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[ { "id": "Cisatracurium Besylate_ddi__text", "type": "abstract", "text": [ "Administration of 0.1-mg/kg (2 x ED95) NIMBEX at 10% or 95% recovery following an intubating dose of succinylcholine (1 mg/kg) produced 95% neuromuscular block. The time to onset of maximum block following NIMBEX is approximately 2 minutes faster with prior administration of succinylcholine. Prior administration of succinylcholine had no effect on the duration of neuromuscular block following initial or maintenance bolus doses of NIMBEX. Infusion requirements of NIMBEX in patients administered succinylcholine prior to infusions of NIMBEX were comparable to or slightly greater than when succinylcholine was not administered. The use of NIMBEX before succinylcholine to attenuate some of the side effects of succinylcholine has not been studied. Although not studied systematically in clinical trials, no drug interactions were observed when vecuronium, pancuronium, or atracurium were administered following varying degrees of recovery from single doses or infusions of NIMBEX. Isoflurane or enflurane administered with nitrous oxide/oxygen to achieve 1.25 MAC [Minimum Alveolar Concentration] may prolong the clinically effective duration of action of initial and maintenance doses of NIMBEX and decrease the required infusion rate of NIMBEX. The magnitude of these effects may depend on the duration of administration of the volatile agents. Fifteen to 30 minutes of exposure to 1.25 MAC isoflurane or enflurane had minimal effects on the duration of action of initial doses of NIMBEX and therefore, no adjustment to the initial dose should be necessary when NIMBEX is administered shortly after initiation of volatile agents. In long surgical procedures during enflurane or isoflurane anesthesia, less frequent maintenance dosing, lower maintenance doses, or reduced infusion rates of NIMBEX may be necessary. The average infusion rate requirement may be decreased by as much as 30% to 40%. In clinical studies propofol had no effect on the duration of action or dosing requirements for NIMBEX. Other drugs which may enhance the neuromuscular blocking action of nondepolarizing agents such as NIMBEX include certain antibiotics (e. g., aminoglycosides, tetracyclines, bacitracin, polymyxins, lincomycin, clindamycin, colistin, and sodium colistemethate), magnesium salts, lithium, local anesthetics, procainamide, and quinidine. Resistance to the neuromuscular blocking action of nondepolarizing neuromuscular blocking agents has been demonstrated in patients chronically administered phenytoin or carbamazepine. While the effects of chronic phenytoin or carbamazepine therapy on the action of NIMBEX are unknown, slightly shorter durations of neuromuscular block may be anticipated and infusion rate requirements may be higher. Drug/Laboratory Test Interactions None known." ], "offsets": [ [ 0, 2784 ] ] } ]

[ { "id": "Cisatracurium Besylate_ddi_T1", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 39, 45 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T2", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 101, 116 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T3", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 207, 213 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T4", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 277, 292 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T5", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 318, 333 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T6", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 435, 441 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T7", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 468, 474 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T8", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 500, 515 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T9", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 538, 544 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T10", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 594, 609 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T11", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 643, 649 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T12", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 657, 672 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T13", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 714, 729 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T14", "type": "DRUG", "text": [ "vecuronium" ], "offsets": [ [ 848, 858 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T15", "type": "DRUG", "text": [ "pancuronium" ], "offsets": [ [ 860, 871 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T16", "type": "DRUG", "text": [ "atracurium" ], "offsets": [ [ 876, 886 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T17", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 977, 983 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T18", "type": "DRUG", "text": [ "Isoflurane" ], "offsets": [ [ 985, 995 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T19", "type": "DRUG", "text": [ "enflurane" ], "offsets": [ [ 999, 1008 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T20", "type": "DRUG", "text": [ "nitrous oxide" ], "offsets": [ [ 1027, 1040 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T21", "type": "DRUG", "text": [ "oxygen" ], "offsets": [ [ 1041, 1047 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T22", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 1193, 1199 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T23", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 1243, 1249 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T24", "type": "DRUG", "text": [ "isoflurane" ], "offsets": [ [ 1397, 1407 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T25", "type": "DRUG", "text": [ "enflurane" ], "offsets": [ [ 1411, 1420 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T26", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 1487, 1493 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T27", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 1568, 1574 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T28", "type": "DRUG", "text": [ "enflurane" ], "offsets": [ [ 1671, 1680 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T29", "type": "DRUG", "text": [ "isoflurane" ], "offsets": [ [ 1684, 1694 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T30", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 1795, 1801 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T31", "type": "DRUG", "text": [ "propofol" ], "offsets": [ [ 1921, 1929 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T32", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 1997, 2003 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T33", "type": "GROUP", "text": [ "nondepolarizing agents" ], "offsets": [ [ 2072, 2094 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T34", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 2103, 2109 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T35", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 2126, 2137 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T36", "type": "GROUP", "text": [ "aminoglycosides" ], "offsets": [ [ 2146, 2161 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T37", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 2163, 2176 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T38", "type": "DRUG", "text": [ "bacitracin" ], "offsets": [ [ 2178, 2188 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T39", "type": "GROUP", "text": [ "polymyxins" ], "offsets": [ [ 2190, 2200 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T40", "type": "DRUG", "text": [ "lincomycin" ], "offsets": [ [ 2202, 2212 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T41", "type": "DRUG", "text": [ "clindamycin" ], "offsets": [ [ 2214, 2225 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T42", "type": "DRUG", "text": [ "colistin" ], "offsets": [ [ 2227, 2235 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T43", "type": "DRUG", "text": [ "sodium colistemethate" ], "offsets": [ [ 2241, 2262 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T44", "type": "GROUP", "text": [ "magnesium" ], "offsets": [ [ 2265, 2274 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T45", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2282, 2289 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T46", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 2297, 2308 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T47", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 2310, 2322 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T48", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 2328, 2337 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T49", "type": "GROUP", "text": [ "nondepolarizing neuromuscular blocking agents" ], "offsets": [ [ 2390, 2435 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T50", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2495, 2504 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T51", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2508, 2521 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T52", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2552, 2561 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T53", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2565, 2578 ] ], "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_T54", "type": "BRAND", "text": [ "NIMBEX" ], "offsets": [ [ 2604, 2610 ] ], "normalized": [] } ]

[]

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[ { "id": "Cisatracurium Besylate_ddi_R1", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T1", "arg2_id": "Cisatracurium Besylate_ddi_T2", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R2", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T3", "arg2_id": "Cisatracurium Besylate_ddi_T4", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R3", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T8", "arg2_id": "Cisatracurium Besylate_ddi_T9", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R4", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T18", "arg2_id": "Cisatracurium Besylate_ddi_T22", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R5", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T18", "arg2_id": "Cisatracurium Besylate_ddi_T23", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R6", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T19", "arg2_id": "Cisatracurium Besylate_ddi_T22", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R7", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T19", "arg2_id": "Cisatracurium Besylate_ddi_T23", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R8", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T20", "arg2_id": "Cisatracurium Besylate_ddi_T22", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R9", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T20", "arg2_id": "Cisatracurium Besylate_ddi_T23", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R10", "type": "ADVISE", "arg1_id": "Cisatracurium Besylate_ddi_T28", "arg2_id": "Cisatracurium Besylate_ddi_T30", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R11", "type": "ADVISE", "arg1_id": "Cisatracurium Besylate_ddi_T29", "arg2_id": "Cisatracurium Besylate_ddi_T30", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R12", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T34", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R13", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T35", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R14", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T36", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R15", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T37", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R16", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T38", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R17", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T39", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R18", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T40", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R19", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T41", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R20", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T42", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R21", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T43", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R22", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T44", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R23", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T45", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R24", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T46", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R25", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T47", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R26", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T33", "arg2_id": "Cisatracurium Besylate_ddi_T48", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R27", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T35", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R28", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T36", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R29", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T37", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R30", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T38", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R31", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T39", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R32", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T40", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R33", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T41", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R34", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T42", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R35", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T43", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R36", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T44", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R37", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T45", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R38", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T46", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R39", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T47", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R40", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T34", "arg2_id": "Cisatracurium Besylate_ddi_T48", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R41", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T49", "arg2_id": "Cisatracurium Besylate_ddi_T50", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R42", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T49", "arg2_id": "Cisatracurium Besylate_ddi_T51", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R43", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T52", "arg2_id": "Cisatracurium Besylate_ddi_T54", "normalized": [] }, { "id": "Cisatracurium Besylate_ddi_R44", "type": "EFFECT", "arg1_id": "Cisatracurium Besylate_ddi_T53", "arg2_id": "Cisatracurium Besylate_ddi_T54", "normalized": [] } ]

[ { "id": "Eplerenone_ddi__text", "type": "abstract", "text": [ "Inhibitors of CYP3A4-Eplerenone metabolism is predominantly mediated via CYP3A4. A pharmacokinetic study evaluating the administration of a single dose of INSPRA 100 mg with ketoconazole 200 mg BID, a potent inhibitor of the CYP3A4 pathway, showed a 1.7-fold increase in Cmax of eplerenone and a 5.4-fold increase in AUC of eplerenone. INSPRA should not be used with drugs described as strong inhibitors of CYP3A4 in their labeling. Administration of eplerenone with other CYP3A4 inhibitors (e.g., erythromycin 500 mg BID, verapamil 240 mg QD, saquinavir 1200 mg TID, fluconazole 200 mg QD) resulted in increases in Cmax of eplerenone ranging from 1.4- to 1.6- fold and AUC from 2.0- to 2.9- fold. ACE Inhibitors and Angiotensin II Receptor Antagonists (Congestive Heart Failure Post-Myocardial Infarction)- In EPHESUS, 3020 (91%) patients receiving INSPRA 25 to 50 mg also received ACE inhibitors or angiotensin II receptor antagonists (ACEI/ARB). Rates of patients with maximum potassium levels 5.5 mEq/L were similar regardless of the use of ACEI/ARB. ACE Inhibitors and Angiotensin II Receptor Antagonists (Hypertension)- In clinical studies of patients with hypertension, the addition of INSPRA 50 to 100 mg to ACE inhibitors and angiotensin II receptor antagonists increased mean serum potassium slightly (about 0.09-0.13 mEq/L). In a study in diabetics with microalbuminuria INSPRA 200 mg combined with the ACE inhibitor enalapril 10 mg increased the frequency of hyperkalemia (serum potassium 5.5 mEq/L) from 17% on enalapril alone to 38%. Lithium-A drug interaction study of eplerenone with lithium has not been conducted. Serum lithium levels should be monitored frequently if INSPRA is administered concomitantly with lithium. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)-A drug interaction study of eplerenone with an NSAID has not been conducted. The administration of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive effect in some patients and result in severe hyperkalemia in patients with impaired renal function. Therefore, when INSPRA and NSAIDs are used concomitantly, patients should be observed to determine whether the desired effect on blood pressure is obtained." ], "offsets": [ [ 0, 2241 ] ] } ]

[ { "id": "Eplerenone_ddi_T1", "type": "DRUG", "text": [ "Eplerenone" ], "offsets": [ [ 21, 31 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T2", "type": "BRAND", "text": [ "INSPRA" ], "offsets": [ [ 155, 161 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T3", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 174, 186 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T4", "type": "DRUG", "text": [ "eplerenone" ], "offsets": [ [ 279, 289 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T5", "type": "DRUG", "text": [ "eplerenone" ], "offsets": [ [ 324, 334 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T6", "type": "BRAND", "text": [ "INSPRA" ], "offsets": [ [ 336, 342 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T7", "type": "DRUG", "text": [ "eplerenone" ], "offsets": [ [ 451, 461 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T8", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 498, 510 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T9", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 523, 532 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T10", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 544, 554 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T11", "type": "DRUG", "text": [ "fluconazole" ], "offsets": [ [ 568, 579 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T12", "type": "DRUG", "text": [ "eplerenone" ], "offsets": [ [ 624, 634 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T13", "type": "GROUP", "text": [ "ACE Inhibitors" ], "offsets": [ [ 698, 712 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T14", "type": "GROUP", "text": [ "Angiotensin II Receptor Antagonists" ], "offsets": [ [ 717, 752 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T15", "type": "BRAND", "text": [ "INSPRA" ], "offsets": [ [ 850, 856 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T16", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 883, 897 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T17", "type": "GROUP", "text": [ "angiotensin II receptor antagonists" ], "offsets": [ [ 901, 936 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T18", "type": "GROUP", "text": [ "ACEI" ], "offsets": [ [ 938, 942 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T19", "type": "GROUP", "text": [ "ARB" ], "offsets": [ [ 943, 946 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T20", "type": "GROUP", "text": [ "ACEI" ], "offsets": [ [ 1046, 1050 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T21", "type": "GROUP", "text": [ "ARB" ], "offsets": [ [ 1051, 1054 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T22", "type": "GROUP", "text": [ "ACE Inhibitors" ], "offsets": [ [ 1056, 1070 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T23", "type": "GROUP", "text": [ "Angiotensin II Receptor Antagonists" ], "offsets": [ [ 1075, 1110 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T24", "type": "BRAND", "text": [ "INSPRA" ], "offsets": [ [ 1194, 1200 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T25", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 1217, 1231 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T26", "type": "GROUP", "text": [ "angiotensin II receptor antagonists" ], "offsets": [ [ 1236, 1271 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T27", "type": "BRAND", "text": [ "INSPRA" ], "offsets": [ [ 1383, 1389 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T28", "type": "GROUP", "text": [ "ACE inhibitor" ], "offsets": [ [ 1415, 1428 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T29", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 1429, 1438 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T30", "type": "DRUG", "text": [ "enalapril" ], "offsets": [ [ 1526, 1535 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T31", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 1550, 1557 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T32", "type": "DRUG", "text": [ "eplerenone" ], "offsets": [ [ 1586, 1596 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T33", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1602, 1609 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T34", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1640, 1647 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T35", "type": "BRAND", "text": [ "INSPRA" ], "offsets": [ [ 1689, 1695 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T36", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1731, 1738 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T37", "type": "GROUP", "text": [ "Nonsteroidal Anti-Inflammatory Drugs" ], "offsets": [ [ 1740, 1776 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T38", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1778, 1784 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T39", "type": "DRUG", "text": [ "eplerenone" ], "offsets": [ [ 1814, 1824 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T40", "type": "GROUP", "text": [ "NSAID" ], "offsets": [ [ 1833, 1838 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T41", "type": "GROUP", "text": [ "potassium-sparing antihypertensives" ], "offsets": [ [ 1891, 1926 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T42", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1932, 1938 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T43", "type": "BRAND", "text": [ "INSPRA" ], "offsets": [ [ 2101, 2107 ] ], "normalized": [] }, { "id": "Eplerenone_ddi_T44", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2112, 2118 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Eplerenone_ddi_R1", "type": "MECHANISM", "arg1_id": "Eplerenone_ddi_T2", "arg2_id": "Eplerenone_ddi_T3", "normalized": [] }, { "id": "Eplerenone_ddi_R2", "type": "MECHANISM", "arg1_id": "Eplerenone_ddi_T7", "arg2_id": "Eplerenone_ddi_T8", "normalized": [] }, { "id": "Eplerenone_ddi_R3", "type": "MECHANISM", "arg1_id": "Eplerenone_ddi_T7", "arg2_id": "Eplerenone_ddi_T9", "normalized": [] }, { "id": "Eplerenone_ddi_R4", "type": "MECHANISM", "arg1_id": "Eplerenone_ddi_T7", "arg2_id": "Eplerenone_ddi_T10", "normalized": [] }, { "id": "Eplerenone_ddi_R5", "type": "MECHANISM", "arg1_id": "Eplerenone_ddi_T7", "arg2_id": "Eplerenone_ddi_T11", "normalized": [] }, { "id": "Eplerenone_ddi_R6", "type": "EFFECT", "arg1_id": "Eplerenone_ddi_T24", "arg2_id": "Eplerenone_ddi_T25", "normalized": [] }, { "id": "Eplerenone_ddi_R7", "type": "EFFECT", "arg1_id": "Eplerenone_ddi_T24", "arg2_id": "Eplerenone_ddi_T26", "normalized": [] }, { "id": "Eplerenone_ddi_R8", "type": "EFFECT", "arg1_id": "Eplerenone_ddi_T27", "arg2_id": "Eplerenone_ddi_T29", "normalized": [] }, { "id": "Eplerenone_ddi_R9", "type": "ADVISE", "arg1_id": "Eplerenone_ddi_T35", "arg2_id": "Eplerenone_ddi_T36", "normalized": [] }, { "id": "Eplerenone_ddi_R10", "type": "EFFECT", "arg1_id": "Eplerenone_ddi_T41", "arg2_id": "Eplerenone_ddi_T42", "normalized": [] }, { "id": "Eplerenone_ddi_R11", "type": "ADVISE", "arg1_id": "Eplerenone_ddi_T43", "arg2_id": "Eplerenone_ddi_T44", "normalized": [] } ]

[ { "id": "Caspofungin_ddi__text", "type": "abstract", "text": [ "Studies in vitro show that caspofungin acetate is not an inhibitor of any enzyme in the cytochrome P450 (CYP) system. In clinical studies, caspofungin did not induce the CYP3A4 metabolism of other drugs. Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome P450 enzymes. Clinical studies in healthy volunteers show that the pharmacokinetics of CANCIDAS are not altered by itraconazole, amphotericin B, mycophenolate, nelfinavir, or tacrolimus. CANCIDAS has no effect on the pharmacokinetics of itraconazole, amphotericin B, or the active metabolite of mycophenolate. CANCIDAS reduced the blood AUC0-12 of tacrolimus by approximately 20%, peak blood concentration (Cmax) by 16%, and 12-hour blood concentration (C12hr) by 26% in healthy subjects when tacrolimus (2 doses of 0.1 mg/kg 12 hours apart) was administered on the 10th day of CANCIDAS 70 mg daily, as compared to results from a control period in which tacrolimus was administered alone. For patients receiving both therapies, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended. In two clinical studies, cyclosporine (one 4 mg/kg dose or two 3 mg/kg doses) increased the AUC of caspofungin by approximately 35%. CANCIDAS did not increase the plasma levels of cyclosporine. There were transient increases in liver ALT and AST when CANCIDAS and cyclosporine were co-administered. A drug-drug interaction study with rifampin in healthy volunteers has shown a 30% decrease in caspofungin trough concentrations. Patients on rifampin should receive 70 mg of CANCIDAS daily. In addition, results from regression analyses of patient pharmacokinetic data suggest that co-administration of other inducers of drug clearance (efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine) with CANCIDAS may result in clinically meaningful reductions in caspofungin concentrations. It is not known which drug clearance mechanism involved in caspofungin disposition may be inducible. When CANCIDAS is co-administered with inducers of drug clearance, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, use of a daily dose of 70 mg of CANCIDAS should be considered ." ], "offsets": [ [ 0, 2238 ] ] } ]

