, { "id": "3964797_T11", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 860, 867 ] ], "normalized": [] }, { "id": "3964797_T12", "type": "DRUG", "text": [ "Amiodarone" ], "offsets": [ [ 922, 932 ] ], "normalized": [] }, { "id": "3964797_T13", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1094, 1101 ] ], "normalized": [] }, { "id": "3964797_T14", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1141, 1148 ] ], "normalized": [] }, { "id": "3964797_T15", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 1178, 1188 ] ], "normalized": [] }, { "id": "3964797_T16", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1219, 1226 ] ], "normalized": [] } ]

[]

[]

[ { "id": "3964797_R1", "type": "MECHANISM", "arg1_id": "3964797_T3", "arg2_id": "3964797_T4", "normalized": [] }, { "id": "3964797_R2", "type": "MECHANISM", "arg1_id": "3964797_T8", "arg2_id": "3964797_T9", "normalized": [] }, { "id": "3964797_R3", "type": "MECHANISM", "arg1_id": "3964797_T14", "arg2_id": "3964797_T15", "normalized": [] } ]

[ { "id": "11181395__text", "type": "abstract", "text": [ "Restoration of vancomycin susceptibility in Enterococcus faecalis by antiresistance determinant gene transfer. We assessed the ability of gene transfer to reverse vancomycin resistance in class A (VanA) glycopeptide-resistant Enterococcus faecalis. Recombinant shuttle vectors containing a vanH promoter-vanA antisense gene cassette fully restored vancomycin susceptibility through a combined transcriptional activator binding domain decoy and inducible vanA antisense RNA effect." ], "offsets": [ [ 0, 480 ] ] } ]

[ { "id": "11181395_T1", "type": "DRUG", "text": [ "vancomycin" ], "offsets": [ [ 15, 25 ] ], "normalized": [] }, { "id": "11181395_T2", "type": "DRUG", "text": [ "vancomycin" ], "offsets": [ [ 163, 173 ] ], "normalized": [] }, { "id": "11181395_T3", "type": "DRUG", "text": [ "vancomycin" ], "offsets": [ [ 348, 358 ] ], "normalized": [] } ]

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[]

[ { "id": "11210404__text", "type": "abstract", "text": [ "Lack of an effect of azithromycin on the disposition of zidovudine and dideoxyinosine in HIV-infected patients. Two studies were conducted in HIV-infected subjects to assess the potential for azithromycin to interact with zidovudine and dideoxyinosine. Both studies used 12 subjects. The zidovudine study dosed subjects with 1200 mg/day of azithromycin (n = 7) (later changed to 600 mg/day [n = 5]) for Days 8 to 21 of a 21-day course of 100 mg, five times/day of zidovudine. Subjects treated with 200 mg of dideoxyinosine twice daily for 21 days received 1200 mg of azithromycin or an equivalent amount of placebo/day for Days 8 to 21. Antiretroviral plasma and urine sampling were conducted on Days 1, 7, and 21 for zidovudine and on Days 7 and 21 for dideoxyinosine. Peripheral mononuclear cells were also collected for quantitation of phosphorylated zidovudine. Azithromycin had no significant impact on the Cmax and AUC of zidovudine, although it significantly decreased the zidovudine tmax by 44% and increased the intracellular exposure to phosphorylated zidovudine by 110%. Azithromycin had no significant effect on dideoxyinosine pharmacokinetics. Based on the results of these studies, it is concluded that azithromycin may be safely coadministered with both zidovudine and dideoxyinosine." ], "offsets": [ [ 0, 1299 ] ] } ]

[ { "id": "11210404_T1", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 21, 33 ] ], "normalized": [] }, { "id": "11210404_T2", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 56, 66 ] ], "normalized": [] }, { "id": "11210404_T3", "type": "DRUG", "text": [ "dideoxyinosine" ], "offsets": [ [ 71, 85 ] ], "normalized": [] }, { "id": "11210404_T4", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 192, 204 ] ], "normalized": [] }, { "id": "11210404_T5", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 222, 232 ] ], "normalized": [] }, { "id": "11210404_T6", "type": "DRUG", "text": [ "dideoxyinosine" ], "offsets": [ [ 237, 251 ] ], "normalized": [] }, { "id": "11210404_T7", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "11210404_T8", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 340, 352 ] ], "normalized": [] }, { "id": "11210404_T9", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 464, 474 ] ], "normalized": [] }, { "id": "11210404_T10", "type": "DRUG", "text": [ "dideoxyinosine" ], "offsets": [ [ 508, 522 ] ], "normalized": [] }, { "id": "11210404_T11", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 567, 579 ] ], "normalized": [] }, { "id": "11210404_T12", "type": "GROUP", "text": [ "Antiretroviral" ], "offsets": [ [ 637, 651 ] ], "normalized": [] }, { "id": "11210404_T13", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 718, 728 ] ], "normalized": [] }, { "id": "11210404_T14", "type": "DRUG", "text": [ "dideoxyinosine" ], "offsets": [ [ 754, 768 ] ], "normalized": [] }, { "id": "11210404_T15", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 854, 864 ] ], "normalized": [] }, { "id": "11210404_T16", "type": "DRUG", "text": [ "Azithromycin" ], "offsets": [ [ 866, 878 ] ], "normalized": [] }, { "id": "11210404_T17", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 928, 938 ] ], "normalized": [] }, { "id": "11210404_T18", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 980, 990 ] ], "normalized": [] }, { "id": "11210404_T19", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 1062, 1072 ] ], "normalized": [] }, { "id": "11210404_T20", "type": "DRUG", "text": [ "Azithromycin" ], "offsets": [ [ 1082, 1094 ] ], "normalized": [] }, { "id": "11210404_T21", "type": "DRUG", "text": [ "dideoxyinosine" ], "offsets": [ [ 1124, 1138 ] ], "normalized": [] }, { "id": "11210404_T22", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 1217, 1229 ] ], "normalized": [] }, { "id": "11210404_T23", "type": "DRUG", "text": [ "zidovudine" ], "offsets": [ [ 1269, 1279 ] ], "normalized": [] }, { "id": "11210404_T24", "type": "DRUG", "text": [ "dideoxyinosine" ], "offsets": [ [ 1284, 1298 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11210404_R1", "type": "MECHANISM", "arg1_id": "11210404_T16", "arg2_id": "11210404_T18", "normalized": [] }, { "id": "11210404_R2", "type": "MECHANISM", "arg1_id": "11210404_T16", "arg2_id": "11210404_T19", "normalized": [] } ]

[ { "id": "7756965__text", "type": "abstract", "text": [ "[The effect of cimetidine on the renal excretion of verografin and iodamide in dogs] The intravenous injection of cimetidine in a dose of 20 mg/kg enhanced verografine and iodamide excretion in chronic canine experiments. The higher verografine and iodamide excretion was due to their increased renal tubular secretion. In dogs, cimetidine unchanged the secretion of cardiotrast, a test agent for anionic transport. Possible extrarenal mechanisms of action of cimetidine on verografine and iodamide transport were also examined." ], "offsets": [ [ 0, 528 ] ] } ]

[ { "id": "7756965_T1", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 15, 25 ] ], "normalized": [] }, { "id": "7756965_T2", "type": "DRUG", "text": [ "verografin" ], "offsets": [ [ 52, 62 ] ], "normalized": [] }, { "id": "7756965_T3", "type": "DRUG", "text": [ "iodamide" ], "offsets": [ [ 67, 75 ] ], "normalized": [] }, { "id": "7756965_T4", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 114, 124 ] ], "normalized": [] }, { "id": "7756965_T5", "type": "DRUG", "text": [ "verografine" ], "offsets": [ [ 156, 167 ] ], "normalized": [] }, { "id": "7756965_T6", "type": "DRUG", "text": [ "iodamide" ], "offsets": [ [ 172, 180 ] ], "normalized": [] }, { "id": "7756965_T7", "type": "DRUG", "text": [ "verografine" ], "offsets": [ [ 233, 244 ] ], "normalized": [] }, { "id": "7756965_T8", "type": "DRUG", "text": [ "iodamide" ], "offsets": [ [ 249, 257 ] ], "normalized": [] }, { "id": "7756965_T9", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 329, 339 ] ], "normalized": [] }, { "id": "7756965_T10", "type": "DRUG", "text": [ "cardiotrast" ], "offsets": [ [ 367, 378 ] ], "normalized": [] }, { "id": "7756965_T11", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 460, 470 ] ], "normalized": [] }, { "id": "7756965_T12", "type": "DRUG", "text": [ "verografine" ], "offsets": [ [ 474, 485 ] ], "normalized": [] }, { "id": "7756965_T13", "type": "DRUG", "text": [ "iodamide" ], "offsets": [ [ 490, 498 ] ], "normalized": [] } ]

[]

[]

[ { "id": "7756965_R1", "type": "MECHANISM", "arg1_id": "7756965_T4", "arg2_id": "7756965_T5", "normalized": [] }, { "id": "7756965_R2", "type": "MECHANISM", "arg1_id": "7756965_T4", "arg2_id": "7756965_T6", "normalized": [] } ]

[ { "id": "6100240__text", "type": "abstract", "text": [ "Failure of neomycin to modify ACTH induced hypertension in sheep. Studies in rats have shown that neomycin administration attenuates certain types of adrenocortical steroid dependent hypertension, including ACTH hypertension. The effects of oral neomycin on ACTH induced hypertension were examined in conscious sheep. Neomycin has no effect on the blood pressure or metabolic responses to ACTH in sheep." ], "offsets": [ [ 0, 403 ] ] } ]

[ { "id": "6100240_T1", "type": "DRUG", "text": [ "neomycin" ], "offsets": [ [ 11, 19 ] ], "normalized": [] }, { "id": "6100240_T2", "type": "GROUP", "text": [ "ACTH" ], "offsets": [ [ 30, 34 ] ], "normalized": [] }, { "id": "6100240_T3", "type": "DRUG", "text": [ "neomycin" ], "offsets": [ [ 98, 106 ] ], "normalized": [] }, { "id": "6100240_T4", "type": "GROUP", "text": [ "adrenocortical steroid" ], "offsets": [ [ 150, 172 ] ], "normalized": [] }, { "id": "6100240_T5", "type": "DRUG", "text": [ "ACTH" ], "offsets": [ [ 207, 211 ] ], "normalized": [] }, { "id": "6100240_T6", "type": "DRUG", "text": [ "neomycin" ], "offsets": [ [ 246, 254 ] ], "normalized": [] }, { "id": "6100240_T7", "type": "GROUP", "text": [ "ACTH" ], "offsets": [ [ 258, 262 ] ], "normalized": [] }, { "id": "6100240_T8", "type": "DRUG", "text": [ "Neomycin" ], "offsets": [ [ 318, 326 ] ], "normalized": [] }, { "id": "6100240_T9", "type": "GROUP", "text": [ "ACTH" ], "offsets": [ [ 389, 393 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6100240_R1", "type": "EFFECT", "arg1_id": "6100240_T3", "arg2_id": "6100240_T5", "normalized": [] } ]

[ { "id": "11148572__text", "type": "abstract", "text": [ "Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy plus highly active antiretroviral therapy in patients with human immunodeficiency virus-related, non-Hodgkin lymphoma. BACKGROUND: The feasibility and efficacy of concomitant chemotherapy and highly active antiretroviral therapy (HAART) is still unknown in patients with human immunodeficiency virus (HIV)-related malignancies. To evaluate the impact of chemotherapy plus HAART on the clinical course of patients with HIV-related, systemic, non-Hodgkin lymphoma (HIV-NHL), the authors compared retrospectively a group of 24 patients with HIV-NHL who were treated with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen plus HAART with a group of 80 patients who were treated with CHOP chemotherapy or a CHOP-like regimen (i.e., cyclophosphamide, doxorubicin, teniposide, and prednisone with vincristine plus bleomycin) without receiving antiretroviral therapy. METHODS: All patients were enrolled in two sequential trials performed at the Aviano Cancer Center, Italy, from April 1988 to December 1998. HAART was included with combination therapy from January 1997. Antiretroviral regimens consisted of two reverse transcriptase inhibitors and one protease inhibitor. RESULTS: The two treatment groups were well matched with regard to patient demographics, NHL characteristics, HIV status, and treatment, i.e., the number of cycles and chemotherapy dose. The response rates were similar between the two groups. Severe anemia (Grade 3-4 according to the World Health Organization criteria) was significantly greater in the patients who received CHOP-HAART compared with the patients who received CHOP alone (33% vs. 7%, respectively; P = 0.001). Leukopenia was similar between the two groups, but colony stimulating factor support was significantly greater in the CHOP-HAART group than in the control group (92% vs. 66%, respectively; P = 0.03). Seventeen percent of CHOP-HAART patients developed severe autonomic neurotoxicity, whereas none of the CHOP patients developed neurotoxicity (P = 0.002). At similar median follow-up, opportunistic infection (OI) rates and mortality were significantly lower in the CHOP-HAART patients than in the CHOP patients (18% vs. 52%, respectively; P = 0.05; and 38% vs. 85%, respectively; P = 0.001). The median survival for CHOP-HAART patients was not reached, whereas the medial survival of CHOP patients was 7 months (P = 0.03). CONCLUSIONS: The combination of CHOP plus HAART is feasible and may reduce the morbidity from OIs in HIV-NHL patients. However, careful attention must be directed to cross toxicity and possible pharmacokinetic interactions between antiretroviral and antineoplastic drugs. The impact of the combined chemotherapy plus HAART treatment on patient survival needs urgently to be evaluated in prospective studies." ], "offsets": [ [ 0, 2897 ] ] } ]

[ { "id": "11148572_T1", "type": "DRUG", "text": [ "cyclophosphamide" ], "offsets": [ [ 12, 28 ] ], "normalized": [] }, { "id": "11148572_T2", "type": "DRUG", "text": [ "doxorubicin" ], "offsets": [ [ 30, 41 ] ], "normalized": [] }, { "id": "11148572_T3", "type": "DRUG", "text": [ "vincristine" ], "offsets": [ [ 43, 54 ] ], "normalized": [] }, { "id": "11148572_T4", "type": "DRUG", "text": [ "prednisone" ], "offsets": [ [ 60, 70 ] ], "normalized": [] }, { "id": "11148572_T5", "type": "GROUP", "text": [ "highly active antiretroviral" ], "offsets": [ [ 89, 117 ] ], "normalized": [] }, { "id": "11148572_T6", "type": "GROUP", "text": [ "highly active antiretroviral" ], "offsets": [ [ 276, 304 ] ], "normalized": [] }, { "id": "11148572_T7", "type": "DRUG", "text": [ "cyclophosphamide" ], "offsets": [ [ 656, 672 ] ], "normalized": [] }, { "id": "11148572_T8", "type": "DRUG", "text": [ "doxorubicin" ], "offsets": [ [ 674, 685 ] ], "normalized": [] }, { "id": "11148572_T9", "type": "DRUG", "text": [ "vincristine" ], "offsets": [ [ 687, 698 ] ], "normalized": [] }, { "id": "11148572_T10", "type": "DRUG", "text": [ "prednisone" ], "offsets": [ [ 704, 714 ] ], "normalized": [] }, { "id": "11148572_T11", "type": "DRUG", "text": [ "cyclophosphamide" ], "offsets": [ [ 852, 868 ] ], "normalized": [] }, { "id": "11148572_T12", "type": "DRUG", "text": [ "doxorubicin" ], "offsets": [ [ 870, 881 ] ], "normalized": [] }, { "id": "11148572_T13", "type": "DRUG", "text": [ "teniposide" ], "offsets": [ [ 883, 893 ] ], "normalized": [] }, { "id": "11148572_T14", "type": "DRUG", "text": [ "prednisone" ], "offsets": [ [ 899, 909 ] ], "normalized": [] }, { "id": "11148572_T15", "type": "DRUG", "text": [ "vincristine" ], "offsets": [ [ 915, 926 ] ], "normalized": [] }, { "id": "11148572_T16", "type": "DRUG", "text": [ "bleomycin" ], "offsets": [ [ 932, 941 ] ], "normalized": [] }, { "id": "11148572_T17", "type": "GROUP", "text": [ "antiretroviral" ], "offsets": [ [ 961, 975 ] ], "normalized": [] }, { "id": "11148572_T18", "type": "GROUP", "text": [ "Antiretroviral" ], "offsets": [ [ 1189, 1203 ] ], "normalized": [] }, { "id": "11148572_T19", "type": "GROUP", "text": [ "reverse transcriptase inhibitors" ], "offsets": [ [ 1230, 1262 ] ], "normalized": [] }, { "id": "11148572_T20", "type": "GROUP", "text": [ "protease inhibitor" ], "offsets": [ [ 1271, 1289 ] ], "normalized": [] }, { "id": "11148572_T21", "type": "GROUP", "text": [ "antiretroviral", "drugs" ], "offsets": [ [ 2721, 2735 ], [ 2755, 2760 ] ], "normalized": [] }, { "id": "11148572_T22", "type": "GROUP", "text": [ "antineoplastic drugs" ], "offsets": [ [ 2740, 2760 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11148572_R1", "type": "ADVISE", "arg1_id": "11148572_T21", "arg2_id": "11148572_T22", "normalized": [] } ]

[ { "id": "1167743__text", "type": "abstract", "text": [ "The effects of ketamine and of Innovar anesthesia on digitalis tolerance in dogs. In a comparison of digitalis tolerance in dogs anesthetized with ketamine, Innovar Vet, or pentobarbital, the dosage of ouabain needed to cause ventricular tachycardia was significantly higher, as was the LD50 of ouabain, with ketamine or Innovar than with pentobarbital. Ventricular tachycardia induced by ouabain was generally converted to sinus rhythm following administration of Innovar, ketamine, or droperidol but not after administration of fentayl alone or after pentobarbital." ], "offsets": [ [ 0, 567 ] ] } ]

[ { "id": "1167743_T1", "type": "DRUG", "text": [ "ketamine" ], "offsets": [ [ 15, 23 ] ], "normalized": [] }, { "id": "1167743_T2", "type": "BRAND", "text": [ "Innovar" ], "offsets": [ [ 31, 38 ] ], "normalized": [] }, { "id": "1167743_T3", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 53, 62 ] ], "normalized": [] }, { "id": "1167743_T4", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 101, 110 ] ], "normalized": [] }, { "id": "1167743_T5", "type": "DRUG", "text": [ "ketamine" ], "offsets": [ [ 147, 155 ] ], "normalized": [] }, { "id": "1167743_T6", "type": "BRAND", "text": [ "Innovar Vet" ], "offsets": [ [ 157, 168 ] ], "normalized": [] }, { "id": "1167743_T7", "type": "DRUG", "text": [ "pentobarbital" ], "offsets": [ [ 173, 186 ] ], "normalized": [] }, { "id": "1167743_T8", "type": "DRUG", "text": [ "ouabain" ], "offsets": [ [ 202, 209 ] ], "normalized": [] }, { "id": "1167743_T9", "type": "DRUG", "text": [ "ouabain" ], "offsets": [ [ 295, 302 ] ], "normalized": [] }, { "id": "1167743_T10", "type": "DRUG", "text": [ "ketamine" ], "offsets": [ [ 309, 317 ] ], "normalized": [] }, { "id": "1167743_T11", "type": "BRAND", "text": [ "Innovar" ], "offsets": [ [ 321, 328 ] ], "normalized": [] }, { "id": "1167743_T12", "type": "DRUG", "text": [ "pentobarbital" ], "offsets": [ [ 339, 352 ] ], "normalized": [] }, { "id": "1167743_T13", "type": "DRUG", "text": [ "ouabain" ], "offsets": [ [ 389, 396 ] ], "normalized": [] }, { "id": "1167743_T14", "type": "BRAND", "text": [ "Innovar" ], "offsets": [ [ 465, 472 ] ], "normalized": [] }, { "id": "1167743_T15", "type": "DRUG", "text": [ "ketamine" ], "offsets": [ [ 474, 482 ] ], "normalized": [] }, { "id": "1167743_T16", "type": "DRUG", "text": [ "droperidol" ], "offsets": [ [ 487, 497 ] ], "normalized": [] }, { "id": "1167743_T17", "type": "DRUG", "text": [ "fentayl" ], "offsets": [ [ 530, 537 ] ], "normalized": [] }, { "id": "1167743_T18", "type": "DRUG", "text": [ "pentobarbital" ], "offsets": [ [ 553, 566 ] ], "normalized": [] } ]

[]

[]

[ { "id": "1167743_R1", "type": "EFFECT", "arg1_id": "1167743_T5", "arg2_id": "1167743_T8", "normalized": [] }, { "id": "1167743_R2", "type": "EFFECT", "arg1_id": "1167743_T6", "arg2_id": "1167743_T8", "normalized": [] }, { "id": "1167743_R3", "type": "EFFECT", "arg1_id": "1167743_T7", "arg2_id": "1167743_T8", "normalized": [] }, { "id": "1167743_R4", "type": "EFFECT", "arg1_id": "1167743_T13", "arg2_id": "1167743_T14", "normalized": [] }, { "id": "1167743_R5", "type": "EFFECT", "arg1_id": "1167743_T13", "arg2_id": "1167743_T15", "normalized": [] }, { "id": "1167743_R6", "type": "EFFECT", "arg1_id": "1167743_T13", "arg2_id": "1167743_T16", "normalized": [] } ]

[ { "id": "10319155__text", "type": "abstract", "text": [ "Antimicrobial activity of Ganoderma lucidum extract alone and in combination with some antibiotics. Antimicrobial activity of GL (the aqueous extract from the carpophores of Ganoderma lucidum (FR)KARST) was tested in vitro against Gram positive and Gram negative bacteria by serial broth dilution method, and the antimicrobial activity was expressed by minimal inhibitory concentration (MIC). Among fifteen species of bacteria tested, the antimicrobial activity of GL was the most potent against Micrococcus luteus (MIC, 0.75 mg/ml). To investigate the effects of antimicrobial combinations of GL with four kinds of antibiotics (ampicillin, cefazolin, oxytetracycline and chloramphenicol), the fractional inhibitory concentration index (FICI) was determined by checkerboard assay for each strain. The antimicrobial combinations of GL with four antibiotics resulted in additive effect in most instances, synergism in two instances, and antagonism in two instances. Synergism was observed when GL was combined with cefazolin against Bacillus subtilis and Klebsiella oxytoca." ], "offsets": [ [ 0, 1072 ] ] } ]

[ { "id": "10319155_T1", "type": "DRUG_N", "text": [ "Ganoderma lucidum extract" ], "offsets": [ [ 26, 51 ] ], "normalized": [] }, { "id": "10319155_T2", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 87, 98 ] ], "normalized": [] }, { "id": "10319155_T3", "type": "DRUG_N", "text": [ "GL" ], "offsets": [ [ 126, 128 ] ], "normalized": [] }, { "id": "10319155_T4", "type": "DRUG_N", "text": [ "GL" ], "offsets": [ [ 465, 467 ] ], "normalized": [] }, { "id": "10319155_T5", "type": "DRUG_N", "text": [ "GL" ], "offsets": [ [ 594, 596 ] ], "normalized": [] }, { "id": "10319155_T6", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 616, 627 ] ], "normalized": [] }, { "id": "10319155_T7", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 629, 639 ] ], "normalized": [] }, { "id": "10319155_T8", "type": "DRUG", "text": [ "cefazolin" ], "offsets": [ [ 641, 650 ] ], "normalized": [] }, { "id": "10319155_T9", "type": "DRUG", "text": [ "oxytetracycline" ], "offsets": [ [ 652, 667 ] ], "normalized": [] }, { "id": "10319155_T10", "type": "DRUG", "text": [ "chloramphenicol" ], "offsets": [ [ 672, 687 ] ], "normalized": [] }, { "id": "10319155_T11", "type": "DRUG_N", "text": [ "GL" ], "offsets": [ [ 831, 833 ] ], "normalized": [] }, { "id": "10319155_T12", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 844, 855 ] ], "normalized": [] }, { "id": "10319155_T13", "type": "DRUG_N", "text": [ "GL" ], "offsets": [ [ 992, 994 ] ], "normalized": [] }, { "id": "10319155_T14", "type": "DRUG", "text": [ "cefazolin" ], "offsets": [ [ 1013, 1022 ] ], "normalized": [] } ]

[]

[]

[ { "id": "10319155_R1", "type": "EFFECT", "arg1_id": "10319155_T11", "arg2_id": "10319155_T12", "normalized": [] }, { "id": "10319155_R2", "type": "EFFECT", "arg1_id": "10319155_T13", "arg2_id": "10319155_T14", "normalized": [] } ]

[ { "id": "8682269__text", "type": "abstract", "text": [ "[Multiple occupational exposure to solvents]\nThis article review papers published over the last 20 years on multiple occupational exposure to solvents. At low-levels of exposure the toxicokinetic interferences between solvents have generally not been observed in man and presumably a threshold limit exists. Conversely, at exposure levels close to the \"limit values\" metabolic interference has sometimes been observed and the behaviour of the biological indicators differs from what would be expected. Toxicodynamic interference between solvents can give rise to additive, potentiation, synergistic, antagonistic effects. For the identification of \"limit values\", it has generally been suggested in the literature that the possible effects deriving from multiple exposure be considered as additive. However, numerous potentiation effects have frequently been reported for combined exposure to substances of widespread use. In this paper lists of multiple exposure in which the doses of the substances, the types of interferences and the behaviour of the biological levels have been drawn up and proposed as a tool for easy consultation." ], "offsets": [ [ 0, 1136 ] ] } ]

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[ { "id": "1089034__text", "type": "abstract", "text": [ "Death in amphetamine users: causes and rates. The world medical literature contains 43 reports of deaths associated with amphetamines in a 35-year period. These included seven cerebrovascular accidents, six sudden cardiac deaths, three cases of hyperpyrexia, eight poisonings of uncertain mechanism and seven cases of medical complications of intravenous injection; the remainder were of uncertain cause. In contrast, in Ontario alone, in 1972 and 1973 there were 26 deaths in amphetamine users, of which 16 were due to accident suicide or homicide. Of the remaining cases, two were cardiac, two hepatic and the rest were mixed drug overdose. Pulmonary granulomata, subacute hepatitis and other lesions resulting from intravenous drug use were common findings at autopsy. On the basis of the estimated number of regular users of intravenous amphetamine in Ontario, the mortality rate in such users is at least four times as high as in the general population of the same age, and is comparable to that in alcoholics and heroin addicts. However, the absolute number of alcohol-related deaths is far greater than the number of deaths in amphetamine or heroin users." ], "offsets": [ [ 0, 1162 ] ] } ]

[ { "id": "1089034_T1", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 9, 20 ] ], "normalized": [] }, { "id": "1089034_T2", "type": "DRUG", "text": [ "amphetamines" ], "offsets": [ [ 121, 133 ] ], "normalized": [] }, { "id": "1089034_T3", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 477, 488 ] ], "normalized": [] }, { "id": "1089034_T4", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 841, 852 ] ], "normalized": [] }, { "id": "1089034_T5", "type": "DRUG_N", "text": [ "heroin" ], "offsets": [ [ 1019, 1025 ] ], "normalized": [] }, { "id": "1089034_T6", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 1067, 1074 ] ], "normalized": [] }, { "id": "1089034_T7", "type": "DRUG", "text": [ "amphetamine" ], "offsets": [ [ 1134, 1145 ] ], "normalized": [] }, { "id": "1089034_T8", "type": "DRUG_N", "text": [ "heroin" ], "offsets": [ [ 1149, 1155 ] ], "normalized": [] } ]

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[ { "id": "7625885__text", "type": "abstract", "text": [ "Analysis of 16,16-dimethylprostaglandin E2-induced diarrhea in cecectomized rats. The 16,16-dimethylprostaglandin E2 (dmPGE2)-induced diarrhea was analyzed in cecectomized rats prepared by resecting the cecum and its vasculature without disturbing the ileocecal junction. dmPGE2 (0.1-1.0 mg/kg, p.o.) dose-dependently increased the number of defecation episodes and induced a soft and watery stool in cecectomized rats. At 0.3 mg/kg, the diarrhea-inducing effects of dmPGE2 were more pronounced in cecectomized than in control rats. When given i.p., dmPGE2 (0.3 mg/kg) induced a watery stool in cecectomized and control rats with the same efficacy, although these effects were short-lasting as compared to oral administration. Castor oil (4 ml/kg, p.o.) also induced diarrhea, but did not produce a watery stool in cecectomized rats. There were no differences between cecectomized and control rats in basal small intestinal transits or in dmPGE2 (0.3 mg/kg, p.o.)-induced enhancements. Moreover, the basal and dmPGE2-induced jejunal net fluid transfers were the same in cecectomized and in control rats. On the other hand, the enhanced secretion of colonic fluid by dmPGE2, given intraluminally, was only half of that in control rats, whereas the colonic transit-enhancing effect of dmPGE2 in cecectomized rats was more pronounced than in control rats at 15 but not at 30 min after its administration. The basal colonic fluid contents and transits were the same in cecectomized and in control rats. Loperamide and morphine (0.1 and 1.0 mg/kg, s.c.) Loperamide and morphine (0.1 and 1.0 mg/kg, s.c.) inhibited the dmPGE2 (0.3 mg/kg, p.o.)-induced diarrhea in cecectomized rats. N-methyllevallorphan (5 mg/kg, s.c.) N-methyllevallorphan (5 mg/kg, s.c.) completely antagonized the inhibitory effect of loperamide and partly antagonized the effect of morphine. These results suggest that oral administration of dmPGE2 induces a more pronounced secretory diarrhea in cecectomized than in control rats, probably due to the lack of the reservoir function of the cecum in the operated animals. This secretory diarrhea model is suitable for evaluating the antidiarrheal activity of drugs." ], "offsets": [ [ 0, 2179 ] ] } ]

[ { "id": "7625885_T1", "type": "DRUG_N", "text": [ "16,16-dimethylprostaglandin E2" ], "offsets": [ [ 12, 42 ] ], "normalized": [] }, { "id": "7625885_T2", "type": "DRUG_N", "text": [ "16,16-dimethylprostaglandin E2" ], "offsets": [ [ 86, 116 ] ], "normalized": [] }, { "id": "7625885_T3", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 118, 124 ] ], "normalized": [] }, { "id": "7625885_T4", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 272, 278 ] ], "normalized": [] }, { "id": "7625885_T5", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 467, 473 ] ], "normalized": [] }, { "id": "7625885_T6", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 550, 556 ] ], "normalized": [] }, { "id": "7625885_T7", "type": "DRUG", "text": [ "Castor oil" ], "offsets": [ [ 727, 737 ] ], "normalized": [] }, { "id": "7625885_T8", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 939, 945 ] ], "normalized": [] }, { "id": "7625885_T9", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 1010, 1016 ] ], "normalized": [] }, { "id": "7625885_T10", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 1166, 1172 ] ], "normalized": [] }, { "id": "7625885_T11", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 1283, 1289 ] ], "normalized": [] }, { "id": "7625885_T12", "type": "DRUG", "text": [ "Loperamide" ], "offsets": [ [ 1499, 1509 ] ], "normalized": [] }, { "id": "7625885_T13", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 1514, 1522 ] ], "normalized": [] }, { "id": "7625885_T14", "type": "DRUG", "text": [ "Loperamide" ], "offsets": [ [ 1549, 1559 ] ], "normalized": [] }, { "id": "7625885_T15", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 1564, 1572 ] ], "normalized": [] }, { "id": "7625885_T16", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 1613, 1619 ] ], "normalized": [] }, { "id": "7625885_T17", "type": "DRUG_N", "text": [ "N-methyllevallorphan" ], "offsets": [ [ 1677, 1697 ] ], "normalized": [] }, { "id": "7625885_T18", "type": "DRUG_N", "text": [ "N-methyllevallorphan" ], "offsets": [ [ 1714, 1734 ] ], "normalized": [] }, { "id": "7625885_T19", "type": "DRUG", "text": [ "loperamide" ], "offsets": [ [ 1799, 1809 ] ], "normalized": [] }, { "id": "7625885_T20", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 1847, 1855 ] ], "normalized": [] }, { "id": "7625885_T21", "type": "DRUG_N", "text": [ "dmPGE2" ], "offsets": [ [ 1907, 1913 ] ], "normalized": [] } ]

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[ { "id": "7625885_R1", "type": "EFFECT", "arg1_id": "7625885_T14", "arg2_id": "7625885_T16", "normalized": [] }, { "id": "7625885_R2", "type": "EFFECT", "arg1_id": "7625885_T15", "arg2_id": "7625885_T16", "normalized": [] }, { "id": "7625885_R3", "type": "EFFECT", "arg1_id": "7625885_T18", "arg2_id": "7625885_T19", "normalized": [] }, { "id": "7625885_R4", "type": "EFFECT", "arg1_id": "7625885_T18", "arg2_id": "7625885_T20", "normalized": [] } ]

[ { "id": "1109248__text", "type": "abstract", "text": [ "Clinical implications of warfarin interactions with five sedatives. The intensity, uniformity and time course of anticoagulant interference by phenobarbital, secobarbital, glutethimide, chloral hydrate and methaqualone were systematically investigated in 16 patients receiving coumarin therapy. Each subject received an individualized fixed daily dose of warfarin and served as his own pre- and postsedative treatment control. Prothrombin times were measured four times weekly during five long-term experiments. Anticoagulant inhibition was observed during the administration of phenobarbital, secobarbital and glutethimide; there was no significant change in prothrombin test results during the trials of chloral hydrate and methaqualone. Barbiturates and glutethimide should not be administered to patients receiving coumarin drugs. The concurrent use of drugs from these groups is decreasing according to a survey of 200 hospital medical records. Chloral hydrate and methaqualone interact pharmacologically with orally administered anticoagulant agents, but the effect is not clinically significant. It is concluded that chloral hydrate and methaqualone may be administered safely without additional caution in prothrombin test monitoring during oral anticoagulant therapy." ], "offsets": [ [ 0, 1276 ] ] } ]

[ { "id": "1109248_T1", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 25, 33 ] ], "normalized": [] }, { "id": "1109248_T2", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 57, 66 ] ], "normalized": [] }, { "id": "1109248_T3", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 113, 126 ] ], "normalized": [] }, { "id": "1109248_T4", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 143, 156 ] ], "normalized": [] }, { "id": "1109248_T5", "type": "DRUG", "text": [ "secobarbital" ], "offsets": [ [ 158, 170 ] ], "normalized": [] }, { "id": "1109248_T6", "type": "DRUG", "text": [ "glutethimide" ], "offsets": [ [ 172, 184 ] ], "normalized": [] }, { "id": "1109248_T7", "type": "DRUG", "text": [ "chloral hydrate" ], "offsets": [ [ 186, 201 ] ], "normalized": [] }, { "id": "1109248_T8", "type": "DRUG", "text": [ "methaqualone" ], "offsets": [ [ 206, 218 ] ], "normalized": [] }, { "id": "1109248_T9", "type": "GROUP", "text": [ "coumarin" ], "offsets": [ [ 277, 285 ] ], "normalized": [] }, { "id": "1109248_T10", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 355, 363 ] ], "normalized": [] }, { "id": "1109248_T11", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 579, 592 ] ], "normalized": [] }, { "id": "1109248_T12", "type": "DRUG", "text": [ "secobarbital" ], "offsets": [ [ 594, 606 ] ], "normalized": [] }, { "id": "1109248_T13", "type": "DRUG", "text": [ "glutethimide" ], "offsets": [ [ 611, 623 ] ], "normalized": [] }, { "id": "1109248_T14", "type": "DRUG", "text": [ "chloral hydrate" ], "offsets": [ [ 706, 721 ] ], "normalized": [] }, { "id": "1109248_T15", "type": "DRUG", "text": [ "methaqualone" ], "offsets": [ [ 726, 738 ] ], "normalized": [] }, { "id": "1109248_T16", "type": "GROUP", "text": [ "Barbiturates" ], "offsets": [ [ 740, 752 ] ], "normalized": [] }, { "id": "1109248_T17", "type": "DRUG", "text": [ "glutethimide" ], "offsets": [ [ 757, 769 ] ], "normalized": [] }, { "id": "1109248_T18", "type": "GROUP", "text": [ "coumarin drugs" ], "offsets": [ [ 819, 833 ] ], "normalized": [] }, { "id": "1109248_T19", "type": "DRUG", "text": [ "Chloral hydrate" ], "offsets": [ [ 950, 965 ] ], "normalized": [] }, { "id": "1109248_T20", "type": "DRUG", "text": [ "methaqualone" ], "offsets": [ [ 970, 982 ] ], "normalized": [] }, { "id": "1109248_T21", "type": "GROUP", "text": [ "anticoagulant agents" ], "offsets": [ [ 1035, 1055 ] ], "normalized": [] }, { "id": "1109248_T22", "type": "DRUG", "text": [ "chloral hydrate" ], "offsets": [ [ 1124, 1139 ] ], "normalized": [] }, { "id": "1109248_T23", "type": "DRUG", "text": [ "methaqualone" ], "offsets": [ [ 1144, 1156 ] ], "normalized": [] }, { "id": "1109248_T24", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 1254, 1267 ] ], "normalized": [] } ]

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[]

[ { "id": "1109248_R1", "type": "INT", "arg1_id": "1109248_T1", "arg2_id": "1109248_T2", "normalized": [] }, { "id": "1109248_R2", "type": "ADVISE", "arg1_id": "1109248_T16", "arg2_id": "1109248_T18", "normalized": [] }, { "id": "1109248_R3", "type": "ADVISE", "arg1_id": "1109248_T17", "arg2_id": "1109248_T18", "normalized": [] }, { "id": "1109248_R4", "type": "INT", "arg1_id": "1109248_T19", "arg2_id": "1109248_T21", "normalized": [] }, { "id": "1109248_R5", "type": "INT", "arg1_id": "1109248_T20", "arg2_id": "1109248_T21", "normalized": [] } ]

[ { "id": "11152438__text", "type": "abstract", "text": [ "Activity of buforin II alone and in combination with azithromycin and minocycline against Cryptosporidium parvum in cell culture. The in vitro anti-cryptosporidial activity of buforin II alone and in combination with azithromycin and minocycline was investigated. Buforin II showed moderate activity, which increased with increasing concentration to 55.7% suppression of growth at 20 microM. Moreover, its activity was enhanced when it was combined with either azithromycin or minocycline with 90% parasite reduction at the highest concentration tested. Buforin II may be active in inhibiting Cryptosporidium parvum growth in vitro upon combination with either azithromycin or minocycline." ], "offsets": [ [ 0, 689 ] ] } ]

[ { "id": "11152438_T1", "type": "DRUG_N", "text": [ "buforin II" ], "offsets": [ [ 12, 22 ] ], "normalized": [] }, { "id": "11152438_T2", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 53, 65 ] ], "normalized": [] }, { "id": "11152438_T3", "type": "DRUG", "text": [ "minocycline" ], "offsets": [ [ 70, 81 ] ], "normalized": [] }, { "id": "11152438_T4", "type": "DRUG_N", "text": [ "buforin II" ], "offsets": [ [ 176, 186 ] ], "normalized": [] }, { "id": "11152438_T5", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 217, 229 ] ], "normalized": [] }, { "id": "11152438_T6", "type": "DRUG", "text": [ "minocycline" ], "offsets": [ [ 234, 245 ] ], "normalized": [] }, { "id": "11152438_T7", "type": "DRUG_N", "text": [ "Buforin II" ], "offsets": [ [ 264, 274 ] ], "normalized": [] }, { "id": "11152438_T8", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 461, 473 ] ], "normalized": [] }, { "id": "11152438_T9", "type": "DRUG", "text": [ "minocycline" ], "offsets": [ [ 477, 488 ] ], "normalized": [] }, { "id": "11152438_T10", "type": "DRUG_N", "text": [ "Buforin II" ], "offsets": [ [ 554, 564 ] ], "normalized": [] }, { "id": "11152438_T11", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 661, 673 ] ], "normalized": [] }, { "id": "11152438_T12", "type": "DRUG", "text": [ "minocycline" ], "offsets": [ [ 677, 688 ] ], "normalized": [] } ]

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[]

[ { "id": "11152438_R1", "type": "EFFECT", "arg1_id": "11152438_T10", "arg2_id": "11152438_T11", "normalized": [] }, { "id": "11152438_R2", "type": "EFFECT", "arg1_id": "11152438_T10", "arg2_id": "11152438_T12", "normalized": [] } ]

[ { "id": "6537219__text", "type": "abstract", "text": [ "Hypothermia as an index of the disulfiram-ethanol reaction in the rat. Decreased core temperature in female rats was investigated as one possible index of the disulfiram-ethanol reaction (DER). Core temperature was decreased in rats in a dose-dependent manner when ethanol was administered to rats treated with disulfiram 8 hours before the ethanol challenge. The decrease in temperature began within 20 minutes after ethanol administration, reaching a maximal decrease between 60 and 120 minutes post ethanol. The core temperature returned to normal 300 minutes after ethanol. The blood pressure (carotid cannulation) decreased along with the core temperature. Maximal hypotension was found 120 minutes post ethanol, and returned to normal 300 minutes after ethanol. Heart rate increased initially and returned to normal 40 minutes after ethanol challenge." ], "offsets": [ [ 0, 857 ] ] } ]

[ { "id": "6537219_T1", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 31, 41 ] ], "normalized": [] }, { "id": "6537219_T2", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 42, 49 ] ], "normalized": [] }, { "id": "6537219_T3", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 159, 169 ] ], "normalized": [] }, { "id": "6537219_T4", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 170, 177 ] ], "normalized": [] }, { "id": "6537219_T5", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 265, 272 ] ], "normalized": [] }, { "id": "6537219_T6", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 311, 321 ] ], "normalized": [] }, { "id": "6537219_T7", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 341, 348 ] ], "normalized": [] }, { "id": "6537219_T8", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 418, 425 ] ], "normalized": [] }, { "id": "6537219_T9", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 502, 509 ] ], "normalized": [] }, { "id": "6537219_T10", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 569, 576 ] ], "normalized": [] }, { "id": "6537219_T11", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 709, 716 ] ], "normalized": [] }, { "id": "6537219_T12", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 759, 766 ] ], "normalized": [] }, { "id": "6537219_T13", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 839, 846 ] ], "normalized": [] } ]

[]

[]

[ { "id": "6537219_R1", "type": "EFFECT", "arg1_id": "6537219_T5", "arg2_id": "6537219_T6", "normalized": [] } ]

[ { "id": "8619063__text", "type": "abstract", "text": [ "Anticoagulants. Treatment plans for patients taking anticoagulants can become complicated. Anticoagulants predispose a patient to bleeding problems. Many drugs used in dentistry cannot be taken concomitantly with these medications." ], "offsets": [ [ 0, 231 ] ] } ]

[ { "id": "8619063_T1", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "8619063_T2", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 52, 66 ] ], "normalized": [] }, { "id": "8619063_T3", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 91, 105 ] ], "normalized": [] } ]

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[ { "id": "6100190__text", "type": "abstract", "text": [ "Diagnostic, treatment and aftercare approaches to cocaine abuse. The general public feels that cocaine is not particularly dangerous because it does not produce a well defined physical dependency and abstinence syndrome. However, when addiction is defined as compulsion, loss of control and continued use in spite of adverse consequences, cocaine drug hunger can be seen as an agent of addictive disease. Withdrawal from cocaine dependence usually involves depression, anxiety and lethargy. These usually clear within a week, leaving only the \"drug hunger\" to contend with. Medication is rarely needed. When cocaine is the primary addiction, after withdrawal the most effective treatment is group therapy with other recovering cocaine abusers. We incorporate the principles of recovery and define positive and constructive alternatives in dealing with cocaine hunger. Recovery programs should be flexible and involve individual and family education on recovery and the nature of addictive disease. Exercise that produces cardiopulmonary stimulation is a helpful means of reducing drug hunger and anxiety during recovery therapy." ], "offsets": [ [ 0, 1128 ] ] } ]

[ { "id": "6100190_T1", "type": "DRUG", "text": [ "cocaine" ], "offsets": [ [ 50, 57 ] ], "normalized": [] }, { "id": "6100190_T2", "type": "DRUG", "text": [ "cocaine" ], "offsets": [ [ 95, 102 ] ], "normalized": [] }, { "id": "6100190_T3", "type": "DRUG", "text": [ "cocaine" ], "offsets": [ [ 339, 346 ] ], "normalized": [] }, { "id": "6100190_T4", "type": "DRUG", "text": [ "cocaine" ], "offsets": [ [ 421, 428 ] ], "normalized": [] }, { "id": "6100190_T5", "type": "DRUG", "text": [ "cocaine" ], "offsets": [ [ 608, 615 ] ], "normalized": [] } ]

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[ { "id": "16649322__text", "type": "abstract", "text": [ "Herbal remedies, nephropathies, and renal disease. The use of herbal remedies is becoming increasingly popular in the United States. Research has shown that herbal remedy use may be associated with acute renal failure. In addition, the use of herbal remedies may be detrimental for the patient with compromised renal function. Patients with renal insufficiency or renal failure may be at risk for further kidney damage as well as complications related to interactions of herbal remedies with complex renal therapy regimens. This article will describe the escalating use of herbal therapy and the hazards of herbal remedy use among patients." ], "offsets": [ [ 0, 640 ] ] } ]

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[ { "id": "15825309__text", "type": "abstract", "text": [ "Interaction of clindamycin and gentamicin in vitro. The minimal inhibitory concentrations of clindamycin and gentamicin alone and in combinations were determined by a microdilution method for 163 aerobic, facultative, and anaerobic clinical isolates. All 77 strains of Staphylococcus aureus, Diplococcus pneumoniae, Streptococcus pyogenes, and anaerobic bacteria (except for three strains of Clostridium) were inhibited by 1.6 mug or less of clindamycin per ml. Gentamicin did not interfere with the activity of clindamycin within the range of concentrations tested (0.1 to 100 mug/ml); for some strains combinations were synergistic. Sixty-two (94%) of 66 strains of Enterobacteriaceae and Pseudomonas aeruginosa were inhibited by 6.2 mug or less of gentamicin per ml. Combinations of clindamycin and gentamicin were indifferent for 29 strains and synergistic for 33 strains. All 20 strains of enterococcus, three strains of Clostridium, three strains of Escherichia coli, and one strain of Proteus rettgeri were resistant to both clindamycin (minimal inhibitory concentration greater than 3.1 mug/ml) and gentamicin (minimal inhibitory concentration greater than 6.2 mug/ml). Combinations of clindamycin and gentamicin were indifferent for 16 and synergistic for 11 of the resistant strains. Except for clindamycin-sensitive isolates, synergy was usually observed only at concentrations of one or both drugs which are not readily obtainable in vivo. Antagonism was never observed." ], "offsets": [ [ 0, 1482 ] ] } ]

[ { "id": "15825309_T1", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 15, 26 ] ], "normalized": [] }, { "id": "15825309_T2", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 31, 41 ] ], "normalized": [] }, { "id": "15825309_T3", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 93, 104 ] ], "normalized": [] }, { "id": "15825309_T4", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 109, 119 ] ], "normalized": [] }, { "id": "15825309_T5", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 442, 453 ] ], "normalized": [] }, { "id": "15825309_T6", "type": "DRUG", "text": [ "Gentamicin" ], "offsets": [ [ 462, 472 ] ], "normalized": [] }, { "id": "15825309_T7", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 512, 523 ] ], "normalized": [] }, { "id": "15825309_T8", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 751, 761 ] ], "normalized": [] }, { "id": "15825309_T9", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 786, 797 ] ], "normalized": [] }, { "id": "15825309_T10", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 802, 812 ] ], "normalized": [] }, { "id": "15825309_T11", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 1032, 1043 ] ], "normalized": [] }, { "id": "15825309_T12", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 1107, 1117 ] ], "normalized": [] }, { "id": "15825309_T13", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 1194, 1205 ] ], "normalized": [] }, { "id": "15825309_T14", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 1210, 1220 ] ], "normalized": [] }, { "id": "15825309_T15", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 1305, 1316 ] ], "normalized": [] } ]

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[ { "id": "15825309_R1", "type": "INT", "arg1_id": "15825309_T1", "arg2_id": "15825309_T2", "normalized": [] }, { "id": "15825309_R2", "type": "EFFECT", "arg1_id": "15825309_T9", "arg2_id": "15825309_T10", "normalized": [] }, { "id": "15825309_R3", "type": "EFFECT", "arg1_id": "15825309_T13", "arg2_id": "15825309_T14", "normalized": [] } ]

[ { "id": "11217867__text", "type": "abstract", "text": [ "Olanzapine: an updated review of its use in the management of schizophrenia. Olanzapine, a thienobenzodiazepine derivative, is a second generation (atypical) antipsychotic agent which has proven efficacy against the positive and negative symptoms of schizophrenia. Compared with conventional antipsychotics, it has greater affinity for serotonin 5-HT2A than for dopamine D2 receptors. In large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine 5 to 20 mg/day was significantly superior to haloperidol 5 to 20 mg/day in overall improvements in psychopathology rating scales and in the treatment of depressive and negative symptoms, and was comparable in effects on positive psychotic symptoms. The 1-year risk of relapse (rehospitalisation) was significantly lower with olanzapine than with haloperidol treatment. In the first double-blind comparative study (28-week) of olanzapine and risperidone, olanzapine 10 to 20 mg/day proved to be significantly more effective than risperidone 4 to 12 mg/day in the treatment of negative and depressive symptoms but not on overall psychopathology symptoms. In contrast, preliminary results from an 8-week controlled study suggested risperidone 2 to 6 mg/day was superior to olanzapine 5 to 20 mg/day against positive and anxiety/depressive symptoms (p < 0.05), although consistent with the first study, both agents demonstrated similar efficacy on measures of overall psychopathology. Improvements in general cognitive function seen with olanzapine treatment in a 1-year controlled study of patients with early-phase schizophrenia, were significantly greater than changes seen with either risperidone or haloperidol. However, preliminary results from an 8-week trial showed comparable cognitive enhancing effects of olanzapine and risperidone treatment in patients with schizophrenia or schizoaffective disorder. Several studies indicate that olanzapine has benefits against symptoms of aggression and agitation, while other studies strongly support the effectiveness of olanzapine in the treatment of depressive symptomatology. Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone. In addition, olanzapine is not associated with a risk of agranulocytosis as seen with clozapine or clinically significant hyperprolactinaemia as seen with risperidone or prolongation of the QT interval. The most common adverse effects reported with olanzapine are bodyweight gain, somnolence, dizziness, anticholinergic effects (constipation and dry mouth) and transient asymptomatic liver enzyme elevations. In comparison with haloperidol, the adverse events reported significantly more frequently with olanzapine in > or = 3.5% of patients were dry mouth, bodyweight gain and increased appetite and compared with risperidone, only bodyweight gain occurred significantly more frequently with olanzapine. The high acquisition cost of olanzapine is offset by reductions in other treatment costs (inpatient and/or outpatient services) of schizophrenia. Pharmacoeconomic analyses indicate that olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Compared with risperidone, olanzapine has also been reported to decrease overall treatment costs, despite the several-fold higher daily acquisition cost of the drug. Olanzapine treatment improves quality of life in patients with schizophrenia and related psychoses to a greater extent than haloperidol, and to broadly the same extent as risperidone. CONCLUSIONS: Olanzapine demonstrated superior antipsychotic efficacy compared with haloperidol in the treatment of acute phase schizophrenia, and in the treatment of some patients with first-episode or treatment-resistant schizophrenia. The reduced risk of adverse events and therapeutic superiority compared with haloperidol and risperidone in the treatment of negative and depressive symptoms support the choice of olanzapine as a first-line option in the management of schizophrenia in the acute phase and for the maintenance of treatment response." ], "offsets": [ [ 0, 4154 ] ] } ]

[ { "id": "11217867_T1", "type": "DRUG", "text": [ "Olanzapine" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "11217867_T2", "type": "DRUG", "text": [ "Olanzapine" ], "offsets": [ [ 77, 87 ] ], "normalized": [] }, { "id": "11217867_T3", "type": "GROUP", "text": [ "thienobenzodiazepine derivative" ], "offsets": [ [ 91, 122 ] ], "normalized": [] }, { "id": "11217867_T4", "type": "GROUP", "text": [ "second generation (atypical) antipsychotic agent" ], "offsets": [ [ 129, 177 ] ], "normalized": [] }, { "id": "11217867_T5", "type": "GROUP", "text": [ "conventional antipsychotics" ], "offsets": [ [ 279, 306 ] ], "normalized": [] }, { "id": "11217867_T6", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 471, 481 ] ], "normalized": [] }, { "id": "11217867_T7", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 527, 538 ] ], "normalized": [] }, { "id": "11217867_T8", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 807, 817 ] ], "normalized": [] }, { "id": "11217867_T9", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 828, 839 ] ], "normalized": [] }, { "id": "11217867_T10", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 908, 918 ] ], "normalized": [] }, { "id": "11217867_T11", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 923, 934 ] ], "normalized": [] }, { "id": "11217867_T12", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 936, 946 ] ], "normalized": [] }, { "id": "11217867_T13", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 1010, 1021 ] ], "normalized": [] }, { "id": "11217867_T14", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 1210, 1221 ] ], "normalized": [] }, { "id": "11217867_T15", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 1252, 1262 ] ], "normalized": [] }, { "id": "11217867_T16", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 1516, 1526 ] ], "normalized": [] }, { "id": "11217867_T17", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 1667, 1678 ] ], "normalized": [] }, { "id": "11217867_T18", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 1682, 1693 ] ], "normalized": [] }, { "id": "11217867_T19", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 1794, 1804 ] ], "normalized": [] }, { "id": "11217867_T20", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 1809, 1820 ] ], "normalized": [] }, { "id": "11217867_T21", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 1921, 1931 ] ], "normalized": [] }, { "id": "11217867_T22", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 2049, 2059 ] ], "normalized": [] }, { "id": "11217867_T23", "type": "DRUG", "text": [ "Olanzapine" ], "offsets": [ [ 2107, 2117 ] ], "normalized": [] }, { "id": "11217867_T24", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 2186, 2197 ] ], "normalized": [] }, { "id": "11217867_T25", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 2202, 2213 ] ], "normalized": [] }, { "id": "11217867_T26", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 2228, 2238 ] ], "normalized": [] }, { "id": "11217867_T27", "type": "DRUG", "text": [ "clozapine" ], "offsets": [ [ 2301, 2310 ] ], "normalized": [] }, { "id": "11217867_T28", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 2370, 2381 ] ], "normalized": [] }, { "id": "11217867_T29", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 2464, 2474 ] ], "normalized": [] }, { "id": "11217867_T30", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 2643, 2654 ] ], "normalized": [] }, { "id": "11217867_T31", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 2719, 2729 ] ], "normalized": [] }, { "id": "11217867_T32", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 2830, 2841 ] ], "normalized": [] }, { "id": "11217867_T33", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 2908, 2918 ] ], "normalized": [] }, { "id": "11217867_T34", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 2949, 2959 ] ], "normalized": [] }, { "id": "11217867_T35", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 3106, 3116 ] ], "normalized": [] }, { "id": "11217867_T36", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 3240, 3251 ] ], "normalized": [] }, { "id": "11217867_T37", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 3267, 3278 ] ], "normalized": [] }, { "id": "11217867_T38", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 3280, 3290 ] ], "normalized": [] }, { "id": "11217867_T39", "type": "DRUG", "text": [ "Olanzapine" ], "offsets": [ [ 3419, 3429 ] ], "normalized": [] }, { "id": "11217867_T40", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 3543, 3554 ] ], "normalized": [] }, { "id": "11217867_T41", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 3590, 3601 ] ], "normalized": [] }, { "id": "11217867_T42", "type": "DRUG", "text": [ "Olanzapine" ], "offsets": [ [ 3616, 3626 ] ], "normalized": [] }, { "id": "11217867_T43", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 3686, 3697 ] ], "normalized": [] }, { "id": "11217867_T44", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 3917, 3928 ] ], "normalized": [] }, { "id": "11217867_T45", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 3933, 3944 ] ], "normalized": [] }, { "id": "11217867_T46", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 4020, 4030 ] ], "normalized": [] } ]

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[ { "id": "3881076__text", "type": "abstract", "text": [ "Cancer in the elderly: basic science and clinical aspects. The incidence of cancer increases progressively with age. Rearrangements of genomes have been found to accompany cellular aging. These factors, in concert with age-dependent alterations in immune function and host defense, may help to explain the increased risk of malignant disease in aged persons. The clinical presentation and natural history of neoplasia are also affected by aging. This conference reviews recent developments in these areas, examines the effects of drug use in the elderly and implications for management, and discusses current information on how age may influence the response of cancer to therapy." ], "offsets": [ [ 0, 680 ] ] } ]

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[ { "id": "6536292__text", "type": "abstract", "text": [ "Cholinergic role in alcohol's effects on evoked potentials in visual cortex of the albino rat. Photic evoked potentials were recorded from the visual cortex of chronically implanted albino rats. Since photic evoked potential components are representations of neural pathways which are activated during photic stimulation, study of the effects of alcohol on these components may help to trace pathways which are affected by alcohol. In the present study, evoked potentials were recorded at 5, 20, and 40 min following IP injections of saline, ethanol (2.0 g/kg), physostigmine (0.6 mg/kg) or atropine (15.0 mg/kg) on separate days. Ethanol depressed the amplitudes of most evoked potential components in comparison to saline administration. Component P2, however, was increased in amplitude. Physostigmine briefly reduced the amplitude of most components, including P2. In contrast, atropine increased the amplitudes of components P1 and P2, while decreasing components N1, N2 and N3 for varying durations of time. Physostigmine pretreatment augmented the depressant effect of alcohol on the early components P1 and N1, while attenuating alcohol's influence on components P2 and P3. Pretreatment with atropine likewise further reduced the amplitudes of components P1 and N1, and produced a similar effect on component N3. Atropine, either alone or in combination with alcohol, produced approximately the same degree of enhancement of component P2. In comparison to saline values, all three agents produced reliable increases in peak latency for most of the components, with only N3 showing no effects. The amplitude data from this study suggest that ethanol's augmentation of component P2 may result, at least in part, from alterations in cholinergic functions." ], "offsets": [ [ 0, 1760 ] ] } ]

[ { "id": "6536292_T1", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 20, 27 ] ], "normalized": [] }, { "id": "6536292_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 346, 353 ] ], "normalized": [] }, { "id": "6536292_T3", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 423, 430 ] ], "normalized": [] }, { "id": "6536292_T4", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 542, 549 ] ], "normalized": [] }, { "id": "6536292_T5", "type": "DRUG", "text": [ "physostigmine" ], "offsets": [ [ 562, 575 ] ], "normalized": [] }, { "id": "6536292_T6", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 591, 599 ] ], "normalized": [] }, { "id": "6536292_T7", "type": "DRUG", "text": [ "Ethanol" ], "offsets": [ [ 631, 638 ] ], "normalized": [] }, { "id": "6536292_T8", "type": "DRUG", "text": [ "Physostigmine" ], "offsets": [ [ 791, 804 ] ], "normalized": [] }, { "id": "6536292_T9", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 882, 890 ] ], "normalized": [] }, { "id": "6536292_T10", "type": "DRUG", "text": [ "Physostigmine" ], "offsets": [ [ 1014, 1027 ] ], "normalized": [] }, { "id": "6536292_T11", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 1076, 1083 ] ], "normalized": [] }, { "id": "6536292_T12", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 1137, 1144 ] ], "normalized": [] }, { "id": "6536292_T13", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 1200, 1208 ] ], "normalized": [] }, { "id": "6536292_T14", "type": "DRUG", "text": [ "Atropine" ], "offsets": [ [ 1321, 1329 ] ], "normalized": [] }, { "id": "6536292_T15", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 1367, 1374 ] ], "normalized": [] }, { "id": "6536292_T16", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 1649, 1656 ] ], "normalized": [] } ]

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[ { "id": "6536292_R1", "type": "EFFECT", "arg1_id": "6536292_T10", "arg2_id": "6536292_T11", "normalized": [] }, { "id": "6536292_R2", "type": "EFFECT", "arg1_id": "6536292_T10", "arg2_id": "6536292_T12", "normalized": [] } ]

[ { "id": "11197581__text", "type": "abstract", "text": [ "Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin. OBJECTIVE: To report a case of rhabdomyolysis resulting from concomitant use of clarithromycin and simvastatin. CASE SUMMARY: A 64-year-old African-American man was admitted to the hospital for worsening renal failure, elevated creatine phosphokinase, diffuse muscle pain, and severe muscle weakness. About three weeks prior to admission, the patient was started on clarithromycin for sinusitis. The patient had been receiving simvastatin for approximately six months. He was treated aggressively with intravenous hydration, sodium bicarbonate, and hemodialysis. A muscle biopsy revealed necrotizing myopathy secondary to a toxin. The patient continued to receive intermittent hemodialysis until his death from infectious complications that occurred three months after admission. There were several factors that could have increased his risk for developing rhabdomyolysis, including chronic renal failure. DISCUSSION: Clarithromycin is a potent inhibitor of CYP3A4, the major enzyme responsible for simvastatin metabolism. The concomitant administration of macrolide antibiotics and other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have resulted in previous reports of rhabdomyolysis. Other factors may increase the risk of this drug interaction, including the administration of other medications that are associated with myopathy, underlying renal insufficiency, and administration of high doses of HMG-CoA reductase inhibitors. CONCLUSIONS: Macrolide antibiotics inhibit the metabolism of HMG-CoA reductase inhibitors that are metabolized by CYP3A4 (i.e., atorvastatin, cerivastatin, lovastatin, simvastatin). This interaction may result in myopathy and rhabdomyolysis, particularly in patients with renal insufficiency or those who are concurrently taking medications associated with myopathy." ], "offsets": [ [ 0, 1904 ] ] } ]

[ { "id": "11197581_T1", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 55, 66 ] ], "normalized": [] }, { "id": "11197581_T2", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 71, 85 ] ], "normalized": [] }, { "id": "11197581_T3", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 167, 181 ] ], "normalized": [] }, { "id": "11197581_T4", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 186, 197 ] ], "normalized": [] }, { "id": "11197581_T5", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 453, 467 ] ], "normalized": [] }, { "id": "11197581_T6", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 514, 525 ] ], "normalized": [] }, { "id": "11197581_T7", "type": "DRUG", "text": [ "sodium bicarbonate" ], "offsets": [ [ 612, 630 ] ], "normalized": [] }, { "id": "11197581_T8", "type": "DRUG", "text": [ "Clarithromycin" ], "offsets": [ [ 1005, 1019 ] ], "normalized": [] }, { "id": "11197581_T9", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 1086, 1097 ] ], "normalized": [] }, { "id": "11197581_T10", "type": "GROUP", "text": [ "macrolide antibiotics" ], "offsets": [ [ 1144, 1165 ] ], "normalized": [] }, { "id": "11197581_T11", "type": "GROUP", "text": [ "hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors" ], "offsets": [ [ 1176, 1239 ] ], "normalized": [] }, { "id": "11197581_T12", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 1508, 1536 ] ], "normalized": [] }, { "id": "11197581_T13", "type": "GROUP", "text": [ "Macrolide antibiotics" ], "offsets": [ [ 1551, 1572 ] ], "normalized": [] }, { "id": "11197581_T14", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 1599, 1627 ] ], "normalized": [] }, { "id": "11197581_T15", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 1666, 1678 ] ], "normalized": [] }, { "id": "11197581_T16", "type": "DRUG", "text": [ "cerivastatin" ], "offsets": [ [ 1680, 1692 ] ], "normalized": [] }, { "id": "11197581_T17", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 1694, 1704 ] ], "normalized": [] }, { "id": "11197581_T18", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 1706, 1717 ] ], "normalized": [] } ]