[ { "id": "Caspofungin_ddi_T1", "type": "DRUG", "text": [ "caspofungin acetate" ], "offsets": [ [ 27, 46 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T2", "type": "DRUG", "text": [ "caspofungin" ], "offsets": [ [ 139, 150 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T3", "type": "DRUG", "text": [ "Caspofungin" ], "offsets": [ [ 204, 215 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T4", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 380, 388 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T5", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 408, 420 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T6", "type": "DRUG", "text": [ "amphotericin B" ], "offsets": [ [ 422, 436 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T7", "type": "DRUG", "text": [ "mycophenolate" ], "offsets": [ [ 438, 451 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T8", "type": "DRUG", "text": [ "nelfinavir" ], "offsets": [ [ 453, 463 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T9", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 468, 478 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T10", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 480, 488 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T11", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 530, 542 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T12", "type": "DRUG", "text": [ "amphotericin B" ], "offsets": [ [ 544, 558 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T13", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 603, 611 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T14", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 641, 651 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T15", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 786, 796 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T16", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 871, 879 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T17", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 947, 957 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T18", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 1044, 1054 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T19", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 1092, 1102 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T20", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1164, 1176 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T21", "type": "DRUG", "text": [ "caspofungin" ], "offsets": [ [ 1238, 1249 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T22", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 1272, 1280 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T23", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1319, 1331 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T24", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 1390, 1398 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T25", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1403, 1415 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T26", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1473, 1481 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T27", "type": "DRUG", "text": [ "caspofungin" ], "offsets": [ [ 1532, 1543 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T28", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1579, 1587 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T29", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 1612, 1620 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T30", "type": "DRUG", "text": [ "efavirenz" ], "offsets": [ [ 1774, 1783 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T31", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 1785, 1795 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T32", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1797, 1806 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T33", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 1808, 1821 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T34", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1826, 1839 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T35", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 1846, 1854 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T36", "type": "DRUG", "text": [ "caspofungin" ], "offsets": [ [ 1905, 1916 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T37", "type": "DRUG", "text": [ "caspofungin" ], "offsets": [ [ 1992, 2003 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T38", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 2039, 2047 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T39", "type": "DRUG", "text": [ "efavirenz" ], "offsets": [ [ 2108, 2117 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T40", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 2119, 2129 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T41", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2131, 2140 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T42", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 2142, 2155 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T43", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2160, 2173 ] ], "normalized": [] }, { "id": "Caspofungin_ddi_T44", "type": "BRAND", "text": [ "CANCIDAS" ], "offsets": [ [ 2207, 2215 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Caspofungin_ddi_R1", "type": "MECHANISM", "arg1_id": "Caspofungin_ddi_T13", "arg2_id": "Caspofungin_ddi_T14", "normalized": [] }, { "id": "Caspofungin_ddi_R2", "type": "MECHANISM", "arg1_id": "Caspofungin_ddi_T20", "arg2_id": "Caspofungin_ddi_T21", "normalized": [] }, { "id": "Caspofungin_ddi_R3", "type": "EFFECT", "arg1_id": "Caspofungin_ddi_T24", "arg2_id": "Caspofungin_ddi_T25", "normalized": [] }, { "id": "Caspofungin_ddi_R4", "type": "MECHANISM", "arg1_id": "Caspofungin_ddi_T26", "arg2_id": "Caspofungin_ddi_T27", "normalized": [] }, { "id": "Caspofungin_ddi_R5", "type": "ADVISE", "arg1_id": "Caspofungin_ddi_T28", "arg2_id": "Caspofungin_ddi_T29", "normalized": [] }, { "id": "Caspofungin_ddi_R6", "type": "MECHANISM", "arg1_id": "Caspofungin_ddi_T30", "arg2_id": "Caspofungin_ddi_T35", "normalized": [] }, { "id": "Caspofungin_ddi_R7", "type": "MECHANISM", "arg1_id": "Caspofungin_ddi_T31", "arg2_id": "Caspofungin_ddi_T35", "normalized": [] }, { "id": "Caspofungin_ddi_R8", "type": "MECHANISM", "arg1_id": "Caspofungin_ddi_T32", "arg2_id": "Caspofungin_ddi_T35", "normalized": [] }, { "id": "Caspofungin_ddi_R9", "type": "MECHANISM", "arg1_id": "Caspofungin_ddi_T33", "arg2_id": "Caspofungin_ddi_T35", "normalized": [] }, { "id": "Caspofungin_ddi_R10", "type": "MECHANISM", "arg1_id": "Caspofungin_ddi_T34", "arg2_id": "Caspofungin_ddi_T35", "normalized": [] }, { "id": "Caspofungin_ddi_R11", "type": "ADVISE", "arg1_id": "Caspofungin_ddi_T38", "arg2_id": "Caspofungin_ddi_T39", "normalized": [] }, { "id": "Caspofungin_ddi_R12", "type": "ADVISE", "arg1_id": "Caspofungin_ddi_T38", "arg2_id": "Caspofungin_ddi_T40", "normalized": [] }, { "id": "Caspofungin_ddi_R13", "type": "ADVISE", "arg1_id": "Caspofungin_ddi_T38", "arg2_id": "Caspofungin_ddi_T41", "normalized": [] }, { "id": "Caspofungin_ddi_R14", "type": "ADVISE", "arg1_id": "Caspofungin_ddi_T38", "arg2_id": "Caspofungin_ddi_T42", "normalized": [] }, { "id": "Caspofungin_ddi_R15", "type": "ADVISE", "arg1_id": "Caspofungin_ddi_T38", "arg2_id": "Caspofungin_ddi_T43", "normalized": [] } ]

[ { "id": "Dopamine_ddi__text", "type": "abstract", "text": [ "Because dopamine is metabolized by monoamine oxidase (MAO), inhibition of this enzyme prolongs and potentiates the effect of dopamine. Patients who have been treated with MAO inhibitors within two to three weeks prior to the administration of dopamine HCl should receive initial doses of dopamine HCl no greater than one-tenth (1/10) of the usual dose. Concurrent administration of low-dose dopamine HCl and diuretic agents may produce an additive or potentiating effect on urine flow. Tricyclic antidepressants may potentiate the cardiovascular effects of adreneric agents. Cardiac effects of dopamine are antagonized by beta-adrenergic blocking agents, such as propranolol and metoprolol. The peripheral vasoconstriction caused by high doses of dopamine HCl is antagonized by alpha-adrenergic blocking agents. Dopamine-induced renal and mesenteric vasodilation is not antagonized by either alpha- or beta-adrenergic blocking agents. Butyrophenones (such as haloperidol) and phenothiazines can suppress the dopaminergic renal and mesenteric vasodilation induced with low dose dopamine infusion. Cyclopropane or halogenated hydrocarbon anesthetics increase cardiac autonomic irritability and may sensitize the myocardium to the action of certain intravenously administered catecholamines, such as dopamine. This interaction appears to be related both to pressor activity and to beta-adrenergic stimulating properties of these catecholamines and may produce ventricular arrhythmias and hypertension. Therefore, EXTREME CAUTION should be exercised when administering dopamine HCl to patients receiving cyclopropane or halogenated hydrocarbon anesthetics. It has been reported that results of studies in animals indicate that dopamine-induced ventricular arrhythmias during anesthesia can be reversed by propranolol. The concomitant use of vasopressors, vasoconstricting agents (such as ergonovine) and some oxytocic drugs may result in severe hypertension. Administration of phenytoin to patients receiving dopamine HCl has been reported to lead to hypotension and bradycardia. It is suggested that in patients receiving dopamine HCl, alternatives to phenytoin should be used if anticonvulsant therapy is needed." ], "offsets": [ [ 0, 2210 ] ] } ]

[ { "id": "Dopamine_ddi_T1", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 8, 16 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T2", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 125, 133 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T3", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 171, 185 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T4", "type": "DRUG", "text": [ "dopamine HCl" ], "offsets": [ [ 243, 255 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T5", "type": "DRUG", "text": [ "dopamine HCl" ], "offsets": [ [ 288, 300 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T6", "type": "DRUG", "text": [ "dopamine HCl" ], "offsets": [ [ 391, 403 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T7", "type": "GROUP", "text": [ "diuretic agents" ], "offsets": [ [ 408, 423 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T8", "type": "GROUP", "text": [ "Tricyclic antidepressants" ], "offsets": [ [ 486, 511 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T9", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 594, 602 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T10", "type": "GROUP", "text": [ "beta-adrenergic blocking agents" ], "offsets": [ [ 622, 653 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T11", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 663, 674 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T12", "type": "DRUG", "text": [ "metoprolol" ], "offsets": [ [ 679, 689 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T13", "type": "DRUG", "text": [ "dopamine HCl" ], "offsets": [ [ 747, 759 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T14", "type": "GROUP", "text": [ "alpha-adrenergic blocking agents" ], "offsets": [ [ 778, 810 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T15", "type": "DRUG", "text": [ "Dopamine" ], "offsets": [ [ 812, 820 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T16", "type": "GROUP", "text": [ "alpha-", "adrenergic blocking agents" ], "offsets": [ [ 892, 898 ], [ 907, 933 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T17", "type": "DRUG", "text": [ "beta-adrenergic blocking agents" ], "offsets": [ [ 902, 933 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T18", "type": "GROUP", "text": [ "Butyrophenones" ], "offsets": [ [ 935, 949 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T19", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 959, 970 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T20", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 976, 990 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T21", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 1008, 1016 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T22", "type": "DRUG", "text": [ "Cyclopropane" ], "offsets": [ [ 1096, 1108 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T23", "type": "GROUP", "text": [ "halogenated hydrocarbon anesthetics" ], "offsets": [ [ 1112, 1147 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T24", "type": "GROUP", "text": [ "catecholamines" ], "offsets": [ [ 1273, 1287 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T25", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 1297, 1305 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T26", "type": "GROUP", "text": [ "catecholamines" ], "offsets": [ [ 1426, 1440 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T27", "type": "DRUG", "text": [ "dopamine HCl" ], "offsets": [ [ 1565, 1577 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T28", "type": "DRUG", "text": [ "cyclopropane" ], "offsets": [ [ 1600, 1612 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T29", "type": "GROUP", "text": [ "halogenated hydrocarbon anesthetics" ], "offsets": [ [ 1616, 1651 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T30", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 1723, 1731 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T31", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 1801, 1812 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T32", "type": "GROUP", "text": [ "vasopressor" ], "offsets": [ [ 1837, 1848 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T33", "type": "DRUG", "text": [ "ergonovine" ], "offsets": [ [ 1884, 1894 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T34", "type": "GROUP", "text": [ "oxytocic drugs" ], "offsets": [ [ 1905, 1919 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T35", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1973, 1982 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T36", "type": "DRUG", "text": [ "dopamine HCl" ], "offsets": [ [ 2005, 2017 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T37", "type": "DRUG", "text": [ "dopamine HCl" ], "offsets": [ [ 2119, 2131 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T38", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2149, 2158 ] ], "normalized": [] }, { "id": "Dopamine_ddi_T39", "type": "GROUP", "text": [ "anticonvulsant" ], "offsets": [ [ 2177, 2191 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Dopamine_ddi_R1", "type": "ADVISE", "arg1_id": "Dopamine_ddi_T3", "arg2_id": "Dopamine_ddi_T4", "normalized": [] }, { "id": "Dopamine_ddi_R2", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T6", "arg2_id": "Dopamine_ddi_T7", "normalized": [] }, { "id": "Dopamine_ddi_R3", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T9", "arg2_id": "Dopamine_ddi_T10", "normalized": [] }, { "id": "Dopamine_ddi_R4", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T9", "arg2_id": "Dopamine_ddi_T11", "normalized": [] }, { "id": "Dopamine_ddi_R5", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T9", "arg2_id": "Dopamine_ddi_T12", "normalized": [] }, { "id": "Dopamine_ddi_R6", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T13", "arg2_id": "Dopamine_ddi_T14", "normalized": [] }, { "id": "Dopamine_ddi_R7", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T18", "arg2_id": "Dopamine_ddi_T21", "normalized": [] }, { "id": "Dopamine_ddi_R8", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T19", "arg2_id": "Dopamine_ddi_T21", "normalized": [] }, { "id": "Dopamine_ddi_R9", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T20", "arg2_id": "Dopamine_ddi_T21", "normalized": [] }, { "id": "Dopamine_ddi_R10", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T22", "arg2_id": "Dopamine_ddi_T24", "normalized": [] }, { "id": "Dopamine_ddi_R11", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T22", "arg2_id": "Dopamine_ddi_T25", "normalized": [] }, { "id": "Dopamine_ddi_R12", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T23", "arg2_id": "Dopamine_ddi_T24", "normalized": [] }, { "id": "Dopamine_ddi_R13", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T23", "arg2_id": "Dopamine_ddi_T25", "normalized": [] }, { "id": "Dopamine_ddi_R14", "type": "ADVISE", "arg1_id": "Dopamine_ddi_T27", "arg2_id": "Dopamine_ddi_T28", "normalized": [] }, { "id": "Dopamine_ddi_R15", "type": "ADVISE", "arg1_id": "Dopamine_ddi_T27", "arg2_id": "Dopamine_ddi_T29", "normalized": [] }, { "id": "Dopamine_ddi_R16", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T30", "arg2_id": "Dopamine_ddi_T31", "normalized": [] }, { "id": "Dopamine_ddi_R17", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T32", "arg2_id": "Dopamine_ddi_T34", "normalized": [] }, { "id": "Dopamine_ddi_R18", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T33", "arg2_id": "Dopamine_ddi_T34", "normalized": [] }, { "id": "Dopamine_ddi_R19", "type": "EFFECT", "arg1_id": "Dopamine_ddi_T35", "arg2_id": "Dopamine_ddi_T36", "normalized": [] }, { "id": "Dopamine_ddi_R20", "type": "ADVISE", "arg1_id": "Dopamine_ddi_T37", "arg2_id": "Dopamine_ddi_T38", "normalized": [] } ]

[ { "id": "Dexfenfluramine_ddi__text", "type": "abstract", "text": [ "In patients receiving nonselective monoamine oxidase inhibitors (MAOIs) (e.g., selegiline hydrochloride) in combination with serotoninergic agents (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine), there have been reports of serious, sometimes fatal, reactions. Because dexfenfluramine is a serotonin releaser and reuptake inhibitor, dexfenfluramine should not be used concomitantly with a MAO inhibitor. At least 14 days should elapse between discontinuation of a MAO inhibitor and initiation of treatment with dexfenfluramine. At least 3 weeks should elapse between discontinuation of dexfenfluramine and initiation of treatment with a MAO inhibitor. A rare, but serious, constellation of symptoms, termed serotonin syndrome, has been reported with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and agents for migraine therapy, such as Imitrex (sumatriptan succinate) and dihydroergotamine. The syndrome requires immediate medical attention and may include one or more of the following symptoms: excitement, hypomania, restlessness, loss of consciousness, confusion, disorientation, anxiety, agitation, motor weakness, myoclonus, tremor, hemiballismus, hyperreflexia, ataxia, dysarthria, incoordination, hyperthermia, shivering, pupillary dilation, diaphoresis, emesis, and tachycardia. Dexfenfluramine should not be administered with other serotoninergic agents. The appropriate interval between administration of these agents and dexfenfluramine has not been established. The use of dexfenfluramine with other CNS-active drugs has not been systematically evaluated; consequently, caution is advised if dexfenfluramine and such drugs are prescribed concurrently." ], "offsets": [ [ 0, 1709 ] ] } ]

[ { "id": "Dexfenfluramine_ddi_T1", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 35, 63 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T2", "type": "GROUP", "text": [ "MAOIs" ], "offsets": [ [ 65, 70 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T3", "type": "DRUG", "text": [ "selegiline hydrochloride" ], "offsets": [ [ 79, 103 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T4", "type": "GROUP", "text": [ "serotoninergic agents" ], "offsets": [ [ 125, 146 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T5", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 154, 164 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T6", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 166, 177 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T7", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 179, 189 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T8", "type": "DRUG", "text": [ "sertraline" ], "offsets": [ [ 191, 201 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T9", "type": "DRUG", "text": [ "venlafaxine" ], "offsets": [ [ 203, 214 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T10", "type": "DRUG", "text": [ "dexfenfluramine" ], "offsets": [ [ 289, 304 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T11", "type": "DRUG", "text": [ "dexfenfluramine" ], "offsets": [ [ 353, 368 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T12", "type": "GROUP", "text": [ "MAO inhibitor" ], "offsets": [ [ 409, 422 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T13", "type": "GROUP", "text": [ "MAO inhibitor" ], "offsets": [ [ 484, 497 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T14", "type": "DRUG", "text": [ "dexfenfluramine" ], "offsets": [ [ 531, 546 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T15", "type": "DRUG", "text": [ "dexfenfluramine" ], "offsets": [ [ 606, 621 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T16", "type": "GROUP", "text": [ "MAO inhibitor" ], "offsets": [ [ 657, 670 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T17", "type": "GROUP", "text": [ "selective serotonin reuptake inhibitors" ], "offsets": [ [ 793, 832 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T18", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 834, 839 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T19", "type": "BRAND", "text": [ "Imitrex" ], "offsets": [ [ 882, 889 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T20", "type": "DRUG", "text": [ "sumatriptan succinate" ], "offsets": [ [ 891, 912 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T21", "type": "DRUG", "text": [ "dihydroergotamine" ], "offsets": [ [ 918, 935 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T22", "type": "DRUG", "text": [ "Dexfenfluramine" ], "offsets": [ [ 1333, 1348 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T23", "type": "GROUP", "text": [ "serotoninergic agents" ], "offsets": [ [ 1387, 1408 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T24", "type": "DRUG", "text": [ "dexfenfluramine" ], "offsets": [ [ 1478, 1493 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T25", "type": "DRUG", "text": [ "dexfenfluramine" ], "offsets": [ [ 1531, 1546 ] ], "normalized": [] }, { "id": "Dexfenfluramine_ddi_T26", "type": "DRUG", "text": [ "dexfenfluramine" ], "offsets": [ [ 1650, 1665 ] ], "normalized": [] } ]

[]