[]

[]

[ { "id": "11197581_R1", "type": "EFFECT", "arg1_id": "11197581_T1", "arg2_id": "11197581_T2", "normalized": [] }, { "id": "11197581_R2", "type": "MECHANISM", "arg1_id": "11197581_T8", "arg2_id": "11197581_T9", "normalized": [] }, { "id": "11197581_R3", "type": "EFFECT", "arg1_id": "11197581_T10", "arg2_id": "11197581_T11", "normalized": [] }, { "id": "11197581_R4", "type": "MECHANISM", "arg1_id": "11197581_T13", "arg2_id": "11197581_T15", "normalized": [] }, { "id": "11197581_R5", "type": "MECHANISM", "arg1_id": "11197581_T13", "arg2_id": "11197581_T16", "normalized": [] }, { "id": "11197581_R6", "type": "MECHANISM", "arg1_id": "11197581_T13", "arg2_id": "11197581_T17", "normalized": [] }, { "id": "11197581_R7", "type": "MECHANISM", "arg1_id": "11197581_T13", "arg2_id": "11197581_T18", "normalized": [] } ]

[ { "id": "Aliskiren_ddi__text", "type": "abstract", "text": [ "Effects of Other Drugs on Aliskiren Based on in-vitro studies, aliskiren is metabolized by CYP 3A4. Co-administration of lovastatin, atenolol, warfarin, furosemide, digoxin, celecoxib, hydrochlorothiazide, ramipril, valsartan, metformin and amlodipine did not result in clinically significant increases in aliskiren exposure. Co-administration of irbesartan reduced aliskiren Cmax up to 50% after multiple dosing. Co-administration of atorvastatin resulted in about a 50% increase in aliskiren Cmax and AUC after multiple dosing. Ketoconazole: Co-administration of 200 mg twice-daily ketoconazole with aliskiren resulted in an approximate 80% increase in plasma levels of aliskiren. A 400 mg once-daily dose was not studied but would be expected to increase aliskiren blood levels further. Effects of Aliskiren on Other Drugs Aliskiren does not inhibit the CYP450 isoenzymes (CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1, and CYP 3A) or induce CYP 3A4. Co-administration of aliskiren did not significantly affect the pharmacokinetics of lovastatin, digoxin, valsartan, amlodipine, metformin, celecoxib, atenolol, atorvastatin, ramipril or hydrochlorothiazide. Warfarin: The effects of aliskiren on warfarin pharmacokinetics have not been evaluated in a well-controlled clinical trial. Furosemide: When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide were reduced by about 30% and 50%, respectively." ], "offsets": [ [ 0, 1416 ] ] } ]

[ { "id": "Aliskiren_ddi_T1", "type": "DRUG", "text": [ "Aliskiren" ], "offsets": [ [ 26, 35 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T2", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 63, 72 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T3", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 121, 131 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T4", "type": "DRUG", "text": [ "atenolol" ], "offsets": [ [ 133, 141 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T5", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 143, 151 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T6", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 153, 163 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T7", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 165, 172 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T8", "type": "DRUG", "text": [ "celecoxib" ], "offsets": [ [ 174, 183 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T9", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 185, 204 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T10", "type": "DRUG", "text": [ "ramipril" ], "offsets": [ [ 206, 214 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T11", "type": "DRUG", "text": [ "valsartan" ], "offsets": [ [ 216, 225 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T12", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 227, 236 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T13", "type": "DRUG", "text": [ "amlodipine" ], "offsets": [ [ 241, 251 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T14", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 306, 315 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T15", "type": "DRUG", "text": [ "irbesartan" ], "offsets": [ [ 347, 357 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T16", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 366, 375 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T17", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 435, 447 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T18", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 484, 493 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T19", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 530, 542 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T20", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 584, 596 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T21", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 602, 611 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T22", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 672, 681 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T23", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 758, 767 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T24", "type": "DRUG", "text": [ "Aliskiren" ], "offsets": [ [ 801, 810 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T25", "type": "DRUG", "text": [ "Aliskiren" ], "offsets": [ [ 826, 835 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T26", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 962, 971 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T27", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 1025, 1035 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T28", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1037, 1044 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T29", "type": "DRUG", "text": [ "valsartan" ], "offsets": [ [ 1046, 1055 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T30", "type": "DRUG", "text": [ "amlodipine" ], "offsets": [ [ 1057, 1067 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T31", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 1069, 1078 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T32", "type": "DRUG", "text": [ "celecoxib" ], "offsets": [ [ 1080, 1089 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T33", "type": "DRUG", "text": [ "atenolol" ], "offsets": [ [ 1091, 1099 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T34", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 1101, 1113 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T35", "type": "DRUG", "text": [ "ramipril" ], "offsets": [ [ 1115, 1123 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T36", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 1127, 1146 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T37", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 1148, 1156 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T38", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 1173, 1182 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T39", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1186, 1194 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T40", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 1273, 1283 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T41", "type": "DRUG", "text": [ "aliskiren" ], "offsets": [ [ 1290, 1299 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T42", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1325, 1335 ] ], "normalized": [] }, { "id": "Aliskiren_ddi_T43", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1357, 1367 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Aliskiren_ddi_R1", "type": "MECHANISM", "arg1_id": "Aliskiren_ddi_T15", "arg2_id": "Aliskiren_ddi_T16", "normalized": [] }, { "id": "Aliskiren_ddi_R2", "type": "MECHANISM", "arg1_id": "Aliskiren_ddi_T17", "arg2_id": "Aliskiren_ddi_T18", "normalized": [] }, { "id": "Aliskiren_ddi_R3", "type": "MECHANISM", "arg1_id": "Aliskiren_ddi_T20", "arg2_id": "Aliskiren_ddi_T21", "normalized": [] }, { "id": "Aliskiren_ddi_R4", "type": "MECHANISM", "arg1_id": "Aliskiren_ddi_T41", "arg2_id": "Aliskiren_ddi_T42", "normalized": [] } ]

[ { "id": "Dactinomycin_ddi__text", "type": "abstract", "text": [ "Drug/LaboratoryTest Interactions Dactinomycin may interfere with bioassay procedures for the determination of antibacterial drug levels." ], "offsets": [ [ 0, 136 ] ] } ]

[ { "id": "Dactinomycin_ddi_T1", "type": "DRUG", "text": [ "Dactinomycin" ], "offsets": [ [ 33, 45 ] ], "normalized": [] }, { "id": "Dactinomycin_ddi_T2", "type": "GROUP", "text": [ "antibacterial drug" ], "offsets": [ [ 110, 128 ] ], "normalized": [] } ]

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[ { "id": "Nitric Oxide_ddi__text", "type": "abstract", "text": [ "No formal drug-interaction studies have been performed, and a clinically significant interaction with other medications used in the treatment of hypoxic respiratory failure cannot be excluded based on the available data. INOmax has been administered with tolazoline, dopamine, dobutamine, steroids, surfactant, and high-frequency ventilation. Although there are no study data to evaluate the possibility, nitric oxide donor compounds, including sodium nitroprusside and nitroglycerin, may have an additive effect with INOmax on the risk of developing methemoglobinemia. An association between prilocaine and an increased risk of methaemoglobinaemia, particularly in infants, has specifically been described in a literature case report. This risk is present whether the drugs are administered as oral, parenteral, or topical formulations." ], "offsets": [ [ 0, 837 ] ] } ]

[ { "id": "Nitric Oxide_ddi_T1", "type": "BRAND", "text": [ "INOmax" ], "offsets": [ [ 221, 227 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T2", "type": "DRUG", "text": [ "tolazoline" ], "offsets": [ [ 255, 265 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T3", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 267, 275 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T4", "type": "DRUG", "text": [ "dobutamine" ], "offsets": [ [ 277, 287 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T5", "type": "GROUP", "text": [ "steroids" ], "offsets": [ [ 289, 297 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T6", "type": "DRUG", "text": [ "surfactant" ], "offsets": [ [ 299, 309 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T7", "type": "GROUP", "text": [ "nitric oxide donor compounds" ], "offsets": [ [ 405, 433 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T8", "type": "DRUG", "text": [ "sodium nitroprusside" ], "offsets": [ [ 445, 465 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T9", "type": "DRUG", "text": [ "nitroglycerin" ], "offsets": [ [ 470, 483 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T10", "type": "BRAND", "text": [ "INOmax" ], "offsets": [ [ 518, 524 ] ], "normalized": [] }, { "id": "Nitric Oxide_ddi_T11", "type": "DRUG", "text": [ "prilocaine" ], "offsets": [ [ 593, 603 ] ], "normalized": [] } ]

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[]

[ { "id": "Nitric Oxide_ddi_R1", "type": "EFFECT", "arg1_id": "Nitric Oxide_ddi_T7", "arg2_id": "Nitric Oxide_ddi_T10", "normalized": [] }, { "id": "Nitric Oxide_ddi_R2", "type": "EFFECT", "arg1_id": "Nitric Oxide_ddi_T8", "arg2_id": "Nitric Oxide_ddi_T10", "normalized": [] }, { "id": "Nitric Oxide_ddi_R3", "type": "EFFECT", "arg1_id": "Nitric Oxide_ddi_T9", "arg2_id": "Nitric Oxide_ddi_T10", "normalized": [] } ]

[ { "id": "Norgestimate_ddi__text", "type": "abstract", "text": [ "Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested with barbiturates, phenylbutazone, phenytoin sodium, carbamazepine, griseofulvin, topiramate, and possibly with ampicillin and tetracyclines 72. A possible interaction has been suggested with hormonal contraceptives and the herbal supplement St. Johns Wort based on some reports of oral contraceptive users experiencing breakthrough bleeding shortly after starting St. Johns Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. Johns Wort. Healthcare prescribers are advised to consult the package inserts of medication administered concomitantly with oral contraceptives." ], "offsets": [ [ 0, 844 ] ] } ]

[ { "id": "Norgestimate_ddi_T1", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 140, 148 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T2", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 217, 229 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T3", "type": "DRUG", "text": [ "phenylbutazone" ], "offsets": [ [ 231, 245 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T4", "type": "DRUG", "text": [ "phenytoin sodium" ], "offsets": [ [ 247, 263 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T5", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 265, 278 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T6", "type": "DRUG", "text": [ "griseofulvin" ], "offsets": [ [ 280, 292 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T7", "type": "DRUG", "text": [ "topiramate" ], "offsets": [ [ 294, 304 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T8", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 324, 334 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T9", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 339, 352 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T10", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 404, 427 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T11", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 499, 512 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T12", "type": "GROUP", "text": [ "combined hormonal contraceptives" ], "offsets": [ [ 636, 668 ] ], "normalized": [] }, { "id": "Norgestimate_ddi_T13", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 829, 843 ] ], "normalized": [] } ]

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[ { "id": "Ampicillin_ddi__text", "type": "abstract", "text": [ "When administered concurrently, the following drugs may interact with ampicillin. Allopurinol: Increased possibility of skin rash, particularly in hyperuricemic patients may occur. Bacteriostatic Antibiotics: Chloramphenicol, erythromycins, sulfonamides, or tetracyclines may interfere with the bactericidal effect of penicillins. This has been demonstrated in view, however, the clinical significance of this interaction is not well documented. Oral Contraceptives: May be less effective and increased breakthrough bleeding may occur. Probenecid: May decrease renal tubular secretion of ampicillin resulting in increased blood levels and/or ampicillin toxicity. Drug/Laboratory Test Interaction After treatment with ampicillin, a false-positive reaction for glucose in the urine may occur with copper sulfate tests (Benedicts solution, Fehlings solution, or Clinitest tablets) but not with enzyme based tests such as Clinistix and Glucose Enzymatic Test Strip USP." ], "offsets": [ [ 0, 965 ] ] } ]

[ { "id": "Ampicillin_ddi_T1", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 70, 80 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T2", "type": "DRUG", "text": [ "Allopurinol" ], "offsets": [ [ 82, 93 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T3", "type": "GROUP", "text": [ "Bacteriostatic Antibiotics" ], "offsets": [ [ 181, 207 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T4", "type": "DRUG", "text": [ "Chloramphenicol" ], "offsets": [ [ 209, 224 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T5", "type": "DRUG", "text": [ "erythromycins" ], "offsets": [ [ 226, 239 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T6", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 241, 253 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T7", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 258, 271 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T8", "type": "GROUP", "text": [ "penicillins" ], "offsets": [ [ 318, 329 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T9", "type": "GROUP", "text": [ "Contraceptives" ], "offsets": [ [ 451, 465 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T10", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 536, 546 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T11", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 588, 598 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T12", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 642, 652 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T13", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 717, 727 ] ], "normalized": [] }, { "id": "Ampicillin_ddi_T14", "type": "DRUG_N", "text": [ "copper sulfate" ], "offsets": [ [ 795, 809 ] ], "normalized": [] } ]

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[ { "id": "Ampicillin_ddi_R1", "type": "EFFECT", "arg1_id": "Ampicillin_ddi_T4", "arg2_id": "Ampicillin_ddi_T8", "normalized": [] }, { "id": "Ampicillin_ddi_R2", "type": "EFFECT", "arg1_id": "Ampicillin_ddi_T5", "arg2_id": "Ampicillin_ddi_T8", "normalized": [] }, { "id": "Ampicillin_ddi_R3", "type": "EFFECT", "arg1_id": "Ampicillin_ddi_T6", "arg2_id": "Ampicillin_ddi_T8", "normalized": [] }, { "id": "Ampicillin_ddi_R4", "type": "EFFECT", "arg1_id": "Ampicillin_ddi_T7", "arg2_id": "Ampicillin_ddi_T8", "normalized": [] }, { "id": "Ampicillin_ddi_R5", "type": "MECHANISM", "arg1_id": "Ampicillin_ddi_T10", "arg2_id": "Ampicillin_ddi_T11", "normalized": [] } ]

[ { "id": "Amantadine_ddi__text", "type": "abstract", "text": [ "Careful observation is required when amantadine is administered concurrently with central nervous system stimulants. Coadministration of thioridazine has been reported to worsen the tremor in elderly patients with Parkinsons disease; however, it is not known if other phenothiazines produce a similar response." ], "offsets": [ [ 0, 310 ] ] } ]

[ { "id": "Amantadine_ddi_T1", "type": "DRUG", "text": [ "amantadine" ], "offsets": [ [ 37, 47 ] ], "normalized": [] }, { "id": "Amantadine_ddi_T2", "type": "GROUP", "text": [ "central nervous system stimulants" ], "offsets": [ [ 82, 115 ] ], "normalized": [] }, { "id": "Amantadine_ddi_T3", "type": "DRUG", "text": [ "thioridazine" ], "offsets": [ [ 137, 149 ] ], "normalized": [] }, { "id": "Amantadine_ddi_T4", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 268, 282 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Amantadine_ddi_R1", "type": "ADVISE", "arg1_id": "Amantadine_ddi_T1", "arg2_id": "Amantadine_ddi_T2", "normalized": [] } ]

[ { "id": "Budesonide_ddi__text", "type": "abstract", "text": [ "Concomitant oral administration of ketoconazole (a known inhibitor of CYP3A4 activity in the liver and in the intestinal mucosa) caused an eight-fold increase of the systemic exposure to oral budesonide. If treatment with inhibitors of CYP3A4 activity (such as ketoconazole, intraconazole, ritonavir, indinavir, saquinavir, erythromycin, etc.) is indicated, reduction of the budesonide dose should be considered. After extensive intake of grapefruit juice (which inhibits CYP3A4 activity predominantly in the intestinal mucosa), the systemic exposure for oral budesonide increased about two times. As with other drugs primarily being metabolized through CYP3A4, ingestion of grapefruit or grapefruit juice should be avoided in connection with budesonide administration." ], "offsets": [ [ 0, 769 ] ] } ]

[ { "id": "Budesonide_ddi_T1", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 35, 47 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T2", "type": "DRUG", "text": [ "budesonide" ], "offsets": [ [ 192, 202 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T3", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 261, 273 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T4", "type": "DRUG", "text": [ "intraconazole" ], "offsets": [ [ 275, 288 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T5", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 290, 299 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T6", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 301, 310 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T7", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 312, 322 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T8", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 324, 336 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T9", "type": "DRUG", "text": [ "budesonide" ], "offsets": [ [ 375, 385 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T10", "type": "DRUG", "text": [ "budesonide" ], "offsets": [ [ 560, 570 ] ], "normalized": [] }, { "id": "Budesonide_ddi_T11", "type": "DRUG", "text": [ "budesonide" ], "offsets": [ [ 743, 753 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Budesonide_ddi_R1", "type": "MECHANISM", "arg1_id": "Budesonide_ddi_T1", "arg2_id": "Budesonide_ddi_T2", "normalized": [] }, { "id": "Budesonide_ddi_R2", "type": "ADVISE", "arg1_id": "Budesonide_ddi_T3", "arg2_id": "Budesonide_ddi_T9", "normalized": [] }, { "id": "Budesonide_ddi_R3", "type": "ADVISE", "arg1_id": "Budesonide_ddi_T4", "arg2_id": "Budesonide_ddi_T9", "normalized": [] }, { "id": "Budesonide_ddi_R4", "type": "ADVISE", "arg1_id": "Budesonide_ddi_T5", "arg2_id": "Budesonide_ddi_T9", "normalized": [] }, { "id": "Budesonide_ddi_R5", "type": "ADVISE", "arg1_id": "Budesonide_ddi_T6", "arg2_id": "Budesonide_ddi_T9", "normalized": [] }, { "id": "Budesonide_ddi_R6", "type": "ADVISE", "arg1_id": "Budesonide_ddi_T7", "arg2_id": "Budesonide_ddi_T9", "normalized": [] }, { "id": "Budesonide_ddi_R7", "type": "ADVISE", "arg1_id": "Budesonide_ddi_T8", "arg2_id": "Budesonide_ddi_T9", "normalized": [] } ]

[ { "id": "Dyphylline_ddi__text", "type": "abstract", "text": [ "Synergism between xanthine bronchodilators (e.g., theophylline), ephedrine, and other sympathomimetic bronchodilators has been reported. This should be considered whenever these agents are prescribed concomitantly. Concurrent administration of dyphylline and probenecid, which competes for tubular secretion, has been shown to increase the plasma half-life of dyphylline ." ], "offsets": [ [ 0, 372 ] ] } ]

[ { "id": "Dyphylline_ddi_T1", "type": "GROUP", "text": [ "xanthine bronchodilators" ], "offsets": [ [ 18, 42 ] ], "normalized": [] }, { "id": "Dyphylline_ddi_T2", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 50, 62 ] ], "normalized": [] }, { "id": "Dyphylline_ddi_T3", "type": "DRUG", "text": [ "ephedrine" ], "offsets": [ [ 65, 74 ] ], "normalized": [] }, { "id": "Dyphylline_ddi_T4", "type": "GROUP", "text": [ "sympathomimetic bronchodilators" ], "offsets": [ [ 86, 117 ] ], "normalized": [] }, { "id": "Dyphylline_ddi_T5", "type": "DRUG", "text": [ "dyphylline" ], "offsets": [ [ 244, 254 ] ], "normalized": [] }, { "id": "Dyphylline_ddi_T6", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 259, 269 ] ], "normalized": [] }, { "id": "Dyphylline_ddi_T7", "type": "DRUG", "text": [ "dyphylline" ], "offsets": [ [ 360, 370 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Dyphylline_ddi_R1", "type": "EFFECT", "arg1_id": "Dyphylline_ddi_T1", "arg2_id": "Dyphylline_ddi_T4", "normalized": [] }, { "id": "Dyphylline_ddi_R2", "type": "EFFECT", "arg1_id": "Dyphylline_ddi_T2", "arg2_id": "Dyphylline_ddi_T4", "normalized": [] }, { "id": "Dyphylline_ddi_R3", "type": "EFFECT", "arg1_id": "Dyphylline_ddi_T3", "arg2_id": "Dyphylline_ddi_T4", "normalized": [] }, { "id": "Dyphylline_ddi_R4", "type": "MECHANISM", "arg1_id": "Dyphylline_ddi_T5", "arg2_id": "Dyphylline_ddi_T6", "normalized": [] } ]

[ { "id": "Becaplermin_ddi__text", "type": "abstract", "text": [ "It is not known if REGRANEX Gel interacts with other topical medications applied to the ulcer site. The use of REGRANEX Gel with other topical drugs has not been studied." ], "offsets": [ [ 0, 170 ] ] } ]

[ { "id": "Becaplermin_ddi_T1", "type": "BRAND", "text": [ "REGRANEX" ], "offsets": [ [ 19, 27 ] ], "normalized": [] }, { "id": "Becaplermin_ddi_T2", "type": "BRAND", "text": [ "REGRANEX" ], "offsets": [ [ 111, 119 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Laronidase_ddi__text", "type": "abstract", "text": [ "No formal drug interaction studies have been conducted." ], "offsets": [ [ 0, 55 ] ] } ]

[]

[]

[]

[]

[ { "id": "Carbamazepine_ddi__text", "type": "abstract", "text": [ "Clinically meaningful drug interactions have occurred with concomitant medications and include, but are not limited to the following: Agents Highly Bound to Plasma Protein Carbamazepine is not highly bound to plasma proteins; therefore, administration of EQUETROTM to a patient taking another drug that is highly protein bound should not cause increased free concentrations of the other drug. Agents that Inhibit Cytochrome P450 Isoenzymes and/or Epoxide Hydrolase Carbamazepine is metabolized mainly by cytochrome P450 (CYP) 3A4 to the active carbamazepine 10,11-epoxide, which is further metabolized to the trans-diol by epoxide hydrolase. Therefore, the potential exists for interaction between carbamazepine and any agent that inhibits CYP3A4 and/or epoxide hydrolase. Agents that are CYP3A4 inhibitors that have been found, or are expected, to increase plasma levels of EQUETROTM are the following: Acetazolamide, azole antifungals, cimetidine, clarithromycin(1), dalfopristin, danazol, delavirdine, diltiazem, erythromycin(1), fluoxetine, fluvoxamine, grapefruit juice, isoniazid, itraconazole, ketoconazole, loratadine, nefazodone, niacinamide, nicotinamide, protease inhibitors, propoxyphene, quinine, quinupristin, troleandomycin, valproate(1), verapamil, zileuton. Thus, if a patient has been titrated to a stable dosage of EQUETROTM, and then begins a course of treatment with one of these CYP3A4 or epoxide hydrolase inhibitors, it is reasonable to expect that a dose reduction for EQUETROTM may be necessary. Agents that Induce Cytochrome P450 Isoenzymes Carbamazepine is metabolized by CYP3A4. Therefore, the potential exists for interaction between carbamazepine and any agent that induces CYP3A4. Agents that are CYP inducers that have been found, or are expected, to decrease plasma levels of EQUETROTM are the following: Cisplatin, doxorubicin HCL, felbamate, rifampin, phenobarbital, Phenytoin(2), primidone, methsuximide, and theophylline Thus, if a patient has been titrated to a stable dosage on EQUETROTM, and then begins a course of treatment with one of these CYP3A4 inducers, it is reasonable to expect that a dose increase for EQUETROTM may be necessary. Agents with Decreased Levels in the Presence of Carbamazepine due to Induction of Cytochrome P450 Enzymes Carbamazepine is known to induce CYP1A2 and CYP3A4. Therefore, the potential exists for interaction between carbamazepine and any agent metabolized by one (or more) of these enzymes. Agents that have been found, or are expected to have decreased plasma levels in the presence of EQUETROTM due to induction of CYP enzymes are the following: Acetaminophen, alprazolam, amitriptyline, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, doxycycline, ethosuximide, felbamate, felodipine, glucocorticoids, haloperidol, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, midazolam, mirtazapine, nortriptyline, olanzapine, oral contraceptives(3), oxcarbazepine, Phenytoin(4), praziquantel, protease inhibitors, quetiapine, risperidone, theophylline, topiramate, tiagabine, tramadol, triazolam, valproate, warfarin(5) , ziprasidone, and zonisamide. Thus, if a patient has been titrated to a stable dosage on one of the agents in this category, and then begins a course of treatment with EQUETROTM, it is reasonable to expect that a dose increase for the concomitant agent may be necessary. Agents with Increased Levels in the Presence of Carbamazepine: EQUETROTM increases the plasma levels of the following agents: Clomipramine HCl, Phenytoin(6), and primidone Thus, if a patient has been titrated to a stable dosage on one of the agents in this category, and then begins a course of the treatment with EQUETROTM, it is reasonable to expect that a dose decrease for the concomitant agent may be necessary. Pharmacological/Pharmacodynamic Interactions with Carbamazepine Concomitant administration of carbamazepine and lithium may increase the risk of neurotoxic side effects. Given the anticonvulsant properties of carbamazepine, EQUETROTM may reduce the thyroid function as has been reported with other anticonvulsants. Additionally, anti-malarial drugs, such as chloroquine and mefloquine, may antagonize the activity of carbamazepine. Thus if a patient has been titrated to a stable dosage on one of the agents in this category, and then begins a course of treatment with EQUETROTM, it is reasonable to expect that a dose adjustment may be necessary. Because of its primary CNS effect, caution should be used when EQUETROTM is taken with other centrally acting drugs and alcohol." ], "offsets": [ [ 0, 4651 ] ] } ]