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[ { "id": "Dexfenfluramine_ddi_R1", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T1", "arg2_id": "Dexfenfluramine_ddi_T4", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R2", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T1", "arg2_id": "Dexfenfluramine_ddi_T5", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R3", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T1", "arg2_id": "Dexfenfluramine_ddi_T6", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R4", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T1", "arg2_id": "Dexfenfluramine_ddi_T7", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R5", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T1", "arg2_id": "Dexfenfluramine_ddi_T8", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R6", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T1", "arg2_id": "Dexfenfluramine_ddi_T9", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R7", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T2", "arg2_id": "Dexfenfluramine_ddi_T4", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R8", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T2", "arg2_id": "Dexfenfluramine_ddi_T5", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R9", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T2", "arg2_id": "Dexfenfluramine_ddi_T6", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R10", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T2", "arg2_id": "Dexfenfluramine_ddi_T7", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R11", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T2", "arg2_id": "Dexfenfluramine_ddi_T8", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R12", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T2", "arg2_id": "Dexfenfluramine_ddi_T9", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R13", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T3", "arg2_id": "Dexfenfluramine_ddi_T4", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R14", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T3", "arg2_id": "Dexfenfluramine_ddi_T5", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R15", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T3", "arg2_id": "Dexfenfluramine_ddi_T6", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R16", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T3", "arg2_id": "Dexfenfluramine_ddi_T7", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R17", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T3", "arg2_id": "Dexfenfluramine_ddi_T8", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R18", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T3", "arg2_id": "Dexfenfluramine_ddi_T9", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R19", "type": "ADVISE", "arg1_id": "Dexfenfluramine_ddi_T11", "arg2_id": "Dexfenfluramine_ddi_T12", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R20", "type": "ADVISE", "arg1_id": "Dexfenfluramine_ddi_T13", "arg2_id": "Dexfenfluramine_ddi_T14", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R21", "type": "ADVISE", "arg1_id": "Dexfenfluramine_ddi_T15", "arg2_id": "Dexfenfluramine_ddi_T16", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R22", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T17", "arg2_id": "Dexfenfluramine_ddi_T19", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R23", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T17", "arg2_id": "Dexfenfluramine_ddi_T20", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R24", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T17", "arg2_id": "Dexfenfluramine_ddi_T21", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R25", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T18", "arg2_id": "Dexfenfluramine_ddi_T19", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R26", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T18", "arg2_id": "Dexfenfluramine_ddi_T20", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R27", "type": "EFFECT", "arg1_id": "Dexfenfluramine_ddi_T18", "arg2_id": "Dexfenfluramine_ddi_T21", "normalized": [] }, { "id": "Dexfenfluramine_ddi_R28", "type": "ADVISE", "arg1_id": "Dexfenfluramine_ddi_T22", "arg2_id": "Dexfenfluramine_ddi_T23", "normalized": [] } ]

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

[]

[]

[]

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[ { "id": "Atomoxetine_ddi__text", "type": "abstract", "text": [ "Drug-Drug Interactions Albuterol - STRATTERA should be administered with caution to patients being treated with systemically-administered (oral or intravenous) albuterol (or other beta2 agonists) because the action of albuterol on the cardiovascular system can be potentiated resulting in increases in heart rate and blood pressure. CYP2D6 inhibitors - Atomoxetine is primarily metabolized by the CYP2D6 pathway to 4-hydroxyatomoxetine. In EMs, selective inhibitors of CYP2D6 increase atomoxetine steady-state plasma concentrations to exposures similar to those observed in PMs. Dosage adjustment of STRATTERA may be necessary when coadministered with CYP2D6 inhibitors, e.g., paroxetine, fluoxetine, and quinidine. In EM individuals treated with paroxetine or fluoxetine, the AUC of atomoxetine is approximately 6- to 8-fold and Css,max is about 3- to 4-fold greater than atomoxetine alone. In vitro studies suggest that coadministration of cytochrome P450 inhibitors to PMs will not increase the plasma concentrations of atomoxetine. Pressor agents - Because of possible effects on blood pressure, STRATTERA should be used cautiously with pressor agents." ], "offsets": [ [ 0, 1156 ] ] } ]

[ { "id": "Atomoxetine_ddi_T1", "type": "DRUG", "text": [ "Albuterol" ], "offsets": [ [ 23, 32 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T2", "type": "BRAND", "text": [ "STRATTERA" ], "offsets": [ [ 35, 44 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T3", "type": "DRUG", "text": [ "albuterol" ], "offsets": [ [ 160, 169 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T4", "type": "GROUP", "text": [ "beta2 agonists" ], "offsets": [ [ 180, 194 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T5", "type": "DRUG", "text": [ "albuterol" ], "offsets": [ [ 218, 227 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T6", "type": "DRUG", "text": [ "Atomoxetine" ], "offsets": [ [ 353, 364 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T7", "type": "DRUG_N", "text": [ "4-hydroxyatomoxetine" ], "offsets": [ [ 415, 435 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T8", "type": "DRUG", "text": [ "atomoxetine" ], "offsets": [ [ 485, 496 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T9", "type": "BRAND", "text": [ "STRATTERA" ], "offsets": [ [ 600, 609 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T10", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 677, 687 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T11", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 689, 699 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T12", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 705, 714 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T13", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 747, 757 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T14", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 761, 771 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T15", "type": "DRUG", "text": [ "atomoxetine" ], "offsets": [ [ 784, 795 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T16", "type": "DRUG", "text": [ "atomoxetine" ], "offsets": [ [ 873, 884 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T17", "type": "DRUG", "text": [ "atomoxetine" ], "offsets": [ [ 1023, 1034 ] ], "normalized": [] }, { "id": "Atomoxetine_ddi_T18", "type": "BRAND", "text": [ "STRATTERA" ], "offsets": [ [ 1100, 1109 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Atomoxetine_ddi_R1", "type": "ADVISE", "arg1_id": "Atomoxetine_ddi_T2", "arg2_id": "Atomoxetine_ddi_T3", "normalized": [] }, { "id": "Atomoxetine_ddi_R2", "type": "ADVISE", "arg1_id": "Atomoxetine_ddi_T9", "arg2_id": "Atomoxetine_ddi_T10", "normalized": [] }, { "id": "Atomoxetine_ddi_R3", "type": "ADVISE", "arg1_id": "Atomoxetine_ddi_T9", "arg2_id": "Atomoxetine_ddi_T11", "normalized": [] }, { "id": "Atomoxetine_ddi_R4", "type": "ADVISE", "arg1_id": "Atomoxetine_ddi_T9", "arg2_id": "Atomoxetine_ddi_T12", "normalized": [] }, { "id": "Atomoxetine_ddi_R5", "type": "MECHANISM", "arg1_id": "Atomoxetine_ddi_T13", "arg2_id": "Atomoxetine_ddi_T15", "normalized": [] }, { "id": "Atomoxetine_ddi_R6", "type": "MECHANISM", "arg1_id": "Atomoxetine_ddi_T14", "arg2_id": "Atomoxetine_ddi_T15", "normalized": [] } ]

[ { "id": "Fludarabine_ddi__text", "type": "abstract", "text": [ "The use of FLUDARA FOR INJECTION in combination with pentostatin is not recommended due to the risk of severe pulmonary toxicity." ], "offsets": [ [ 0, 129 ] ] } ]

[ { "id": "Fludarabine_ddi_T1", "type": "BRAND", "text": [ "FLUDARA" ], "offsets": [ [ 11, 18 ] ], "normalized": [] }, { "id": "Fludarabine_ddi_T2", "type": "DRUG", "text": [ "pentostatin" ], "offsets": [ [ 53, 64 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Fludarabine_ddi_R1", "type": "ADVISE", "arg1_id": "Fludarabine_ddi_T1", "arg2_id": "Fludarabine_ddi_T2", "normalized": [] } ]

[ { "id": "Levobupivacaine_ddi__text", "type": "abstract", "text": [ "Chirocaine should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics since the toxic effects of these drugs could be additive. In vitro studies indicate CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. Thus agents likely to be concomitantly administered with Chirocaine that are metabolized by this isoenzyme family may potentially interact with Chirocaine. Although no clinical studies have been conducted, it is likely that the metabolism of levobupivacaine may be affected by the known CYP3A4 inducers (such as phenytoin, phenobarbital, rifampin), CYP3A4 inhibitors (azole antimycotics e.g., ketoconazole; certain protease inhibitors e.g., ritanovir; macrolide antibiotics e.g., erythromycin; and calcium channel antagonists e.g., verapamil), CYP1A2 inducers (omeprazole) and CYP1A2 inhibitors (furafylline and clarithromycin). Dosage adjustment may be warranted when levobupivacaine is concurrently administered with CYP3A4 inhibitors and CYP1A2 inhibitors as systemic levobupivacaine levels may rise resulting in toxicity." ], "offsets": [ [ 0, 1208 ] ] } ]

[ { "id": "Levobupivacaine_ddi_T1", "type": "BRAND", "text": [ "Chirocaine" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T2", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 75, 86 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T3", "type": "DRUG", "text": [ "levobupivacaine" ], "offsets": [ [ 294, 309 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T4", "type": "DRUG_N", "text": [ "desbutyl levobupivacaine" ], "offsets": [ [ 313, 337 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T5", "type": "DRUG_N", "text": [ "3-hydroxy levobupivacaine" ], "offsets": [ [ 342, 367 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T6", "type": "BRAND", "text": [ "Chirocaine" ], "offsets": [ [ 440, 450 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T7", "type": "BRAND", "text": [ "Chirocaine" ], "offsets": [ [ 527, 537 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T8", "type": "DRUG", "text": [ "levobupivacaine" ], "offsets": [ [ 625, 640 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T9", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 695, 704 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T10", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 706, 719 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T11", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 721, 729 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T12", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 776, 788 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T13", "type": "GROUP", "text": [ "protease inhibitors" ], "offsets": [ [ 798, 817 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T14", "type": "GROUP", "text": [ "macrolide antibiotics" ], "offsets": [ [ 835, 856 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T15", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 863, 875 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T16", "type": "GROUP", "text": [ "calcium channel antagonists" ], "offsets": [ [ 881, 908 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T17", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 915, 924 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T18", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 944, 954 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T19", "type": "DRUG", "text": [ "furafylline" ], "offsets": [ [ 979, 990 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T20", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 995, 1009 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T21", "type": "DRUG", "text": [ "levobupivacaine" ], "offsets": [ [ 1052, 1067 ] ], "normalized": [] }, { "id": "Levobupivacaine_ddi_T22", "type": "DRUG", "text": [ "levobupivacaine" ], "offsets": [ [ 1154, 1169 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Levobupivacaine_ddi_R1", "type": "ADVISE", "arg1_id": "Levobupivacaine_ddi_T1", "arg2_id": "Levobupivacaine_ddi_T2", "normalized": [] }, { "id": "Levobupivacaine_ddi_R2", "type": "MECHANISM", "arg1_id": "Levobupivacaine_ddi_T8", "arg2_id": "Levobupivacaine_ddi_T9", "normalized": [] }, { "id": "Levobupivacaine_ddi_R3", "type": "MECHANISM", "arg1_id": "Levobupivacaine_ddi_T8", "arg2_id": "Levobupivacaine_ddi_T10", "normalized": [] }, { "id": "Levobupivacaine_ddi_R4", "type": "MECHANISM", "arg1_id": "Levobupivacaine_ddi_T8", "arg2_id": "Levobupivacaine_ddi_T11", "normalized": [] }, { "id": "Levobupivacaine_ddi_R5", "type": "MECHANISM", "arg1_id": "Levobupivacaine_ddi_T8", "arg2_id": "Levobupivacaine_ddi_T12", "normalized": [] } ]

[ { "id": "Cortisone acetate_ddi__text", "type": "abstract", "text": [ "The pharmacokinetic interactions listed below are potentially clinically important. Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampin may increase the clearance of corticosteroids and may require increases in corticosteroid dose to achieve the desired response. Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of corticosteroids and thus decrease their clearance. Therefore, the dose of corticosteroid should be titrated to avoid steroid toxicity. Corticosteroids may increase the clearance of chronic high dose aspirin. This could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn. Aspirin should be used cautiously in conjunction with cortico-steroids in patients suffering from hypopro-thrombinemia. The effect of corticosteroids on oral anticoagulants is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids. Therefore, coagulation indices should be monitored to maintain the desired anticoagulant effect." ], "offsets": [ [ 0, 1113 ] ] } ]

[ { "id": "Cortisone acetate_ddi_T1", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 126, 139 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T2", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 141, 150 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T3", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 155, 163 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T4", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 194, 209 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T5", "type": "GROUP", "text": [ "corticosteroid" ], "offsets": [ [ 239, 253 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T6", "type": "DRUG", "text": [ "troleandomycin" ], "offsets": [ [ 306, 320 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T7", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 325, 337 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T8", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 368, 383 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T9", "type": "GROUP", "text": [ "corticosteroid" ], "offsets": [ [ 442, 456 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T10", "type": "GROUP", "text": [ "Corticosteroids" ], "offsets": [ [ 503, 518 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T11", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 567, 574 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T12", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 605, 615 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T13", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 653, 663 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T14", "type": "DRUG", "text": [ "corticosteroid" ], "offsets": [ [ 678, 692 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T15", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 707, 714 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T16", "type": "GROUP", "text": [ "cortico-steroids" ], "offsets": [ [ 761, 777 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T17", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 841, 856 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T18", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 865, 879 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T19", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 956, 970 ] ], "normalized": [] }, { "id": "Cortisone acetate_ddi_T20", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 1000, 1015 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cortisone acetate_ddi_R1", "type": "MECHANISM", "arg1_id": "Cortisone acetate_ddi_T1", "arg2_id": "Cortisone acetate_ddi_T4", "normalized": [] }, { "id": "Cortisone acetate_ddi_R2", "type": "ADVISE", "arg1_id": "Cortisone acetate_ddi_T1", "arg2_id": "Cortisone acetate_ddi_T5", "normalized": [] }, { "id": "Cortisone acetate_ddi_R3", "type": "MECHANISM", "arg1_id": "Cortisone acetate_ddi_T2", "arg2_id": "Cortisone acetate_ddi_T4", "normalized": [] }, { "id": "Cortisone acetate_ddi_R4", "type": "ADVISE", "arg1_id": "Cortisone acetate_ddi_T2", "arg2_id": "Cortisone acetate_ddi_T5", "normalized": [] }, { "id": "Cortisone acetate_ddi_R5", "type": "MECHANISM", "arg1_id": "Cortisone acetate_ddi_T3", "arg2_id": "Cortisone acetate_ddi_T4", "normalized": [] }, { "id": "Cortisone acetate_ddi_R6", "type": "ADVISE", "arg1_id": "Cortisone acetate_ddi_T3", "arg2_id": "Cortisone acetate_ddi_T5", "normalized": [] }, { "id": "Cortisone acetate_ddi_R7", "type": "MECHANISM", "arg1_id": "Cortisone acetate_ddi_T6", "arg2_id": "Cortisone acetate_ddi_T8", "normalized": [] }, { "id": "Cortisone acetate_ddi_R8", "type": "MECHANISM", "arg1_id": "Cortisone acetate_ddi_T7", "arg2_id": "Cortisone acetate_ddi_T8", "normalized": [] }, { "id": "Cortisone acetate_ddi_R9", "type": "EFFECT", "arg1_id": "Cortisone acetate_ddi_T10", "arg2_id": "Cortisone acetate_ddi_T11", "normalized": [] }, { "id": "Cortisone acetate_ddi_R10", "type": "EFFECT", "arg1_id": "Cortisone acetate_ddi_T13", "arg2_id": "Cortisone acetate_ddi_T14", "normalized": [] }, { "id": "Cortisone acetate_ddi_R11", "type": "ADVISE", "arg1_id": "Cortisone acetate_ddi_T15", "arg2_id": "Cortisone acetate_ddi_T16", "normalized": [] }, { "id": "Cortisone acetate_ddi_R12", "type": "EFFECT", "arg1_id": "Cortisone acetate_ddi_T17", "arg2_id": "Cortisone acetate_ddi_T18", "normalized": [] }, { "id": "Cortisone acetate_ddi_R13", "type": "EFFECT", "arg1_id": "Cortisone acetate_ddi_T19", "arg2_id": "Cortisone acetate_ddi_T20", "normalized": [] } ]

[ { "id": "Hydroxyzine_ddi__text", "type": "abstract", "text": [ "THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS SUCH AS NARCOTICS, NON-NARCOTIC ANALGESICS AND BARBITURATES. Therefore when central nervous system depressants are administered concomitantly with hydroxyzine their dosage should be reduced. Since drowsiness may occur with use of this drug, patients should be warned of this possibility and cautioned against driving a car or operating dangerous machinery while taking Atarax. Patients should be advised against the simultaneous use of other CNS depressant drugs, and cautioned that the effect of alcohol may be increased." ], "offsets": [ [ 0, 657 ] ] } ]

[ { "id": "Hydroxyzine_ddi_T1", "type": "DRUG", "text": [ "HYDROXYZINE" ], "offsets": [ [ 27, 38 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T2", "type": "GROUP", "text": [ "CENTRAL NERVOUS SYSTEM DEPRESSANTS" ], "offsets": [ [ 100, 134 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T3", "type": "GROUP", "text": [ "NARCOTICS" ], "offsets": [ [ 143, 152 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T4", "type": "GROUP", "text": [ "NON-NARCOTIC ANALGESICS" ], "offsets": [ [ 154, 177 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T5", "type": "GROUP", "text": [ "BARBITURATES" ], "offsets": [ [ 182, 194 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T6", "type": "GROUP", "text": [ "central nervous system depressants" ], "offsets": [ [ 211, 245 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T7", "type": "DRUG", "text": [ "hydroxyzine" ], "offsets": [ [ 282, 293 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T8", "type": "BRAND", "text": [ "Atarax" ], "offsets": [ [ 504, 510 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T9", "type": "GROUP", "text": [ "CNS depressant drugs" ], "offsets": [ [ 577, 597 ] ], "normalized": [] }, { "id": "Hydroxyzine_ddi_T10", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 632, 639 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Hydroxyzine_ddi_R1", "type": "EFFECT", "arg1_id": "Hydroxyzine_ddi_T1", "arg2_id": "Hydroxyzine_ddi_T2", "normalized": [] }, { "id": "Hydroxyzine_ddi_R2", "type": "EFFECT", "arg1_id": "Hydroxyzine_ddi_T1", "arg2_id": "Hydroxyzine_ddi_T3", "normalized": [] }, { "id": "Hydroxyzine_ddi_R3", "type": "EFFECT", "arg1_id": "Hydroxyzine_ddi_T1", "arg2_id": "Hydroxyzine_ddi_T4", "normalized": [] }, { "id": "Hydroxyzine_ddi_R4", "type": "EFFECT", "arg1_id": "Hydroxyzine_ddi_T1", "arg2_id": "Hydroxyzine_ddi_T5", "normalized": [] }, { "id": "Hydroxyzine_ddi_R5", "type": "ADVISE", "arg1_id": "Hydroxyzine_ddi_T6", "arg2_id": "Hydroxyzine_ddi_T7", "normalized": [] } ]

[ { "id": "Erythromycin_ddi__text", "type": "abstract", "text": [ "Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase in serum theophylline levels and potential theophylline toxicity. In case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy. Concomitant administration of erythromycin and digoxin has been reported to result in elevated digoxin serum levels. There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly. Increased anticoagulation effects due to interactions of erythromycin with various oral anticoagulents may be more pronounced in the elderly. Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia. Erythromycin has been reported to decrease the clearance of triazolam and midazolam and thus may increase the pharmacologic effect of these benzodiazepines. The use of erythromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system may be associated with elevations in serum levels of these other drugs. There have been reports of interactions of erythromycin with carbamazepine, cyclosporine, tacrolimus, hexobarbital, phenytoin, alfentanil, cisapride, disopyramide, lovastatin, bromocriptine, valproate, terfenadine, and astemizole. Serum concentrations of drugs metabolized by the cytochrome P450 system should be monitored closely in patients concurrently receiving erythromycin. Erythromycin has been reported to significantly alter the metabolism of nonsedating antihistamines terfenadine and astemizole when taken concomitantly. Rare cases of serious cardiovascular adverse events, including electrocardiographic QT/QTc interval prolongation, cardiac arrest, torsades de pointes, and other ventricular arrhythmias have been observed. In addition, deaths have been reported rarely with concomitant administration of terfenadine and erythromycin. There have been postmarketing reports of drug interactions when erythromycin is coadministered with cisapride, resulting in QT prolongation, cardiac arrythmias, ventricular tachycardia, ventricular fibrulation, and torsades de pointes, most like due to inhibition of hepatic metabolism of cisapride by erythromycin. Fatalities have been reported. Patients receiving concomitant lovastatin and erythromycin should be carefully monitored; cases of rhabdomyolysis have been reported in seriously ill patients." ], "offsets": [ [ 0, 2623 ] ] } ]

[ { "id": "Erythromycin_ddi_T1", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T2", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 61, 73 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T3", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 118, 130 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T4", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 152, 164 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T5", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 186, 198 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T6", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 230, 242 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T7", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 263, 275 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T8", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 337, 349 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T9", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 389, 401 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T10", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 406, 413 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T11", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 454, 461 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T12", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 540, 552 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T13", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 562, 576 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T14", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 659, 671 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T15", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 762, 774 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T16", "type": "DRUG", "text": [ "ergotamine" ], "offsets": [ [ 779, 789 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T17", "type": "DRUG", "text": [ "dihydroergotamine" ], "offsets": [ [ 793, 810 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T18", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 936, 948 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T19", "type": "DRUG", "text": [ "triazolam" ], "offsets": [ [ 996, 1005 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T20", "type": "DRUG", "text": [ "midazolam" ], "offsets": [ [ 1010, 1019 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T21", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 1076, 1091 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T22", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1104, 1116 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T23", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1312, 1324 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T24", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1330, 1343 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T25", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1345, 1357 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T26", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 1359, 1369 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T27", "type": "DRUG", "text": [ "hexobarbital" ], "offsets": [ [ 1371, 1383 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T28", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1385, 1394 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T29", "type": "DRUG", "text": [ "alfentanil" ], "offsets": [ [ 1396, 1406 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T30", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 1408, 1417 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T31", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 1419, 1431 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T32", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 1433, 1443 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T33", "type": "DRUG", "text": [ "bromocriptine" ], "offsets": [ [ 1445, 1458 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T34", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 1460, 1469 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T35", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 1471, 1482 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T36", "type": "DRUG", "text": [ "astemizole" ], "offsets": [ [ 1488, 1498 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T37", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1635, 1647 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T38", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 1649, 1661 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T39", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 1733, 1747 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T40", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 1748, 1759 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T41", "type": "DRUG", "text": [ "astemizole" ], "offsets": [ [ 1764, 1774 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T42", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 2087, 2098 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T43", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 2103, 2115 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T44", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 2181, 2193 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T45", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 2217, 2226 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T46", "type": "DRUG", "text": [ "cisapride" ], "offsets": [ [ 2406, 2415 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T47", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 2419, 2431 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T48", "type": "DRUG", "text": [ "lovastatin" ], "offsets": [ [ 2495, 2505 ] ], "normalized": [] }, { "id": "Erythromycin_ddi_T49", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 2510, 2522 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Erythromycin_ddi_R1", "type": "EFFECT", "arg1_id": "Erythromycin_ddi_T1", "arg2_id": "Erythromycin_ddi_T2", "normalized": [] }, { "id": "Erythromycin_ddi_R2", "type": "ADVISE", "arg1_id": "Erythromycin_ddi_T7", "arg2_id": "Erythromycin_ddi_T8", "normalized": [] }, { "id": "Erythromycin_ddi_R3", "type": "MECHANISM", "arg1_id": "Erythromycin_ddi_T9", "arg2_id": "Erythromycin_ddi_T10", "normalized": [] }, { "id": "Erythromycin_ddi_R4", "type": "EFFECT", "arg1_id": "Erythromycin_ddi_T12", "arg2_id": "Erythromycin_ddi_T13", "normalized": [] }, { "id": "Erythromycin_ddi_R5", "type": "EFFECT", "arg1_id": "Erythromycin_ddi_T15", "arg2_id": "Erythromycin_ddi_T16", "normalized": [] }, { "id": "Erythromycin_ddi_R6", "type": "EFFECT", "arg1_id": "Erythromycin_ddi_T15", "arg2_id": "Erythromycin_ddi_T17", "normalized": [] }, { "id": "Erythromycin_ddi_R7", "type": "MECHANISM", "arg1_id": "Erythromycin_ddi_T18", "arg2_id": "Erythromycin_ddi_T19", "normalized": [] }, { "id": "Erythromycin_ddi_R8", "type": "MECHANISM", "arg1_id": "Erythromycin_ddi_T18", "arg2_id": "Erythromycin_ddi_T20", "normalized": [] }, { "id": "Erythromycin_ddi_R9", "type": "EFFECT", "arg1_id": "Erythromycin_ddi_T18", "arg2_id": "Erythromycin_ddi_T21", "normalized": [] }, { "id": "Erythromycin_ddi_R10", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T24", "normalized": [] }, { "id": "Erythromycin_ddi_R11", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T25", "normalized": [] }, { "id": "Erythromycin_ddi_R12", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T26", "normalized": [] }, { "id": "Erythromycin_ddi_R13", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T27", "normalized": [] }, { "id": "Erythromycin_ddi_R14", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T28", "normalized": [] }, { "id": "Erythromycin_ddi_R15", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T29", "normalized": [] }, { "id": "Erythromycin_ddi_R16", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T30", "normalized": [] }, { "id": "Erythromycin_ddi_R17", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T31", "normalized": [] }, { "id": "Erythromycin_ddi_R18", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T32", "normalized": [] }, { "id": "Erythromycin_ddi_R19", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T33", "normalized": [] }, { "id": "Erythromycin_ddi_R20", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T34", "normalized": [] }, { "id": "Erythromycin_ddi_R21", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T35", "normalized": [] }, { "id": "Erythromycin_ddi_R22", "type": "INT", "arg1_id": "Erythromycin_ddi_T23", "arg2_id": "Erythromycin_ddi_T36", "normalized": [] }, { "id": "Erythromycin_ddi_R23", "type": "MECHANISM", "arg1_id": "Erythromycin_ddi_T38", "arg2_id": "Erythromycin_ddi_T40", "normalized": [] }, { "id": "Erythromycin_ddi_R24", "type": "MECHANISM", "arg1_id": "Erythromycin_ddi_T38", "arg2_id": "Erythromycin_ddi_T41", "normalized": [] }, { "id": "Erythromycin_ddi_R25", "type": "EFFECT", "arg1_id": "Erythromycin_ddi_T42", "arg2_id": "Erythromycin_ddi_T43", "normalized": [] }, { "id": "Erythromycin_ddi_R26", "type": "EFFECT", "arg1_id": "Erythromycin_ddi_T44", "arg2_id": "Erythromycin_ddi_T45", "normalized": [] }, { "id": "Erythromycin_ddi_R27", "type": "MECHANISM", "arg1_id": "Erythromycin_ddi_T46", "arg2_id": "Erythromycin_ddi_T47", "normalized": [] }, { "id": "Erythromycin_ddi_R28", "type": "ADVISE", "arg1_id": "Erythromycin_ddi_T48", "arg2_id": "Erythromycin_ddi_T49", "normalized": [] } ]

[ { "id": "Astemizole_ddi__text", "type": "abstract", "text": [ "Ketoconazole/Itraconazole, Macrolides, Including Erythromycin" ], "offsets": [ [ 0, 61 ] ] } ]

[ { "id": "Astemizole_ddi_T1", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Astemizole_ddi_T2", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 13, 25 ] ], "normalized": [] }, { "id": "Astemizole_ddi_T3", "type": "GROUP", "text": [ "Macrolides" ], "offsets": [ [ 27, 37 ] ], "normalized": [] }, { "id": "Astemizole_ddi_T4", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 49, 61 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "L-Lysine_ddi__text", "type": "abstract", "text": [ "Concomitant use of calcium supplements and L-lysine may increase calcium absorption" ], "offsets": [ [ 0, 83 ] ] } ]

[ { "id": "L-Lysine_ddi_T1", "type": "DRUG", "text": [ "calcium" ], "offsets": [ [ 19, 26 ] ], "normalized": [] }, { "id": "L-Lysine_ddi_T2", "type": "DRUG", "text": [ "L-lysine" ], "offsets": [ [ 43, 51 ] ], "normalized": [] }, { "id": "L-Lysine_ddi_T3", "type": "DRUG", "text": [ "calcium" ], "offsets": [ [ 65, 72 ] ], "normalized": [] } ]

[]

[]

[ { "id": "L-Lysine_ddi_R1", "type": "MECHANISM", "arg1_id": "L-Lysine_ddi_T1", "arg2_id": "L-Lysine_ddi_T2", "normalized": [] } ]

[ { "id": "Griseofulvin_ddi__text", "type": "abstract", "text": [ "Patients on warfarin-type anticoagulant therapy may require dosage adjustment of the anticoagulant during and after griseofulvin therapy. Concomitant use of barbiturates usually depresses griseofulvin activity and may necessitate raising the dosage. The concomitant administration of griseofulvin has been reported to reduce the efficacy of oral contraceptives and to increase the incidence of breakthrough bleeding." ], "offsets": [ [ 0, 416 ] ] } ]

[ { "id": "Griseofulvin_ddi_T1", "type": "GROUP", "text": [ "warfarin-type anticoagulant" ], "offsets": [ [ 12, 39 ] ], "normalized": [] }, { "id": "Griseofulvin_ddi_T2", "type": "DRUG", "text": [ "griseofulvin" ], "offsets": [ [ 116, 128 ] ], "normalized": [] }, { "id": "Griseofulvin_ddi_T3", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 157, 169 ] ], "normalized": [] }, { "id": "Griseofulvin_ddi_T4", "type": "DRUG", "text": [ "griseofulvin" ], "offsets": [ [ 188, 200 ] ], "normalized": [] }, { "id": "Griseofulvin_ddi_T5", "type": "DRUG", "text": [ "griseofulvin" ], "offsets": [ [ 284, 296 ] ], "normalized": [] }, { "id": "Griseofulvin_ddi_T6", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 346, 360 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Griseofulvin_ddi_R1", "type": "ADVISE", "arg1_id": "Griseofulvin_ddi_T1", "arg2_id": "Griseofulvin_ddi_T2", "normalized": [] }, { "id": "Griseofulvin_ddi_R2", "type": "EFFECT", "arg1_id": "Griseofulvin_ddi_T3", "arg2_id": "Griseofulvin_ddi_T4", "normalized": [] }, { "id": "Griseofulvin_ddi_R3", "type": "EFFECT", "arg1_id": "Griseofulvin_ddi_T5", "arg2_id": "Griseofulvin_ddi_T6", "normalized": [] } ]

[ { "id": "Fosfomycin_ddi__text", "type": "abstract", "text": [ "Metoclopramide: When coadministered with MONUROL, metoclopramide, a drug which increases gastrointestinal motility, lowers the serum concentration and urinary excretion of fosfomycin. Other drugs that increase gastrointestinal motility may produce similar effects. Cimetidine: Cimetidine does not affect the pharmacokinetics of fosfomycin when coadministered with MONUROL." ], "offsets": [ [ 0, 372 ] ] } ]

[ { "id": "Fosfomycin_ddi_T1", "type": "DRUG", "text": [ "Metoclopramide" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "Fosfomycin_ddi_T2", "type": "BRAND", "text": [ "MONUROL" ], "offsets": [ [ 41, 48 ] ], "normalized": [] }, { "id": "Fosfomycin_ddi_T3", "type": "DRUG", "text": [ "metoclopramide" ], "offsets": [ [ 50, 64 ] ], "normalized": [] }, { "id": "Fosfomycin_ddi_T4", "type": "DRUG", "text": [ "fosfomycin" ], "offsets": [ [ 172, 182 ] ], "normalized": [] }, { "id": "Fosfomycin_ddi_T5", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 265, 275 ] ], "normalized": [] }, { "id": "Fosfomycin_ddi_T6", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 277, 287 ] ], "normalized": [] }, { "id": "Fosfomycin_ddi_T7", "type": "DRUG", "text": [ "fosfomycin" ], "offsets": [ [ 328, 338 ] ], "normalized": [] }, { "id": "Fosfomycin_ddi_T8", "type": "BRAND", "text": [ "MONUROL" ], "offsets": [ [ 364, 371 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Fosfomycin_ddi_R1", "type": "MECHANISM", "arg1_id": "Fosfomycin_ddi_T2", "arg2_id": "Fosfomycin_ddi_T3", "normalized": [] } ]

[ { "id": "Adalimumab_ddi__text", "type": "abstract", "text": [ "Methotrexate: HUMIRA has been studied in rheumatoid arthritis patients taking concomitant MTX. The data do not suggest the need for dose adjustment of either HUMIRA or MTX. Anakinra: Concurrent administration of anakinra (an interleukin-1 antagonist) and another TNF-blocking agent has been associated with an increased risk of serious infections, an increased risk of neutropenia and no additional benefit compared to these medicinal products alone. The safety and efficacy of anakinra used in combination with HUMIRA has not been studied. Therefore the, combination of anakinra with other TNF-blocking agents, including HUMIRA, may also result i n similar toxicities." ], "offsets": [ [ 0, 669 ] ] } ]

[ { "id": "Adalimumab_ddi_T1", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T2", "type": "BRAND", "text": [ "HUMIRA" ], "offsets": [ [ 14, 20 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T3", "type": "DRUG", "text": [ "MTX" ], "offsets": [ [ 90, 93 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T4", "type": "BRAND", "text": [ "HUMIRA" ], "offsets": [ [ 158, 164 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T5", "type": "DRUG", "text": [ "MTX" ], "offsets": [ [ 168, 171 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T6", "type": "DRUG", "text": [ "Anakinra" ], "offsets": [ [ 173, 181 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T7", "type": "DRUG", "text": [ "anakinra" ], "offsets": [ [ 212, 220 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T8", "type": "GROUP", "text": [ "interleukin-1 antagonist" ], "offsets": [ [ 225, 249 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T9", "type": "GROUP", "text": [ "TNF-blocking agent" ], "offsets": [ [ 263, 281 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T10", "type": "DRUG", "text": [ "anakinra" ], "offsets": [ [ 478, 486 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T11", "type": "BRAND", "text": [ "HUMIRA" ], "offsets": [ [ 512, 518 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T12", "type": "DRUG", "text": [ "anakinra" ], "offsets": [ [ 571, 579 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T13", "type": "GROUP", "text": [ "TNF-blocking agents" ], "offsets": [ [ 591, 610 ] ], "normalized": [] }, { "id": "Adalimumab_ddi_T14", "type": "BRAND", "text": [ "HUMIRA" ], "offsets": [ [ 622, 628 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Adalimumab_ddi_R1", "type": "EFFECT", "arg1_id": "Adalimumab_ddi_T7", "arg2_id": "Adalimumab_ddi_T9", "normalized": [] }, { "id": "Adalimumab_ddi_R2", "type": "EFFECT", "arg1_id": "Adalimumab_ddi_T8", "arg2_id": "Adalimumab_ddi_T9", "normalized": [] }, { "id": "Adalimumab_ddi_R3", "type": "EFFECT", "arg1_id": "Adalimumab_ddi_T12", "arg2_id": "Adalimumab_ddi_T13", "normalized": [] }, { "id": "Adalimumab_ddi_R4", "type": "EFFECT", "arg1_id": "Adalimumab_ddi_T12", "arg2_id": "Adalimumab_ddi_T14", "normalized": [] } ]

[ { "id": "Ethoxzolamide_ddi__text", "type": "abstract", "text": [ "Ethoxzolamide may increase the action of tricyclics, amphetamines, procainamide, and quinidine. It may increase excretion of barbiturates, lithium, and ASA and may also increase the toxicity of salicylates. Coadministration of ethoxzolamide with other diuretics, amphotericin B, and corticosteroids may cause hypokalemia." ], "offsets": [ [ 0, 321 ] ] } ]

[ { "id": "Ethoxzolamide_ddi_T1", "type": "DRUG", "text": [ "Ethoxzolamide" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T2", "type": "GROUP", "text": [ "tricyclics" ], "offsets": [ [ 41, 51 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T3", "type": "GROUP", "text": [ "amphetamines" ], "offsets": [ [ 53, 65 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T4", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 67, 79 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T5", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 85, 94 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T6", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 125, 137 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T7", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 139, 146 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T8", "type": "DRUG", "text": [ "ASA" ], "offsets": [ [ 152, 155 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T9", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 194, 205 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T10", "type": "DRUG", "text": [ "ethoxzolamide" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T11", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 252, 261 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T12", "type": "DRUG", "text": [ "amphotericin B" ], "offsets": [ [ 263, 277 ] ], "normalized": [] }, { "id": "Ethoxzolamide_ddi_T13", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 283, 298 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ethoxzolamide_ddi_R1", "type": "EFFECT", "arg1_id": "Ethoxzolamide_ddi_T1", "arg2_id": "Ethoxzolamide_ddi_T2", "normalized": [] }, { "id": "Ethoxzolamide_ddi_R2", "type": "EFFECT", "arg1_id": "Ethoxzolamide_ddi_T1", "arg2_id": "Ethoxzolamide_ddi_T3", "normalized": [] }, { "id": "Ethoxzolamide_ddi_R3", "type": "EFFECT", "arg1_id": "Ethoxzolamide_ddi_T1", "arg2_id": "Ethoxzolamide_ddi_T4", "normalized": [] }, { "id": "Ethoxzolamide_ddi_R4", "type": "EFFECT", "arg1_id": "Ethoxzolamide_ddi_T1", "arg2_id": "Ethoxzolamide_ddi_T5", "normalized": [] }, { "id": "Ethoxzolamide_ddi_R5", "type": "EFFECT", "arg1_id": "Ethoxzolamide_ddi_T10", "arg2_id": "Ethoxzolamide_ddi_T11", "normalized": [] }, { "id": "Ethoxzolamide_ddi_R6", "type": "EFFECT", "arg1_id": "Ethoxzolamide_ddi_T10", "arg2_id": "Ethoxzolamide_ddi_T12", "normalized": [] }, { "id": "Ethoxzolamide_ddi_R7", "type": "EFFECT", "arg1_id": "Ethoxzolamide_ddi_T10", "arg2_id": "Ethoxzolamide_ddi_T13", "normalized": [] } ]