[ { "id": "Carbamazepine_ddi_T1", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 172, 185 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T2", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 255, 264 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T3", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 465, 478 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T4", "type": "DRUG", "text": [ "carbamazepine 10,11-epoxide" ], "offsets": [ [ 544, 571 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T5", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 698, 711 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T6", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 875, 884 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T7", "type": "DRUG", "text": [ "Acetazolamide" ], "offsets": [ [ 904, 917 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T8", "type": "GROUP", "text": [ "azole antifungals" ], "offsets": [ [ 919, 936 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T9", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 938, 948 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T10", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 950, 964 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T11", "type": "DRUG", "text": [ "dalfopristin" ], "offsets": [ [ 969, 981 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T12", "type": "DRUG", "text": [ "danazol" ], "offsets": [ [ 983, 990 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T13", "type": "DRUG", "text": [ "delavirdine" ], "offsets": [ [ 992, 1003 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T14", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 1005, 1014 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T15", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1016, 1028 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T16", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1033, 1043 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T17", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 1045, 1056 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T18", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 1076, 1085 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T19", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1087, 1099 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T20", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1101, 1113 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T21", "type": "DRUG", "text": [ "loratadine" ], "offsets": [ [ 1115, 1125 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T22", "type": "DRUG", "text": [ "nefazodone" ], "offsets": [ [ 1127, 1137 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T23", "type": "DRUG", "text": [ "niacinamide" ], "offsets": [ [ 1139, 1150 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T24", "type": "DRUG", "text": [ "nicotinamide" ], "offsets": [ [ 1152, 1164 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T25", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 1166, 1185 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T26", "type": "DRUG", "text": [ "propoxyphene" ], "offsets": [ [ 1187, 1199 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T27", "type": "DRUG", "text": [ "quinine" ], "offsets": [ [ 1201, 1208 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T28", "type": "DRUG", "text": [ "quinupristin" ], "offsets": [ [ 1210, 1222 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T29", "type": "DRUG", "text": [ "troleandomycin" ], "offsets": [ [ 1224, 1238 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T30", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 1240, 1249 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T31", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 1254, 1263 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T32", "type": "DRUG", "text": [ "zileuton" ], "offsets": [ [ 1265, 1273 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T33", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 1334, 1343 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T34", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 1494, 1503 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T35", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 1568, 1581 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T36", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1664, 1677 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T37", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 1810, 1819 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T38", "type": "DRUG", "text": [ "Cisplatin" ], "offsets": [ [ 1839, 1848 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T39", "type": "DRUG", "text": [ "doxorubicin HCL" ], "offsets": [ [ 1850, 1865 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T40", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 1867, 1876 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T41", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1878, 1886 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T42", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1888, 1901 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T43", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 1903, 1912 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T44", "type": "DRUG", "text": [ "primidone" ], "offsets": [ [ 1917, 1926 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T45", "type": "DRUG", "text": [ "methsuximide" ], "offsets": [ [ 1928, 1940 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T46", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1946, 1958 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T47", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 2018, 2027 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T48", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 2154, 2163 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T49", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 2230, 2243 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T50", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 2288, 2301 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T51", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2396, 2409 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T52", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 2567, 2576 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T53", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 2628, 2641 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T54", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 2643, 2653 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T55", "type": "DRUG", "text": [ "amitriptyline" ], "offsets": [ [ 2655, 2668 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T56", "type": "DRUG", "text": [ "bupropion" ], "offsets": [ [ 2670, 2679 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T57", "type": "DRUG", "text": [ "buspirone" ], "offsets": [ [ 2681, 2690 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T58", "type": "DRUG", "text": [ "citalopram" ], "offsets": [ [ 2692, 2702 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T59", "type": "DRUG", "text": [ "clobazam" ], "offsets": [ [ 2704, 2712 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T60", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 2714, 2724 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T61", "type": "DRUG", "text": [ "clozapine" ], "offsets": [ [ 2726, 2735 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T62", "type": "DRUG", "text": [ "cyclosporin" ], "offsets": [ [ 2737, 2748 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T63", "type": "DRUG", "text": [ "delavirdine" ], "offsets": [ [ 2750, 2761 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T64", "type": "DRUG", "text": [ "desipramine" ], "offsets": [ [ 2763, 2774 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T65", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 2776, 2784 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T66", "type": "DRUG", "text": [ "dicumarol" ], "offsets": [ [ 2786, 2795 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T67", "type": "DRUG", "text": [ "doxycycline" ], "offsets": [ [ 2797, 2808 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T68", "type": "DRUG", "text": [ "ethosuximide" ], "offsets": [ [ 2810, 2822 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T69", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 2824, 2833 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T70", "type": "DRUG", "text": [ "felodipine" ], "offsets": [ [ 2835, 2845 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T71", "type": "GROUP", "text": [ "glucocorticoids" ], "offsets": [ [ 2847, 2862 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T72", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 2864, 2875 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T73", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 2877, 2889 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T74", "type": "DRUG", "text": [ "lamotrigine" ], "offsets": [ [ 2891, 2902 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T75", "type": "DRUG", "text": [ "levothyroxine" ], "offsets": [ [ 2904, 2917 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T76", "type": "DRUG", "text": [ "lorazepam" ], "offsets": [ [ 2919, 2928 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T77", "type": "DRUG", "text": [ "methadone" ], "offsets": [ [ 2930, 2939 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T78", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 2941, 2950 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T79", "type": "DRUG", "text": [ "mirtazapine" ], "offsets": [ [ 2952, 2963 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T80", "type": "DRUG", "text": [ "nortriptyline" ], "offsets": [ [ 2965, 2978 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T81", "type": "DRUG", "text": [ "olanzapine" ], "offsets": [ [ 2980, 2990 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T82", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 2997, 3011 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T83", "type": "DRUG", "text": [ "oxcarbazepine" ], "offsets": [ [ 3016, 3029 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T84", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 3031, 3040 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T85", "type": "DRUG", "text": [ "praziquantel" ], "offsets": [ [ 3045, 3057 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T86", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 3059, 3078 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T87", "type": "DRUG", "text": [ "quetiapine" ], "offsets": [ [ 3080, 3090 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T88", "type": "DRUG", "text": [ "risperidone" ], "offsets": [ [ 3092, 3103 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T89", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 3105, 3117 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T90", "type": "DRUG", "text": [ "topiramate" ], "offsets": [ [ 3119, 3129 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T91", "type": "DRUG", "text": [ "tiagabine" ], "offsets": [ [ 3131, 3140 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T92", "type": "DRUG", "text": [ "tramadol" ], "offsets": [ [ 3142, 3150 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T93", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 3152, 3161 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T94", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 3163, 3172 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T95", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3174, 3182 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T96", "type": "DRUG", "text": [ "ziprasidone" ], "offsets": [ [ 3188, 3199 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T97", "type": "DRUG", "text": [ "zonisamide" ], "offsets": [ [ 3205, 3215 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T98", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 3355, 3364 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T99", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 3506, 3519 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T100", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 3521, 3530 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T101", "type": "DRUG", "text": [ "Clomipramine HCl" ], "offsets": [ [ 3584, 3600 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T102", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 3602, 3611 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T103", "type": "DRUG", "text": [ "primidone" ], "offsets": [ [ 3620, 3629 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T104", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 3772, 3781 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T105", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 3925, 3938 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T106", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 3969, 3982 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T107", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 3987, 3994 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T108", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 4084, 4097 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T109", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 4099, 4108 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T110", "type": "GROUP", "text": [ "anticonvulsants" ], "offsets": [ [ 4173, 4188 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T111", "type": "GROUP", "text": [ "anti-malarial drugs" ], "offsets": [ [ 4204, 4223 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T112", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 4233, 4244 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T113", "type": "DRUG", "text": [ "mefloquine" ], "offsets": [ [ 4249, 4259 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T114", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 4292, 4305 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T115", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 4444, 4453 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T116", "type": "BRAND", "text": [ "EQUETROTM" ], "offsets": [ [ 4586, 4595 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T117", "type": "GROUP", "text": [ "centrally acting drugs" ], "offsets": [ [ 4616, 4638 ] ], "normalized": [] }, { "id": "Carbamazepine_ddi_T118", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 4643, 4650 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Carbamazepine_ddi_R1", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T7", "normalized": [] }, { "id": "Carbamazepine_ddi_R2", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T8", "normalized": [] }, { "id": "Carbamazepine_ddi_R3", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T9", "normalized": [] }, { "id": "Carbamazepine_ddi_R4", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T10", "normalized": [] }, { "id": "Carbamazepine_ddi_R5", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T11", "normalized": [] }, { "id": "Carbamazepine_ddi_R6", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T12", "normalized": [] }, { "id": "Carbamazepine_ddi_R7", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T13", "normalized": [] }, { "id": "Carbamazepine_ddi_R8", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T14", "normalized": [] }, { "id": "Carbamazepine_ddi_R9", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T15", "normalized": [] }, { "id": "Carbamazepine_ddi_R10", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T16", "normalized": [] }, { "id": "Carbamazepine_ddi_R11", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T17", "normalized": [] }, { "id": "Carbamazepine_ddi_R12", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T18", "normalized": [] }, { "id": "Carbamazepine_ddi_R13", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T19", "normalized": [] }, { "id": "Carbamazepine_ddi_R14", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T20", "normalized": [] }, { "id": "Carbamazepine_ddi_R15", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T21", "normalized": [] }, { "id": "Carbamazepine_ddi_R16", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T22", "normalized": [] }, { "id": "Carbamazepine_ddi_R17", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T23", "normalized": [] }, { "id": "Carbamazepine_ddi_R18", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T24", "normalized": [] }, { "id": "Carbamazepine_ddi_R19", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T25", "normalized": [] }, { "id": "Carbamazepine_ddi_R20", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T26", "normalized": [] }, { "id": "Carbamazepine_ddi_R21", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T27", "normalized": [] }, { "id": "Carbamazepine_ddi_R22", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T28", "normalized": [] }, { "id": "Carbamazepine_ddi_R23", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T29", "normalized": [] }, { "id": "Carbamazepine_ddi_R24", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T30", "normalized": [] }, { "id": "Carbamazepine_ddi_R25", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T31", "normalized": [] }, { "id": "Carbamazepine_ddi_R26", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T6", "arg2_id": "Carbamazepine_ddi_T32", "normalized": [] }, { "id": "Carbamazepine_ddi_R27", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T38", "normalized": [] }, { "id": "Carbamazepine_ddi_R28", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T39", "normalized": [] }, { "id": "Carbamazepine_ddi_R29", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T40", "normalized": [] }, { "id": "Carbamazepine_ddi_R30", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T41", "normalized": [] }, { "id": "Carbamazepine_ddi_R31", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T42", "normalized": [] }, { "id": "Carbamazepine_ddi_R32", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T43", "normalized": [] }, { "id": "Carbamazepine_ddi_R33", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T44", "normalized": [] }, { "id": "Carbamazepine_ddi_R34", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T45", "normalized": [] }, { "id": "Carbamazepine_ddi_R35", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T37", "arg2_id": "Carbamazepine_ddi_T46", "normalized": [] }, { "id": "Carbamazepine_ddi_R36", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T53", "normalized": [] }, { "id": "Carbamazepine_ddi_R37", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T54", "normalized": [] }, { "id": "Carbamazepine_ddi_R38", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T55", "normalized": [] }, { "id": "Carbamazepine_ddi_R39", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T56", "normalized": [] }, { "id": "Carbamazepine_ddi_R40", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T57", "normalized": [] }, { "id": "Carbamazepine_ddi_R41", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T58", "normalized": [] }, { "id": "Carbamazepine_ddi_R42", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T59", "normalized": [] }, { "id": "Carbamazepine_ddi_R43", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T60", "normalized": [] }, { "id": "Carbamazepine_ddi_R44", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T61", "normalized": [] }, { "id": "Carbamazepine_ddi_R45", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T62", "normalized": [] }, { "id": "Carbamazepine_ddi_R46", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T63", "normalized": [] }, { "id": "Carbamazepine_ddi_R47", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T64", "normalized": [] }, { "id": "Carbamazepine_ddi_R48", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T65", "normalized": [] }, { "id": "Carbamazepine_ddi_R49", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T66", "normalized": [] }, { "id": "Carbamazepine_ddi_R50", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T67", "normalized": [] }, { "id": "Carbamazepine_ddi_R51", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T68", "normalized": [] }, { "id": "Carbamazepine_ddi_R52", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T69", "normalized": [] }, { "id": "Carbamazepine_ddi_R53", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T70", "normalized": [] }, { "id": "Carbamazepine_ddi_R54", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T71", "normalized": [] }, { "id": "Carbamazepine_ddi_R55", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T72", "normalized": [] }, { "id": "Carbamazepine_ddi_R56", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T73", "normalized": [] }, { "id": "Carbamazepine_ddi_R57", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T74", "normalized": [] }, { "id": "Carbamazepine_ddi_R58", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T75", "normalized": [] }, { "id": "Carbamazepine_ddi_R59", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T76", "normalized": [] }, { "id": "Carbamazepine_ddi_R60", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T77", "normalized": [] }, { "id": "Carbamazepine_ddi_R61", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T78", "normalized": [] }, { "id": "Carbamazepine_ddi_R62", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T79", "normalized": [] }, { "id": "Carbamazepine_ddi_R63", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T80", "normalized": [] }, { "id": "Carbamazepine_ddi_R64", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T81", "normalized": [] }, { "id": "Carbamazepine_ddi_R65", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T82", "normalized": [] }, { "id": "Carbamazepine_ddi_R66", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T83", "normalized": [] }, { "id": "Carbamazepine_ddi_R67", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T84", "normalized": [] }, { "id": "Carbamazepine_ddi_R68", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T85", "normalized": [] }, { "id": "Carbamazepine_ddi_R69", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T86", "normalized": [] }, { "id": "Carbamazepine_ddi_R70", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T87", "normalized": [] }, { "id": "Carbamazepine_ddi_R71", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T88", "normalized": [] }, { "id": "Carbamazepine_ddi_R72", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T89", "normalized": [] }, { "id": "Carbamazepine_ddi_R73", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T90", "normalized": [] }, { "id": "Carbamazepine_ddi_R74", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T91", "normalized": [] }, { "id": "Carbamazepine_ddi_R75", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T92", "normalized": [] }, { "id": "Carbamazepine_ddi_R76", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T93", "normalized": [] }, { "id": "Carbamazepine_ddi_R77", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T94", "normalized": [] }, { "id": "Carbamazepine_ddi_R78", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T95", "normalized": [] }, { "id": "Carbamazepine_ddi_R79", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T96", "normalized": [] }, { "id": "Carbamazepine_ddi_R80", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T52", "arg2_id": "Carbamazepine_ddi_T97", "normalized": [] }, { "id": "Carbamazepine_ddi_R81", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T100", "arg2_id": "Carbamazepine_ddi_T101", "normalized": [] }, { "id": "Carbamazepine_ddi_R82", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T100", "arg2_id": "Carbamazepine_ddi_T102", "normalized": [] }, { "id": "Carbamazepine_ddi_R83", "type": "MECHANISM", "arg1_id": "Carbamazepine_ddi_T100", "arg2_id": "Carbamazepine_ddi_T103", "normalized": [] }, { "id": "Carbamazepine_ddi_R84", "type": "EFFECT", "arg1_id": "Carbamazepine_ddi_T106", "arg2_id": "Carbamazepine_ddi_T107", "normalized": [] }, { "id": "Carbamazepine_ddi_R85", "type": "EFFECT", "arg1_id": "Carbamazepine_ddi_T111", "arg2_id": "Carbamazepine_ddi_T114", "normalized": [] }, { "id": "Carbamazepine_ddi_R86", "type": "EFFECT", "arg1_id": "Carbamazepine_ddi_T112", "arg2_id": "Carbamazepine_ddi_T114", "normalized": [] }, { "id": "Carbamazepine_ddi_R87", "type": "EFFECT", "arg1_id": "Carbamazepine_ddi_T113", "arg2_id": "Carbamazepine_ddi_T114", "normalized": [] }, { "id": "Carbamazepine_ddi_R88", "type": "ADVISE", "arg1_id": "Carbamazepine_ddi_T116", "arg2_id": "Carbamazepine_ddi_T117", "normalized": [] }, { "id": "Carbamazepine_ddi_R89", "type": "ADVISE", "arg1_id": "Carbamazepine_ddi_T116", "arg2_id": "Carbamazepine_ddi_T118", "normalized": [] } ]

[ { "id": "Loperamide_ddi__text", "type": "abstract", "text": [ "There was no evidence in clinical trials of drug interactions with concurrent medications." ], "offsets": [ [ 0, 90 ] ] } ]

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[ { "id": "Neomycin_ddi__text", "type": "abstract", "text": [ "Caution should be taken in concurrent or serial use of other neurotoxic and/ or nephrotoxic drugs because of possible enhancement of the nephrotoxicity and/or ototoxicity of neomycin. Caution should also be taken in concurrent or serial use of other aminoglycosides and polymyxins because they may enhance neomycin s nephrotoxicity and/or ototoxicity and potentiate neomycin sulfate neuromuscular blocking effects. Oral neomycin inhibits the gastrointestinal absorption of penicillin V, oral vitamin B-12, methotrexate and 5-fluorouracil. The gastrointestinal absorption of digoxin also appears to be inhibited. Therefore, digoxin serum levels should be monitored. Oral neomycin sulfate may enhance the effect of coumarin in anticoagulants by decreasing vitamin K availability." ], "offsets": [ [ 0, 777 ] ] } ]

[ { "id": "Neomycin_ddi_T1", "type": "DRUG", "text": [ "neomycin" ], "offsets": [ [ 174, 182 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T2", "type": "GROUP", "text": [ "aminoglycosides" ], "offsets": [ [ 250, 265 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T3", "type": "GROUP", "text": [ "polymyxins" ], "offsets": [ [ 270, 280 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T4", "type": "DRUG", "text": [ "neomycin sulfate" ], "offsets": [ [ 366, 382 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T5", "type": "DRUG", "text": [ "neomycin" ], "offsets": [ [ 420, 428 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T6", "type": "DRUG", "text": [ "penicillin V" ], "offsets": [ [ 473, 485 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T7", "type": "DRUG", "text": [ "vitamin B-12" ], "offsets": [ [ 492, 504 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T8", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 506, 518 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T9", "type": "DRUG", "text": [ "5-fluorouracil" ], "offsets": [ [ 523, 537 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T10", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 574, 581 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T11", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 623, 630 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T12", "type": "DRUG", "text": [ "neomycin sulfate" ], "offsets": [ [ 670, 686 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T13", "type": "GROUP", "text": [ "coumarin" ], "offsets": [ [ 713, 721 ] ], "normalized": [] }, { "id": "Neomycin_ddi_T14", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 725, 739 ] ], "normalized": [] } ]

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[ { "id": "Neomycin_ddi_R1", "type": "MECHANISM", "arg1_id": "Neomycin_ddi_T5", "arg2_id": "Neomycin_ddi_T6", "normalized": [] }, { "id": "Neomycin_ddi_R2", "type": "MECHANISM", "arg1_id": "Neomycin_ddi_T5", "arg2_id": "Neomycin_ddi_T7", "normalized": [] }, { "id": "Neomycin_ddi_R3", "type": "MECHANISM", "arg1_id": "Neomycin_ddi_T5", "arg2_id": "Neomycin_ddi_T8", "normalized": [] }, { "id": "Neomycin_ddi_R4", "type": "MECHANISM", "arg1_id": "Neomycin_ddi_T5", "arg2_id": "Neomycin_ddi_T9", "normalized": [] }, { "id": "Neomycin_ddi_R5", "type": "EFFECT", "arg1_id": "Neomycin_ddi_T12", "arg2_id": "Neomycin_ddi_T13", "normalized": [] }, { "id": "Neomycin_ddi_R6", "type": "EFFECT", "arg1_id": "Neomycin_ddi_T12", "arg2_id": "Neomycin_ddi_T14", "normalized": [] } ]

[ { "id": "Bentiromide_ddi__text", "type": "abstract", "text": [ "Bentiromide may interact with acetaminophen (e.g., Tylenol), chloramphenicol (e.g., Chloromycetin), local anesthetics (e.g., benzocaine and lidocaine), para-aminobenzoic acid (PABA)-containing preparations (e.g., sunscreens and some multivitamins), procainamide (e.g., Pronestyl), sulfonamides (sulfa medicines), thiazide diuretics (use of these medicines during the test period will affect the test results), and pancreatic supplements (use of pancreatic supplements may give false test results)." ], "offsets": [ [ 0, 497 ] ] } ]

[ { "id": "Bentiromide_ddi_T1", "type": "DRUG", "text": [ "Bentiromide" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T2", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 30, 43 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T3", "type": "BRAND", "text": [ "Tylenol" ], "offsets": [ [ 51, 58 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T4", "type": "DRUG", "text": [ "chloramphenicol" ], "offsets": [ [ 61, 76 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T5", "type": "BRAND", "text": [ "Chloromycetin" ], "offsets": [ [ 84, 97 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T6", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 106, 117 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T7", "type": "DRUG", "text": [ "benzocaine" ], "offsets": [ [ 125, 135 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T8", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 140, 149 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T9", "type": "DRUG_N", "text": [ "para-aminobenzoic acid" ], "offsets": [ [ 152, 174 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T10", "type": "DRUG_N", "text": [ "PABA" ], "offsets": [ [ 176, 180 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T11", "type": "GROUP", "text": [ "multivitamins" ], "offsets": [ [ 233, 246 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T12", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 249, 261 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T13", "type": "BRAND", "text": [ "Pronestyl" ], "offsets": [ [ 269, 278 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T14", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 281, 293 ] ], "normalized": [] }, { "id": "Bentiromide_ddi_T15", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 313, 331 ] ], "normalized": [] } ]

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[ { "id": "Bentiromide_ddi_R1", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T2", "normalized": [] }, { "id": "Bentiromide_ddi_R2", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T3", "normalized": [] }, { "id": "Bentiromide_ddi_R3", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T4", "normalized": [] }, { "id": "Bentiromide_ddi_R4", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T5", "normalized": [] }, { "id": "Bentiromide_ddi_R5", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T6", "normalized": [] }, { "id": "Bentiromide_ddi_R6", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T7", "normalized": [] }, { "id": "Bentiromide_ddi_R7", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T8", "normalized": [] }, { "id": "Bentiromide_ddi_R8", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T9", "normalized": [] }, { "id": "Bentiromide_ddi_R9", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T10", "normalized": [] }, { "id": "Bentiromide_ddi_R10", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T11", "normalized": [] }, { "id": "Bentiromide_ddi_R11", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T12", "normalized": [] }, { "id": "Bentiromide_ddi_R12", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T13", "normalized": [] }, { "id": "Bentiromide_ddi_R13", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T14", "normalized": [] }, { "id": "Bentiromide_ddi_R14", "type": "INT", "arg1_id": "Bentiromide_ddi_T1", "arg2_id": "Bentiromide_ddi_T15", "normalized": [] } ]

[ { "id": "Bleomycin_ddi__text", "type": "abstract", "text": [ "Certain antibiotic, cisplatin, cyclosporine, diuretic, foscarnet, and vaccines." ], "offsets": [ [ 0, 79 ] ] } ]

[ { "id": "Bleomycin_ddi_T1", "type": "GROUP", "text": [ "antibiotic" ], "offsets": [ [ 8, 18 ] ], "normalized": [] }, { "id": "Bleomycin_ddi_T2", "type": "DRUG", "text": [ "cisplatin" ], "offsets": [ [ 20, 29 ] ], "normalized": [] }, { "id": "Bleomycin_ddi_T3", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 31, 43 ] ], "normalized": [] }, { "id": "Bleomycin_ddi_T4", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 45, 53 ] ], "normalized": [] }, { "id": "Bleomycin_ddi_T5", "type": "DRUG", "text": [ "foscarnet" ], "offsets": [ [ 55, 64 ] ], "normalized": [] }, { "id": "Bleomycin_ddi_T6", "type": "GROUP", "text": [ "vaccines" ], "offsets": [ [ 70, 78 ] ], "normalized": [] } ]

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[ { "id": "Filgrastim_ddi__text", "type": "abstract", "text": [ "Drug interactions between NEUPOGEN and other drugs have not been fully evaluated. Drugs which may potentiate the release of neutrophils, such as lithium, should be used with caution." ], "offsets": [ [ 0, 183 ] ] } ]

[ { "id": "Filgrastim_ddi_T1", "type": "BRAND", "text": [ "NEUPOGEN" ], "offsets": [ [ 26, 34 ] ], "normalized": [] }, { "id": "Filgrastim_ddi_T2", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 146, 153 ] ], "normalized": [] } ]

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[ { "id": "L-Tryptophan_ddi__text", "type": "abstract", "text": [ "Monoamine oxidase (MAO) inhibitors such as isocarboxazid (e.g., Marplan), phenelzine (e.g., Nardil), procarbazine (e.g., Matulane), selegiline (e.g., Eldepryl), and tranylcypromine (e.g., Parnate): Using these medicines with L-tryptophan may increase the chance of side effects." ], "offsets": [ [ 0, 278 ] ] } ]

[ { "id": "L-Tryptophan_ddi_T1", "type": "GROUP", "text": [ "Monoamine oxidase (MAO) inhibitors" ], "offsets": [ [ 0, 34 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T2", "type": "DRUG", "text": [ "isocarboxazid" ], "offsets": [ [ 43, 56 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T3", "type": "BRAND", "text": [ "Marplan" ], "offsets": [ [ 64, 71 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T4", "type": "DRUG", "text": [ "phenelzine" ], "offsets": [ [ 74, 84 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T5", "type": "BRAND", "text": [ "Nardil" ], "offsets": [ [ 92, 98 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T6", "type": "DRUG", "text": [ "procarbazine" ], "offsets": [ [ 101, 113 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T7", "type": "BRAND", "text": [ "Matulane" ], "offsets": [ [ 121, 129 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T8", "type": "DRUG", "text": [ "selegiline" ], "offsets": [ [ 132, 142 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T9", "type": "BRAND", "text": [ "Eldepryl" ], "offsets": [ [ 150, 158 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T10", "type": "DRUG", "text": [ "tranylcypromine" ], "offsets": [ [ 165, 180 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T11", "type": "BRAND", "text": [ "Parnate" ], "offsets": [ [ 188, 195 ] ], "normalized": [] }, { "id": "L-Tryptophan_ddi_T12", "type": "DRUG", "text": [ "L-tryptophan" ], "offsets": [ [ 225, 237 ] ], "normalized": [] } ]

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[ { "id": "Cysteamine_ddi__text", "type": "abstract", "text": [ "No drug interactions have been reported." ], "offsets": [ [ 0, 40 ] ] } ]

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[ { "id": "Niacin_ddi__text", "type": "abstract", "text": [ "Interactions for Vitamin B3 (Niacin): Antihypertensive Therapy: Nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension. Aspirin: Concomitant aspirin may decrease the metabolic clearance of nicotinic acid. The clinical relevance of this finding is unclear. Other: Concomitant alcohol or hot drinks may increase the side effects of flushing and pruritus and should be avoided at the time of drug ingestion." ], "offsets": [ [ 0, 476 ] ] } ]

[ { "id": "Niacin_ddi_T1", "type": "DRUG", "text": [ "Vitamin B3" ], "offsets": [ [ 17, 27 ] ], "normalized": [] }, { "id": "Niacin_ddi_T2", "type": "DRUG", "text": [ "Niacin" ], "offsets": [ [ 29, 35 ] ], "normalized": [] }, { "id": "Niacin_ddi_T3", "type": "GROUP", "text": [ "Antihypertensive" ], "offsets": [ [ 38, 54 ] ], "normalized": [] }, { "id": "Niacin_ddi_T4", "type": "DRUG", "text": [ "Nicotinic acid" ], "offsets": [ [ 64, 78 ] ], "normalized": [] }, { "id": "Niacin_ddi_T5", "type": "GROUP", "text": [ "ganglionic blocking agents" ], "offsets": [ [ 109, 135 ] ], "normalized": [] }, { "id": "Niacin_ddi_T6", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 192, 199 ] ], "normalized": [] }, { "id": "Niacin_ddi_T7", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 213, 220 ] ], "normalized": [] }, { "id": "Niacin_ddi_T8", "type": "DRUG", "text": [ "nicotinic acid" ], "offsets": [ [ 261, 275 ] ], "normalized": [] }, { "id": "Niacin_ddi_T9", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 347, 354 ] ], "normalized": [] } ]

[]

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[ { "id": "Niacin_ddi_R1", "type": "EFFECT", "arg1_id": "Niacin_ddi_T4", "arg2_id": "Niacin_ddi_T5", "normalized": [] }, { "id": "Niacin_ddi_R2", "type": "MECHANISM", "arg1_id": "Niacin_ddi_T7", "arg2_id": "Niacin_ddi_T8", "normalized": [] } ]

[ { "id": "Fludrocortisone_ddi__text", "type": "abstract", "text": [ "When administered concurrently, the following drugs may interact with adrenal corticosteroids. Amphotericin B or potassium-depleting diuretics (benzothiadiazines and related drugs, ethacrynic acid and furosemide) enhanced hypokalemia. Check serum potassium levels at frequent intervals; use potassium supplements if necessary . Digitalis glycosides enhanced possibility of arrhythmias or digitalis toxicity associated with hypokalemia. Monitor serum potassium levels; use potassium supplements if necessary. Oral anticoagulants decreased prothrombin time response. Monitor prothrombin levels and adjust anticoagulant dosage accordingly. Antidiabetic drugs (oral agents and insulin) diminished antidiabetic effect. Monitor for symptoms of hyperglycemia; adjust dosage of antidiabetic drug upward if necessary. Aspirin increased ulcerogenic effect; decreased pharmacologic effect of aspirin. Rarely salicylate toxicity may occur in patients who discontinue steroids after concurrent high-dose aspirin therapy. Monitor salicylate levels or the therapeutic effect for which aspirin is given; adjust salicylate dosage accordingly if effect is altered. Barbiturates, phenytoin, or rifampin increased metabolic clearance of fludrocortisone acetate because of the induction of hepatic enzymes. Observe the patient for possible diminished effect of steroid and increase the steroid dosage accordingly. Anabolic steroids (particularly C-17 alkylated androgens such as oxymetholone, methandrostenolone, norethandrolone, and similar compounds) enhanced tendency toward edema. Use caution when giving these drugs together, especially in patients with hepatic or cardiac disease. Vaccines neurological complications and lack of antibody response . Estrogen increased levels of corticosteroid-binding globulin, thereby increasing the bound (inactive) fraction; this effect is at least balanced by decreased metabolism of corticosteroids. When estrogen therapy is initiated, a reduction in corticosteroid dosage may be required, and increased amounts may be required when estrogen is terminated. Drug/Laboratory Test Interactions Corticosteroids may affect the nitrobluetetrazolium test for bacterial infection and produce false-negative results ." ], "offsets": [ [ 0, 2231 ] ] } ]

[ { "id": "Fludrocortisone_ddi_T1", "type": "GROUP", "text": [ "adrenal corticosteroids" ], "offsets": [ [ 70, 93 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T2", "type": "DRUG", "text": [ "Amphotericin B" ], "offsets": [ [ 95, 109 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T3", "type": "GROUP", "text": [ "potassium-depleting diuretics" ], "offsets": [ [ 113, 142 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T4", "type": "GROUP", "text": [ "benzothiadiazines" ], "offsets": [ [ 144, 161 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T5", "type": "DRUG", "text": [ "ethacrynic acid" ], "offsets": [ [ 181, 196 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T6", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 201, 211 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T7", "type": "DRUG", "text": [ "potassium" ], "offsets": [ [ 291, 300 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T8", "type": "GROUP", "text": [ "Digitalis glycosides" ], "offsets": [ [ 328, 348 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T9", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 388, 397 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T10", "type": "DRUG", "text": [ "potassium" ], "offsets": [ [ 472, 481 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T11", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 513, 527 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T12", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 603, 616 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T13", "type": "GROUP", "text": [ "Antidiabetic drugs" ], "offsets": [ [ 637, 655 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T14", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 673, 680 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T15", "type": "GROUP", "text": [ "antidiabetic drug" ], "offsets": [ [ 770, 787 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T16", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 809, 816 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T17", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 881, 888 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T18", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 897, 907 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T19", "type": "GROUP", "text": [ "steroids" ], "offsets": [ [ 955, 963 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T20", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 991, 998 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T21", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 1016, 1026 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T22", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 1070, 1077 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T23", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 1095, 1105 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T24", "type": "GROUP", "text": [ "Barbiturates" ], "offsets": [ [ 1147, 1159 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T25", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1161, 1170 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T26", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1175, 1183 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T27", "type": "DRUG", "text": [ "fludrocortisone acetate" ], "offsets": [ [ 1217, 1240 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T28", "type": "GROUP", "text": [ "steroid" ], "offsets": [ [ 1340, 1347 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T29", "type": "GROUP", "text": [ "steroid" ], "offsets": [ [ 1365, 1372 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T30", "type": "GROUP", "text": [ "Anabolic steroids" ], "offsets": [ [ 1393, 1410 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T31", "type": "GROUP", "text": [ "androgens" ], "offsets": [ [ 1440, 1449 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T32", "type": "DRUG", "text": [ "oxymetholone" ], "offsets": [ [ 1458, 1470 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T33", "type": "DRUG", "text": [ "methandrostenolone" ], "offsets": [ [ 1472, 1490 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T34", "type": "DRUG", "text": [ "norethandrolone" ], "offsets": [ [ 1492, 1507 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T35", "type": "GROUP", "text": [ "Vaccines" ], "offsets": [ [ 1666, 1674 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T36", "type": "GROUP", "text": [ "Estrogen" ], "offsets": [ [ 1734, 1742 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T37", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 1906, 1921 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T38", "type": "GROUP", "text": [ "estrogen" ], "offsets": [ [ 1928, 1936 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T39", "type": "GROUP", "text": [ "corticosteroid" ], "offsets": [ [ 1974, 1988 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T40", "type": "GROUP", "text": [ "estrogen" ], "offsets": [ [ 2056, 2064 ] ], "normalized": [] }, { "id": "Fludrocortisone_ddi_T41", "type": "GROUP", "text": [ "Corticosteroids" ], "offsets": [ [ 2114, 2129 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Fludrocortisone_ddi_R1", "type": "EFFECT", "arg1_id": "Fludrocortisone_ddi_T19", "arg2_id": "Fludrocortisone_ddi_T20", "normalized": [] }, { "id": "Fludrocortisone_ddi_R2", "type": "MECHANISM", "arg1_id": "Fludrocortisone_ddi_T24", "arg2_id": "Fludrocortisone_ddi_T27", "normalized": [] }, { "id": "Fludrocortisone_ddi_R3", "type": "MECHANISM", "arg1_id": "Fludrocortisone_ddi_T25", "arg2_id": "Fludrocortisone_ddi_T27", "normalized": [] }, { "id": "Fludrocortisone_ddi_R4", "type": "MECHANISM", "arg1_id": "Fludrocortisone_ddi_T26", "arg2_id": "Fludrocortisone_ddi_T27", "normalized": [] } ]

[ { "id": "Apomorphine_ddi__text", "type": "abstract", "text": [ "5HT3 Antagonists: Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with drugs of the 5HT3 antagonist class (including, for example, ondansetron, granisetron, dolasetron, palonosetron, and alosetron) is contraindicated . Antihypertensive Medications and Vasodilators: The following adverse events were experienced more commonly in patients receiving concomitant antihypertensive medications or vasodilators (n = 94) compared to patients not receiving these concomitant drugs (n = 456): hypotension 10% vs 4%, myocardial infarction 3% vs 1%, serious pneumonia 5% vs 3%, serious falls 9% vs 3%, and bone and joint injuries 6% vs 2%. The mechanism underlying many of these events is unknown, but may represent increased hypotension . Dopamine Antagonists: Since apomorphine is a dopamine agonist, it is possible that dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of APOKYN. Patients with major psychotic disorders, treated with neuroleptics, should be treated with dopamine agonists only if the potential benefits outweigh the risks. Drugs Prolonging the QT/QTc Interval Caution should be exercised when prescribing apomorphine concomitantly with drugs that prolong the QT/QTc interval. Drug/Laboratory Test Interactions There are no known interactions between APOKYN and laboratory tests." ], "offsets": [ [ 0, 1489 ] ] } ]

[ { "id": "Apomorphine_ddi_T1", "type": "GROUP", "text": [ "5HT3 Antagonists" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T2", "type": "DRUG", "text": [ "apomorphine" ], "offsets": [ [ 90, 101 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T3", "type": "DRUG", "text": [ "ondansetron" ], "offsets": [ [ 124, 135 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T4", "type": "DRUG", "text": [ "apomorphine" ], "offsets": [ [ 160, 171 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T5", "type": "GROUP", "text": [ "5HT3 antagonist class" ], "offsets": [ [ 190, 211 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T6", "type": "DRUG", "text": [ "ondansetron" ], "offsets": [ [ 237, 248 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T7", "type": "DRUG", "text": [ "granisetron" ], "offsets": [ [ 250, 261 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T8", "type": "DRUG", "text": [ "dolasetron" ], "offsets": [ [ 263, 273 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T9", "type": "DRUG", "text": [ "palonosetron" ], "offsets": [ [ 275, 287 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T10", "type": "DRUG", "text": [ "alosetron" ], "offsets": [ [ 293, 302 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T11", "type": "GROUP", "text": [ "Antihypertensive Medication" ], "offsets": [ [ 325, 352 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T12", "type": "GROUP", "text": [ "Vasodilators" ], "offsets": [ [ 358, 370 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T13", "type": "GROUP", "text": [ "antihypertensive medications" ], "offsets": [ [ 466, 494 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T14", "type": "GROUP", "text": [ "vasodilators" ], "offsets": [ [ 498, 510 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T15", "type": "GROUP", "text": [ "Dopamine Antagonists" ], "offsets": [ [ 835, 855 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T16", "type": "DRUG", "text": [ "apomorphine" ], "offsets": [ [ 863, 874 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T17", "type": "GROUP", "text": [ "dopamine agonist" ], "offsets": [ [ 880, 896 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T18", "type": "GROUP", "text": [ "dopamine antagonists" ], "offsets": [ [ 918, 938 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T19", "type": "GROUP", "text": [ "neuroleptics" ], "offsets": [ [ 952, 964 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T20", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 966, 980 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T21", "type": "GROUP", "text": [ "butyrophenones" ], "offsets": [ [ 982, 996 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T22", "type": "GROUP", "text": [ "thioxanthenes" ], "offsets": [ [ 998, 1011 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T23", "type": "DRUG", "text": [ "metoclopramide" ], "offsets": [ [ 1016, 1030 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T24", "type": "BRAND", "text": [ "APOKYN" ], "offsets": [ [ 1066, 1072 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T25", "type": "GROUP", "text": [ "neuroleptics" ], "offsets": [ [ 1128, 1140 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T26", "type": "GROUP", "text": [ "dopamine agonists" ], "offsets": [ [ 1165, 1182 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T27", "type": "DRUG", "text": [ "apomorphine" ], "offsets": [ [ 1316, 1327 ] ], "normalized": [] }, { "id": "Apomorphine_ddi_T28", "type": "BRAND", "text": [ "APOKYN" ], "offsets": [ [ 1461, 1467 ] ], "normalized": [] } ]