[ { "id": "Imatinib_ddi__text", "type": "abstract", "text": [ "Drugs that may alter imatinib plasma concentrations Drugs that may increase imatinib plasma concentrations: Caution is recommended when administering Gleevec with inhibitors of the CYP3A4 family (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin). Substances that inhibit the cytochrome P450 isoenzyme (CYP3A4) activity may decrease metabolism and increase imatinib concentrations. There is a significant increase in exposure to imatinib when Gleevec is coadministered with ketoconazole (CYP3A4 inhibitor). Drugs that may decrease imatinib plasma concentrations: Substances that are inducers of CYP3A4 activity may increase metabolism and decrease imatinib plasma concentrations. Co-medications that induce CYP3A4 (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital or St. Johns Wort) may significantly reduce exposure to Gleevec. Pretreatment of healthy volunteers with multiple doses of rifampin followed by a single dose of Gleevec, increased Gleevec oral-dose clearance by 3.8-fold, which significantly (p 0.05) decreased mean cmax and AUC(0-8). In patients where rifampin or other CYP3A4 inducers are indicated, alternative therapeutic agents with less enzyme induction potential should be considered. Drugs that may have their plasma concentration altered by Gleevec Gleevec increases the mean cmax and AUC of simvastatin (CYP3A4 substrate) 2- and 3.5-fold, respectively, suggesting an inhibition of the CYP3A4 by Gleevec. Particular caution is recommended when administering Gleevec with CYP3A4 substrates that have a narrow therapeutic window (e.g., cyclosporine or pimozide). Gleevec will increase plasmaconcentration of other CYP3A4 metabolized drugs (e.g., triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.). Because warfarin is metabolized by CYP2C9 and CYP3A4, patients who require anticoagulation should receive low-molecular weight or standard heparin. in vitro, Gleevec inhibits the cytochrome P450 isoenzyme CYP2D6 activity at similar concentrations that affect CYP3A4 activity. Systemic exposure to substrates of CYP2D6 is expected to be increased when coadministered with Gleevec. No specific studies have been performed and caution is recommended. in vitro, Gleevec inhibits acetaminophen O-glucuronidation (Ki value of 58.5 M) at therapeutic levels. Systemic exposure to acetaminophen is expected to be increased when coadministered with Gleevec. No specific studies in humans have been performed and caution is recommended." ], "offsets": [ [ 0, 2540 ] ] } ]

[ { "id": "Imatinib_ddi_T1", "type": "DRUG", "text": [ "imatinib" ], "offsets": [ [ 21, 29 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T2", "type": "DRUG", "text": [ "imatinib" ], "offsets": [ [ 76, 84 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T3", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 150, 157 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T4", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 202, 214 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T5", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 216, 228 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T6", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 230, 242 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T7", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 244, 258 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T8", "type": "DRUG", "text": [ "imatinib" ], "offsets": [ [ 370, 378 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T9", "type": "DRUG", "text": [ "imatinib" ], "offsets": [ [ 442, 450 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T10", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 456, 463 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T11", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 487, 499 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T12", "type": "DRUG", "text": [ "imatinib" ], "offsets": [ [ 544, 552 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T13", "type": "DRUG", "text": [ "imatinib" ], "offsets": [ [ 661, 669 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T14", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 734, 747 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T15", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 749, 758 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T16", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 760, 773 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T17", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 775, 783 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T18", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 785, 798 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T19", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 855, 862 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T20", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 922, 930 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T21", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 960, 967 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T22", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 979, 986 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T23", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 1101, 1109 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T24", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 1298, 1305 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T25", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 1306, 1313 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T26", "type": "DRUG", "text": [ "simvastatin" ], "offsets": [ [ 1349, 1360 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T27", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 1453, 1460 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T28", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 1515, 1522 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T29", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 1591, 1603 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T30", "type": "DRUG", "text": [ "pimozide" ], "offsets": [ [ 1607, 1615 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T31", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 1618, 1625 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T32", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 1710, 1725 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T33", "type": "GROUP", "text": [ "dihydropyridine calcium channel blockers" ], "offsets": [ [ 1727, 1767 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T34", "type": "GROUP", "text": [ "HMG-CoA reductase inhibitors" ], "offsets": [ [ 1777, 1805 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T35", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1822, 1830 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T36", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 1953, 1960 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T37", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 1972, 1979 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T38", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 2272, 2279 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T39", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 2387, 2400 ] ], "normalized": [] }, { "id": "Imatinib_ddi_T40", "type": "BRAND", "text": [ "Gleevec" ], "offsets": [ [ 2454, 2461 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Imatinib_ddi_R1", "type": "ADVISE", "arg1_id": "Imatinib_ddi_T3", "arg2_id": "Imatinib_ddi_T4", "normalized": [] }, { "id": "Imatinib_ddi_R2", "type": "ADVISE", "arg1_id": "Imatinib_ddi_T3", "arg2_id": "Imatinib_ddi_T5", "normalized": [] }, { "id": "Imatinib_ddi_R3", "type": "ADVISE", "arg1_id": "Imatinib_ddi_T3", "arg2_id": "Imatinib_ddi_T6", "normalized": [] }, { "id": "Imatinib_ddi_R4", "type": "ADVISE", "arg1_id": "Imatinib_ddi_T3", "arg2_id": "Imatinib_ddi_T7", "normalized": [] }, { "id": "Imatinib_ddi_R5", "type": "MECHANISM", "arg1_id": "Imatinib_ddi_T10", "arg2_id": "Imatinib_ddi_T11", "normalized": [] }, { "id": "Imatinib_ddi_R6", "type": "MECHANISM", "arg1_id": "Imatinib_ddi_T20", "arg2_id": "Imatinib_ddi_T21", "normalized": [] }, { "id": "Imatinib_ddi_R7", "type": "MECHANISM", "arg1_id": "Imatinib_ddi_T25", "arg2_id": "Imatinib_ddi_T26", "normalized": [] }, { "id": "Imatinib_ddi_R8", "type": "ADVISE", "arg1_id": "Imatinib_ddi_T28", "arg2_id": "Imatinib_ddi_T29", "normalized": [] }, { "id": "Imatinib_ddi_R9", "type": "ADVISE", "arg1_id": "Imatinib_ddi_T28", "arg2_id": "Imatinib_ddi_T30", "normalized": [] }, { "id": "Imatinib_ddi_R10", "type": "MECHANISM", "arg1_id": "Imatinib_ddi_T31", "arg2_id": "Imatinib_ddi_T32", "normalized": [] }, { "id": "Imatinib_ddi_R11", "type": "MECHANISM", "arg1_id": "Imatinib_ddi_T31", "arg2_id": "Imatinib_ddi_T33", "normalized": [] }, { "id": "Imatinib_ddi_R12", "type": "MECHANISM", "arg1_id": "Imatinib_ddi_T31", "arg2_id": "Imatinib_ddi_T34", "normalized": [] }, { "id": "Imatinib_ddi_R13", "type": "MECHANISM", "arg1_id": "Imatinib_ddi_T39", "arg2_id": "Imatinib_ddi_T40", "normalized": [] } ]

[ { "id": "Alendronate_ddi__text", "type": "abstract", "text": [ "Intravenous ranitidine was shown to double the bioavailability of oral alendronate. The clinical significance of this increased bioavailability and whether similar increases will occur in patients given oral H2-antagonists is unknown; no other specific drug interaction studies were performed. Products containing calcium and other multivalent cations likely will interfere with absorption of alendronate." ], "offsets": [ [ 0, 405 ] ] } ]

[ { "id": "Alendronate_ddi_T1", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 12, 22 ] ], "normalized": [] }, { "id": "Alendronate_ddi_T2", "type": "DRUG", "text": [ "alendronate" ], "offsets": [ [ 71, 82 ] ], "normalized": [] }, { "id": "Alendronate_ddi_T3", "type": "GROUP", "text": [ "H2-antagonists" ], "offsets": [ [ 208, 222 ] ], "normalized": [] }, { "id": "Alendronate_ddi_T4", "type": "DRUG", "text": [ "calcium" ], "offsets": [ [ 314, 321 ] ], "normalized": [] }, { "id": "Alendronate_ddi_T5", "type": "DRUG", "text": [ "multivalent cations" ], "offsets": [ [ 332, 351 ] ], "normalized": [] }, { "id": "Alendronate_ddi_T6", "type": "DRUG", "text": [ "alendronate" ], "offsets": [ [ 393, 404 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Alendronate_ddi_R1", "type": "MECHANISM", "arg1_id": "Alendronate_ddi_T1", "arg2_id": "Alendronate_ddi_T2", "normalized": [] }, { "id": "Alendronate_ddi_R2", "type": "MECHANISM", "arg1_id": "Alendronate_ddi_T4", "arg2_id": "Alendronate_ddi_T6", "normalized": [] }, { "id": "Alendronate_ddi_R3", "type": "MECHANISM", "arg1_id": "Alendronate_ddi_T5", "arg2_id": "Alendronate_ddi_T6", "normalized": [] } ]

[ { "id": "Cladribine_ddi__text", "type": "abstract", "text": [ "There are no known drug interactions with LEUSTATIN Injection. Caution should be exercised if LEUSTATIN Injection is administered before, after, or in conjunction with other drugs known to cause immunosuppression or myelosuppression." ], "offsets": [ [ 0, 233 ] ] } ]

[ { "id": "Cladribine_ddi_T1", "type": "BRAND", "text": [ "LEUSTATIN" ], "offsets": [ [ 42, 51 ] ], "normalized": [] }, { "id": "Cladribine_ddi_T2", "type": "BRAND", "text": [ "LEUSTATIN" ], "offsets": [ [ 94, 103 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "Ketoprofen_ddi__text", "type": "abstract", "text": [ "The following drug interactions were studied with ketoprofen doses of 200 mg/day. The possibility of increased interaction should be kept in mind when Orudis doses greater than 50 mg as a single dose or 200 mg of ketoprofen per day are used concomitantly with highly bound drugs. 1. Antacids: Concomitant administration of magnesium hydroxide and aluminum hydroxide does not interfere with the rate or extent of the absorption of ketoprofen administered as Orudis. 2. Aspirin: Ketoprofen does not alter aspirin absorption; however, in a study of 12 normal subjects, concurrent administration of aspirin decreased ketoprofen protein binding and increased ketoprofen plasma clearance from 0.07 L/kg/h without aspirin to 0.11 L/kg/h with aspirin. The clinical significance of these changes has not been adequately studied. Therefore, concurrent use of aspirin and ketoprofen is not recommended. 3. Diuretic: Hydrochlorothiazide, given concomitantly with ketoprofen, produces a reduction in urinary potassium and chloride excretion compared to hydrochlorothiazide alone. Patients taking diuretics are at a greater risk of developing renal failure secondary to a decrease in renal blood flow caused by prostaglandin inhibition. 4. Digoxin: In a study in 12 patients with congestive heart failure where ketoprofen and digoxin were concomitantly administered, ketoprofen did not alter the serum levels of digoxin. 5. Warfarin: In a short-term controlled study in 14 normal volunteers, ketoprofen did not significantly interfere with the effect of warfarin on prothrombin time. Bleeding from a number of sites may be a complication of warfarin treatment and GI bleeding a complication of ketoprofen treatment. Because prostaglandina play an important role in hemostasis and ketoprofen has an effect on platelet function as well, concurent therapy with ketoprofen and warfarin requires close monitoring of patients on both drugs. 6. Probenecid: Probenecid increases both free and bound ketoprofen by reducing the plasma clearance of ketoprofen to about one-third, as well as decreasing its protein binding. Therefore, the combination of ketoprofen and probenecid is not recommended. 7. Methotrexate: Ketoprofen, like other NSAIDs, may cause changes in the elimination of methotrexate leading to elevated serum levels of the drug and increased toxicity. 8. Lithium: Nonsteroidal anti-inflammatory agents have been reported to increase steadystate plasma lithium levels. It is recommended that plasma lithium levels be monitored when ketoprofen is coadministered with lithium. DRUG/LABORATORY TEST INTERACTIONS: EFFECT ON BLOOD COAGULATION Ketoprofen decreases platelet adhesion and aggregation. Therefore, it can prolong bleeding time by approximately 3 to 4 minutes from baseline values. There is no significant change in platelet count, prothrombin time, partial thromboplastin time, or thrombin time." ], "offsets": [ [ 0, 2893 ] ] } ]

[ { "id": "Ketoprofen_ddi_T1", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 50, 60 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T2", "type": "BRAND", "text": [ "Orudis" ], "offsets": [ [ 151, 157 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T3", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 213, 223 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T4", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 283, 291 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T5", "type": "DRUG", "text": [ "magnesium hydroxide" ], "offsets": [ [ 323, 342 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T6", "type": "DRUG", "text": [ "aluminum hydroxide" ], "offsets": [ [ 347, 365 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T7", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 430, 440 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T8", "type": "BRAND", "text": [ "Orudis" ], "offsets": [ [ 457, 463 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T9", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 468, 475 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T10", "type": "DRUG", "text": [ "Ketoprofen" ], "offsets": [ [ 477, 487 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T11", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 503, 510 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T12", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 595, 602 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T13", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 613, 623 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T14", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 654, 664 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T15", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 707, 714 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T16", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 735, 742 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T17", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 849, 856 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T18", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 861, 871 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T19", "type": "GROUP", "text": [ "Diuretic" ], "offsets": [ [ 895, 903 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T20", "type": "DRUG", "text": [ "Hydrochlorothiazide" ], "offsets": [ [ 905, 924 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T21", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 951, 961 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T22", "type": "DRUG", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 1040, 1059 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T23", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 1083, 1092 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T24", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 1226, 1233 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T25", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 1297, 1307 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T26", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1312, 1319 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T27", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 1353, 1363 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T28", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1398, 1405 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T29", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 1410, 1418 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T30", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 1478, 1488 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T31", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1540, 1548 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T32", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1627, 1635 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T33", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 1680, 1690 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T34", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 1766, 1776 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T35", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 1844, 1854 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T36", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1859, 1867 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T37", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 1924, 1934 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T38", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 1936, 1946 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T39", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 1977, 1987 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T40", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 2024, 2034 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T41", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 2128, 2138 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T42", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 2143, 2153 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T43", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 2177, 2189 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T44", "type": "DRUG", "text": [ "Ketoprofen" ], "offsets": [ [ 2191, 2201 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T45", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2214, 2220 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T46", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2262, 2274 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T47", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 2347, 2354 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T48", "type": "GROUP", "text": [ "Nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 2356, 2393 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T49", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2444, 2451 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T50", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2490, 2497 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T51", "type": "DRUG", "text": [ "ketoprofen" ], "offsets": [ [ 2523, 2533 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T52", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2557, 2564 ] ], "normalized": [] }, { "id": "Ketoprofen_ddi_T53", "type": "DRUG", "text": [ "Ketoprofen" ], "offsets": [ [ 2629, 2639 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ketoprofen_ddi_R1", "type": "MECHANISM", "arg1_id": "Ketoprofen_ddi_T12", "arg2_id": "Ketoprofen_ddi_T13", "normalized": [] }, { "id": "Ketoprofen_ddi_R2", "type": "MECHANISM", "arg1_id": "Ketoprofen_ddi_T12", "arg2_id": "Ketoprofen_ddi_T14", "normalized": [] }, { "id": "Ketoprofen_ddi_R3", "type": "ADVISE", "arg1_id": "Ketoprofen_ddi_T17", "arg2_id": "Ketoprofen_ddi_T18", "normalized": [] }, { "id": "Ketoprofen_ddi_R4", "type": "EFFECT", "arg1_id": "Ketoprofen_ddi_T20", "arg2_id": "Ketoprofen_ddi_T21", "normalized": [] }, { "id": "Ketoprofen_ddi_R5", "type": "ADVISE", "arg1_id": "Ketoprofen_ddi_T35", "arg2_id": "Ketoprofen_ddi_T36", "normalized": [] }, { "id": "Ketoprofen_ddi_R6", "type": "MECHANISM", "arg1_id": "Ketoprofen_ddi_T38", "arg2_id": "Ketoprofen_ddi_T39", "normalized": [] }, { "id": "Ketoprofen_ddi_R7", "type": "ADVISE", "arg1_id": "Ketoprofen_ddi_T41", "arg2_id": "Ketoprofen_ddi_T42", "normalized": [] }, { "id": "Ketoprofen_ddi_R8", "type": "MECHANISM", "arg1_id": "Ketoprofen_ddi_T44", "arg2_id": "Ketoprofen_ddi_T46", "normalized": [] }, { "id": "Ketoprofen_ddi_R9", "type": "MECHANISM", "arg1_id": "Ketoprofen_ddi_T45", "arg2_id": "Ketoprofen_ddi_T46", "normalized": [] }, { "id": "Ketoprofen_ddi_R10", "type": "MECHANISM", "arg1_id": "Ketoprofen_ddi_T48", "arg2_id": "Ketoprofen_ddi_T49", "normalized": [] }, { "id": "Ketoprofen_ddi_R11", "type": "ADVISE", "arg1_id": "Ketoprofen_ddi_T51", "arg2_id": "Ketoprofen_ddi_T52", "normalized": [] } ]

[ { "id": "Bromocriptine_ddi__text", "type": "abstract", "text": [ "The risk of using bromocriptine mesylate in combination with other drugs has not been systematically evaluated, but alcohol may potentiate the side effects of bromocriptine mesylate. Bromocriptine mesylate may interact with dopamine antagonists, butyrophenones, and certain other agents. Compounds in these categories result in a decreased efficacy of bromocriptine mesylate: phenothiazines, haloperidol, metoclopramide, pimozide. Concomitant use of bromocriptine mesylate with other ergot alkaloids is not recommended." ], "offsets": [ [ 0, 519 ] ] } ]

[ { "id": "Bromocriptine_ddi_T1", "type": "DRUG", "text": [ "bromocriptine mesylate" ], "offsets": [ [ 18, 40 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 116, 123 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T3", "type": "DRUG", "text": [ "bromocriptine mesylate" ], "offsets": [ [ 159, 181 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T4", "type": "DRUG", "text": [ "Bromocriptine mesylate" ], "offsets": [ [ 183, 205 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T5", "type": "GROUP", "text": [ "dopamine antagonists" ], "offsets": [ [ 224, 244 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T6", "type": "GROUP", "text": [ "butyrophenones" ], "offsets": [ [ 246, 260 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T7", "type": "DRUG", "text": [ "bromocriptine mesylate" ], "offsets": [ [ 352, 374 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T8", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 376, 390 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T9", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 392, 403 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T10", "type": "DRUG", "text": [ "metoclopramide" ], "offsets": [ [ 405, 419 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T11", "type": "DRUG", "text": [ "pimozide" ], "offsets": [ [ 421, 429 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T12", "type": "DRUG", "text": [ "bromocriptine mesylate" ], "offsets": [ [ 450, 472 ] ], "normalized": [] }, { "id": "Bromocriptine_ddi_T13", "type": "GROUP", "text": [ "ergot alkaloids" ], "offsets": [ [ 484, 499 ] ], "normalized": [] } ]