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[]

[ { "id": "Apomorphine_ddi_R1", "type": "EFFECT", "arg1_id": "Apomorphine_ddi_T2", "arg2_id": "Apomorphine_ddi_T3", "normalized": [] }, { "id": "Apomorphine_ddi_R2", "type": "ADVISE", "arg1_id": "Apomorphine_ddi_T4", "arg2_id": "Apomorphine_ddi_T5", "normalized": [] }, { "id": "Apomorphine_ddi_R3", "type": "ADVISE", "arg1_id": "Apomorphine_ddi_T4", "arg2_id": "Apomorphine_ddi_T6", "normalized": [] }, { "id": "Apomorphine_ddi_R4", "type": "ADVISE", "arg1_id": "Apomorphine_ddi_T4", "arg2_id": "Apomorphine_ddi_T7", "normalized": [] }, { "id": "Apomorphine_ddi_R5", "type": "ADVISE", "arg1_id": "Apomorphine_ddi_T4", "arg2_id": "Apomorphine_ddi_T8", "normalized": [] }, { "id": "Apomorphine_ddi_R6", "type": "ADVISE", "arg1_id": "Apomorphine_ddi_T4", "arg2_id": "Apomorphine_ddi_T9", "normalized": [] }, { "id": "Apomorphine_ddi_R7", "type": "ADVISE", "arg1_id": "Apomorphine_ddi_T4", "arg2_id": "Apomorphine_ddi_T10", "normalized": [] }, { "id": "Apomorphine_ddi_R8", "type": "EFFECT", "arg1_id": "Apomorphine_ddi_T13", "arg2_id": "Apomorphine_ddi_T14", "normalized": [] }, { "id": "Apomorphine_ddi_R9", "type": "EFFECT", "arg1_id": "Apomorphine_ddi_T18", "arg2_id": "Apomorphine_ddi_T23", "normalized": [] }, { "id": "Apomorphine_ddi_R10", "type": "EFFECT", "arg1_id": "Apomorphine_ddi_T20", "arg2_id": "Apomorphine_ddi_T24", "normalized": [] }, { "id": "Apomorphine_ddi_R11", "type": "EFFECT", "arg1_id": "Apomorphine_ddi_T21", "arg2_id": "Apomorphine_ddi_T24", "normalized": [] }, { "id": "Apomorphine_ddi_R12", "type": "EFFECT", "arg1_id": "Apomorphine_ddi_T22", "arg2_id": "Apomorphine_ddi_T24", "normalized": [] }, { "id": "Apomorphine_ddi_R13", "type": "EFFECT", "arg1_id": "Apomorphine_ddi_T23", "arg2_id": "Apomorphine_ddi_T24", "normalized": [] }, { "id": "Apomorphine_ddi_R14", "type": "ADVISE", "arg1_id": "Apomorphine_ddi_T25", "arg2_id": "Apomorphine_ddi_T26", "normalized": [] } ]

[ { "id": "Fenoprofen_ddi__text", "type": "abstract", "text": [ "The coadministration of aspirin decreases the biologic half-life of fenoprofen because of an increase in metabolic clearance that results in a greater amount of hydroxylated fenoprofen in the urine. Although the mechanism of interaction between fenoprofen and aspirin is not totally known, enzyme induction and displacement of fenoprofen from plasma albumin binding sites are possibilities. Because Nalfon has not been shown to produce any additional effect beyond that obtained with aspirin alone and because aspirin increases the rate of excretion of Nalfon, the concomitant use of Nalfon and salicylates is not recommended. Chronic administration of phenobarbital, a known enzyme inducer, may be associated with a decrease in the plasma half-life of fenoprofen. When phenobarbital is added to or withdrawn from treatment, dosage adjustment of Nalfon may be required. In vitro studies have shown that fenoprofen, because of its affinity for albumin, may displace from their binding sites other drugs that are also albumin bound, and this may lead to drug interaction. Theoretically, fenoprofen could likewise be displaced. Patients receiving hydantoins, sulfonamides, or sulfonylureas should be observed for increased activity of these drugs and, therefore, signs of toxicity from these drugs. In patients receiving coumarin-type anticoagulants, the addition of Nalfon to therapy could prolong the prothrombin time. Patients receiving both drugs should be under careful observation. Patients treated with Nalfon may be resistant to the effects of loop diuretics. In patients receiving Nalfon and a steroid concomitantly, any reduction in steroid dosage should be gradual in order to avoid the possible complications of sudden steroid withdrawal." ], "offsets": [ [ 0, 1747 ] ] } ]

[ { "id": "Fenoprofen_ddi_T1", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 24, 31 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T2", "type": "DRUG", "text": [ "fenoprofen" ], "offsets": [ [ 68, 78 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T3", "type": "DRUG_N", "text": [ "hydroxylated fenoprofen" ], "offsets": [ [ 161, 184 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T4", "type": "DRUG", "text": [ "fenoprofen" ], "offsets": [ [ 245, 255 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T5", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 260, 267 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T6", "type": "DRUG", "text": [ "fenoprofen" ], "offsets": [ [ 327, 337 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T7", "type": "BRAND", "text": [ "Nalfon" ], "offsets": [ [ 399, 405 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T8", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 484, 491 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T9", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 510, 517 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T10", "type": "BRAND", "text": [ "Nalfon" ], "offsets": [ [ 553, 559 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T11", "type": "BRAND", "text": [ "Nalfon" ], "offsets": [ [ 584, 590 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T12", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 595, 606 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T13", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 653, 666 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T14", "type": "DRUG", "text": [ "fenoprofen" ], "offsets": [ [ 753, 763 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T15", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 770, 783 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T16", "type": "BRAND", "text": [ "Nalfon" ], "offsets": [ [ 846, 852 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T17", "type": "DRUG", "text": [ "fenoprofen" ], "offsets": [ [ 903, 913 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T18", "type": "DRUG", "text": [ "fenoprofen" ], "offsets": [ [ 1085, 1095 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T19", "type": "GROUP", "text": [ "hydantoins" ], "offsets": [ [ 1144, 1154 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T20", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 1156, 1168 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T21", "type": "GROUP", "text": [ "sulfonylureas" ], "offsets": [ [ 1173, 1186 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T22", "type": "GROUP", "text": [ "coumarin-type anticoagulants" ], "offsets": [ [ 1318, 1346 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T23", "type": "BRAND", "text": [ "Nalfon" ], "offsets": [ [ 1364, 1370 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T24", "type": "BRAND", "text": [ "Nalfon" ], "offsets": [ [ 1507, 1513 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T25", "type": "GROUP", "text": [ "loop diuretics" ], "offsets": [ [ 1549, 1563 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T26", "type": "BRAND", "text": [ "Nalfon" ], "offsets": [ [ 1587, 1593 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T27", "type": "GROUP", "text": [ "steroid" ], "offsets": [ [ 1600, 1607 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T28", "type": "GROUP", "text": [ "steroid" ], "offsets": [ [ 1640, 1647 ] ], "normalized": [] }, { "id": "Fenoprofen_ddi_T29", "type": "GROUP", "text": [ "steroid" ], "offsets": [ [ 1728, 1735 ] ], "normalized": [] } ]

[]

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[ { "id": "Fenoprofen_ddi_R1", "type": "MECHANISM", "arg1_id": "Fenoprofen_ddi_T1", "arg2_id": "Fenoprofen_ddi_T2", "normalized": [] }, { "id": "Fenoprofen_ddi_R2", "type": "MECHANISM", "arg1_id": "Fenoprofen_ddi_T4", "arg2_id": "Fenoprofen_ddi_T5", "normalized": [] }, { "id": "Fenoprofen_ddi_R3", "type": "MECHANISM", "arg1_id": "Fenoprofen_ddi_T9", "arg2_id": "Fenoprofen_ddi_T10", "normalized": [] }, { "id": "Fenoprofen_ddi_R4", "type": "ADVISE", "arg1_id": "Fenoprofen_ddi_T11", "arg2_id": "Fenoprofen_ddi_T12", "normalized": [] }, { "id": "Fenoprofen_ddi_R5", "type": "MECHANISM", "arg1_id": "Fenoprofen_ddi_T13", "arg2_id": "Fenoprofen_ddi_T14", "normalized": [] }, { "id": "Fenoprofen_ddi_R6", "type": "ADVISE", "arg1_id": "Fenoprofen_ddi_T15", "arg2_id": "Fenoprofen_ddi_T16", "normalized": [] }, { "id": "Fenoprofen_ddi_R7", "type": "EFFECT", "arg1_id": "Fenoprofen_ddi_T22", "arg2_id": "Fenoprofen_ddi_T23", "normalized": [] }, { "id": "Fenoprofen_ddi_R8", "type": "EFFECT", "arg1_id": "Fenoprofen_ddi_T24", "arg2_id": "Fenoprofen_ddi_T25", "normalized": [] }, { "id": "Fenoprofen_ddi_R9", "type": "ADVISE", "arg1_id": "Fenoprofen_ddi_T26", "arg2_id": "Fenoprofen_ddi_T27", "normalized": [] } ]

[ { "id": "Biperiden_ddi__text", "type": "abstract", "text": [ "Drug Interactions: The central anticholinergic syndrome can occur when anticholinergic agents such as AKINETON are administered concomitantly with drugs that have secondary anticholinergic actions, e.g., certain narcotic analgesics such as meperidine, the phenothiazines and other antipsychotics, tricyclic antidepressants, certain antiarrhythmics such as the quinidine salts, and antihistamines." ], "offsets": [ [ 0, 396 ] ] } ]

[ { "id": "Biperiden_ddi_T1", "type": "GROUP", "text": [ "anticholinergic" ], "offsets": [ [ 31, 46 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T2", "type": "BRAND", "text": [ "AKINETON" ], "offsets": [ [ 102, 110 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T3", "type": "GROUP", "text": [ "narcotic analgesics" ], "offsets": [ [ 212, 231 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T4", "type": "DRUG", "text": [ "meperidine" ], "offsets": [ [ 240, 250 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T5", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 256, 270 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T6", "type": "GROUP", "text": [ "antipsychotics" ], "offsets": [ [ 281, 295 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T7", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 297, 322 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T8", "type": "GROUP", "text": [ "antiarrhythmics" ], "offsets": [ [ 332, 347 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T9", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 360, 369 ] ], "normalized": [] }, { "id": "Biperiden_ddi_T10", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 381, 395 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Biperiden_ddi_R1", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T1", "arg2_id": "Biperiden_ddi_T3", "normalized": [] }, { "id": "Biperiden_ddi_R2", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T1", "arg2_id": "Biperiden_ddi_T4", "normalized": [] }, { "id": "Biperiden_ddi_R3", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T1", "arg2_id": "Biperiden_ddi_T5", "normalized": [] }, { "id": "Biperiden_ddi_R4", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T1", "arg2_id": "Biperiden_ddi_T6", "normalized": [] }, { "id": "Biperiden_ddi_R5", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T1", "arg2_id": "Biperiden_ddi_T7", "normalized": [] }, { "id": "Biperiden_ddi_R6", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T1", "arg2_id": "Biperiden_ddi_T8", "normalized": [] }, { "id": "Biperiden_ddi_R7", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T1", "arg2_id": "Biperiden_ddi_T9", "normalized": [] }, { "id": "Biperiden_ddi_R8", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T1", "arg2_id": "Biperiden_ddi_T10", "normalized": [] }, { "id": "Biperiden_ddi_R9", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T2", "arg2_id": "Biperiden_ddi_T3", "normalized": [] }, { "id": "Biperiden_ddi_R10", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T2", "arg2_id": "Biperiden_ddi_T4", "normalized": [] }, { "id": "Biperiden_ddi_R11", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T2", "arg2_id": "Biperiden_ddi_T5", "normalized": [] }, { "id": "Biperiden_ddi_R12", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T2", "arg2_id": "Biperiden_ddi_T6", "normalized": [] }, { "id": "Biperiden_ddi_R13", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T2", "arg2_id": "Biperiden_ddi_T7", "normalized": [] }, { "id": "Biperiden_ddi_R14", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T2", "arg2_id": "Biperiden_ddi_T8", "normalized": [] }, { "id": "Biperiden_ddi_R15", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T2", "arg2_id": "Biperiden_ddi_T9", "normalized": [] }, { "id": "Biperiden_ddi_R16", "type": "EFFECT", "arg1_id": "Biperiden_ddi_T2", "arg2_id": "Biperiden_ddi_T10", "normalized": [] } ]

[ { "id": "Cytarabine_ddi__text", "type": "abstract", "text": [ "Steady state plasma digitoxin concentrations did not appear to change. Therefore, monitoring of plasma digoxin levels may be indicated in patients receiving similar combination chemotherapy regimens. The utilization of digitoxin for such patients may be considered as an alternative. Also flucytosine." ], "offsets": [ [ 0, 301 ] ] } ]

[ { "id": "Cytarabine_ddi_T1", "type": "DRUG", "text": [ "digitoxin" ], "offsets": [ [ 20, 29 ] ], "normalized": [] }, { "id": "Cytarabine_ddi_T2", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 103, 110 ] ], "normalized": [] }, { "id": "Cytarabine_ddi_T3", "type": "DRUG", "text": [ "digitoxin" ], "offsets": [ [ 219, 228 ] ], "normalized": [] }, { "id": "Cytarabine_ddi_T4", "type": "DRUG", "text": [ "flucytosine" ], "offsets": [ [ 289, 300 ] ], "normalized": [] } ]

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[]

[ { "id": "Atropine_ddi__text", "type": "abstract", "text": [ "When atropine and pralidoxime are used together, the signs of atropinization (flushing, mydriasis, tachycardia, dryness of the mouth and nose) may occur earlier than might be expected than when atropine is used alone because pralidoxime may potentiate the effect of atropine. The following precautions should be kept in mind in the treatment of anticholinesterase poisoning although they do not bear directly on the use of atropine and pralidoxime. Since barbiturates are potentiated by the anticholinesterases, they should be used cautiously in the treatment of convulsions." ], "offsets": [ [ 0, 575 ] ] } ]

[ { "id": "Atropine_ddi_T1", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 5, 13 ] ], "normalized": [] }, { "id": "Atropine_ddi_T2", "type": "DRUG", "text": [ "pralidoxime" ], "offsets": [ [ 18, 29 ] ], "normalized": [] }, { "id": "Atropine_ddi_T3", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 194, 202 ] ], "normalized": [] }, { "id": "Atropine_ddi_T4", "type": "DRUG", "text": [ "pralidoxime" ], "offsets": [ [ 225, 236 ] ], "normalized": [] }, { "id": "Atropine_ddi_T5", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 266, 274 ] ], "normalized": [] }, { "id": "Atropine_ddi_T6", "type": "DRUG", "text": [ "atropine" ], "offsets": [ [ 423, 431 ] ], "normalized": [] }, { "id": "Atropine_ddi_T7", "type": "DRUG", "text": [ "pralidoxime" ], "offsets": [ [ 436, 447 ] ], "normalized": [] }, { "id": "Atropine_ddi_T8", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 455, 467 ] ], "normalized": [] }, { "id": "Atropine_ddi_T9", "type": "GROUP", "text": [ "anticholinesterases" ], "offsets": [ [ 491, 510 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Atropine_ddi_R1", "type": "EFFECT", "arg1_id": "Atropine_ddi_T1", "arg2_id": "Atropine_ddi_T2", "normalized": [] }, { "id": "Atropine_ddi_R2", "type": "EFFECT", "arg1_id": "Atropine_ddi_T4", "arg2_id": "Atropine_ddi_T5", "normalized": [] }, { "id": "Atropine_ddi_R3", "type": "ADVISE", "arg1_id": "Atropine_ddi_T6", "arg2_id": "Atropine_ddi_T7", "normalized": [] }, { "id": "Atropine_ddi_R4", "type": "ADVISE", "arg1_id": "Atropine_ddi_T8", "arg2_id": "Atropine_ddi_T9", "normalized": [] } ]

[ { "id": "Cetuximab_ddi__text", "type": "abstract", "text": [ "A drug interaction study was performed in which ERBITUX was administered in combination with irinotecan. There was no evidence of any pharmacokinetic interactions between ERBITUX and irinotecan." ], "offsets": [ [ 0, 194 ] ] } ]

[ { "id": "Cetuximab_ddi_T1", "type": "BRAND", "text": [ "ERBITUX" ], "offsets": [ [ 48, 55 ] ], "normalized": [] }, { "id": "Cetuximab_ddi_T2", "type": "DRUG", "text": [ "irinotecan" ], "offsets": [ [ 93, 103 ] ], "normalized": [] }, { "id": "Cetuximab_ddi_T3", "type": "BRAND", "text": [ "ERBITUX" ], "offsets": [ [ 171, 178 ] ], "normalized": [] }, { "id": "Cetuximab_ddi_T4", "type": "DRUG", "text": [ "irinotecan" ], "offsets": [ [ 183, 193 ] ], "normalized": [] } ]

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[ { "id": "Flupenthixol_ddi__text", "type": "abstract", "text": [ "Drug Interactions: Flupenthixol may interact with some drugs, like Monoamine oxidase inhibitors (MAOI): MAOI could theoretically affect flupenthixol pharmacodynamics - Arecoline - Eproxindine - Ethanol: Flupenthixol and Ethanol cause additive CNS depression - Tricyclic antidepressants: Flupenthixol increases the effect of Tricyclic antidepressants" ], "offsets": [ [ 0, 349 ] ] } ]

[ { "id": "Flupenthixol_ddi_T1", "type": "DRUG", "text": [ "Flupenthixol" ], "offsets": [ [ 19, 31 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T2", "type": "GROUP", "text": [ "Monoamine oxidase inhibitors" ], "offsets": [ [ 67, 95 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T3", "type": "GROUP", "text": [ "MAOI" ], "offsets": [ [ 97, 101 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T4", "type": "GROUP", "text": [ "MAOI" ], "offsets": [ [ 104, 108 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T5", "type": "DRUG", "text": [ "flupenthixol" ], "offsets": [ [ 136, 148 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T6", "type": "DRUG_N", "text": [ "Arecoline" ], "offsets": [ [ 168, 177 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T7", "type": "DRUG", "text": [ "Ethanol" ], "offsets": [ [ 194, 201 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T8", "type": "DRUG", "text": [ "Flupenthixol" ], "offsets": [ [ 203, 215 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T9", "type": "DRUG", "text": [ "Ethanol" ], "offsets": [ [ 220, 227 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T10", "type": "GROUP", "text": [ "Tricyclic antidepressants" ], "offsets": [ [ 260, 285 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T11", "type": "DRUG", "text": [ "Flupenthixol" ], "offsets": [ [ 287, 299 ] ], "normalized": [] }, { "id": "Flupenthixol_ddi_T12", "type": "GROUP", "text": [ "Tricyclic antidepressants" ], "offsets": [ [ 324, 349 ] ], "normalized": [] } ]

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[ { "id": "Flupenthixol_ddi_R1", "type": "INT", "arg1_id": "Flupenthixol_ddi_T1", "arg2_id": "Flupenthixol_ddi_T2", "normalized": [] }, { "id": "Flupenthixol_ddi_R2", "type": "INT", "arg1_id": "Flupenthixol_ddi_T1", "arg2_id": "Flupenthixol_ddi_T3", "normalized": [] }, { "id": "Flupenthixol_ddi_R3", "type": "EFFECT", "arg1_id": "Flupenthixol_ddi_T4", "arg2_id": "Flupenthixol_ddi_T5", "normalized": [] }, { "id": "Flupenthixol_ddi_R4", "type": "EFFECT", "arg1_id": "Flupenthixol_ddi_T8", "arg2_id": "Flupenthixol_ddi_T9", "normalized": [] }, { "id": "Flupenthixol_ddi_R5", "type": "EFFECT", "arg1_id": "Flupenthixol_ddi_T11", "arg2_id": "Flupenthixol_ddi_T12", "normalized": [] } ]

[ { "id": "Digoxin_ddi__text", "type": "abstract", "text": [ "Potassium-depleting diuretics are a major contributing factor to digitalis toxicity. Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result. Erythromycin and clarithromycin (and possibly other macrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result. The risk of this interaction may be reduced if digoxin is given as capsules. Propantheline and diphenoxylate, by decreasing gut motility, may increase digoxin absorption. Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine, certain anticancer drugs, and metoclopramide may interfere with intestinal digoxin absorption, resulting in unexpectedly low serum concentrations. Rifampin may decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin. There have been inconsistent reports regarding the effects of other drugs (e.g., quinine, penicillamine) on serum digoxin concentration. Thyroid administration to a digitalized, hypothyroid patient may increase the dose requirement of digoxin. Concomitant use of digoxin and sympathomimetics increases the risk of cardiac arrhythmias. Succinylcholine may cause a sudden extrusion of potassium from muscle cells, and may thereby cause arrhythmias in digitalized patients. Although beta-adrenergic blockers or calcium channel blockers and digoxin may be useful in combination to control atrial fibrillation, their additive effects on AV node conduction can result in advanced or complete heart block. Due to the considerable variability of these interactions, the dosage of digoxin should be individualized when patients receive these medications concurrently. Furthermore, caution should be exercised when combining digoxin with any drug that may cause a significant deterioration in renal function, since a decline in glomerular filtration or tubular secretion may impair the excretion of digoxin." ], "offsets": [ [ 0, 2376 ] ] } ]

[ { "id": "Digoxin_ddi_T1", "type": "GROUP", "text": [ "Potassium-depleting diuretics" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T2", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 65, 74 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T3", "type": "DRUG", "text": [ "Calcium" ], "offsets": [ [ 85, 92 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T4", "type": "DRUG", "text": [ "Quinidine" ], "offsets": [ [ 214, 223 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T5", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 225, 234 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T6", "type": "DRUG", "text": [ "amiodarone" ], "offsets": [ [ 236, 246 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T7", "type": "DRUG", "text": [ "propafenone" ], "offsets": [ [ 248, 259 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T8", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 261, 273 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T9", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 275, 287 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T10", "type": "DRUG", "text": [ "alprazolam" ], "offsets": [ [ 289, 299 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T11", "type": "DRUG", "text": [ "spironolactone" ], "offsets": [ [ 305, 319 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T12", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 336, 343 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T13", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 462, 471 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T14", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 497, 509 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T15", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 514, 528 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T16", "type": "GROUP", "text": [ "macrolide antibiotics" ], "offsets": [ [ 549, 570 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T17", "type": "DRUG", "text": [ "tetracycline" ], "offsets": [ [ 576, 588 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T18", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 602, 609 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T19", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 648, 655 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T20", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 712, 721 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T21", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 794, 801 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T22", "type": "DRUG", "text": [ "Propantheline" ], "offsets": [ [ 824, 837 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T23", "type": "DRUG", "text": [ "diphenoxylate" ], "offsets": [ [ 842, 855 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T24", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 898, 905 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T25", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 918, 926 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T26", "type": "DRUG", "text": [ "kaolin" ], "offsets": [ [ 928, 934 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T27", "type": "DRUG", "text": [ "sulfasalazine" ], "offsets": [ [ 943, 956 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T28", "type": "DRUG", "text": [ "neomycin" ], "offsets": [ [ 958, 966 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T29", "type": "DRUG", "text": [ "cholestyramine" ], "offsets": [ [ 968, 982 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T30", "type": "DRUG", "text": [ "metoclopramide" ], "offsets": [ [ 1014, 1028 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T31", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1059, 1066 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T32", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 1131, 1139 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T33", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1159, 1166 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T34", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1270, 1277 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T35", "type": "DRUG", "text": [ "quinine" ], "offsets": [ [ 1360, 1367 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T36", "type": "DRUG", "text": [ "penicillamine" ], "offsets": [ [ 1369, 1382 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T37", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1393, 1400 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T38", "type": "GROUP", "text": [ "Thyroid" ], "offsets": [ [ 1416, 1423 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T39", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1514, 1521 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T40", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1542, 1549 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T41", "type": "GROUP", "text": [ "sympathomimetics" ], "offsets": [ [ 1554, 1570 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T42", "type": "DRUG", "text": [ "Succinylcholine" ], "offsets": [ [ 1614, 1629 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T43", "type": "GROUP", "text": [ "beta-adrenergic blockers" ], "offsets": [ [ 1759, 1783 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T44", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 1787, 1811 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T45", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1816, 1823 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T46", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2051, 2058 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T47", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2194, 2201 ] ], "normalized": [] }, { "id": "Digoxin_ddi_T48", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2368, 2375 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Digoxin_ddi_R1", "type": "EFFECT", "arg1_id": "Digoxin_ddi_T1", "arg2_id": "Digoxin_ddi_T2", "normalized": [] }, { "id": "Digoxin_ddi_R2", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T4", "arg2_id": "Digoxin_ddi_T12", "normalized": [] }, { "id": "Digoxin_ddi_R3", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T5", "arg2_id": "Digoxin_ddi_T12", "normalized": [] }, { "id": "Digoxin_ddi_R4", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T6", "arg2_id": "Digoxin_ddi_T12", "normalized": [] }, { "id": "Digoxin_ddi_R5", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T7", "arg2_id": "Digoxin_ddi_T12", "normalized": [] }, { "id": "Digoxin_ddi_R6", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T8", "arg2_id": "Digoxin_ddi_T12", "normalized": [] }, { "id": "Digoxin_ddi_R7", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T9", "arg2_id": "Digoxin_ddi_T12", "normalized": [] }, { "id": "Digoxin_ddi_R8", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T10", "arg2_id": "Digoxin_ddi_T12", "normalized": [] }, { "id": "Digoxin_ddi_R9", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T11", "arg2_id": "Digoxin_ddi_T12", "normalized": [] }, { "id": "Digoxin_ddi_R10", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T14", "arg2_id": "Digoxin_ddi_T18", "normalized": [] }, { "id": "Digoxin_ddi_R11", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T15", "arg2_id": "Digoxin_ddi_T18", "normalized": [] }, { "id": "Digoxin_ddi_R12", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T16", "arg2_id": "Digoxin_ddi_T18", "normalized": [] }, { "id": "Digoxin_ddi_R13", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T17", "arg2_id": "Digoxin_ddi_T18", "normalized": [] }, { "id": "Digoxin_ddi_R14", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T22", "arg2_id": "Digoxin_ddi_T24", "normalized": [] }, { "id": "Digoxin_ddi_R15", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T23", "arg2_id": "Digoxin_ddi_T24", "normalized": [] }, { "id": "Digoxin_ddi_R16", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T25", "arg2_id": "Digoxin_ddi_T31", "normalized": [] }, { "id": "Digoxin_ddi_R17", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T26", "arg2_id": "Digoxin_ddi_T31", "normalized": [] }, { "id": "Digoxin_ddi_R18", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T27", "arg2_id": "Digoxin_ddi_T31", "normalized": [] }, { "id": "Digoxin_ddi_R19", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T28", "arg2_id": "Digoxin_ddi_T31", "normalized": [] }, { "id": "Digoxin_ddi_R20", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T29", "arg2_id": "Digoxin_ddi_T31", "normalized": [] }, { "id": "Digoxin_ddi_R21", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T30", "arg2_id": "Digoxin_ddi_T31", "normalized": [] }, { "id": "Digoxin_ddi_R22", "type": "MECHANISM", "arg1_id": "Digoxin_ddi_T32", "arg2_id": "Digoxin_ddi_T33", "normalized": [] }, { "id": "Digoxin_ddi_R23", "type": "ADVISE", "arg1_id": "Digoxin_ddi_T38", "arg2_id": "Digoxin_ddi_T39", "normalized": [] }, { "id": "Digoxin_ddi_R24", "type": "EFFECT", "arg1_id": "Digoxin_ddi_T40", "arg2_id": "Digoxin_ddi_T41", "normalized": [] }, { "id": "Digoxin_ddi_R25", "type": "EFFECT", "arg1_id": "Digoxin_ddi_T43", "arg2_id": "Digoxin_ddi_T45", "normalized": [] }, { "id": "Digoxin_ddi_R26", "type": "EFFECT", "arg1_id": "Digoxin_ddi_T44", "arg2_id": "Digoxin_ddi_T45", "normalized": [] } ]

[ { "id": "Aripiprazole_ddi__text", "type": "abstract", "text": [ "Drug-Drug Interactions Given the primary CNS effects of aripiprazole, caution should be used when ABILIFY is taken in combination with other centrally acting drugs and alcohol. Due to its 1- adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents. Potential for Other Drugs to Affect ABILIFY Aripiprazole is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2E1 enzymes. Aripiprazole also does not undergo direct glucuronidation. This suggests that an interaction of aripiprazole with inhibitors or inducers of these enzymes, or other factors, like smoking, is unlikely. Both CYP3A4 and CYP2D6 are responsible for aripiprazole metabolism. Agents that induce CYP3A4 (eg, carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (eg, ketoconazole) or CYP2D6 (eg, quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels. Ketoconazole: Coadministration of ketoconazole (200 mg/day for 14 days) with a 15-mg single dose of aripiprazole increased the AUC of aripiprazole and its active metabolite by 63% and 77%, respectively. The effect of a higher ketoconazole dose (400 mg/day) has not been studied. When concomitant administration of ketoconazole with aripiprazole occurs, aripiprazole dose should be reduced to one-half of its normal dose. Other strong inhibitors of CYP3A4 (itraconazole) would be expected to have similar effects and need similar dose reductions; weaker inhibitors (erythromycin, grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased. Quinidine: Coadministration of a 10-mg single dose of aripiprazole with quinidine (166 mg/day for 13 days), a potent inhibitor of CYP2D6, increased the AUC of aripiprazole by 112% but decreased the AUC of its active metabolite, dehydroaripiprazole, by 35%. Aripiprazole dose should be reduced to one-half of its normal dose when concomitant administration of quinidine with aripiprazole occurs. Other significant inhibitors of CYP2D6, such as fluoxetine or paroxetine, would be expected to have similar effects and, therefore, should be accompanied by similar dose reductions. When the CYP2D6 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased. Carbamazepine: Coadministration of carbamazepine (200 mg BID), a potent CYP3A4 inducer, with aripiprazole (30 mg QD) resulted in an approximate 70% decrease in Cmax and AUC values of both aripiprazole and its active metabolite, dehydro-aripiprazole. When carbamazepine is added to aripiprazole therapy, aripiprazole dose should be doubled. Additional dose increases should be based on clinical evaluation. When carbamazepine is withdrawn from the combination therapy, aripiprazole dose should then be reduced. No clinically significant effect of famotidine, valproate, or lithium was seen on the pharmacokinetics of aripiprazole (see CLINICAL PHARMACOLOGY: Drug- Drug Interactions). Potential for ABILIFY to Affect Other Drugs Aripiprazole is unlikely to cause clinically important pharmacokinetic interactions with drugs metabolized by cytochrome P450 enzymes. In in vivo studies, 10- to 30-mg/day doses of aripiprazole had no significant effect on metabolism by CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin), and CYP3A4 (dextromethorphan) substrates. Additionally, aripiprazole and dehydroaripiprazole did not show potential for altering CYP1A2-mediated metabolism in vitro. Alcohol: There was no significant difference between aripiprazole coadministered with ethanol and placebo coadministered with ethanol on performance of gross motor skills or stimulus response in healthy subjects. As with most psychoactive medications, patients should be advised to avoid alcohol while taking ABILIFY ." ], "offsets": [ [ 0, 3968 ] ] } ]