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[ { "id": "Bromocriptine_ddi_R1", "type": "EFFECT", "arg1_id": "Bromocriptine_ddi_T2", "arg2_id": "Bromocriptine_ddi_T3", "normalized": [] }, { "id": "Bromocriptine_ddi_R2", "type": "INT", "arg1_id": "Bromocriptine_ddi_T4", "arg2_id": "Bromocriptine_ddi_T5", "normalized": [] }, { "id": "Bromocriptine_ddi_R3", "type": "INT", "arg1_id": "Bromocriptine_ddi_T4", "arg2_id": "Bromocriptine_ddi_T6", "normalized": [] }, { "id": "Bromocriptine_ddi_R4", "type": "EFFECT", "arg1_id": "Bromocriptine_ddi_T7", "arg2_id": "Bromocriptine_ddi_T8", "normalized": [] }, { "id": "Bromocriptine_ddi_R5", "type": "EFFECT", "arg1_id": "Bromocriptine_ddi_T7", "arg2_id": "Bromocriptine_ddi_T9", "normalized": [] }, { "id": "Bromocriptine_ddi_R6", "type": "EFFECT", "arg1_id": "Bromocriptine_ddi_T7", "arg2_id": "Bromocriptine_ddi_T10", "normalized": [] }, { "id": "Bromocriptine_ddi_R7", "type": "EFFECT", "arg1_id": "Bromocriptine_ddi_T7", "arg2_id": "Bromocriptine_ddi_T11", "normalized": [] }, { "id": "Bromocriptine_ddi_R8", "type": "ADVISE", "arg1_id": "Bromocriptine_ddi_T12", "arg2_id": "Bromocriptine_ddi_T13", "normalized": [] } ]

[ { "id": "Arsenic trioxide_ddi__text", "type": "abstract", "text": [ "No formal assessments of pharmacokinetic drug-drug interactions between TRISENOX and other agents have been conducted. Caution is advised when TRISENOX is coadministered with other medications that can prolong the QT interval (e.g. certain antiarrhythmics or thioridazine) or lead to electrolyte abnormalities (such as diuretics or amphotericin B)." ], "offsets": [ [ 0, 348 ] ] } ]

[ { "id": "Arsenic trioxide_ddi_T1", "type": "BRAND", "text": [ "TRISENOX" ], "offsets": [ [ 72, 80 ] ], "normalized": [] }, { "id": "Arsenic trioxide_ddi_T2", "type": "BRAND", "text": [ "TRISENOX" ], "offsets": [ [ 143, 151 ] ], "normalized": [] }, { "id": "Arsenic trioxide_ddi_T3", "type": "GROUP", "text": [ "antiarrhythmics" ], "offsets": [ [ 240, 255 ] ], "normalized": [] }, { "id": "Arsenic trioxide_ddi_T4", "type": "DRUG", "text": [ "thioridazine" ], "offsets": [ [ 259, 271 ] ], "normalized": [] }, { "id": "Arsenic trioxide_ddi_T5", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 319, 328 ] ], "normalized": [] }, { "id": "Arsenic trioxide_ddi_T6", "type": "DRUG", "text": [ "amphotericin B" ], "offsets": [ [ 332, 346 ] ], "normalized": [] } ]

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[]

[ { "id": "Arsenic trioxide_ddi_R1", "type": "ADVISE", "arg1_id": "Arsenic trioxide_ddi_T2", "arg2_id": "Arsenic trioxide_ddi_T3", "normalized": [] }, { "id": "Arsenic trioxide_ddi_R2", "type": "ADVISE", "arg1_id": "Arsenic trioxide_ddi_T2", "arg2_id": "Arsenic trioxide_ddi_T4", "normalized": [] }, { "id": "Arsenic trioxide_ddi_R3", "type": "ADVISE", "arg1_id": "Arsenic trioxide_ddi_T2", "arg2_id": "Arsenic trioxide_ddi_T5", "normalized": [] }, { "id": "Arsenic trioxide_ddi_R4", "type": "ADVISE", "arg1_id": "Arsenic trioxide_ddi_T2", "arg2_id": "Arsenic trioxide_ddi_T6", "normalized": [] } ]

[ { "id": "Bethanechol_ddi__text", "type": "abstract", "text": [ "Special care is required if this drug is given to patients receiving ganglion blocking compounds because a critical fall in blood pressure may occur. Usually, severe abdominal symptoms appear before there is such a fall in the blood pressure." ], "offsets": [ [ 0, 242 ] ] } ]

[ { "id": "Bethanechol_ddi_T1", "type": "GROUP", "text": [ "ganglion blocking compounds" ], "offsets": [ [ 69, 96 ] ], "normalized": [] } ]

[]

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[ { "id": "Cerivastatin_ddi__text", "type": "abstract", "text": [ "Immunosuppressive Drugs, Fibric Acid Derivatives, Niacin (Nicotinic Acid, Erythromycin, Azole Antifungals: Skeletal Muscle. ANTACID (Magnesium-Aluminum Hydroxide): Cerivastatin plasma concentrations were not affected by co-administration of antacid. CIMETlDINE: Cerivastatin plasma concentrations were not affected by co-administration of cimetidine. CHOLESTYRAMINE: The influence of the bile-acidsequestering agent cholestyramine on the pharmacokinetits of cerivastatin sodium was evaluated in 12 healthy males in 2 separate randomized crossover studies. In the first study, concomitant administration of 0.2 mg cerivastatin sodium and 12 g cholestyramine resulted in decreases of more than 22% for AUC and 40% for Cmax when compared to dosing cerivastatin sodium alone. However, in the second study, administration of 12 g cholestyramine 1 hour before the evening meal and 0.3 mg cerivastatin sodium approximately 4 hours after the same evening meal resulted in a decrease in the cerivastatin AUC of less than 8%, and a decrease in Cmax of about 30% when compared to dosing cerivastatin sodium alone. Therefore, it would be expected that a dosing schedule of cerivastatin sodium given at bedtime and cholestyramine given before the evening meal would not result in a significant decrease in the clinical effect of cerivastatin sodium. DIGOXIN: Plasma digoxin levels and digoxin clearance at steady-state were not affected by co-administration of 0.2 mg cerivastatin sodium. Cerivastatin plasma concentrations were also not affected by co-administration of digoxin. WARFARIN: Co- administration of warfarin and cerivastatin to healthy volunteers did not result in any changes in prothrombin time or clotting factor VII when compared to co-administration of warfarin and placebo. The AUC and Cmax of both the (R) and (S) isomers of warfarin were unaffected by concurrent dosing of 0.3 mg cerivastatin sodium. Co-administration of warfarin and cerivastatin did not alter the pharmacokinetics of cerivastatin sodium. ERYTHROMYCIN: In hypercholesterolemic patients, steady-state cerivastatin AUC and Cmax increased approximately 50% and 24% respectively after 10 days with co-administration of erythromycin, a known inhibitor of cytochrome P450 3A4. OTHER CONCOMITANT THERAPY: Although specific interaction studies were not performed, in clinical studies, cerivastatin sodium was used concomitantly with angiotensin- converting enzyme (ACE) inhibitors, betablockers, calcium-channel blockers, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) without evidence of clinically significant adverse interactions." ], "offsets": [ [ 0, 2615 ] ] } ]

[ { "id": "Cerivastatin_ddi_T1", "type": "GROUP", "text": [ "Immunosuppressive Drugs" ], "offsets": [ [ 0, 23 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T2", "type": "GROUP", "text": [ "Fibric Acid Derivatives" ], "offsets": [ [ 25, 48 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T3", "type": "DRUG", "text": [ "Niacin" ], "offsets": [ [ 50, 56 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T4", "type": "DRUG", "text": [ "Nicotinic Acid" ], "offsets": [ [ 58, 72 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T5", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 74, 86 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T6", "type": "GROUP", "text": [ "Azole Antifungals" ], "offsets": [ [ 88, 105 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T7", "type": "GROUP", "text": [ "ANTACID" ], "offsets": [ [ 124, 131 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T8", "type": "DRUG", "text": [ "Magnesium-Aluminum Hydroxide" ], "offsets": [ [ 133, 161 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T9", "type": "DRUG", "text": [ "Cerivastatin" ], "offsets": [ [ 164, 176 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T10", "type": "GROUP", "text": [ "antacid" ], "offsets": [ [ 241, 248 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T11", "type": "DRUG", "text": [ "CIMETlDINE" ], "offsets": [ [ 250, 260 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T12", "type": "DRUG", "text": [ "Cerivastatin" ], "offsets": [ [ 262, 274 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T13", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 339, 349 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T14", "type": "DRUG", "text": [ "CHOLESTYRAMINE" ], "offsets": [ [ 351, 365 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T15", "type": "DRUG", "text": [ "cholestyramine" ], "offsets": [ [ 416, 430 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T16", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 458, 477 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T17", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 613, 632 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T18", "type": "DRUG", "text": [ "cholestyramine" ], "offsets": [ [ 642, 656 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T19", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 745, 764 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T20", "type": "DRUG", "text": [ "cholestyramine" ], "offsets": [ [ 825, 839 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T21", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 882, 901 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T22", "type": "DRUG", "text": [ "cerivastatin" ], "offsets": [ [ 982, 994 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T23", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 1076, 1095 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T24", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 1161, 1180 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T25", "type": "DRUG", "text": [ "cholestyramine" ], "offsets": [ [ 1202, 1216 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T26", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 1316, 1335 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T27", "type": "DRUG", "text": [ "DIGOXIN" ], "offsets": [ [ 1337, 1344 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T28", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1353, 1360 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T29", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1372, 1379 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T30", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 1455, 1474 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T31", "type": "DRUG", "text": [ "Cerivastatin" ], "offsets": [ [ 1476, 1488 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T32", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1558, 1565 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T33", "type": "DRUG", "text": [ "WARFARIN" ], "offsets": [ [ 1567, 1575 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T34", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1599, 1607 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T35", "type": "DRUG", "text": [ "cerivastatin" ], "offsets": [ [ 1612, 1624 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T36", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1758, 1766 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T37", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1832, 1840 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T38", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 1888, 1907 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T39", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1930, 1938 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T40", "type": "DRUG", "text": [ "cerivastatin" ], "offsets": [ [ 1943, 1955 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T41", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 1994, 2013 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T42", "type": "DRUG", "text": [ "ERYTHROMYCIN" ], "offsets": [ [ 2015, 2027 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T43", "type": "DRUG", "text": [ "cerivastatin" ], "offsets": [ [ 2076, 2088 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T44", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 2191, 2203 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T45", "type": "DRUG", "text": [ "cerivastatin sodium" ], "offsets": [ [ 2353, 2372 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T46", "type": "GROUP", "text": [ "angiotensin- converting enzyme (ACE) inhibitors" ], "offsets": [ [ 2401, 2448 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T47", "type": "GROUP", "text": [ "betablockers" ], "offsets": [ [ 2450, 2462 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T48", "type": "GROUP", "text": [ "calcium-channel blockers" ], "offsets": [ [ 2464, 2488 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T49", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 2490, 2499 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T50", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory drugs" ], "offsets": [ [ 2505, 2541 ] ], "normalized": [] }, { "id": "Cerivastatin_ddi_T51", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2543, 2549 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cerivastatin_ddi_R1", "type": "MECHANISM", "arg1_id": "Cerivastatin_ddi_T17", "arg2_id": "Cerivastatin_ddi_T18", "normalized": [] }, { "id": "Cerivastatin_ddi_R2", "type": "MECHANISM", "arg1_id": "Cerivastatin_ddi_T20", "arg2_id": "Cerivastatin_ddi_T21", "normalized": [] }, { "id": "Cerivastatin_ddi_R3", "type": "MECHANISM", "arg1_id": "Cerivastatin_ddi_T43", "arg2_id": "Cerivastatin_ddi_T44", "normalized": [] } ]

[ { "id": "Atracurium_ddi__text", "type": "abstract", "text": [ "Drugs which may enhance the neuromuscular blocking action of TRACRIUM include: enflurane; isoflurane; halothane; certain antibiotics, especially the aminoglycosides and polymyxins; lithium; magnesium salts; procainamide; Drugs which may enhance the neuromuscular blocking action of TRACRIUM include: enflurane;isoflurane;halothane;certain antibiotics, especially the aminoglycosides and polymyxins;lithium;magnesium salts;procainamide;and quinidine. If other muscle relaxants are used during the same procedure, the possibility of a synergistic or antagonist effect should be considered. The prior administration of succinylcholine does not enhance the duration, but quickens the onset and may increase the depth, of neuromuscular block induced by TRACRIUM. TRACRIUM should not be administered until a patient has recovered from succinylcholine-induced neuromuscular block." ], "offsets": [ [ 0, 873 ] ] } ]

[ { "id": "Atracurium_ddi_T1", "type": "BRAND", "text": [ "TRACRIUM" ], "offsets": [ [ 61, 69 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T2", "type": "DRUG", "text": [ "enflurane" ], "offsets": [ [ 79, 88 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T3", "type": "DRUG", "text": [ "isoflurane" ], "offsets": [ [ 90, 100 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T4", "type": "DRUG", "text": [ "halothane" ], "offsets": [ [ 102, 111 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T5", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 121, 132 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T6", "type": "GROUP", "text": [ "aminoglycosides" ], "offsets": [ [ 149, 164 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T7", "type": "GROUP", "text": [ "polymyxins" ], "offsets": [ [ 169, 179 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T8", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 181, 188 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T9", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 190, 199 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T10", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 207, 219 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T11", "type": "BRAND", "text": [ "TRACRIUM" ], "offsets": [ [ 282, 290 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T12", "type": "DRUG", "text": [ "enflurane" ], "offsets": [ [ 300, 309 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T13", "type": "DRUG", "text": [ "isoflurane" ], "offsets": [ [ 310, 320 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T14", "type": "DRUG", "text": [ "halothane" ], "offsets": [ [ 321, 330 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T15", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 339, 350 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T16", "type": "GROUP", "text": [ "aminoglycosides" ], "offsets": [ [ 367, 382 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T17", "type": "GROUP", "text": [ "polymyxins" ], "offsets": [ [ 387, 397 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T18", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 398, 405 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T19", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 406, 415 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T20", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 422, 434 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T21", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 439, 448 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T22", "type": "GROUP", "text": [ "muscle relaxants" ], "offsets": [ [ 459, 475 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T23", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 616, 631 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T24", "type": "BRAND", "text": [ "TRACRIUM" ], "offsets": [ [ 748, 756 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T25", "type": "BRAND", "text": [ "TRACRIUM" ], "offsets": [ [ 758, 766 ] ], "normalized": [] }, { "id": "Atracurium_ddi_T26", "type": "DRUG", "text": [ "succinylcholine" ], "offsets": [ [ 829, 844 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Atracurium_ddi_R1", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T1", "arg2_id": "Atracurium_ddi_T2", "normalized": [] }, { "id": "Atracurium_ddi_R2", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T12", "normalized": [] }, { "id": "Atracurium_ddi_R3", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T13", "normalized": [] }, { "id": "Atracurium_ddi_R4", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T14", "normalized": [] }, { "id": "Atracurium_ddi_R5", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T15", "normalized": [] }, { "id": "Atracurium_ddi_R6", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T16", "normalized": [] }, { "id": "Atracurium_ddi_R7", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T17", "normalized": [] }, { "id": "Atracurium_ddi_R8", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T18", "normalized": [] }, { "id": "Atracurium_ddi_R9", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T19", "normalized": [] }, { "id": "Atracurium_ddi_R10", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T20", "normalized": [] }, { "id": "Atracurium_ddi_R11", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T11", "arg2_id": "Atracurium_ddi_T21", "normalized": [] }, { "id": "Atracurium_ddi_R12", "type": "EFFECT", "arg1_id": "Atracurium_ddi_T23", "arg2_id": "Atracurium_ddi_T24", "normalized": [] }, { "id": "Atracurium_ddi_R13", "type": "ADVISE", "arg1_id": "Atracurium_ddi_T25", "arg2_id": "Atracurium_ddi_T26", "normalized": [] } ]

[ { "id": "Insulin Glargine recombinant_ddi__text", "type": "abstract", "text": [ "A number of substances affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring. The following are examples of substances that may increase the blood-glucose-lowering effect and susceptibility to hypoglycemia: oral antidiabetes products, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, propoxyphene, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics. The following are examples of substances that may reduce the blood-glucose-lowering effect of insulin: corticosteroids, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, albuterol, terbutaline), isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives). Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine, and reserpine, the signs of hypoglycemia may be reduced or absent." ], "offsets": [ [ 0, 1173 ] ] } ]

[ { "id": "Insulin Glargine recombinant_ddi_T1", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 65, 72 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T2", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 281, 295 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T3", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 297, 309 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T4", "type": "GROUP", "text": [ "fibrates" ], "offsets": [ [ 311, 319 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T5", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 321, 331 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T6", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 333, 347 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T7", "type": "DRUG", "text": [ "propoxyphene" ], "offsets": [ [ 349, 361 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T8", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 363, 374 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T9", "type": "GROUP", "text": [ "somatostatin analog" ], "offsets": [ [ 376, 395 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T10", "type": "DRUG", "text": [ "octreotide" ], "offsets": [ [ 403, 413 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T11", "type": "GROUP", "text": [ "sulfonamide antibiotics" ], "offsets": [ [ 416, 439 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T12", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 535, 542 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T13", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 544, 559 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T14", "type": "DRUG", "text": [ "danazol" ], "offsets": [ [ 561, 568 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T15", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 570, 579 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T16", "type": "GROUP", "text": [ "sympathomimetic agents" ], "offsets": [ [ 581, 603 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T17", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 611, 622 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T18", "type": "DRUG", "text": [ "albuterol" ], "offsets": [ [ 624, 633 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T19", "type": "DRUG", "text": [ "terbutaline" ], "offsets": [ [ 635, 646 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T20", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 649, 658 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T21", "type": "GROUP", "text": [ "phenothiazine derivatives" ], "offsets": [ [ 660, 685 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T22", "type": "DRUG", "text": [ "somatropin" ], "offsets": [ [ 687, 697 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T23", "type": "GROUP", "text": [ "thyroid hormones" ], "offsets": [ [ 699, 715 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T24", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 717, 726 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T25", "type": "GROUP", "text": [ "progestogens" ], "offsets": [ [ 728, 740 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T26", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 756, 770 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T27", "type": "GROUP", "text": [ "Beta-blockers" ], "offsets": [ [ 773, 786 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T28", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 788, 797 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T29", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 799, 806 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T30", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 818, 825 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T31", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 895, 902 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T32", "type": "DRUG", "text": [ "Pentamidine" ], "offsets": [ [ 904, 915 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T33", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 1067, 1080 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T34", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 1082, 1091 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T35", "type": "DRUG", "text": [ "guanethidine" ], "offsets": [ [ 1093, 1105 ] ], "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_T36", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 1111, 1120 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Insulin Glargine recombinant_ddi_R1", "type": "EFFECT", "arg1_id": "Insulin Glargine recombinant_ddi_T27", "arg2_id": "Insulin Glargine recombinant_ddi_T31", "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_R2", "type": "EFFECT", "arg1_id": "Insulin Glargine recombinant_ddi_T28", "arg2_id": "Insulin Glargine recombinant_ddi_T31", "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_R3", "type": "EFFECT", "arg1_id": "Insulin Glargine recombinant_ddi_T29", "arg2_id": "Insulin Glargine recombinant_ddi_T31", "normalized": [] }, { "id": "Insulin Glargine recombinant_ddi_R4", "type": "EFFECT", "arg1_id": "Insulin Glargine recombinant_ddi_T30", "arg2_id": "Insulin Glargine recombinant_ddi_T31", "normalized": [] } ]

[ { "id": "Chlorpromazine_ddi__text", "type": "abstract", "text": [ "The concurrent use of two or more drugs with anticholinergic activity--such as an antipsychotic drug (eg, chlorpromazine), an antiparkinsonian drug (eg, trihexyphenidyl), and/or a tricyclic antidepressant (eg, amitriptyline)--commonly results in excessive anticholinergic effects, including dry mouth and associated dental complications, blurred vision, and, in patients exposed to high temperature and humidity, hyperpyrexia. Interactions may also occur with the following: anti-depressants/anti-anxiety drugs, drugs used to treat an overactive thyroid, beta-blockers (e.g., propranolol), sparfloxacin, grepafloxacin, guanethidine, guanadrel, metrizamide, cabergoline, lithium, narcotic pain medication (e.g., codeine), drugs used to aid sleep, drowsiness-causing antihistamines (e.g., diphenhydramine), any other drugs that may make you drowsy." ], "offsets": [ [ 0, 846 ] ] } ]

[ { "id": "Chlorpromazine_ddi_T1", "type": "GROUP", "text": [ "antipsychotic drug" ], "offsets": [ [ 82, 100 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T2", "type": "DRUG", "text": [ "chlorpromazine" ], "offsets": [ [ 106, 120 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T3", "type": "GROUP", "text": [ "antiparkinsonian drug" ], "offsets": [ [ 126, 147 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T4", "type": "DRUG", "text": [ "trihexyphenidyl" ], "offsets": [ [ 153, 168 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T5", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 180, 204 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T6", "type": "DRUG", "text": [ "amitriptyline" ], "offsets": [ [ 210, 223 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T7", "type": "GROUP", "text": [ "anti-depressants" ], "offsets": [ [ 475, 491 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T8", "type": "GROUP", "text": [ "anti-anxiety drugs" ], "offsets": [ [ 492, 510 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T9", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 555, 568 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T10", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 576, 587 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T11", "type": "DRUG", "text": [ "sparfloxacin" ], "offsets": [ [ 590, 602 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T12", "type": "DRUG", "text": [ "grepafloxacin" ], "offsets": [ [ 604, 617 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T13", "type": "DRUG", "text": [ "guanethidine" ], "offsets": [ [ 619, 631 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T14", "type": "DRUG", "text": [ "guanadrel" ], "offsets": [ [ 633, 642 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T15", "type": "DRUG", "text": [ "metrizamide" ], "offsets": [ [ 644, 655 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T16", "type": "DRUG", "text": [ "cabergoline" ], "offsets": [ [ 657, 668 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T17", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 670, 677 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T18", "type": "GROUP", "text": [ "narcotic" ], "offsets": [ [ 679, 687 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T19", "type": "DRUG", "text": [ "codeine" ], "offsets": [ [ 711, 718 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T20", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 765, 779 ] ], "normalized": [] }, { "id": "Chlorpromazine_ddi_T21", "type": "DRUG", "text": [ "diphenhydramine" ], "offsets": [ [ 787, 802 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Chlorpromazine_ddi_R1", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T1", "arg2_id": "Chlorpromazine_ddi_T3", "normalized": [] }, { "id": "Chlorpromazine_ddi_R2", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T1", "arg2_id": "Chlorpromazine_ddi_T4", "normalized": [] }, { "id": "Chlorpromazine_ddi_R3", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T1", "arg2_id": "Chlorpromazine_ddi_T5", "normalized": [] }, { "id": "Chlorpromazine_ddi_R4", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T1", "arg2_id": "Chlorpromazine_ddi_T6", "normalized": [] }, { "id": "Chlorpromazine_ddi_R5", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T2", "arg2_id": "Chlorpromazine_ddi_T3", "normalized": [] }, { "id": "Chlorpromazine_ddi_R6", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T2", "arg2_id": "Chlorpromazine_ddi_T4", "normalized": [] }, { "id": "Chlorpromazine_ddi_R7", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T2", "arg2_id": "Chlorpromazine_ddi_T5", "normalized": [] }, { "id": "Chlorpromazine_ddi_R8", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T2", "arg2_id": "Chlorpromazine_ddi_T6", "normalized": [] }, { "id": "Chlorpromazine_ddi_R9", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T3", "arg2_id": "Chlorpromazine_ddi_T5", "normalized": [] }, { "id": "Chlorpromazine_ddi_R10", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T3", "arg2_id": "Chlorpromazine_ddi_T6", "normalized": [] }, { "id": "Chlorpromazine_ddi_R11", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T4", "arg2_id": "Chlorpromazine_ddi_T5", "normalized": [] }, { "id": "Chlorpromazine_ddi_R12", "type": "EFFECT", "arg1_id": "Chlorpromazine_ddi_T4", "arg2_id": "Chlorpromazine_ddi_T6", "normalized": [] } ]

[ { "id": "Butabarbital_ddi__text", "type": "abstract", "text": [ "Interactions may occur with the following: adrenocorticoids (cortisone-like medicine), anticoagulants (blood thinners), carbamazepine, corticotropin (barbiturates may decrease the effects of these medicines), central nervous system (CNS) depressants (using these medicines with barbiturates may result in increased CNS depressant effects), divalproex sodium, valproic acid (using these medicines with barbiturates may change the amount of either medicine that you need to take), and oral contraceptives containing estrogens (barbiturates may decrease the effectiveness of these oral contraceptives, and you may need to change to a different type of birth control)." ], "offsets": [ [ 0, 664 ] ] } ]

[ { "id": "Butabarbital_ddi_T1", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 87, 101 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T2", "type": "GROUP", "text": [ "blood thinner" ], "offsets": [ [ 103, 116 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T3", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 120, 133 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T4", "type": "DRUG", "text": [ "corticotropin" ], "offsets": [ [ 135, 148 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T5", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 150, 162 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T6", "type": "GROUP", "text": [ "central nervous system (CNS) depressants" ], "offsets": [ [ 209, 249 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T7", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 278, 290 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T8", "type": "DRUG", "text": [ "divalproex sodium" ], "offsets": [ [ 340, 357 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T9", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 359, 372 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T10", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 401, 413 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T11", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 488, 502 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T12", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 514, 523 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T13", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 525, 537 ] ], "normalized": [] }, { "id": "Butabarbital_ddi_T14", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 583, 597 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Butabarbital_ddi_R1", "type": "EFFECT", "arg1_id": "Butabarbital_ddi_T13", "arg2_id": "Butabarbital_ddi_T14", "normalized": [] } ]

[ { "id": "Bretylium_ddi__text", "type": "abstract", "text": [ "Digitalis toxicity may be aggravated by the initial release of norepinephrine caused by Bretylium Tosylate Injection. The pressor effects of catecholamines such as dopamine or norepinephrine are enhanced by Bretylium Tosylate. When catecholamines are administered, dilute solutions should be used and blood pressure should be monitored closely. Although there is little published information on concomitant administration of lidocaine and Bretylium Tosylate, these drugs are often administered concurrently without any evidence of interactions resulting in adverse effects or diminished efficacy." ], "offsets": [ [ 0, 596 ] ] } ]

[ { "id": "Bretylium_ddi_T1", "type": "GROUP", "text": [ "Digitalis" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Bretylium_ddi_T2", "type": "DRUG", "text": [ "Bretylium Tosylate" ], "offsets": [ [ 88, 106 ] ], "normalized": [] }, { "id": "Bretylium_ddi_T3", "type": "GROUP", "text": [ "catecholamines" ], "offsets": [ [ 141, 155 ] ], "normalized": [] }, { "id": "Bretylium_ddi_T4", "type": "DRUG", "text": [ "dopamine" ], "offsets": [ [ 164, 172 ] ], "normalized": [] }, { "id": "Bretylium_ddi_T5", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 176, 190 ] ], "normalized": [] }, { "id": "Bretylium_ddi_T6", "type": "DRUG", "text": [ "Bretylium Tosylate" ], "offsets": [ [ 207, 225 ] ], "normalized": [] }, { "id": "Bretylium_ddi_T7", "type": "GROUP", "text": [ "catecholamines" ], "offsets": [ [ 232, 246 ] ], "normalized": [] }, { "id": "Bretylium_ddi_T8", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 425, 434 ] ], "normalized": [] }, { "id": "Bretylium_ddi_T9", "type": "DRUG", "text": [ "Bretylium Tosylate" ], "offsets": [ [ 439, 457 ] ], "normalized": [] } ]

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[ { "id": "Bretylium_ddi_R1", "type": "EFFECT", "arg1_id": "Bretylium_ddi_T1", "arg2_id": "Bretylium_ddi_T2", "normalized": [] }, { "id": "Bretylium_ddi_R2", "type": "EFFECT", "arg1_id": "Bretylium_ddi_T3", "arg2_id": "Bretylium_ddi_T6", "normalized": [] }, { "id": "Bretylium_ddi_R3", "type": "EFFECT", "arg1_id": "Bretylium_ddi_T4", "arg2_id": "Bretylium_ddi_T6", "normalized": [] }, { "id": "Bretylium_ddi_R4", "type": "EFFECT", "arg1_id": "Bretylium_ddi_T5", "arg2_id": "Bretylium_ddi_T6", "normalized": [] } ]

[ { "id": "Bexarotene_ddi__text", "type": "abstract", "text": [ "No formal studies to evaluate drug interactions with bexarotene have been conducted. Bexarotene oxidative metabolites appear to be formed by cytochrome P450 3A4. On the basis of the metabolism of bexarotene by cytochrome P450 3A4, ketoconazole, itraconazole, erythromycin, gemfibrozil, grapefruit juice, and other inhibitors of cytochrome P450 3A4 would be expected to lead to an increase in plasma bexarotene concentrations. Furthermore, rifampin, phenytoin, phenobarbital, and other inducers of cytochrome P450 3A4 may cause a reduction in plasma bexarotene concentrations. Concomitant administration of Targretin capsules and gemfibrozil resulted in substantial increases in plasma concentrations of bexarotene, probably at least partially related to cytochrome P450 3A4 inhibition by gemfibrozil. Under similar conditions, bexarotene concentrations were not affected by concomitant atorvastatin administration. Concomitant administration of gemfibrozil with Targretin capsules is not recommended." ], "offsets": [ [ 0, 1000 ] ] } ]

[ { "id": "Bexarotene_ddi_T1", "type": "DRUG", "text": [ "bexarotene" ], "offsets": [ [ 53, 63 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T2", "type": "DRUG", "text": [ "Bexarotene" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T3", "type": "DRUG", "text": [ "bexarotene" ], "offsets": [ [ 196, 206 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T4", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 231, 243 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T5", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 245, 257 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T6", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 259, 271 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T7", "type": "DRUG", "text": [ "gemfibrozil" ], "offsets": [ [ 273, 284 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T8", "type": "DRUG", "text": [ "bexarotene" ], "offsets": [ [ 399, 409 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T9", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 439, 447 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T10", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 449, 458 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T11", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 460, 473 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T12", "type": "DRUG", "text": [ "bexarotene" ], "offsets": [ [ 549, 559 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T13", "type": "BRAND", "text": [ "Targretin" ], "offsets": [ [ 606, 615 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T14", "type": "DRUG", "text": [ "gemfibrozil" ], "offsets": [ [ 629, 640 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T15", "type": "DRUG", "text": [ "bexarotene" ], "offsets": [ [ 703, 713 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T16", "type": "DRUG", "text": [ "gemfibrozil" ], "offsets": [ [ 788, 799 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T17", "type": "DRUG", "text": [ "bexarotene" ], "offsets": [ [ 827, 837 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T18", "type": "DRUG", "text": [ "atorvastatin" ], "offsets": [ [ 886, 898 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T19", "type": "DRUG", "text": [ "gemfibrozil" ], "offsets": [ [ 945, 956 ] ], "normalized": [] }, { "id": "Bexarotene_ddi_T20", "type": "BRAND", "text": [ "Targretin" ], "offsets": [ [ 962, 971 ] ], "normalized": [] } ]

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[ { "id": "Bexarotene_ddi_R1", "type": "MECHANISM", "arg1_id": "Bexarotene_ddi_T4", "arg2_id": "Bexarotene_ddi_T8", "normalized": [] }, { "id": "Bexarotene_ddi_R2", "type": "MECHANISM", "arg1_id": "Bexarotene_ddi_T5", "arg2_id": "Bexarotene_ddi_T8", "normalized": [] }, { "id": "Bexarotene_ddi_R3", "type": "MECHANISM", "arg1_id": "Bexarotene_ddi_T6", "arg2_id": "Bexarotene_ddi_T8", "normalized": [] }, { "id": "Bexarotene_ddi_R4", "type": "MECHANISM", "arg1_id": "Bexarotene_ddi_T7", "arg2_id": "Bexarotene_ddi_T8", "normalized": [] }, { "id": "Bexarotene_ddi_R5", "type": "MECHANISM", "arg1_id": "Bexarotene_ddi_T9", "arg2_id": "Bexarotene_ddi_T12", "normalized": [] }, { "id": "Bexarotene_ddi_R6", "type": "MECHANISM", "arg1_id": "Bexarotene_ddi_T10", "arg2_id": "Bexarotene_ddi_T12", "normalized": [] }, { "id": "Bexarotene_ddi_R7", "type": "MECHANISM", "arg1_id": "Bexarotene_ddi_T11", "arg2_id": "Bexarotene_ddi_T12", "normalized": [] }, { "id": "Bexarotene_ddi_R8", "type": "MECHANISM", "arg1_id": "Bexarotene_ddi_T13", "arg2_id": "Bexarotene_ddi_T14", "normalized": [] }, { "id": "Bexarotene_ddi_R9", "type": "ADVISE", "arg1_id": "Bexarotene_ddi_T19", "arg2_id": "Bexarotene_ddi_T20", "normalized": [] } ]

[ { "id": "Bortezomib_ddi__text", "type": "abstract", "text": [ "No formal drug interaction studies have been conducted with VELCADE. In vitro studies with human liver microsomes indicate that bortezomib is primarily a substrate for cytochrome P450 3A4, 2C19, and 1A2. Patients who are concomitantly receiving VELCADE and drugs that are inhibitors or inducers of cytochrome P450 3A4 should be closely monitored for either toxicities or reduced efficacy . During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADE treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication. Drug Laboratory Test Interactions None known." ], "offsets": [ [ 0, 740 ] ] } ]

[ { "id": "Bortezomib_ddi_T1", "type": "BRAND", "text": [ "VELCADE" ], "offsets": [ [ 60, 67 ] ], "normalized": [] }, { "id": "Bortezomib_ddi_T2", "type": "DRUG", "text": [ "bortezomib" ], "offsets": [ [ 128, 138 ] ], "normalized": [] }, { "id": "Bortezomib_ddi_T3", "type": "BRAND", "text": [ "VELCADE" ], "offsets": [ [ 245, 252 ] ], "normalized": [] }, { "id": "Bortezomib_ddi_T4", "type": "GROUP", "text": [ "hypoglycemics" ], "offsets": [ [ 495, 508 ] ], "normalized": [] }, { "id": "Bortezomib_ddi_T5", "type": "GROUP", "text": [ "antidiabetic agents" ], "offsets": [ [ 527, 546 ] ], "normalized": [] }, { "id": "Bortezomib_ddi_T6", "type": "BRAND", "text": [ "VELCADE" ], "offsets": [ [ 557, 564 ] ], "normalized": [] }, { "id": "Bortezomib_ddi_T7", "type": "GROUP", "text": [ "antidiabetic medication" ], "offsets": [ [ 670, 693 ] ], "normalized": [] } ]

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[ { "id": "Bortezomib_ddi_R1", "type": "ADVISE", "arg1_id": "Bortezomib_ddi_T5", "arg2_id": "Bortezomib_ddi_T6", "normalized": [] } ]

[ { "id": "Cromoglicate_ddi__text", "type": "abstract", "text": [ "Drug Interaction During Pregnancy: Cromolyn sodium and isoproterenol were studied following subcutaneous injections in pregnant mice. Cromolyn sodium alone in doses up to 540 mg/kg/day (approximately 340 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis) did not cause significant increases in resorptions or major malformations. Isoproterenol alone at a dose of 2.7 mg/kg/day (approximately 7 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis) increased both resorptions and malformations. The addition of 540 mg/kg/day of cromolyn sodium (approximately 340 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis) to 2.7 mg/kg/day of isoproterenol (approximately 7 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis) appears to have increased the incidence of both resorptions and malformations." ], "offsets": [ [ 0, 906 ] ] } ]

[ { "id": "Cromoglicate_ddi_T1", "type": "DRUG", "text": [ "Cromolyn sodium" ], "offsets": [ [ 35, 50 ] ], "normalized": [] }, { "id": "Cromoglicate_ddi_T2", "type": "DRUG", "text": [ "isoproterenol" ], "offsets": [ [ 55, 68 ] ], "normalized": [] }, { "id": "Cromoglicate_ddi_T3", "type": "DRUG", "text": [ "Cromolyn sodium" ], "offsets": [ [ 134, 149 ] ], "normalized": [] }, { "id": "Cromoglicate_ddi_T4", "type": "DRUG", "text": [ "Isoproterenol" ], "offsets": [ [ 359, 372 ] ], "normalized": [] }, { "id": "Cromoglicate_ddi_T5", "type": "DRUG", "text": [ "cromolyn sodium" ], "offsets": [ [ 582, 597 ] ], "normalized": [] }, { "id": "Cromoglicate_ddi_T6", "type": "DRUG", "text": [ "isoproterenol" ], "offsets": [ [ 717, 730 ] ], "normalized": [] } ]

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[ { "id": "Cromoglicate_ddi_R1", "type": "EFFECT", "arg1_id": "Cromoglicate_ddi_T5", "arg2_id": "Cromoglicate_ddi_T6", "normalized": [] } ]

[ { "id": "Desflurane_ddi__text", "type": "abstract", "text": [ "No clinically significant adverse interactions with commonly used preanesthetic drugs, or drugs used during anesthesia (muscle relaxants, intravenous agents, and local anesthetic agents) were reported in clinical trials. The effect of desflurane on the disposition of other drugs has not been determined. Like isoflurane, desflurane does not predispose to premature ventricular arrhythmias in the presence of exogenously infused epinephrine in swine." ], "offsets": [ [ 0, 450 ] ] } ]

[ { "id": "Desflurane_ddi_T1", "type": "GROUP", "text": [ "muscle relaxants" ], "offsets": [ [ 120, 136 ] ], "normalized": [] }, { "id": "Desflurane_ddi_T2", "type": "GROUP", "text": [ "anesthetic agents" ], "offsets": [ [ 168, 185 ] ], "normalized": [] }, { "id": "Desflurane_ddi_T3", "type": "DRUG", "text": [ "desflurane" ], "offsets": [ [ 235, 245 ] ], "normalized": [] }, { "id": "Desflurane_ddi_T4", "type": "DRUG", "text": [ "isoflurane" ], "offsets": [ [ 310, 320 ] ], "normalized": [] }, { "id": "Desflurane_ddi_T5", "type": "DRUG", "text": [ "desflurane" ], "offsets": [ [ 322, 332 ] ], "normalized": [] }, { "id": "Desflurane_ddi_T6", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 429, 440 ] ], "normalized": [] } ]

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[]