[ { "id": "Aripiprazole_ddi_T1", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 56, 68 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T2", "type": "BRAND", "text": [ "ABILIFY" ], "offsets": [ [ 98, 105 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T3", "type": "GROUP", "text": [ "centrally acting drugs" ], "offsets": [ [ 141, 163 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T4", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 168, 175 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T5", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 223, 235 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T6", "type": "GROUP", "text": [ "antihypertensive agents" ], "offsets": [ [ 287, 310 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T7", "type": "BRAND", "text": [ "ABILIFY" ], "offsets": [ [ 348, 355 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T8", "type": "BRAND", "text": [ "Aripiprazole" ], "offsets": [ [ 356, 368 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T9", "type": "DRUG", "text": [ "Aripiprazole" ], "offsets": [ [ 467, 479 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T10", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 563, 575 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T11", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 710, 722 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T12", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 766, 779 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T13", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 808, 820 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T14", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 881, 893 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T15", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 910, 919 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T16", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 921, 931 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T17", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 936, 946 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T18", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 960, 972 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T19", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 1019, 1031 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T20", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1053, 1065 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T21", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 1119, 1131 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T22", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 1153, 1165 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T23", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1245, 1257 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T24", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1333, 1345 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T25", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 1351, 1363 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T26", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 1372, 1384 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T27", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 1475, 1487 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T28", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1584, 1596 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T29", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 1708, 1720 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T30", "type": "DRUG", "text": [ "Quinidine" ], "offsets": [ [ 1752, 1761 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T31", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 1806, 1818 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T32", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1824, 1833 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T33", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 1911, 1923 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T34", "type": "DRUG_N", "text": [ "dehydroaripiprazole" ], "offsets": [ [ 1980, 1999 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T35", "type": "DRUG", "text": [ "Aripiprazole" ], "offsets": [ [ 2009, 2021 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T36", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 2111, 2120 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T37", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 2126, 2138 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T38", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 2195, 2205 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T39", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 2209, 2219 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T40", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 2398, 2410 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T41", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 2442, 2455 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T42", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2477, 2490 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T43", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 2535, 2547 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T44", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 2630, 2642 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T45", "type": "DRUG_N", "text": [ "dehydro-aripiprazole" ], "offsets": [ [ 2670, 2690 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T46", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2697, 2710 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T47", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 2723, 2735 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T48", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 2745, 2757 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T49", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2853, 2866 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T50", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 2910, 2922 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T51", "type": "DRUG", "text": [ "famotidine" ], "offsets": [ [ 2988, 2998 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T52", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 3000, 3009 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T53", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 3014, 3021 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T54", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 3058, 3070 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T55", "type": "BRAND", "text": [ "ABILIFY" ], "offsets": [ [ 3139, 3146 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T56", "type": "DRUG", "text": [ "Aripiprazole" ], "offsets": [ [ 3169, 3181 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T57", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 3350, 3362 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T58", "type": "DRUG", "text": [ "dextromethorphan" ], "offsets": [ [ 3414, 3430 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T59", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3441, 3449 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T60", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 3461, 3471 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T61", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3473, 3481 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T62", "type": "DRUG", "text": [ "dextromethorphan" ], "offsets": [ [ 3496, 3512 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T63", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 3540, 3552 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T64", "type": "DRUG_N", "text": [ "dehydroaripiprazole" ], "offsets": [ [ 3557, 3576 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T65", "type": "DRUG", "text": [ "Alcohol" ], "offsets": [ [ 3650, 3657 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T66", "type": "DRUG", "text": [ "aripiprazole" ], "offsets": [ [ 3703, 3715 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T67", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 3736, 3743 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T68", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 3776, 3783 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T69", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 3938, 3945 ] ], "normalized": [] }, { "id": "Aripiprazole_ddi_T70", "type": "BRAND", "text": [ "ABILIFY" ], "offsets": [ [ 3959, 3966 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Aripiprazole_ddi_R1", "type": "ADVISE", "arg1_id": "Aripiprazole_ddi_T2", "arg2_id": "Aripiprazole_ddi_T3", "normalized": [] }, { "id": "Aripiprazole_ddi_R2", "type": "ADVISE", "arg1_id": "Aripiprazole_ddi_T2", "arg2_id": "Aripiprazole_ddi_T4", "normalized": [] }, { "id": "Aripiprazole_ddi_R3", "type": "EFFECT", "arg1_id": "Aripiprazole_ddi_T5", "arg2_id": "Aripiprazole_ddi_T6", "normalized": [] }, { "id": "Aripiprazole_ddi_R4", "type": "MECHANISM", "arg1_id": "Aripiprazole_ddi_T12", "arg2_id": "Aripiprazole_ddi_T13", "normalized": [] }, { "id": "Aripiprazole_ddi_R5", "type": "MECHANISM", "arg1_id": "Aripiprazole_ddi_T14", "arg2_id": "Aripiprazole_ddi_T18", "normalized": [] }, { "id": "Aripiprazole_ddi_R6", "type": "MECHANISM", "arg1_id": "Aripiprazole_ddi_T15", "arg2_id": "Aripiprazole_ddi_T18", "normalized": [] }, { "id": "Aripiprazole_ddi_R7", "type": "MECHANISM", "arg1_id": "Aripiprazole_ddi_T16", "arg2_id": "Aripiprazole_ddi_T18", "normalized": [] }, { "id": "Aripiprazole_ddi_R8", "type": "MECHANISM", "arg1_id": "Aripiprazole_ddi_T17", "arg2_id": "Aripiprazole_ddi_T18", "normalized": [] }, { "id": "Aripiprazole_ddi_R9", "type": "MECHANISM", "arg1_id": "Aripiprazole_ddi_T20", "arg2_id": "Aripiprazole_ddi_T21", "normalized": [] }, { "id": "Aripiprazole_ddi_R10", "type": "ADVISE", "arg1_id": "Aripiprazole_ddi_T24", "arg2_id": "Aripiprazole_ddi_T25", "normalized": [] }, { "id": "Aripiprazole_ddi_R11", "type": "MECHANISM", "arg1_id": "Aripiprazole_ddi_T31", "arg2_id": "Aripiprazole_ddi_T32", "normalized": [] }, { "id": "Aripiprazole_ddi_R12", "type": "ADVISE", "arg1_id": "Aripiprazole_ddi_T36", "arg2_id": "Aripiprazole_ddi_T37", "normalized": [] }, { "id": "Aripiprazole_ddi_R13", "type": "MECHANISM", "arg1_id": "Aripiprazole_ddi_T42", "arg2_id": "Aripiprazole_ddi_T43", "normalized": [] }, { "id": "Aripiprazole_ddi_R14", "type": "ADVISE", "arg1_id": "Aripiprazole_ddi_T46", "arg2_id": "Aripiprazole_ddi_T47", "normalized": [] }, { "id": "Aripiprazole_ddi_R15", "type": "ADVISE", "arg1_id": "Aripiprazole_ddi_T49", "arg2_id": "Aripiprazole_ddi_T50", "normalized": [] }, { "id": "Aripiprazole_ddi_R16", "type": "ADVISE", "arg1_id": "Aripiprazole_ddi_T69", "arg2_id": "Aripiprazole_ddi_T70", "normalized": [] } ]

[ { "id": "Etidronic acid_ddi__text", "type": "abstract", "text": [ "There have been isolated reports of patients experiencing increases in their prothrombin times when etidronate was added to warfarin therapy. The majority of these reports concerned variable elevations in prothrombin times without clinically significant sequelae. Although the relevance of these reports and any mechanism of coagulation alterations is unclear, patients on warfarin should have their prothrombin time monitored." ], "offsets": [ [ 0, 427 ] ] } ]

[ { "id": "Etidronic acid_ddi_T1", "type": "DRUG", "text": [ "etidronate" ], "offsets": [ [ 100, 110 ] ], "normalized": [] }, { "id": "Etidronic acid_ddi_T2", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 124, 132 ] ], "normalized": [] }, { "id": "Etidronic acid_ddi_T3", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 373, 381 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Etidronic acid_ddi_R1", "type": "EFFECT", "arg1_id": "Etidronic acid_ddi_T1", "arg2_id": "Etidronic acid_ddi_T2", "normalized": [] } ]

[ { "id": "Anastrozole_ddi__text", "type": "abstract", "text": [ "Anastrozole inhibited in vitro metabolic reactions catalyzed by cytochromes P450 1A2, 2C8/9, and 3A4 but only at relatively high concentrations. Anastrozole did not inhibit P450 2A6 or the polymorphic P450 2D6 in human liver microsomes. Anastrozole did not alter the pharmacokinetics of antipyrine. Although there have been no formal interaction studies other than with antipyrine, based on these in vivo and in vitro studies, it is unlikely that co-administration of a 1 mg dose of ARIMIDEX with other drugs will result in clinically significant drug inhibition of cytochrome P450-mediated metabolism of the other drugs. An interaction study with warfarin showed no clinically significant effect of anastrozole on warfarin pharmacokinetics or anticoagulant activity. At a median follow-up of 33 months, the combination of ARIMIDEX and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole (see CLINICAL PHARMACOLOGY Drug Interactions and CLINICAL PHARMACOLOGY - Clinical Studies - Adjuvant Treatment of Breast Cancer in Postmenopausal Women subsections). Co-administration of anastrozole and tamoxifen resulted in a reduction of anastrozole plasma levels by 27% compared with those achieved with anastrozole alone. Estrogen-containing therapies should not be used with ARIMIDEX as they may diminish its pharmacologic action. Drug/Laboratory Test Interactions No clinically significant changes in the results of clinical laboratory tests have been observed ." ], "offsets": [ [ 0, 1734 ] ] } ]

[ { "id": "Anastrozole_ddi_T1", "type": "DRUG", "text": [ "Anastrozole" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T2", "type": "DRUG", "text": [ "Anastrozole" ], "offsets": [ [ 145, 156 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T3", "type": "DRUG", "text": [ "Anastrozole" ], "offsets": [ [ 237, 248 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T4", "type": "DRUG", "text": [ "antipyrine" ], "offsets": [ [ 287, 297 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T5", "type": "DRUG", "text": [ "antipyrine" ], "offsets": [ [ 370, 380 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T6", "type": "BRAND", "text": [ "ARIMIDEX" ], "offsets": [ [ 483, 491 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T7", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 648, 656 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T8", "type": "DRUG", "text": [ "anastrozole" ], "offsets": [ [ 700, 711 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T9", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 715, 723 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T10", "type": "BRAND", "text": [ "ARIMIDEX" ], "offsets": [ [ 823, 831 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T11", "type": "DRUG", "text": [ "tamoxifen" ], "offsets": [ [ 836, 845 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T12", "type": "DRUG", "text": [ "tamoxifen" ], "offsets": [ [ 906, 915 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T13", "type": "DRUG", "text": [ "tamoxifen" ], "offsets": [ [ 1110, 1119 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T14", "type": "DRUG", "text": [ "anastrozole" ], "offsets": [ [ 1152, 1163 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T15", "type": "DRUG", "text": [ "anastrozole" ], "offsets": [ [ 1353, 1364 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T16", "type": "DRUG", "text": [ "tamoxifen" ], "offsets": [ [ 1369, 1378 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T17", "type": "DRUG", "text": [ "anastrozole" ], "offsets": [ [ 1406, 1417 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T18", "type": "DRUG", "text": [ "anastrozole" ], "offsets": [ [ 1473, 1484 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T19", "type": "GROUP", "text": [ "Estrogen" ], "offsets": [ [ 1492, 1500 ] ], "normalized": [] }, { "id": "Anastrozole_ddi_T20", "type": "BRAND", "text": [ "ARIMIDEX" ], "offsets": [ [ 1546, 1554 ] ], "normalized": [] } ]

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[ { "id": "Anastrozole_ddi_R1", "type": "ADVISE", "arg1_id": "Anastrozole_ddi_T13", "arg2_id": "Anastrozole_ddi_T14", "normalized": [] }, { "id": "Anastrozole_ddi_R2", "type": "MECHANISM", "arg1_id": "Anastrozole_ddi_T15", "arg2_id": "Anastrozole_ddi_T16", "normalized": [] }, { "id": "Anastrozole_ddi_R3", "type": "ADVISE", "arg1_id": "Anastrozole_ddi_T19", "arg2_id": "Anastrozole_ddi_T20", "normalized": [] } ]

[ { "id": "Amyl Nitrite_ddi__text", "type": "abstract", "text": [ "Taking amyl nitrite after drinking alcohol may worsen side effects and may cause severe hypotension and cardiovascular collapse." ], "offsets": [ [ 0, 128 ] ] } ]

[ { "id": "Amyl Nitrite_ddi_T1", "type": "DRUG", "text": [ "amyl nitrite" ], "offsets": [ [ 7, 19 ] ], "normalized": [] }, { "id": "Amyl Nitrite_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 35, 42 ] ], "normalized": [] } ]

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[ { "id": "Amyl Nitrite_ddi_R1", "type": "EFFECT", "arg1_id": "Amyl Nitrite_ddi_T1", "arg2_id": "Amyl Nitrite_ddi_T2", "normalized": [] } ]

[ { "id": "Isocarboxazid_ddi__text", "type": "abstract", "text": [ "Isocarboxazid should be administered with caution to patients receiving Antabuse (disulfiram, Wyeth-Ayerst Laboratories). In a single study, rats given high intraperitoneal doses of an MAO inhibitor plus disulfiram experienced severe toxicity, including convulsions and death. Concomitant use of Isocarboxazid and other psychotropic agents is generally not recommended because of possible potentiating effects. This is especially true in patients who may subject themselves to an overdosage of drugs. If combination therapy is needed, careful consideration should be given to the pharmacology of all agents to be used. The monoamine oxidase inhibitory effects of Isocarboxazid may persist for a substantial period after discontinuation of the drug, and this should be borne in mind when another drug is prescribed following Isocarboxazid. To avoid potentiation, the physician wishing to terminate treatment with Isocarboxazid and begin therapy with another agent should allow for an interval of 10 days." ], "offsets": [ [ 0, 1003 ] ] } ]

[ { "id": "Isocarboxazid_ddi_T1", "type": "DRUG", "text": [ "Isocarboxazid" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T2", "type": "BRAND", "text": [ "Antabuse" ], "offsets": [ [ 72, 80 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T3", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 82, 92 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T4", "type": "GROUP", "text": [ "MAO inhibitor" ], "offsets": [ [ 185, 198 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T5", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 204, 214 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T6", "type": "DRUG", "text": [ "Isocarboxazid" ], "offsets": [ [ 296, 309 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T7", "type": "GROUP", "text": [ "psychotropic agents" ], "offsets": [ [ 320, 339 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T8", "type": "DRUG", "text": [ "Isocarboxazid" ], "offsets": [ [ 663, 676 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T9", "type": "DRUG", "text": [ "Isocarboxazid" ], "offsets": [ [ 824, 837 ] ], "normalized": [] }, { "id": "Isocarboxazid_ddi_T10", "type": "DRUG", "text": [ "Isocarboxazid" ], "offsets": [ [ 912, 925 ] ], "normalized": [] } ]

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[ { "id": "Isocarboxazid_ddi_R1", "type": "ADVISE", "arg1_id": "Isocarboxazid_ddi_T1", "arg2_id": "Isocarboxazid_ddi_T2", "normalized": [] }, { "id": "Isocarboxazid_ddi_R2", "type": "ADVISE", "arg1_id": "Isocarboxazid_ddi_T1", "arg2_id": "Isocarboxazid_ddi_T3", "normalized": [] }, { "id": "Isocarboxazid_ddi_R3", "type": "EFFECT", "arg1_id": "Isocarboxazid_ddi_T4", "arg2_id": "Isocarboxazid_ddi_T5", "normalized": [] }, { "id": "Isocarboxazid_ddi_R4", "type": "ADVISE", "arg1_id": "Isocarboxazid_ddi_T6", "arg2_id": "Isocarboxazid_ddi_T7", "normalized": [] } ]

[ { "id": "Alitretinoin_ddi__text", "type": "abstract", "text": [ "Patients who are applying Panretin gel should not concurrently use products that contain DEET (N, N-diethyl-m-toluamide), a common component of insect repellent products. Animal toxicology studies showed increased DEET toxicity when DEET was included as proof of the formulation. Although there was no clinical evidence in the vehicle-controlled studies of drug interactions with systemic antiretroviral agents, including protease inhibitors, macrolide antibiotics, and azole antifungals, the effect of Panretin gel on the steady-state concentrations of these drugs is not known. No drug interaction data are available on concomitant administration of Panretin gel and systemic anti-KS agents." ], "offsets": [ [ 0, 693 ] ] } ]

[ { "id": "Alitretinoin_ddi_T1", "type": "BRAND", "text": [ "Panretin" ], "offsets": [ [ 26, 34 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T2", "type": "DRUG", "text": [ "DEET" ], "offsets": [ [ 89, 93 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T3", "type": "DRUG", "text": [ "N-diethyl-m-toluamide" ], "offsets": [ [ 98, 119 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T4", "type": "DRUG", "text": [ "DEET" ], "offsets": [ [ 214, 218 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T5", "type": "DRUG", "text": [ "DEET" ], "offsets": [ [ 233, 237 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T6", "type": "GROUP", "text": [ "antiretroviral agents" ], "offsets": [ [ 389, 410 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T7", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 422, 441 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T8", "type": "GROUP", "text": [ "macrolide antibiotics" ], "offsets": [ [ 443, 464 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T9", "type": "GROUP", "text": [ "azole antifungals" ], "offsets": [ [ 470, 487 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T10", "type": "BRAND", "text": [ "Panretin" ], "offsets": [ [ 503, 511 ] ], "normalized": [] }, { "id": "Alitretinoin_ddi_T11", "type": "BRAND", "text": [ "Panretin" ], "offsets": [ [ 652, 660 ] ], "normalized": [] } ]

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[ { "id": "Alitretinoin_ddi_R1", "type": "ADVISE", "arg1_id": "Alitretinoin_ddi_T1", "arg2_id": "Alitretinoin_ddi_T2", "normalized": [] }, { "id": "Alitretinoin_ddi_R2", "type": "ADVISE", "arg1_id": "Alitretinoin_ddi_T1", "arg2_id": "Alitretinoin_ddi_T3", "normalized": [] } ]

[ { "id": "Clomifene_ddi__text", "type": "abstract", "text": [ "Drug interactions with clomiphene citrate tablets USP have not been documented." ], "offsets": [ [ 0, 79 ] ] } ]

[ { "id": "Clomifene_ddi_T1", "type": "DRUG", "text": [ "clomiphene citrate" ], "offsets": [ [ 23, 41 ] ], "normalized": [] } ]

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[ { "id": "Nitrofurantoin_ddi__text", "type": "abstract", "text": [ "Antacids containing magnesium trisilicate, when administered concomitantly with nitrofurantoin, reduce both the rate and extent of absorption. The mechanism for this interaction probably is adsorption of nitrofurantoin onto the surface of magnesium trisilicate. Uricosuric drugs, such as probenecid and sulfinpyrazone, can inhibit renal tubular secretion of nitrofurantoin. The resulting increase in nitrofurantoin serum levels may increase toxicity, and the decreased urinary levels could lessen its efficacy as a urinary tract antibacterial. Drug/Laboratory Test Interactions As a result of the presence of nitrofurantoin, a false-positive reaction for glucose in the urine may occur. This has been observed with Benedict s and Fehling s solutions but not with the glucose enzymatic test." ], "offsets": [ [ 0, 790 ] ] } ]

[ { "id": "Nitrofurantoin_ddi_T1", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T2", "type": "DRUG", "text": [ "magnesium trisilicate" ], "offsets": [ [ 20, 41 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T3", "type": "DRUG", "text": [ "nitrofurantoin" ], "offsets": [ [ 80, 94 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T4", "type": "DRUG", "text": [ "nitrofurantoin" ], "offsets": [ [ 204, 218 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T5", "type": "DRUG", "text": [ "magnesium trisilicate" ], "offsets": [ [ 239, 260 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T6", "type": "GROUP", "text": [ "Uricosuric drugs" ], "offsets": [ [ 262, 278 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T7", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 288, 298 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T8", "type": "DRUG", "text": [ "sulfinpyrazone" ], "offsets": [ [ 303, 317 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T9", "type": "DRUG", "text": [ "nitrofurantoin" ], "offsets": [ [ 358, 372 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T10", "type": "DRUG", "text": [ "nitrofurantoin" ], "offsets": [ [ 400, 414 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T11", "type": "GROUP", "text": [ "antibacterial" ], "offsets": [ [ 529, 542 ] ], "normalized": [] }, { "id": "Nitrofurantoin_ddi_T12", "type": "DRUG", "text": [ "nitrofurantoin" ], "offsets": [ [ 609, 623 ] ], "normalized": [] } ]

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[ { "id": "Nitrofurantoin_ddi_R1", "type": "MECHANISM", "arg1_id": "Nitrofurantoin_ddi_T2", "arg2_id": "Nitrofurantoin_ddi_T3", "normalized": [] }, { "id": "Nitrofurantoin_ddi_R2", "type": "MECHANISM", "arg1_id": "Nitrofurantoin_ddi_T4", "arg2_id": "Nitrofurantoin_ddi_T5", "normalized": [] }, { "id": "Nitrofurantoin_ddi_R3", "type": "MECHANISM", "arg1_id": "Nitrofurantoin_ddi_T6", "arg2_id": "Nitrofurantoin_ddi_T9", "normalized": [] }, { "id": "Nitrofurantoin_ddi_R4", "type": "MECHANISM", "arg1_id": "Nitrofurantoin_ddi_T7", "arg2_id": "Nitrofurantoin_ddi_T9", "normalized": [] }, { "id": "Nitrofurantoin_ddi_R5", "type": "MECHANISM", "arg1_id": "Nitrofurantoin_ddi_T8", "arg2_id": "Nitrofurantoin_ddi_T9", "normalized": [] } ]

[ { "id": "Aminosalicylic Acid_ddi__text", "type": "abstract", "text": [ "Aminosalicylic acid may decrease the amount of digoxin (Lanoxin, Lanoxicaps) that gets absorbed into your body. In the case that you are taking digoxin while taking aminosalicylic acid, higher doses of digoxin may be needed. Aminosalicylic acid may also decrease the absorption of vitamin B12, which can lead to a deficiency. Therefore you may need to take a vitamin B12 supplement while taking aminosalicylic acid." ], "offsets": [ [ 0, 415 ] ] } ]

[ { "id": "Aminosalicylic Acid_ddi_T1", "type": "DRUG", "text": [ "Aminosalicylic acid" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T2", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 47, 54 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T3", "type": "BRAND", "text": [ "Lanoxin" ], "offsets": [ [ 56, 63 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T4", "type": "DRUG", "text": [ "Lanoxicaps" ], "offsets": [ [ 65, 75 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T5", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 144, 151 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T6", "type": "DRUG", "text": [ "aminosalicylic acid" ], "offsets": [ [ 165, 184 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T7", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 202, 209 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T8", "type": "DRUG", "text": [ "Aminosalicylic acid" ], "offsets": [ [ 225, 244 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T9", "type": "DRUG", "text": [ "vitamin B12" ], "offsets": [ [ 281, 292 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T10", "type": "DRUG", "text": [ "vitamin B12" ], "offsets": [ [ 359, 370 ] ], "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_T11", "type": "DRUG", "text": [ "aminosalicylic acid" ], "offsets": [ [ 395, 414 ] ], "normalized": [] } ]

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[ { "id": "Aminosalicylic Acid_ddi_R1", "type": "MECHANISM", "arg1_id": "Aminosalicylic Acid_ddi_T1", "arg2_id": "Aminosalicylic Acid_ddi_T2", "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_R2", "type": "MECHANISM", "arg1_id": "Aminosalicylic Acid_ddi_T1", "arg2_id": "Aminosalicylic Acid_ddi_T3", "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_R3", "type": "ADVISE", "arg1_id": "Aminosalicylic Acid_ddi_T5", "arg2_id": "Aminosalicylic Acid_ddi_T6", "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_R4", "type": "MECHANISM", "arg1_id": "Aminosalicylic Acid_ddi_T8", "arg2_id": "Aminosalicylic Acid_ddi_T9", "normalized": [] }, { "id": "Aminosalicylic Acid_ddi_R5", "type": "ADVISE", "arg1_id": "Aminosalicylic Acid_ddi_T10", "arg2_id": "Aminosalicylic Acid_ddi_T11", "normalized": [] } ]

[ { "id": "Neostigmine_ddi__text", "type": "abstract", "text": [ "Certain antibiotics, especially neomycin, streptomycin and kanamycin, have a mild but definite nondepolarizing blocking action which may accentuate neuromuscular block. These antibiotics should be used in the myasthenic patient only where definitely indicated, and then careful adjustment should be made of adjunctive anticholinesterase dosage. Local and some general anesthetics, antiarrhythmic agents and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all, in patients with myasthenia gravis; the dose of Prostigmin may have to be increased accordingly." ], "offsets": [ [ 0, 600 ] ] } ]

[ { "id": "Neostigmine_ddi_T1", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 8, 19 ] ], "normalized": [] }, { "id": "Neostigmine_ddi_T2", "type": "DRUG", "text": [ "neomycin" ], "offsets": [ [ 32, 40 ] ], "normalized": [] }, { "id": "Neostigmine_ddi_T3", "type": "DRUG", "text": [ "streptomycin" ], "offsets": [ [ 42, 54 ] ], "normalized": [] }, { "id": "Neostigmine_ddi_T4", "type": "DRUG", "text": [ "kanamycin" ], "offsets": [ [ 59, 68 ] ], "normalized": [] }, { "id": "Neostigmine_ddi_T5", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 175, 186 ] ], "normalized": [] }, { "id": "Neostigmine_ddi_T6", "type": "GROUP", "text": [ "anticholinesterase" ], "offsets": [ [ 318, 336 ] ], "normalized": [] }, { "id": "Neostigmine_ddi_T7", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 368, 379 ] ], "normalized": [] }, { "id": "Neostigmine_ddi_T8", "type": "GROUP", "text": [ "antiarrhythmic agents" ], "offsets": [ [ 381, 402 ] ], "normalized": [] }, { "id": "Neostigmine_ddi_T9", "type": "BRAND", "text": [ "Prostigmin" ], "offsets": [ [ 552, 562 ] ], "normalized": [] } ]

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[ { "id": "Neostigmine_ddi_R1", "type": "ADVISE", "arg1_id": "Neostigmine_ddi_T5", "arg2_id": "Neostigmine_ddi_T6", "normalized": [] } ]

[ { "id": "Gonadorelin_ddi__text", "type": "abstract", "text": [ "The Factrel test should be conducted in the absence of other drugs which directly affect the pituitary secretion of the gonadotropins. These would include a variety of preparations which contain androgens, estrogens, progestins, or glucocorticoids. The gonadotropin levels may be transiently elevated by spironolactone, minimally elevated by levodopa, and suppressed by oral contraceptives and digoxin. The response to Factrel may be blunted by phenothiazines and dopamine antagonists which cause a rise in prolactin." ], "offsets": [ [ 0, 517 ] ] } ]

[ { "id": "Gonadorelin_ddi_T1", "type": "BRAND", "text": [ "Factrel" ], "offsets": [ [ 4, 11 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T2", "type": "GROUP", "text": [ "androgens" ], "offsets": [ [ 195, 204 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T3", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 206, 215 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T4", "type": "GROUP", "text": [ "progestins" ], "offsets": [ [ 217, 227 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T5", "type": "GROUP", "text": [ "glucocorticoids" ], "offsets": [ [ 232, 247 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T6", "type": "DRUG", "text": [ "spironolactone" ], "offsets": [ [ 304, 318 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T7", "type": "DRUG", "text": [ "levodopa" ], "offsets": [ [ 342, 350 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T8", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 375, 389 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T9", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 394, 401 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T10", "type": "BRAND", "text": [ "Factrel" ], "offsets": [ [ 419, 426 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T11", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 445, 459 ] ], "normalized": [] }, { "id": "Gonadorelin_ddi_T12", "type": "GROUP", "text": [ "dopamine antagonists" ], "offsets": [ [ 464, 484 ] ], "normalized": [] } ]

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[]

[ { "id": "Gonadorelin_ddi_R1", "type": "EFFECT", "arg1_id": "Gonadorelin_ddi_T10", "arg2_id": "Gonadorelin_ddi_T11", "normalized": [] }, { "id": "Gonadorelin_ddi_R2", "type": "EFFECT", "arg1_id": "Gonadorelin_ddi_T10", "arg2_id": "Gonadorelin_ddi_T12", "normalized": [] } ]

[ { "id": "Ciclesonide_ddi__text", "type": "abstract", "text": [ "Based on in vitro studies in human liver microsomes, des-ciclesonide appears to have no inhibitory or induction potential on the metabolism of other drugs metabolized by CYP 450 enzymes. The inhibitory potential of ciclesonide on CYP450 isoenzymes has not been studied. In vitro studies demonstrated that the plasma protein binding of des-ciclesonide was not affected by warfarin or salicylic acid, indicating no potential for protein binding-based drug interactions. In a drug interaction study, co-administration of orally inhaled ciclesonide and oral erythromycin, an inhibitor of cytochrome P450 3A4, had no effect on the pharmacokinetics of either des-ciclesonide or erythromycin. In another drug interaction study, co-administration of orally inhaled ciclesonide and oral ketoconazole, a potent inhibitor of cytochrome P450 3A4, increased the exposure (AUC) of des-ciclesonide by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. Therefore, ketoconazole should be administered with caution with intranasal ciclesonide." ], "offsets": [ [ 0, 1062 ] ] } ]

[ { "id": "Ciclesonide_ddi_T1", "type": "DRUG", "text": [ "des-ciclesonide" ], "offsets": [ [ 53, 68 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T2", "type": "DRUG", "text": [ "ciclesonide" ], "offsets": [ [ 215, 226 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T3", "type": "DRUG", "text": [ "des-ciclesonide" ], "offsets": [ [ 335, 350 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T4", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 371, 379 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T5", "type": "DRUG", "text": [ "salicylic acid" ], "offsets": [ [ 383, 397 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T6", "type": "DRUG", "text": [ "ciclesonide" ], "offsets": [ [ 533, 544 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T7", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 554, 566 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T8", "type": "DRUG", "text": [ "des-ciclesonide" ], "offsets": [ [ 653, 668 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T9", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 672, 684 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T10", "type": "DRUG", "text": [ "ciclesonide" ], "offsets": [ [ 757, 768 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T11", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 778, 790 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T12", "type": "DRUG", "text": [ "des-ciclesonide" ], "offsets": [ [ 867, 882 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T13", "type": "DRUG", "text": [ "ciclesonide" ], "offsets": [ [ 942, 953 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T14", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 985, 997 ] ], "normalized": [] }, { "id": "Ciclesonide_ddi_T15", "type": "DRUG", "text": [ "ciclesonide" ], "offsets": [ [ 1050, 1061 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ciclesonide_ddi_R1", "type": "MECHANISM", "arg1_id": "Ciclesonide_ddi_T10", "arg2_id": "Ciclesonide_ddi_T11", "normalized": [] }, { "id": "Ciclesonide_ddi_R2", "type": "ADVISE", "arg1_id": "Ciclesonide_ddi_T14", "arg2_id": "Ciclesonide_ddi_T15", "normalized": [] } ]

[ { "id": "Isoniazid_ddi__text", "type": "abstract", "text": [ "Food: Isoniazid should not be administered with food. Studies have shown that the bioavailability of isoniazid is reduced significantly when administered with food. Acetaminophen: A report of severe acetaminophen toxicity was reported in a patient receiving Isoniazid. It is believed that the toxicity may have resulted from a previously unrecognized interaction between isoniazid and acetaminophen and a molecular basis for this interaction has been proposed. However, current evidence suggests that isoniazid does induce P-450IIE1, a mixed-function oxidase enzyme that appears to generate the toxic metabolites, in the liver. Furthermore it has been proposed that isoniazid resulted In induction of P-450IIE1 in the patients liver which, in turn, resulted in a greater proportion of the ingested acetaminophen being converted to the toxic metabolites. Studies have demonstrated that pretreatment with isoniazid potentiates a cetaminophen hepatoxicity in rats. Carbamazepine: Isoniazid is known to slow the metabolism of carbamazepine and increase its serum levels Carbamazepine levels should be determined prior to concurrent administration with isoniazid, signs and symptoms of carbamazepine toxicity should be monitored closely, and appropriate dosage adjustment of the anticonvulsant should be made. Ketoconazole: Potential interaction of Ketoconazole and Isoniazid may exist. Phenytoin: Isoniazid may increase serum levels of phenytoin. To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made. Therophylline: A recent study has shown that concomitan administration of isoniazid and theophylline may cause elevated plasma levels of theophylline, and in some instances a slight decrease in the elimination of isoniazid. Since the therapeutic range of theophylline is narrow theophylline serum levels should be monitored closely, and appropriate dosage adjustments of theophylline should be made. Valproate: A recent case study has shown a possible increase in the plasma level of valproate when co administered with isoniazid. Plasma valproate concentration should be monitored when isoniazid and valproate are co administered, and appropriate dosage adjustments of valproate should be made." ], "offsets": [ [ 0, 2232 ] ] } ]

[ { "id": "Isoniazid_ddi_T1", "type": "DRUG", "text": [ "Isoniazid" ], "offsets": [ [ 6, 15 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T2", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 101, 110 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T3", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 165, 178 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T4", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 199, 212 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T5", "type": "DRUG", "text": [ "Isoniazid" ], "offsets": [ [ 258, 267 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T6", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 371, 380 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T7", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 385, 398 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T8", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 501, 510 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T9", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 666, 675 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T10", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 798, 811 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T11", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 903, 912 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T12", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 962, 975 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T13", "type": "DRUG", "text": [ "Isoniazid" ], "offsets": [ [ 977, 986 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T14", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1022, 1035 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T15", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 1066, 1079 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T16", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 1148, 1157 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T17", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1181, 1194 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T18", "type": "GROUP", "text": [ "anticonvulsant" ], "offsets": [ [ 1274, 1288 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T19", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 1305, 1317 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T20", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 1344, 1356 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T21", "type": "DRUG", "text": [ "Isoniazid" ], "offsets": [ [ 1361, 1370 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T22", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 1382, 1391 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T23", "type": "DRUG", "text": [ "Isoniazid" ], "offsets": [ [ 1393, 1402 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T24", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1432, 1441 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T25", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1452, 1461 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T26", "type": "GROUP", "text": [ "anticonvulsant" ], "offsets": [ [ 1506, 1520 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T27", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 1611, 1620 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T28", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1625, 1637 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T29", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1674, 1686 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T30", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 1750, 1759 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T31", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1792, 1804 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T32", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1815, 1827 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T33", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 1908, 1920 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T34", "type": "DRUG", "text": [ "Valproate" ], "offsets": [ [ 1937, 1946 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T35", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2021, 2030 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T36", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 2057, 2066 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T37", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2075, 2084 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T38", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 2124, 2133 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T39", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2138, 2147 ] ], "normalized": [] }, { "id": "Isoniazid_ddi_T40", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2207, 2216 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Isoniazid_ddi_R1", "type": "EFFECT", "arg1_id": "Isoniazid_ddi_T4", "arg2_id": "Isoniazid_ddi_T5", "normalized": [] }, { "id": "Isoniazid_ddi_R2", "type": "EFFECT", "arg1_id": "Isoniazid_ddi_T6", "arg2_id": "Isoniazid_ddi_T7", "normalized": [] }, { "id": "Isoniazid_ddi_R3", "type": "MECHANISM", "arg1_id": "Isoniazid_ddi_T9", "arg2_id": "Isoniazid_ddi_T10", "normalized": [] }, { "id": "Isoniazid_ddi_R4", "type": "MECHANISM", "arg1_id": "Isoniazid_ddi_T13", "arg2_id": "Isoniazid_ddi_T14", "normalized": [] }, { "id": "Isoniazid_ddi_R5", "type": "ADVISE", "arg1_id": "Isoniazid_ddi_T15", "arg2_id": "Isoniazid_ddi_T16", "normalized": [] }, { "id": "Isoniazid_ddi_R6", "type": "INT", "arg1_id": "Isoniazid_ddi_T20", "arg2_id": "Isoniazid_ddi_T21", "normalized": [] }, { "id": "Isoniazid_ddi_R7", "type": "MECHANISM", "arg1_id": "Isoniazid_ddi_T23", "arg2_id": "Isoniazid_ddi_T24", "normalized": [] }, { "id": "Isoniazid_ddi_R8", "type": "MECHANISM", "arg1_id": "Isoniazid_ddi_T27", "arg2_id": "Isoniazid_ddi_T28", "normalized": [] }, { "id": "Isoniazid_ddi_R9", "type": "MECHANISM", "arg1_id": "Isoniazid_ddi_T35", "arg2_id": "Isoniazid_ddi_T36", "normalized": [] }, { "id": "Isoniazid_ddi_R10", "type": "ADVISE", "arg1_id": "Isoniazid_ddi_T38", "arg2_id": "Isoniazid_ddi_T39", "normalized": [] } ]

[ { "id": "Epirubicin_ddi__text", "type": "abstract", "text": [ "ELLENCE when used in combination with other cytotoxic drugs may show on-treatment additive toxicity, especially hematologic and gastrointestinal effects. Concomitant use of ELLENCE with other cardioactive compounds that could cause heart failure (e.g., calcium channel blockers), requires close monitoring of cardiac function throughout treatment. There are few data regarding the coadministration of radiation therapy and epirubicin. In adjuvant trials of epirubicin-containing CEF-120 or FEC-100 chemotherapies, breast irradiation was delayed until after chemotherapy was completed. This practice resulted in no apparent increase in local breast cancer recurrence relative to published accounts in the literature. A small number of patients received epirubicin-based chemotherapy concomitantly with radiation therapy but had chemotherapy interrupted in order to avoid potential overlapping toxicities. It is likely that use of epirubicin with radiotherapy may sensitize tissues to the cytotoxic actions of irradiation. Administration of ELLENCE after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation. Epirubicin is extensively metabolized by the liver. Changes in hepatic function induced by concomitant therapies may affect epirubicin metabolism, pharmacokinetics, therapeutic efficacy, and/or toxicity. Cimetidine increased the AUC of epirubicin by 50%. Cimetidine treatment should be stopped during treatment with ELLENCE. Drug-Laboratory Test Interactions There are no known interactions between ELLENCE and laboratory tests." ], "offsets": [ [ 0, 1583 ] ] } ]

[ { "id": "Epirubicin_ddi_T1", "type": "BRAND", "text": [ "ELLENCE" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T2", "type": "BRAND", "text": [ "ELLENCE" ], "offsets": [ [ 173, 180 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T3", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 253, 277 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T4", "type": "DRUG", "text": [ "epirubicin" ], "offsets": [ [ 423, 433 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T5", "type": "DRUG", "text": [ "epirubicin" ], "offsets": [ [ 457, 467 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T6", "type": "DRUG", "text": [ "epirubicin" ], "offsets": [ [ 752, 762 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T7", "type": "DRUG", "text": [ "epirubicin" ], "offsets": [ [ 929, 939 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T8", "type": "BRAND", "text": [ "ELLENCE" ], "offsets": [ [ 1039, 1046 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T9", "type": "DRUG", "text": [ "Epirubicin" ], "offsets": [ [ 1155, 1165 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T10", "type": "DRUG", "text": [ "epirubicin" ], "offsets": [ [ 1279, 1289 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T11", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 1359, 1369 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T12", "type": "DRUG", "text": [ "epirubicin" ], "offsets": [ [ 1391, 1401 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T13", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 1410, 1420 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T14", "type": "BRAND", "text": [ "ELLENCE" ], "offsets": [ [ 1471, 1478 ] ], "normalized": [] }, { "id": "Epirubicin_ddi_T15", "type": "BRAND", "text": [ "ELLENCE" ], "offsets": [ [ 1554, 1561 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Epirubicin_ddi_R1", "type": "ADVISE", "arg1_id": "Epirubicin_ddi_T2", "arg2_id": "Epirubicin_ddi_T3", "normalized": [] }, { "id": "Epirubicin_ddi_R2", "type": "MECHANISM", "arg1_id": "Epirubicin_ddi_T11", "arg2_id": "Epirubicin_ddi_T12", "normalized": [] }, { "id": "Epirubicin_ddi_R3", "type": "ADVISE", "arg1_id": "Epirubicin_ddi_T13", "arg2_id": "Epirubicin_ddi_T14", "normalized": [] } ]

[ { "id": "Dorzolamide_ddi__text", "type": "abstract", "text": [ "Although acid-base and electrolyte disturbances were not reported in the clinical trials with dorzolamide, these disturbances have been reported with oral carbonic anhydrase inhibitors and have, in some instances, resulted in drug interactions (e.g., toxicity associated with high-dose salicylate therapy). Therefore, the potential for such drug interactions should be considered in patients receiving dorzolamide." ], "offsets": [ [ 0, 414 ] ] } ]

[ { "id": "Dorzolamide_ddi_T1", "type": "DRUG", "text": [ "dorzolamide" ], "offsets": [ [ 94, 105 ] ], "normalized": [] }, { "id": "Dorzolamide_ddi_T2", "type": "GROUP", "text": [ "carbonic anhydrase inhibitors" ], "offsets": [ [ 155, 184 ] ], "normalized": [] }, { "id": "Dorzolamide_ddi_T3", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 286, 296 ] ], "normalized": [] }, { "id": "Dorzolamide_ddi_T4", "type": "DRUG", "text": [ "dorzolamide" ], "offsets": [ [ 402, 413 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Dorzolamide_ddi_R1", "type": "EFFECT", "arg1_id": "Dorzolamide_ddi_T1", "arg2_id": "Dorzolamide_ddi_T2", "normalized": [] } ]

[ { "id": "L-Histidine_ddi__text", "type": "abstract", "text": [ "Medroxyprogesterone Acetate - L-histidine was observed to enhance (in tissue culture) the effect of medroxyprogesterone acetate in reducing the number of human breast cancer cells that were in the S phase. H1 and H2 Blockers - Although not reported, L-histidine, via its metabolism to histamine, might decrease the efficacy of H1 and H2 blockers." ], "offsets": [ [ 0, 346 ] ] } ]

[ { "id": "L-Histidine_ddi_T1", "type": "DRUG", "text": [ "Medroxyprogesterone Acetate" ], "offsets": [ [ 0, 27 ] ], "normalized": [] }, { "id": "L-Histidine_ddi_T2", "type": "DRUG", "text": [ "L-histidine" ], "offsets": [ [ 30, 41 ] ], "normalized": [] }, { "id": "L-Histidine_ddi_T3", "type": "DRUG", "text": [ "medroxyprogesterone acetate" ], "offsets": [ [ 100, 127 ] ], "normalized": [] }, { "id": "L-Histidine_ddi_T4", "type": "GROUP", "text": [ "H1", "Blockers" ], "offsets": [ [ 206, 208 ], [ 216, 224 ] ], "normalized": [] }, { "id": "L-Histidine_ddi_T5", "type": "GROUP", "text": [ "H2 Blockers" ], "offsets": [ [ 213, 224 ] ], "normalized": [] }, { "id": "L-Histidine_ddi_T6", "type": "DRUG", "text": [ "L-histidine" ], "offsets": [ [ 250, 261 ] ], "normalized": [] }, { "id": "L-Histidine_ddi_T7", "type": "GROUP", "text": [ "H1", "blockers" ], "offsets": [ [ 327, 329 ], [ 337, 345 ] ], "normalized": [] }, { "id": "L-Histidine_ddi_T8", "type": "GROUP", "text": [ "H2 blockers" ], "offsets": [ [ 334, 345 ] ], "normalized": [] } ]

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[]

[ { "id": "L-Histidine_ddi_R1", "type": "EFFECT", "arg1_id": "L-Histidine_ddi_T2", "arg2_id": "L-Histidine_ddi_T3", "normalized": [] }, { "id": "L-Histidine_ddi_R2", "type": "EFFECT", "arg1_id": "L-Histidine_ddi_T6", "arg2_id": "L-Histidine_ddi_T7", "normalized": [] }, { "id": "L-Histidine_ddi_R3", "type": "EFFECT", "arg1_id": "L-Histidine_ddi_T6", "arg2_id": "L-Histidine_ddi_T8", "normalized": [] } ]

[ { "id": "Epoprostenol_ddi__text", "type": "abstract", "text": [ "Additional reductions in blood pressure may occur when FLOLAN is administered with diuretics, antihypertensive agents, or other vasodilators. When other antiplatelet agents or anticoagulants are used concomitantly, there is the potential for FLOLAN to increase the risk of bleeding. However, patients receiving infusions of FLOLAN in clinical trials were maintained on anticoagulants without evidence of increased bleeding. In clinical trials, FLOLAN was used with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen.In a pharmacokinetic substudy in patients with congestive heart failure receiving furosemide or digoxin in whom therapy with FLOLAN was initiated, apparent oral clearance values for furosemide (n = 23) and digoxin (n = 30) were decreased by 13% and 15%, respectively, on the second day of therapy and had returned to baseline values by day 87. The change in furosemide clearance value is not likely to be clinically significant. However, patients on digoxin may show elevations of digoxin concentrations after initiation of therapy with FLOLAN, which may be clinically significant in patients prone to digoxin toxicity." ], "offsets": [ [ 0, 1163 ] ] } ]

[ { "id": "Epoprostenol_ddi_T1", "type": "BRAND", "text": [ "FLOLAN" ], "offsets": [ [ 55, 61 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T2", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 83, 92 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T3", "type": "GROUP", "text": [ "antihypertensive agents" ], "offsets": [ [ 94, 117 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T4", "type": "GROUP", "text": [ "vasodilators" ], "offsets": [ [ 128, 140 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T5", "type": "GROUP", "text": [ "antiplatelet agents" ], "offsets": [ [ 153, 172 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T6", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 176, 190 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T7", "type": "BRAND", "text": [ "FLOLAN" ], "offsets": [ [ 242, 248 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T8", "type": "BRAND", "text": [ "FLOLAN" ], "offsets": [ [ 324, 330 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T9", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 369, 383 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T10", "type": "BRAND", "text": [ "FLOLAN" ], "offsets": [ [ 444, 450 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T11", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 465, 472 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T12", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 474, 483 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T13", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 485, 499 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T14", "type": "GROUP", "text": [ "vasodilators" ], "offsets": [ [ 506, 518 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T15", "type": "DRUG", "text": [ "oxygen" ], "offsets": [ [ 537, 543 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T16", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 626, 636 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T17", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 640, 647 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T18", "type": "BRAND", "text": [ "FLOLAN" ], "offsets": [ [ 669, 675 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T19", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 726, 736 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T20", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 750, 757 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T21", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 902, 912 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T22", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 994, 1001 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T23", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1025, 1032 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T24", "type": "BRAND", "text": [ "FLOLAN" ], "offsets": [ [ 1081, 1087 ] ], "normalized": [] }, { "id": "Epoprostenol_ddi_T25", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1146, 1153 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Epoprostenol_ddi_R1", "type": "EFFECT", "arg1_id": "Epoprostenol_ddi_T1", "arg2_id": "Epoprostenol_ddi_T2", "normalized": [] }, { "id": "Epoprostenol_ddi_R2", "type": "EFFECT", "arg1_id": "Epoprostenol_ddi_T1", "arg2_id": "Epoprostenol_ddi_T3", "normalized": [] }, { "id": "Epoprostenol_ddi_R3", "type": "EFFECT", "arg1_id": "Epoprostenol_ddi_T1", "arg2_id": "Epoprostenol_ddi_T4", "normalized": [] }, { "id": "Epoprostenol_ddi_R4", "type": "EFFECT", "arg1_id": "Epoprostenol_ddi_T5", "arg2_id": "Epoprostenol_ddi_T7", "normalized": [] }, { "id": "Epoprostenol_ddi_R5", "type": "EFFECT", "arg1_id": "Epoprostenol_ddi_T6", "arg2_id": "Epoprostenol_ddi_T7", "normalized": [] }, { "id": "Epoprostenol_ddi_R6", "type": "MECHANISM", "arg1_id": "Epoprostenol_ddi_T16", "arg2_id": "Epoprostenol_ddi_T18", "normalized": [] }, { "id": "Epoprostenol_ddi_R7", "type": "MECHANISM", "arg1_id": "Epoprostenol_ddi_T17", "arg2_id": "Epoprostenol_ddi_T18", "normalized": [] }, { "id": "Epoprostenol_ddi_R8", "type": "MECHANISM", "arg1_id": "Epoprostenol_ddi_T22", "arg2_id": "Epoprostenol_ddi_T24", "normalized": [] } ]

[ { "id": "Eptifibatide_ddi__text", "type": "abstract", "text": [ "Enoxaparin dosed as a 1.0 mg/kg subcutaneous injection q12h for four doses did not alter the pharmacokinetics of eptifibatide or the level of platelet aggregation in healthy adults." ], "offsets": [ [ 0, 181 ] ] } ]

[ { "id": "Eptifibatide_ddi_T1", "type": "DRUG", "text": [ "Enoxaparin" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Eptifibatide_ddi_T2", "type": "DRUG", "text": [ "eptifibatide" ], "offsets": [ [ 113, 125 ] ], "normalized": [] } ]

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[ { "id": "Diethylpropion_ddi__text", "type": "abstract", "text": [ "Antidiabetic drug requirements (i.e., insulin) may be altered. Concurrent use with general anesthetics may result in arrhythmias. The pressor effects of diethylpropion and those of other drugs may be additive when the drugs are used concomitantly; conversely, diethylpropion may interfere with antihypertensive drugs (i.e., guanethidine, a-methyldopa). Concurrent use of phenothiazines may antagonize the anorectic effect of diethylpropion." ], "offsets": [ [ 0, 440 ] ] } ]

[ { "id": "Diethylpropion_ddi_T1", "type": "GROUP", "text": [ "Antidiabetic drug" ], "offsets": [ [ 0, 17 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T2", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 38, 45 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T3", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 91, 102 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T4", "type": "DRUG", "text": [ "diethylpropion" ], "offsets": [ [ 153, 167 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T5", "type": "DRUG", "text": [ "diethylpropion" ], "offsets": [ [ 260, 274 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T6", "type": "GROUP", "text": [ "antihypertensive drugs" ], "offsets": [ [ 294, 316 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T7", "type": "DRUG", "text": [ "guanethidine" ], "offsets": [ [ 324, 336 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T8", "type": "DRUG", "text": [ "a-methyldopa" ], "offsets": [ [ 338, 350 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T9", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 371, 385 ] ], "normalized": [] }, { "id": "Diethylpropion_ddi_T10", "type": "DRUG", "text": [ "diethylpropion" ], "offsets": [ [ 425, 439 ] ], "normalized": [] } ]

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[ { "id": "Diethylpropion_ddi_R1", "type": "INT", "arg1_id": "Diethylpropion_ddi_T5", "arg2_id": "Diethylpropion_ddi_T6", "normalized": [] }, { "id": "Diethylpropion_ddi_R2", "type": "INT", "arg1_id": "Diethylpropion_ddi_T5", "arg2_id": "Diethylpropion_ddi_T7", "normalized": [] }, { "id": "Diethylpropion_ddi_R3", "type": "INT", "arg1_id": "Diethylpropion_ddi_T5", "arg2_id": "Diethylpropion_ddi_T8", "normalized": [] }, { "id": "Diethylpropion_ddi_R4", "type": "EFFECT", "arg1_id": "Diethylpropion_ddi_T9", "arg2_id": "Diethylpropion_ddi_T10", "normalized": [] } ]

[ { "id": "Acebutolol_ddi__text", "type": "abstract", "text": [ "Catecholamine-depleting drugs, such as reserpine, may have an additive effect when given with beta-blocking agents. Patients treated with acebutolol plus catecholamine depletors should, therefore, be observed closely for evidence of marked bradycardia or hypotension which may present as vertigo, syncope/presyncope, or orthostatic changes in blood pressure without compensatory tachycardia. Exaggerated hypertensive responses have been reported from the combined use of beta-adrenergic antagonists and alpha-adrenergic stimulants, including those contained in proprietary cold remedies and vasoconstrictive nasal drops. Patients receiving beta-blockers should be warned of this potential hazard. Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by nonsteroidal anti-inflammatory drugs has been reported. No significant interactions with digoxin, hydrochlorothiazide, hydralazine, sulfinpyrazone, oral contraceptives, tolbutamide, or warfarin have been observed." ], "offsets": [ [ 0, 990 ] ] } ]

[ { "id": "Acebutolol_ddi_T1", "type": "GROUP", "text": [ "Catecholamine-depleting drugs" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T2", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 39, 48 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T3", "type": "GROUP", "text": [ "beta-blocking agents" ], "offsets": [ [ 94, 114 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T4", "type": "DRUG", "text": [ "acebutolol" ], "offsets": [ [ 138, 148 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T5", "type": "GROUP", "text": [ "catecholamine depletors" ], "offsets": [ [ 154, 177 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T6", "type": "GROUP", "text": [ "beta-adrenergic antagonists" ], "offsets": [ [ 471, 498 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T7", "type": "GROUP", "text": [ "alpha-adrenergic stimulants" ], "offsets": [ [ 503, 530 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T8", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 640, 653 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T9", "type": "GROUP", "text": [ "beta-adrenoceptor blocking agents" ], "offsets": [ [ 740, 773 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T10", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory drugs" ], "offsets": [ [ 777, 813 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T11", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 866, 873 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T12", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 875, 894 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T13", "type": "DRUG", "text": [ "hydralazine" ], "offsets": [ [ 896, 907 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T14", "type": "DRUG", "text": [ "sulfinpyrazone" ], "offsets": [ [ 909, 923 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T15", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 930, 944 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T16", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 946, 957 ] ], "normalized": [] }, { "id": "Acebutolol_ddi_T17", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 962, 970 ] ], "normalized": [] } ]

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[ { "id": "Acebutolol_ddi_R1", "type": "EFFECT", "arg1_id": "Acebutolol_ddi_T1", "arg2_id": "Acebutolol_ddi_T3", "normalized": [] }, { "id": "Acebutolol_ddi_R2", "type": "EFFECT", "arg1_id": "Acebutolol_ddi_T2", "arg2_id": "Acebutolol_ddi_T3", "normalized": [] }, { "id": "Acebutolol_ddi_R3", "type": "ADVISE", "arg1_id": "Acebutolol_ddi_T4", "arg2_id": "Acebutolol_ddi_T5", "normalized": [] }, { "id": "Acebutolol_ddi_R4", "type": "EFFECT", "arg1_id": "Acebutolol_ddi_T6", "arg2_id": "Acebutolol_ddi_T7", "normalized": [] }, { "id": "Acebutolol_ddi_R5", "type": "EFFECT", "arg1_id": "Acebutolol_ddi_T9", "arg2_id": "Acebutolol_ddi_T10", "normalized": [] } ]

[ { "id": "Clonazepam_ddi__text", "type": "abstract", "text": [ "Effect of Clonazepam on the Pharmacokinetics of Other Drugs: Clonazepam does not appear to alter the pharmacokinetics of phenytoin, carbamazepine, or phenobarbital. The effect of clonazepam on the metabolism of other drugs has not been investigated. Effect of Other Drugs on the Pharmacokinetics of Clonazepam: Literature reports suggest that ranitidine, an agent that decreases stomach acidity, does not greatly alter clonazepam pharmacokinetics. In a study in which the 2 mg clonazepam orally disintegrating tablet was administered with and without propantheline (an anticholinergic agent with multiple effects on the GI tract) to healthy volunteers, the AUC of clonazepam was 10% lower and the Cmax of clonazepam was 20% lower when the orally disintegrating tablet was given with propantheline compared to when it was given alone. Fluoxetine does not affect the pharmacokinetics of clonazepam. Cytochrome P-450 inducers, such as phenytoin, carbamazepine and phenobarbital, induce clonazepam metabolism, causing an approximately 30% decrease in plasma clonazepam levels. Although clinical studies have not been performed, based on the involvement of the cytochrome P-450 3A family in clonazepam metabolism, inhibitors of this enzyme system, notably oral antifungal agents, should be used cautiously in patients receiving clonazepam. Pharmacodynamic Interactions: The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs." ], "offsets": [ [ 0, 1712 ] ] } ]

[ { "id": "Clonazepam_ddi_T1", "type": "DRUG", "text": [ "Clonazepam" ], "offsets": [ [ 10, 20 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T2", "type": "DRUG", "text": [ "Clonazepam" ], "offsets": [ [ 61, 71 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T3", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 121, 130 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T4", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 132, 145 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T5", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 150, 163 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T6", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 179, 189 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T7", "type": "DRUG", "text": [ "Clonazepam" ], "offsets": [ [ 299, 309 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T8", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 343, 353 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T9", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 419, 429 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T10", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 477, 487 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T11", "type": "DRUG", "text": [ "propantheline" ], "offsets": [ [ 551, 564 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T12", "type": "GROUP", "text": [ "anticholinergic agent" ], "offsets": [ [ 569, 590 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T13", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 664, 674 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T14", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 705, 715 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T15", "type": "DRUG", "text": [ "propantheline" ], "offsets": [ [ 783, 796 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T16", "type": "DRUG", "text": [ "Fluoxetine" ], "offsets": [ [ 834, 844 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T17", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 885, 895 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T18", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 932, 941 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T19", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 943, 956 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T20", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 961, 974 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T21", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 983, 993 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T22", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 1054, 1064 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T23", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 1186, 1196 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T24", "type": "GROUP", "text": [ "antifungal agents" ], "offsets": [ [ 1256, 1273 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T25", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 1323, 1333 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T26", "type": "GROUP", "text": [ "benzodiazepine class" ], "offsets": [ [ 1398, 1418 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T27", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 1450, 1457 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T28", "type": "GROUP", "text": [ "narcotics" ], "offsets": [ [ 1459, 1468 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T29", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 1470, 1482 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T30", "type": "GROUP", "text": [ "nonbarbiturate hypnotics" ], "offsets": [ [ 1484, 1508 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T31", "type": "GROUP", "text": [ "antianxiety agents" ], "offsets": [ [ 1510, 1528 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T32", "type": "GROUP", "text": [ "phenothiazines", "classes of antipsychotic agents" ], "offsets": [ [ 1534, 1548 ], [ 1581, 1612 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T33", "type": "GROUP", "text": [ "thioxanthene", "classes of antipsychotic agents" ], "offsets": [ [ 1550, 1562 ], [ 1581, 1612 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T34", "type": "GROUP", "text": [ "butyrophenone classes of antipsychotic agents" ], "offsets": [ [ 1567, 1612 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T35", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 1614, 1642 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T36", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 1651, 1676 ] ], "normalized": [] }, { "id": "Clonazepam_ddi_T37", "type": "GROUP", "text": [ "anticonvulsant drugs" ], "offsets": [ [ 1691, 1711 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Clonazepam_ddi_R1", "type": "MECHANISM", "arg1_id": "Clonazepam_ddi_T10", "arg2_id": "Clonazepam_ddi_T11", "normalized": [] }, { "id": "Clonazepam_ddi_R2", "type": "MECHANISM", "arg1_id": "Clonazepam_ddi_T14", "arg2_id": "Clonazepam_ddi_T15", "normalized": [] }, { "id": "Clonazepam_ddi_R3", "type": "MECHANISM", "arg1_id": "Clonazepam_ddi_T18", "arg2_id": "Clonazepam_ddi_T21", "normalized": [] }, { "id": "Clonazepam_ddi_R4", "type": "MECHANISM", "arg1_id": "Clonazepam_ddi_T19", "arg2_id": "Clonazepam_ddi_T21", "normalized": [] }, { "id": "Clonazepam_ddi_R5", "type": "MECHANISM", "arg1_id": "Clonazepam_ddi_T20", "arg2_id": "Clonazepam_ddi_T21", "normalized": [] }, { "id": "Clonazepam_ddi_R6", "type": "ADVISE", "arg1_id": "Clonazepam_ddi_T24", "arg2_id": "Clonazepam_ddi_T25", "normalized": [] }, { "id": "Clonazepam_ddi_R7", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T27", "normalized": [] }, { "id": "Clonazepam_ddi_R8", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T28", "normalized": [] }, { "id": "Clonazepam_ddi_R9", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T29", "normalized": [] }, { "id": "Clonazepam_ddi_R10", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T30", "normalized": [] }, { "id": "Clonazepam_ddi_R11", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T31", "normalized": [] }, { "id": "Clonazepam_ddi_R12", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T32", "normalized": [] }, { "id": "Clonazepam_ddi_R13", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T33", "normalized": [] }, { "id": "Clonazepam_ddi_R14", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T34", "normalized": [] }, { "id": "Clonazepam_ddi_R15", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T35", "normalized": [] }, { "id": "Clonazepam_ddi_R16", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T36", "normalized": [] }, { "id": "Clonazepam_ddi_R17", "type": "EFFECT", "arg1_id": "Clonazepam_ddi_T26", "arg2_id": "Clonazepam_ddi_T37", "normalized": [] } ]

[ { "id": "Diethylstilbestrol_ddi__text", "type": "abstract", "text": [ "May interact anticoagulants (altered hypo-prothrombinemic effect), barbiturates, rifampin and other inducers of hepatic microsomal enzyme oxidation system (decreased effect of diethylstilbestrol), corticosteroids (increased effect of corticosteroids)." ], "offsets": [ [ 0, 251 ] ] } ]

[ { "id": "Diethylstilbestrol_ddi_T1", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 13, 27 ] ], "normalized": [] }, { "id": "Diethylstilbestrol_ddi_T2", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 67, 79 ] ], "normalized": [] }, { "id": "Diethylstilbestrol_ddi_T3", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 81, 89 ] ], "normalized": [] }, { "id": "Diethylstilbestrol_ddi_T4", "type": "DRUG", "text": [ "diethylstilbestrol" ], "offsets": [ [ 176, 194 ] ], "normalized": [] }, { "id": "Diethylstilbestrol_ddi_T5", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 197, 212 ] ], "normalized": [] }, { "id": "Diethylstilbestrol_ddi_T6", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 234, 249 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Levofloxacin_ddi__text", "type": "abstract", "text": [ "Specific drug interaction studies have not been conducted with Levofloxacin. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, and enhance the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with transient elevations in serum creatinine in patients receiving systemic cyclosporine concomitantly." ], "offsets": [ [ 0, 449 ] ] } ]

[ { "id": "Levofloxacin_ddi_T1", "type": "DRUG", "text": [ "Levofloxacin" ], "offsets": [ [ 63, 75 ] ], "normalized": [] }, { "id": "Levofloxacin_ddi_T2", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 122, 132 ] ], "normalized": [] }, { "id": "Levofloxacin_ddi_T3", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 184, 196 ] ], "normalized": [] }, { "id": "Levofloxacin_ddi_T4", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 231, 239 ] ], "normalized": [] }, { "id": "Levofloxacin_ddi_T5", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 277, 290 ] ], "normalized": [] }, { "id": "Levofloxacin_ddi_T6", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 291, 299 ] ], "normalized": [] }, { "id": "Levofloxacin_ddi_T7", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 422, 434 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Levofloxacin_ddi_R1", "type": "MECHANISM", "arg1_id": "Levofloxacin_ddi_T2", "arg2_id": "Levofloxacin_ddi_T3", "normalized": [] }, { "id": "Levofloxacin_ddi_R2", "type": "MECHANISM", "arg1_id": "Levofloxacin_ddi_T2", "arg2_id": "Levofloxacin_ddi_T4", "normalized": [] }, { "id": "Levofloxacin_ddi_R3", "type": "EFFECT", "arg1_id": "Levofloxacin_ddi_T2", "arg2_id": "Levofloxacin_ddi_T6", "normalized": [] }, { "id": "Levofloxacin_ddi_R4", "type": "EFFECT", "arg1_id": "Levofloxacin_ddi_T2", "arg2_id": "Levofloxacin_ddi_T7", "normalized": [] } ]

[ { "id": "Bosentan_ddi__text", "type": "abstract", "text": [ "Bosentan is metabolized by CYP2C9 and CYP3A4. Inhibition of these isoenzymes may increase the plasma concentration of bosentan. Bosentan is an inducer of CYP3A4 and CYP2C9. Consequently, plasma concentrations of drugs metabolized by these two isoenzymes will be decreased when TRACLEER is co-administered. Bosentan had no relevant inhibitory effect on any CYP isoenzymes tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4). Consequently, TRACLEER is not expected to increase the plasma concentrations of drugs metabolized by these enzymes. Hormonal Contraceptives, Including Oral, Injectable, Transdermal, and Implantable Contraceptives: An interaction study demonstrated that co-administration of bosentan and the oral hormonal contraceptive Ortho-Novum produced average decreases of norethindrone and ethinyl estradiol levels of 14% and 31%, respectively. However, decreases in exposure were as much as 56% and 66%, respectively, in individual subjects. Therefore, hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when TRACLEER is co-administered. Women should practice additional methods of contraception and not rely on hormonal contraception alone when taking TRACLEER. Specific interaction studies have demonstrated the following: Cyclosporine A: During the first day of concomitant administration, trough concentrations of bosentan were increased by about 30-fold. Steady-state bosentan plasma concentrations were 3- to 4-fold higher than in the absence of cyclosporine A. The concomitant administration of bosentan and cyclosporine A is contraindicated. Co-administration of bosentan decreased the plasma concentrations of cyclosporine A (a CYP3A4 substrate) by approximately 50%. Tacrolimus: Co-administration of tacrolimus and bosentan has not been studied in man. Co-administration of tacrolimus and bosentan resulted in markedly increased plasma concentrations of bosentan in animals. Caution should be exercised if tacrolimus and bosentan are used together. Glyburide: An increased risk of elevated liver aminotransferases was observed in patients receiving concomitant therapy with glyburide. Therefore, the concomitant administration of TRACLEER and glyburide is contraindicated, and alternative hypoglycemic agents should be considered. Co-administration of bosentan decreased the plasma concentrations of glyburide by approximately 40%. The plasma concentrations of bosentan were also decreased by approximately 30%. Bosentan is also expected to reduce plasma concentrations of other oral hypoglycemic agents that are predominantly metabolized by CYP2C9 or CYP3A4. The possibility of worsened glucose control in patients using these agents should be considered. Ketoconazole: Co-administration of bosentan 125 mg b.i.d. and ketoconazole, a potent CYP3A4 inhibitor, increased the plasma concentrations of bosentan by approximately 2-fold. No dose adjustment of bosentan is necessary, but increased effects of bosentan should be considered. Simvastatin and Other Statins: Co-administration of bosentan decreased the plasma concentrations of simvastatin (a CYP3A4 substrate), and its active -hydroxy acid metabolite, by approximately 50%. The plasma concentrations of bosentan were not affected. Bosentan is also expected to reduce plasma concentrations of other statins that have significant metabolism by CYP3A4, such as lovastatin and atorvastatin. The possibility of reduced statin efficacy should be considered. Patients using CYP3A4 metabolized statins should have cholesterol levels monitored after TRACLEER is initiated to see whether the statin dose needs adjustment. Warfarin: Co-administration of bosentan 500 mg b.i.d. for 6 days decreased the plasma concentrations of both S-warfarin (a CYP2C9 substrate) and R-warfarin (a CYP3A4 substrate) by 29 and 38%, respectively. Clinical experience with concomitant administration of bosentan and warfarin in patients with pulmonary arterial hypertension did not show clinically relevant changes in INR or warfarin dose (baseline vs. end of the clinical studies), and the need to change the warfarin dose during the trials due to changes in INR or due to adverse events was similar among bosentan- and placebo-treated patients. Digoxin, Nimodipine and Losartan: Bosentan has no significant pharmacokinetic interactions with digoxin and nimodipine, and losartan has no significant effect on plasma levels of bosentan." ], "offsets": [ [ 0, 4442 ] ] } ]

[ { "id": "Bosentan_ddi_T1", "type": "DRUG", "text": [ "Bosentan" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T2", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 118, 126 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T3", "type": "DRUG", "text": [ "Bosentan" ], "offsets": [ [ 128, 136 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T4", "type": "BRAND", "text": [ "TRACLEER" ], "offsets": [ [ 277, 285 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T5", "type": "DRUG", "text": [ "Bosentan" ], "offsets": [ [ 306, 314 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T6", "type": "BRAND", "text": [ "TRACLEER" ], "offsets": [ [ 435, 443 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T7", "type": "GROUP", "text": [ "Hormonal Contraceptives" ], "offsets": [ [ 537, 560 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T8", "type": "GROUP", "text": [ "Contraceptives" ], "offsets": [ [ 619, 633 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T9", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 695, 703 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T10", "type": "GROUP", "text": [ "hormonal contraceptive" ], "offsets": [ [ 717, 739 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T11", "type": "BRAND", "text": [ "Ortho-Novum" ], "offsets": [ [ 740, 751 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T12", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 782, 795 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T13", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 800, 817 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T14", "type": "GROUP", "text": [ "hormonal contraceptives" ], "offsets": [ [ 964, 987 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T15", "type": "BRAND", "text": [ "TRACLEER" ], "offsets": [ [ 1078, 1086 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T16", "type": "BRAND", "text": [ "TRACLEER" ], "offsets": [ [ 1222, 1230 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T17", "type": "DRUG", "text": [ "Cyclosporine A" ], "offsets": [ [ 1294, 1308 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T18", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 1387, 1395 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T19", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 1442, 1450 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T20", "type": "DRUG", "text": [ "cyclosporine A" ], "offsets": [ [ 1521, 1535 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T21", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 1571, 1579 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T22", "type": "DRUG", "text": [ "cyclosporine A" ], "offsets": [ [ 1584, 1598 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T23", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 1640, 1648 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T24", "type": "DRUG", "text": [ "cyclosporine A" ], "offsets": [ [ 1688, 1702 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T25", "type": "DRUG", "text": [ "Tacrolimus" ], "offsets": [ [ 1746, 1756 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T26", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 1779, 1789 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T27", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 1794, 1802 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T28", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 1853, 1863 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T29", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 1868, 1876 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T30", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 1933, 1941 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T31", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 1985, 1995 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T32", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 2000, 2008 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T33", "type": "DRUG", "text": [ "Glyburide" ], "offsets": [ [ 2028, 2037 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T34", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 2153, 2162 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T35", "type": "BRAND", "text": [ "TRACLEER" ], "offsets": [ [ 2209, 2217 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T36", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 2222, 2231 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T37", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 2268, 2287 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T38", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 2331, 2339 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T39", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 2379, 2388 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T40", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 2440, 2448 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T41", "type": "DRUG", "text": [ "Bosentan" ], "offsets": [ [ 2491, 2499 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T42", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 2563, 2582 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T43", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 2736, 2748 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T44", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 2771, 2779 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T45", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 2798, 2810 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T46", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 2878, 2886 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T47", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 2934, 2942 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T48", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 2982, 2990 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T49", "type": "DRUG", "text": [ "Simvastatin" ], "offsets": [ [ 3013, 3024 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T50", "type": "GROUP", "text": [ "Statins" ], "offsets": [ [ 3035, 3042 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T51", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 3065, 3073 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T52", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 3113, 3124 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T53", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 3240, 3248 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T54", "type": "DRUG", "text": [ "Bosentan" ], "offsets": [ [ 3268, 3276 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T55", "type": "GROUP", "text": [ "statins" ], "offsets": [ [ 3335, 3342 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T56", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 3395, 3405 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T57", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 3410, 3422 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T58", "type": "GROUP", "text": [ "statin" ], "offsets": [ [ 3451, 3457 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T59", "type": "GROUP", "text": [ "statins" ], "offsets": [ [ 3523, 3530 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T60", "type": "BRAND", "text": [ "TRACLEER" ], "offsets": [ [ 3578, 3586 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T61", "type": "GROUP", "text": [ "statin" ], "offsets": [ [ 3619, 3625 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T62", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 3649, 3657 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T63", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 3680, 3688 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T64", "type": "DRUG", "text": [ "S-warfarin" ], "offsets": [ [ 3758, 3768 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T65", "type": "DRUG", "text": [ "R-warfarin" ], "offsets": [ [ 3794, 3804 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T66", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 3910, 3918 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T67", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3923, 3931 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T68", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4032, 4040 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T69", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4117, 4125 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T70", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 4214, 4222 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T71", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 4254, 4261 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T72", "type": "DRUG", "text": [ "Nimodipine" ], "offsets": [ [ 4263, 4273 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T73", "type": "DRUG", "text": [ "Losartan" ], "offsets": [ [ 4278, 4286 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T74", "type": "DRUG", "text": [ "Bosentan" ], "offsets": [ [ 4288, 4296 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T75", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 4350, 4357 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T76", "type": "DRUG", "text": [ "nimodipine" ], "offsets": [ [ 4362, 4372 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T77", "type": "DRUG", "text": [ "losartan" ], "offsets": [ [ 4378, 4386 ] ], "normalized": [] }, { "id": "Bosentan_ddi_T78", "type": "DRUG", "text": [ "bosentan" ], "offsets": [ [ 4433, 4441 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Bosentan_ddi_R1", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T9", "arg2_id": "Bosentan_ddi_T11", "normalized": [] }, { "id": "Bosentan_ddi_R2", "type": "EFFECT", "arg1_id": "Bosentan_ddi_T14", "arg2_id": "Bosentan_ddi_T15", "normalized": [] }, { "id": "Bosentan_ddi_R3", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T19", "arg2_id": "Bosentan_ddi_T20", "normalized": [] }, { "id": "Bosentan_ddi_R4", "type": "ADVISE", "arg1_id": "Bosentan_ddi_T21", "arg2_id": "Bosentan_ddi_T22", "normalized": [] }, { "id": "Bosentan_ddi_R5", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T23", "arg2_id": "Bosentan_ddi_T24", "normalized": [] }, { "id": "Bosentan_ddi_R6", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T28", "arg2_id": "Bosentan_ddi_T29", "normalized": [] }, { "id": "Bosentan_ddi_R7", "type": "ADVISE", "arg1_id": "Bosentan_ddi_T31", "arg2_id": "Bosentan_ddi_T32", "normalized": [] }, { "id": "Bosentan_ddi_R8", "type": "ADVISE", "arg1_id": "Bosentan_ddi_T35", "arg2_id": "Bosentan_ddi_T36", "normalized": [] }, { "id": "Bosentan_ddi_R9", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T38", "arg2_id": "Bosentan_ddi_T39", "normalized": [] }, { "id": "Bosentan_ddi_R10", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T41", "arg2_id": "Bosentan_ddi_T42", "normalized": [] }, { "id": "Bosentan_ddi_R11", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T44", "arg2_id": "Bosentan_ddi_T45", "normalized": [] }, { "id": "Bosentan_ddi_R12", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T51", "arg2_id": "Bosentan_ddi_T52", "normalized": [] }, { "id": "Bosentan_ddi_R13", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T54", "arg2_id": "Bosentan_ddi_T55", "normalized": [] }, { "id": "Bosentan_ddi_R14", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T54", "arg2_id": "Bosentan_ddi_T56", "normalized": [] }, { "id": "Bosentan_ddi_R15", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T54", "arg2_id": "Bosentan_ddi_T57", "normalized": [] }, { "id": "Bosentan_ddi_R16", "type": "ADVISE", "arg1_id": "Bosentan_ddi_T59", "arg2_id": "Bosentan_ddi_T60", "normalized": [] }, { "id": "Bosentan_ddi_R17", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T63", "arg2_id": "Bosentan_ddi_T64", "normalized": [] }, { "id": "Bosentan_ddi_R18", "type": "MECHANISM", "arg1_id": "Bosentan_ddi_T63", "arg2_id": "Bosentan_ddi_T65", "normalized": [] } ]

[ { "id": "Clorazepate_ddi__text", "type": "abstract", "text": [ "If TRANXENE is to be combined with other drugs acting on the central nervous system, careful consideration should be given to the pharmacology of the agents to be employed. Animal experience indicates that clorazepate dipotassium prolongs the sleeping time after hexobarbital or after ethyl alcohol, increases the inhibitory effects of chlorpromazine, but does not exhibit monoamine oxidase inhibition. Clinical studies have shown increased sedation with concurrent hypnotic medications. The actions of the benzodiazepines may be potentiated by barbiturates, narcotics, phenothiazines, monoamine oxidase inhibitors or other antidepressants. If TRANXENE tablets are used to treat anxiety associated with somatic disease states, careful attention must be paid to possible drug interaction with concomitant medication. In bioavailability studies with normal subjects, the concurrent administration of antacids at therapeutic levels did not significantly influence the bioavailability of TRANXENE tablets." ], "offsets": [ [ 0, 1001 ] ] } ]

[ { "id": "Clorazepate_ddi_T1", "type": "BRAND", "text": [ "TRANXENE" ], "offsets": [ [ 3, 11 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T2", "type": "DRUG", "text": [ "clorazepate dipotassium" ], "offsets": [ [ 206, 229 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T3", "type": "DRUG", "text": [ "hexobarbital" ], "offsets": [ [ 263, 275 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T4", "type": "DRUG", "text": [ "ethyl alcohol" ], "offsets": [ [ 285, 298 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T5", "type": "DRUG", "text": [ "chlorpromazine" ], "offsets": [ [ 336, 350 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T6", "type": "GROUP", "text": [ "hypnotic medications" ], "offsets": [ [ 466, 486 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T7", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 507, 522 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T8", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 545, 557 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T9", "type": "GROUP", "text": [ "narcotics" ], "offsets": [ [ 559, 568 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T10", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 570, 584 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T11", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 586, 614 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T12", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 624, 639 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T13", "type": "BRAND", "text": [ "TRANXENE" ], "offsets": [ [ 644, 652 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T14", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 898, 906 ] ], "normalized": [] }, { "id": "Clorazepate_ddi_T15", "type": "BRAND", "text": [ "TRANXENE" ], "offsets": [ [ 984, 992 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Clorazepate_ddi_R1", "type": "EFFECT", "arg1_id": "Clorazepate_ddi_T2", "arg2_id": "Clorazepate_ddi_T3", "normalized": [] }, { "id": "Clorazepate_ddi_R2", "type": "EFFECT", "arg1_id": "Clorazepate_ddi_T2", "arg2_id": "Clorazepate_ddi_T4", "normalized": [] }, { "id": "Clorazepate_ddi_R3", "type": "EFFECT", "arg1_id": "Clorazepate_ddi_T2", "arg2_id": "Clorazepate_ddi_T5", "normalized": [] }, { "id": "Clorazepate_ddi_R4", "type": "EFFECT", "arg1_id": "Clorazepate_ddi_T7", "arg2_id": "Clorazepate_ddi_T8", "normalized": [] }, { "id": "Clorazepate_ddi_R5", "type": "EFFECT", "arg1_id": "Clorazepate_ddi_T7", "arg2_id": "Clorazepate_ddi_T9", "normalized": [] }, { "id": "Clorazepate_ddi_R6", "type": "EFFECT", "arg1_id": "Clorazepate_ddi_T7", "arg2_id": "Clorazepate_ddi_T10", "normalized": [] }, { "id": "Clorazepate_ddi_R7", "type": "EFFECT", "arg1_id": "Clorazepate_ddi_T7", "arg2_id": "Clorazepate_ddi_T11", "normalized": [] }, { "id": "Clorazepate_ddi_R8", "type": "EFFECT", "arg1_id": "Clorazepate_ddi_T7", "arg2_id": "Clorazepate_ddi_T12", "normalized": [] } ]

[ { "id": "Linezolid_ddi__text", "type": "abstract", "text": [ "Monoamine Oxidase Inhibition: Linezolid is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents. Adrenergic Agents:Some individuals receiving ZYVOX may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Commonly used drugs such as phenylpropanolamine and pseudoephedrine have been specifically studied. Initial doses of adrenergic agents, such as dopamine or epinephrine, should be reduced and titrated to achieve the desired response. Serotonergic Agents: Co-administration of linezolid and serotonergic agents was not associated with serotonin syndrome in Phase 1, 2 or 3 studies. Spontaneous reports of serotonin syndrome associated with co-administration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported. Patients who are treated with ZYVOX and concomitant serotonergic agents should be closely observed for signs and symptoms of serotonin syndrome (e.g., cognitive dysfunction, hyperpyrexia, hyperreflexia, incoordination). If any signs or symptoms occur physicians should consider discontinuation of either one or both agents (ZYVOX or concomitant serotonergic agents). Drug-Laboratory Test Interactions There are no reported drug-laboratory test interactions." ], "offsets": [ [ 0, 1442 ] ] } ]

[ { "id": "Linezolid_ddi_T1", "type": "DRUG", "text": [ "Linezolid" ], "offsets": [ [ 30, 39 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T2", "type": "DRUG", "text": [ "linezolid" ], "offsets": [ [ 113, 122 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T3", "type": "GROUP", "text": [ "adrenergic" ], "offsets": [ [ 162, 172 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T4", "type": "GROUP", "text": [ "serotonergic agents" ], "offsets": [ [ 177, 196 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T5", "type": "GROUP", "text": [ "Adrenergic Agents" ], "offsets": [ [ 198, 215 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T6", "type": "BRAND", "text": [ "ZYVOX" ], "offsets": [ [ 243, 248 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T7", "type": "GROUP", "text": [ "sympathomimetic agents" ], "offsets": [ [ 332, 354 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T8", "type": "GROUP", "text": [ "vasopressor" ], "offsets": [ [ 356, 367 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T9", "type": "GROUP", "text": [ "dopaminergic agents" ], "offsets": [ [ 371, 390 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T10", "type": "DRUG", "text": [ "phenylpropanolamine" ], "offsets": [ [ 420, 439 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T11", "type": "DRUG", "text": [ "pseudoephedrine" ], "offsets": [ [ 444, 459 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T12", "type": "GROUP", "text": [ "adrenergic agents" ], "offsets": [ [ 509, 526 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T13", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 536, 544 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T14", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 548, 559 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T15", "type": "GROUP", "text": [ "Serotonergic Agents" ], "offsets": [ [ 625, 644 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T16", "type": "DRUG", "text": [ "linezolid" ], "offsets": [ [ 667, 676 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T17", "type": "GROUP", "text": [ "serotonergic agents" ], "offsets": [ [ 681, 700 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T18", "type": "BRAND", "text": [ "ZYVOX" ], "offsets": [ [ 851, 856 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T19", "type": "GROUP", "text": [ "serotonergic agents" ], "offsets": [ [ 861, 880 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T20", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 892, 907 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T21", "type": "GROUP", "text": [ "selective serotonin reuptake inhibitors" ], "offsets": [ [ 916, 955 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T22", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 957, 962 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T23", "type": "BRAND", "text": [ "ZYVOX" ], "offsets": [ [ 1015, 1020 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T24", "type": "GROUP", "text": [ "serotonergic agents" ], "offsets": [ [ 1037, 1056 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T25", "type": "BRAND", "text": [ "ZYVOX" ], "offsets": [ [ 1309, 1314 ] ], "normalized": [] }, { "id": "Linezolid_ddi_T26", "type": "GROUP", "text": [ "serotonergic agents" ], "offsets": [ [ 1330, 1349 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Linezolid_ddi_R1", "type": "INT", "arg1_id": "Linezolid_ddi_T2", "arg2_id": "Linezolid_ddi_T3", "normalized": [] }, { "id": "Linezolid_ddi_R2", "type": "INT", "arg1_id": "Linezolid_ddi_T2", "arg2_id": "Linezolid_ddi_T4", "normalized": [] }, { "id": "Linezolid_ddi_R3", "type": "EFFECT", "arg1_id": "Linezolid_ddi_T6", "arg2_id": "Linezolid_ddi_T7", "normalized": [] }, { "id": "Linezolid_ddi_R4", "type": "EFFECT", "arg1_id": "Linezolid_ddi_T6", "arg2_id": "Linezolid_ddi_T8", "normalized": [] }, { "id": "Linezolid_ddi_R5", "type": "EFFECT", "arg1_id": "Linezolid_ddi_T6", "arg2_id": "Linezolid_ddi_T9", "normalized": [] }, { "id": "Linezolid_ddi_R6", "type": "EFFECT", "arg1_id": "Linezolid_ddi_T18", "arg2_id": "Linezolid_ddi_T19", "normalized": [] }, { "id": "Linezolid_ddi_R7", "type": "EFFECT", "arg1_id": "Linezolid_ddi_T18", "arg2_id": "Linezolid_ddi_T20", "normalized": [] }, { "id": "Linezolid_ddi_R8", "type": "EFFECT", "arg1_id": "Linezolid_ddi_T18", "arg2_id": "Linezolid_ddi_T21", "normalized": [] }, { "id": "Linezolid_ddi_R9", "type": "EFFECT", "arg1_id": "Linezolid_ddi_T18", "arg2_id": "Linezolid_ddi_T22", "normalized": [] }, { "id": "Linezolid_ddi_R10", "type": "EFFECT", "arg1_id": "Linezolid_ddi_T23", "arg2_id": "Linezolid_ddi_T24", "normalized": [] }, { "id": "Linezolid_ddi_R11", "type": "ADVISE", "arg1_id": "Linezolid_ddi_T25", "arg2_id": "Linezolid_ddi_T26", "normalized": [] } ]

[ { "id": "Edrophonium_ddi__text", "type": "abstract", "text": [ "Care should be given when administering this drug to patients with symptoms of myasthenic weakness who are also on anticholinesterase drugs. Since symptoms of anticholinesterase overdose (cholinergic crisis) may mimic underdosage (myasthenic weakness), their condition may be worsened by the use of this drug." ], "offsets": [ [ 0, 309 ] ] } ]

[ { "id": "Edrophonium_ddi_T1", "type": "GROUP", "text": [ "anticholinesterase drugs" ], "offsets": [ [ 115, 139 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "Donepezil_ddi__text", "type": "abstract", "text": [ "Drugs that inhibit or Induce CYP 2D6 and CYP 3A4 may affect the concentration on Aricept." ], "offsets": [ [ 0, 89 ] ] } ]

[ { "id": "Donepezil_ddi_T1", "type": "BRAND", "text": [ "Aricept" ], "offsets": [ [ 81, 88 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "Ibuprofen_ddi__text", "type": "abstract", "text": [ "Coumarin-Type Anticoagulants: Several short-term controlled studies failed to wshow that ibuprofen significantly affected prothrombin times or a variety of other clotting factors when administered to individuals on coumarin-type anticoagulants. However, because bleeding has been reported when ibuprofen and other nonsteroidal anti-inflammatory agents have been administered to patients on coumarin-type anticoagulants, the physician should be cautious when administering ibuprofen to patients on anticoagulants. Aspirin: Animal studies wshow that aspirin given with nonsteroidal anti-inflammatory agents, including ibuprofen, yields a net decrease in anti-inflammatory activity with lowered blood levels of the non-aspirin drug. Single dose bioavailability studies in normal volunteers have failed to wshow an effect of aspirin on ibuprofen blood levels. Correlative clinical studies have not been performed. Methotrexate: Ibuprofen, as well as other nonsteroidal anti-inflammatory drugs, probably reduces the tubular secretion of methotrexate based on in vitro studies in rabbit kidney slices. This may indicate that ibuprofen could enhance the toxicity of methotrexate. Caution should be used if ibuprofen is administered concomitantly with methotrexate. H-2 Antagonists: In studies with human volunteers, co-administration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations. Furosemide: Clinical studies, as well as random observations, have shown that ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with ibuprofen, the patient should be observed closely for signs of renal failure, as well as to assure diuretic efficacy. Lithium: Ibuprofen produced an elevation of plasma lithium levels and a reduction in renal lithium clearance in a study of eleven normal volunteers. The mean minimum lithium concentration increased 15% and the renal clearance of lithium was decreased by 19% during this period of concomitant drug administration. This effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen. Thus, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparation before use of such concurrent therapy)." ], "offsets": [ [ 0, 2449 ] ] } ]

[ { "id": "Ibuprofen_ddi_T1", "type": "GROUP", "text": [ "Coumarin-Type Anticoagulants" ], "offsets": [ [ 0, 28 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T2", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 89, 98 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T3", "type": "GROUP", "text": [ "coumarin-type anticoagulants" ], "offsets": [ [ 215, 243 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T4", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 294, 303 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T5", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 314, 351 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T6", "type": "GROUP", "text": [ "coumarin-type anticoagulants" ], "offsets": [ [ 390, 418 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T7", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 472, 481 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T8", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 497, 511 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T9", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 513, 520 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T10", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 548, 555 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T11", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 567, 604 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T12", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 616, 625 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T13", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 821, 828 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T14", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 832, 841 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T15", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 910, 922 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T16", "type": "DRUG", "text": [ "Ibuprofen" ], "offsets": [ [ 924, 933 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T17", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory drugs" ], "offsets": [ [ 952, 988 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T18", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1032, 1044 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T19", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 1119, 1128 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T20", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1159, 1171 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T21", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 1199, 1208 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T22", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1244, 1256 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T23", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1330, 1340 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T24", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 1344, 1354 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T25", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 1360, 1369 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T26", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 1399, 1408 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T27", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 1431, 1441 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T28", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 1509, 1518 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T29", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1556, 1566 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T30", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 1571, 1580 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T31", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 1713, 1722 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T32", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 1812, 1820 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T33", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 1831, 1838 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T34", "type": "DRUG", "text": [ "Ibuprofen" ], "offsets": [ [ 1840, 1849 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T35", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1882, 1889 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T36", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1922, 1929 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T37", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1997, 2004 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T38", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2060, 2067 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T39", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 2226, 2235 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T40", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 2248, 2257 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T41", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2262, 2269 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T42", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2352, 2359 ] ], "normalized": [] }, { "id": "Ibuprofen_ddi_T43", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2390, 2397 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ibuprofen_ddi_R1", "type": "EFFECT", "arg1_id": "Ibuprofen_ddi_T4", "arg2_id": "Ibuprofen_ddi_T6", "normalized": [] }, { "id": "Ibuprofen_ddi_R2", "type": "EFFECT", "arg1_id": "Ibuprofen_ddi_T5", "arg2_id": "Ibuprofen_ddi_T6", "normalized": [] }, { "id": "Ibuprofen_ddi_R3", "type": "ADVISE", "arg1_id": "Ibuprofen_ddi_T7", "arg2_id": "Ibuprofen_ddi_T8", "normalized": [] }, { "id": "Ibuprofen_ddi_R4", "type": "EFFECT", "arg1_id": "Ibuprofen_ddi_T10", "arg2_id": "Ibuprofen_ddi_T11", "normalized": [] }, { "id": "Ibuprofen_ddi_R5", "type": "EFFECT", "arg1_id": "Ibuprofen_ddi_T10", "arg2_id": "Ibuprofen_ddi_T12", "normalized": [] }, { "id": "Ibuprofen_ddi_R6", "type": "MECHANISM", "arg1_id": "Ibuprofen_ddi_T16", "arg2_id": "Ibuprofen_ddi_T18", "normalized": [] }, { "id": "Ibuprofen_ddi_R7", "type": "MECHANISM", "arg1_id": "Ibuprofen_ddi_T17", "arg2_id": "Ibuprofen_ddi_T18", "normalized": [] }, { "id": "Ibuprofen_ddi_R8", "type": "EFFECT", "arg1_id": "Ibuprofen_ddi_T19", "arg2_id": "Ibuprofen_ddi_T20", "normalized": [] }, { "id": "Ibuprofen_ddi_R9", "type": "ADVISE", "arg1_id": "Ibuprofen_ddi_T21", "arg2_id": "Ibuprofen_ddi_T22", "normalized": [] }, { "id": "Ibuprofen_ddi_R10", "type": "EFFECT", "arg1_id": "Ibuprofen_ddi_T28", "arg2_id": "Ibuprofen_ddi_T29", "normalized": [] }, { "id": "Ibuprofen_ddi_R11", "type": "EFFECT", "arg1_id": "Ibuprofen_ddi_T28", "arg2_id": "Ibuprofen_ddi_T30", "normalized": [] }, { "id": "Ibuprofen_ddi_R12", "type": "MECHANISM", "arg1_id": "Ibuprofen_ddi_T34", "arg2_id": "Ibuprofen_ddi_T35", "normalized": [] }, { "id": "Ibuprofen_ddi_R13", "type": "ADVISE", "arg1_id": "Ibuprofen_ddi_T40", "arg2_id": "Ibuprofen_ddi_T41", "normalized": [] } ]

[ { "id": "Fomepizole_ddi__text", "type": "abstract", "text": [ "Oral doses of Antizol (10-20 mg/kg), via alcohol dehydrogenase inhibition, significantly reduced the rate of elimination of ethanol (by approximately 40%) given to healthy volunteers in moderate doses. Similarly, ethanol decreased the rate of elimination of Antizol (by approximately 50%) by the same mechanism. Reciprocal interactions may occur with concomitant use of Antizol and drugs that increase or inhibit the cytochrome P450 system (e.g., phenytoin, carbamazepine, cimetidine, ketoconazole), though this has not been studied ." ], "offsets": [ [ 0, 534 ] ] } ]

[ { "id": "Fomepizole_ddi_T1", "type": "BRAND", "text": [ "Antizol" ], "offsets": [ [ 14, 21 ] ], "normalized": [] }, { "id": "Fomepizole_ddi_T2", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 124, 131 ] ], "normalized": [] }, { "id": "Fomepizole_ddi_T3", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 213, 220 ] ], "normalized": [] }, { "id": "Fomepizole_ddi_T4", "type": "BRAND", "text": [ "Antizol" ], "offsets": [ [ 258, 265 ] ], "normalized": [] }, { "id": "Fomepizole_ddi_T5", "type": "BRAND", "text": [ "Antizol" ], "offsets": [ [ 370, 377 ] ], "normalized": [] }, { "id": "Fomepizole_ddi_T6", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 447, 456 ] ], "normalized": [] }, { "id": "Fomepizole_ddi_T7", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 458, 471 ] ], "normalized": [] }, { "id": "Fomepizole_ddi_T8", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 473, 483 ] ], "normalized": [] }, { "id": "Fomepizole_ddi_T9", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 485, 497 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Fomepizole_ddi_R1", "type": "MECHANISM", "arg1_id": "Fomepizole_ddi_T1", "arg2_id": "Fomepizole_ddi_T2", "normalized": [] }, { "id": "Fomepizole_ddi_R2", "type": "MECHANISM", "arg1_id": "Fomepizole_ddi_T3", "arg2_id": "Fomepizole_ddi_T4", "normalized": [] }, { "id": "Fomepizole_ddi_R3", "type": "MECHANISM", "arg1_id": "Fomepizole_ddi_T5", "arg2_id": "Fomepizole_ddi_T6", "normalized": [] }, { "id": "Fomepizole_ddi_R4", "type": "MECHANISM", "arg1_id": "Fomepizole_ddi_T5", "arg2_id": "Fomepizole_ddi_T7", "normalized": [] }, { "id": "Fomepizole_ddi_R5", "type": "MECHANISM", "arg1_id": "Fomepizole_ddi_T5", "arg2_id": "Fomepizole_ddi_T8", "normalized": [] }, { "id": "Fomepizole_ddi_R6", "type": "MECHANISM", "arg1_id": "Fomepizole_ddi_T5", "arg2_id": "Fomepizole_ddi_T9", "normalized": [] } ]