[ { "id": "Cefotetan_ddi__text", "type": "abstract", "text": [ "Increases in serum creatinine have occurred when CEFOTAN was given alone. If CEFOTAN and an aminoglycoside are used concomitantly, renal function should be carefully monitored, because nephrotoxicity may be potentiated. Drug/Laboratory Test Interactions: The administration of CEFOTAN may result in a false positive reaction for glucose in the urine using Clinitest , Benedicts solution, or Fehlings solution. It is recommended that glucose tests based on enzymatic glucose oxidase be used. As with other cephalosporins, high concentrations of cefotetan may interfere with measurement of serum and urine creatinine levels by Jaffe reaction and produce false increases in the levels of creatinine reported." ], "offsets": [ [ 0, 707 ] ] } ]

[ { "id": "Cefotetan_ddi_T1", "type": "BRAND", "text": [ "CEFOTAN" ], "offsets": [ [ 49, 56 ] ], "normalized": [] }, { "id": "Cefotetan_ddi_T2", "type": "BRAND", "text": [ "CEFOTAN" ], "offsets": [ [ 77, 84 ] ], "normalized": [] }, { "id": "Cefotetan_ddi_T3", "type": "GROUP", "text": [ "aminoglycoside" ], "offsets": [ [ 92, 106 ] ], "normalized": [] }, { "id": "Cefotetan_ddi_T4", "type": "BRAND", "text": [ "CEFOTAN" ], "offsets": [ [ 277, 284 ] ], "normalized": [] }, { "id": "Cefotetan_ddi_T5", "type": "GROUP", "text": [ "cephalosporins" ], "offsets": [ [ 506, 520 ] ], "normalized": [] }, { "id": "Cefotetan_ddi_T6", "type": "DRUG", "text": [ "cefotetan" ], "offsets": [ [ 545, 554 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cefotetan_ddi_R1", "type": "EFFECT", "arg1_id": "Cefotetan_ddi_T2", "arg2_id": "Cefotetan_ddi_T3", "normalized": [] } ]

[ { "id": "Chlorpropamide_ddi__text", "type": "abstract", "text": [ "The hypoglycemic action of sulfonylurea may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving DIABINESE, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving DIABINESE, the patient should be observed closely for loss of control. Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving DIABINESE, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving DIABINESE, the patient should be observed closely for hypoglycemia. Since animal studies suggest that the action of barbiturates may be prolonged by therapy with chlorpropamide, barbiturates should be employed with caution. In some patients, a disulfiram-like reaction may be produced by the ingestion of alcohol. A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known." ], "offsets": [ [ 0, 1604 ] ] } ]

[ { "id": "Chlorpropamide_ddi_T1", "type": "GROUP", "text": [ "sulfonylurea" ], "offsets": [ [ 27, 39 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T2", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 86, 123 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T3", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 171, 182 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T4", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 184, 196 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T5", "type": "DRUG", "text": [ "chloramphenicol" ], "offsets": [ [ 198, 213 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T6", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 215, 225 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T7", "type": "GROUP", "text": [ "coumarins" ], "offsets": [ [ 227, 236 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T8", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 238, 266 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T9", "type": "GROUP", "text": [ "beta adrenergic blocking agents" ], "offsets": [ [ 272, 303 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T10", "type": "BRAND", "text": [ "DIABINESE" ], "offsets": [ [ 361, 370 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T11", "type": "BRAND", "text": [ "DIABINESE" ], "offsets": [ [ 484, 493 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T12", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 656, 665 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T13", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 676, 685 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T14", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 687, 702 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T15", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 704, 718 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T16", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 738, 747 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T17", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 754, 768 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T18", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 770, 779 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T19", "type": "DRUG", "text": [ "nicotinic acid" ], "offsets": [ [ 781, 795 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T20", "type": "GROUP", "text": [ "sympathomimetics" ], "offsets": [ [ 797, 813 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T21", "type": "GROUP", "text": [ "calcium channel blocking drugs" ], "offsets": [ [ 815, 845 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T22", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 851, 860 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T23", "type": "BRAND", "text": [ "DIABINESE" ], "offsets": [ [ 918, 927 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T24", "type": "BRAND", "text": [ "DIABINESE" ], "offsets": [ [ 1044, 1053 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T25", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 1160, 1172 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T26", "type": "DRUG", "text": [ "chlorpropamide" ], "offsets": [ [ 1206, 1220 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T27", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 1222, 1234 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T28", "type": "DRUG", "text": [ "disulfiram" ], "offsets": [ [ 1288, 1298 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T29", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 1349, 1356 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T30", "type": "DRUG", "text": [ "miconazole" ], "offsets": [ [ 1395, 1405 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T31", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 1415, 1434 ] ], "normalized": [] }, { "id": "Chlorpropamide_ddi_T32", "type": "DRUG", "text": [ "miconazole" ], "offsets": [ [ 1580, 1590 ] ], "normalized": [] } ]

[]

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[ { "id": "Chlorpropamide_ddi_R1", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T1", "arg2_id": "Chlorpropamide_ddi_T2", "normalized": [] }, { "id": "Chlorpropamide_ddi_R2", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T1", "arg2_id": "Chlorpropamide_ddi_T3", "normalized": [] }, { "id": "Chlorpropamide_ddi_R3", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T1", "arg2_id": "Chlorpropamide_ddi_T4", "normalized": [] }, { "id": "Chlorpropamide_ddi_R4", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T1", "arg2_id": "Chlorpropamide_ddi_T5", "normalized": [] }, { "id": "Chlorpropamide_ddi_R5", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T1", "arg2_id": "Chlorpropamide_ddi_T6", "normalized": [] }, { "id": "Chlorpropamide_ddi_R6", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T1", "arg2_id": "Chlorpropamide_ddi_T7", "normalized": [] }, { "id": "Chlorpropamide_ddi_R7", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T1", "arg2_id": "Chlorpropamide_ddi_T8", "normalized": [] }, { "id": "Chlorpropamide_ddi_R8", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T1", "arg2_id": "Chlorpropamide_ddi_T9", "normalized": [] }, { "id": "Chlorpropamide_ddi_R9", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T25", "arg2_id": "Chlorpropamide_ddi_T26", "normalized": [] }, { "id": "Chlorpropamide_ddi_R10", "type": "EFFECT", "arg1_id": "Chlorpropamide_ddi_T30", "arg2_id": "Chlorpropamide_ddi_T31", "normalized": [] } ]

[ { "id": "Chlorothiazide_ddi__text", "type": "abstract", "text": [ "When given concurrently the following drugs may interact with thiazide diuretics. - Alcohol, barbiturates, or narcotics: Potentiation of otthostatic hypotension may occur . - Antidiabetic drugs: (Oral agents and insulin) Dosage adjustment of the antidiabetic drug may be required . - Other antihypertensive drugs: Additive effect or potentiation . - Cholestyramine and colestipol resins: Cholestytamine and colestipol resins have the potential of binding thiazide diuretics and reducing diuretic absorption from the gastrointestinal tract . - Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia . - Pressor amines (e.g., norepinephrine): Possible decreased response to pressor amines but not sufficient to preclude their use . - Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased responsiveness to the muscle relaxant . - Lithium: Generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with chlorothiazide . - Non-steroidal Anti-inflammatory Drugs: In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when chlorothiazide and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained . - Drug/Laboratory Test Interactions: Thiazides should be discontinued before carrying out tests for parathyroid function." ], "offsets": [ [ 0, 1705 ] ] } ]

[ { "id": "Chlorothiazide_ddi_T1", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 62, 80 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T2", "type": "DRUG", "text": [ "Alcohol" ], "offsets": [ [ 84, 91 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T3", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 93, 105 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T4", "type": "GROUP", "text": [ "narcotics" ], "offsets": [ [ 110, 119 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T5", "type": "GROUP", "text": [ "Antidiabetic drugs" ], "offsets": [ [ 175, 193 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T6", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 212, 219 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T7", "type": "GROUP", "text": [ "antidiabetic drug" ], "offsets": [ [ 246, 263 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T8", "type": "GROUP", "text": [ "antihypertensive drugs" ], "offsets": [ [ 290, 312 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T9", "type": "DRUG", "text": [ "Cholestyramine" ], "offsets": [ [ 350, 364 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T10", "type": "DRUG", "text": [ "colestipol" ], "offsets": [ [ 369, 379 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T11", "type": "GROUP", "text": [ "resins" ], "offsets": [ [ 380, 386 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T12", "type": "DRUG", "text": [ "Cholestytamine" ], "offsets": [ [ 388, 402 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T13", "type": "DRUG", "text": [ "colestipol" ], "offsets": [ [ 407, 417 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T14", "type": "GROUP", "text": [ "resins" ], "offsets": [ [ 418, 424 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T15", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 455, 473 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T16", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 487, 495 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T17", "type": "GROUP", "text": [ "Corticosteroids" ], "offsets": [ [ 543, 558 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T18", "type": "DRUG", "text": [ "ACTH" ], "offsets": [ [ 560, 564 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T19", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 652, 666 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T20", "type": "GROUP", "text": [ "Skeletal muscle relaxants" ], "offsets": [ [ 760, 785 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T21", "type": "DRUG", "text": [ "tubocurarine" ], "offsets": [ [ 810, 822 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T22", "type": "GROUP", "text": [ "muscle relaxant" ], "offsets": [ [ 866, 881 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T23", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 886, 893 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T24", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 930, 939 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T25", "type": "GROUP", "text": [ "Diuretic agents" ], "offsets": [ [ 941, 956 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T26", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 987, 994 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T27", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1018, 1025 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T28", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1068, 1075 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T29", "type": "DRUG", "text": [ "chlorothiazide" ], "offsets": [ [ 1126, 1140 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T30", "type": "GROUP", "text": [ "Non-steroidal Anti-inflammatory Drugs" ], "offsets": [ [ 1145, 1182 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T31", "type": "GROUP", "text": [ "non-steroidal anti-inflammatory agent" ], "offsets": [ [ 1226, 1263 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T32", "type": "GROUP", "text": [ "loop", "diuretics" ], "offsets": [ [ 1334, 1338 ], [ 1371, 1380 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T33", "type": "GROUP", "text": [ "potassium-sparing", "diuretics" ], "offsets": [ [ 1340, 1357 ], [ 1371, 1380 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T34", "type": "DRUG", "text": [ "thiazide diuretics" ], "offsets": [ [ 1362, 1380 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T35", "type": "DRUG", "text": [ "chlorothiazide" ], "offsets": [ [ 1398, 1412 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T36", "type": "GROUP", "text": [ "non-steroidal anti-inflammatory agents" ], "offsets": [ [ 1417, 1455 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T37", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 1561, 1569 ] ], "normalized": [] }, { "id": "Chlorothiazide_ddi_T38", "type": "GROUP", "text": [ "Thiazides" ], "offsets": [ [ 1621, 1630 ] ], "normalized": [] } ]

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[ { "id": "Chlorothiazide_ddi_R1", "type": "MECHANISM", "arg1_id": "Chlorothiazide_ddi_T12", "arg2_id": "Chlorothiazide_ddi_T15", "normalized": [] }, { "id": "Chlorothiazide_ddi_R2", "type": "MECHANISM", "arg1_id": "Chlorothiazide_ddi_T13", "arg2_id": "Chlorothiazide_ddi_T15", "normalized": [] }, { "id": "Chlorothiazide_ddi_R3", "type": "ADVISE", "arg1_id": "Chlorothiazide_ddi_T23", "arg2_id": "Chlorothiazide_ddi_T24", "normalized": [] }, { "id": "Chlorothiazide_ddi_R4", "type": "MECHANISM", "arg1_id": "Chlorothiazide_ddi_T25", "arg2_id": "Chlorothiazide_ddi_T26", "normalized": [] }, { "id": "Chlorothiazide_ddi_R5", "type": "MECHANISM", "arg1_id": "Chlorothiazide_ddi_T25", "arg2_id": "Chlorothiazide_ddi_T27", "normalized": [] }, { "id": "Chlorothiazide_ddi_R6", "type": "ADVISE", "arg1_id": "Chlorothiazide_ddi_T28", "arg2_id": "Chlorothiazide_ddi_T29", "normalized": [] }, { "id": "Chlorothiazide_ddi_R7", "type": "EFFECT", "arg1_id": "Chlorothiazide_ddi_T31", "arg2_id": "Chlorothiazide_ddi_T32", "normalized": [] }, { "id": "Chlorothiazide_ddi_R8", "type": "EFFECT", "arg1_id": "Chlorothiazide_ddi_T31", "arg2_id": "Chlorothiazide_ddi_T33", "normalized": [] }, { "id": "Chlorothiazide_ddi_R9", "type": "EFFECT", "arg1_id": "Chlorothiazide_ddi_T31", "arg2_id": "Chlorothiazide_ddi_T34", "normalized": [] }, { "id": "Chlorothiazide_ddi_R10", "type": "ADVISE", "arg1_id": "Chlorothiazide_ddi_T35", "arg2_id": "Chlorothiazide_ddi_T36", "normalized": [] } ]

[ { "id": "Dexrazoxane_ddi__text", "type": "abstract", "text": [ "ZINECARD does not influence the pharmacokinetics of doxorubicin. Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term carcinogenicity studies have been carried out with dexrazoxane in animals. Dexrazoxane was not mutagenic in the Ames test but was found to be clastogenic to human lymphocytes in vitro and to mouse bone marrow erythrocytes in vivo (micronucleus test). The possible adverse effects of ZINECARD on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (1/3 the human dose on a mg/m 2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (approximately equal to the human dose on a mg/m 2 basis)." ], "offsets": [ [ 0, 789 ] ] } ]

[ { "id": "Dexrazoxane_ddi_T1", "type": "BRAND", "text": [ "ZINECARD" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Dexrazoxane_ddi_T2", "type": "DRUG", "text": [ "doxorubicin" ], "offsets": [ [ 52, 63 ] ], "normalized": [] }, { "id": "Dexrazoxane_ddi_T3", "type": "DRUG", "text": [ "dexrazoxane" ], "offsets": [ [ 182, 193 ] ], "normalized": [] }, { "id": "Dexrazoxane_ddi_T4", "type": "DRUG", "text": [ "Dexrazoxane" ], "offsets": [ [ 206, 217 ] ], "normalized": [] }, { "id": "Dexrazoxane_ddi_T5", "type": "BRAND", "text": [ "ZINECARD" ], "offsets": [ [ 414, 422 ] ], "normalized": [] }, { "id": "Dexrazoxane_ddi_T6", "type": "DRUG", "text": [ "dexrazoxane" ], "offsets": [ [ 559, 570 ] ], "normalized": [] } ]

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[]

[ { "id": "Ergoloid mesylate_ddi__text", "type": "abstract", "text": [ "No reported interactions." ], "offsets": [ [ 0, 25 ] ] } ]

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[ { "id": "Bevacizumab_ddi__text", "type": "abstract", "text": [ "No formal drug interaction studies with anti-neoplastic agents have been conducted. In Study 1, patients with colorectal cancer were given irinotecan/5-FU/leucovorin (bolus-IFL) with or without AVASTIN. Irinotecan concentrations were similar in patients receiving bolus-IFL alone and in combination with AVASTIN. The concentrations of SN38, the active metabolite of irinotecan, were on average 33% higher in patients receiving bolus-IFL in combination with AVASTIN when compared with bolus-IFL alone. In Study 1, patients receiving bolus-IFL plus AVASTIN had a higher incidence of Grade 3-4 diarrhea and neutropenia. Due to high inter-patient variability and limited sampling, the extent of the increase in SN38 levels in patients receiving concurrent irinotecan and AVASTIN is uncertain." ], "offsets": [ [ 0, 788 ] ] } ]

[ { "id": "Bevacizumab_ddi_T1", "type": "GROUP", "text": [ "anti-neoplastic agents" ], "offsets": [ [ 40, 62 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T2", "type": "DRUG", "text": [ "irinotecan" ], "offsets": [ [ 139, 149 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T3", "type": "DRUG", "text": [ "5-FU" ], "offsets": [ [ 150, 154 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T4", "type": "DRUG", "text": [ "leucovorin" ], "offsets": [ [ 155, 165 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T5", "type": "BRAND", "text": [ "AVASTIN" ], "offsets": [ [ 194, 201 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T6", "type": "DRUG", "text": [ "Irinotecan" ], "offsets": [ [ 203, 213 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T7", "type": "BRAND", "text": [ "AVASTIN" ], "offsets": [ [ 304, 311 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T8", "type": "DRUG_N", "text": [ "SN38" ], "offsets": [ [ 335, 339 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T9", "type": "DRUG", "text": [ "irinotecan" ], "offsets": [ [ 366, 376 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T10", "type": "BRAND", "text": [ "AVASTIN" ], "offsets": [ [ 457, 464 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T11", "type": "BRAND", "text": [ "AVASTIN" ], "offsets": [ [ 547, 554 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T12", "type": "DRUG_N", "text": [ "SN38" ], "offsets": [ [ 707, 711 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T13", "type": "DRUG", "text": [ "irinotecan" ], "offsets": [ [ 752, 762 ] ], "normalized": [] }, { "id": "Bevacizumab_ddi_T14", "type": "BRAND", "text": [ "AVASTIN" ], "offsets": [ [ 767, 774 ] ], "normalized": [] } ]

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[ { "id": "Dofetilide_ddi__text", "type": "abstract", "text": [ "Drug/Laboratory Test Interactions None known. Drug-Drug Interactions Cimetidine: Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with TIKOSYN (500 mcg BID) for 7 days has been shown to increase dofetilide plasma levels by 58%. Cimetidine at doses of 100 mg BID (OTC dose) resulted in a 13% increase in dofetilide plasma levels (500 mcg single dose). No studies have been conducted at intermediate doses of cimetidine. If a patient requires TIKOSYN and anti-ulcer therapy, it is suggested that omeprazole, ranitidine, or antacids (aluminum and magnesium hydroxides) be used as alternatives to cimetidine, as these agents have no effect on the pharmacokinetic profile of TIKOSYN. Verapamil: Concomitant use of verapamil is contraindicated. Co-administration of TIKOSYN with verapamil resulted in increases in dofetilide peak plasma levels of 42%, although overall exposure to dofetilide was not significantly increased. In an analysis of the supraventricular arrhythmia and DIAMOND patient populations, the concomitant administration of verapamil with dofetilide was associated with a higher occurrence of torsade de pointes. Ketoconazole: Concomitant use of ketoconazole is contraindicated. Ketoconazole at 400 mg daily (the maximum approved prescription dose) co-administered with TIKOSYN (500 mcg BID) for 7 days has been shown to increase dofetilide Cmax by 53% in males and 97% in females, and AUC by 41% in males and 69% in females. Trimethoprim Alone or in Combination with Sulfamethoxazole: Concomitant use of trimethoprim alone or in combination with sulfamethoxazole is contraindicated. Hydrochlorothiazide (HCTZ) Alone or in Combination with Triamterene: Concomitant use of HCTZ alone or in combination with triamterene is contraindicated. HCTZ 50 mg QD or HCTZ/triamterene 50/100 mg QD was co-administered with TIKOSYN (500 mcg BID) for 5 days (following 2 days of diuretic use at half dose). In patients receiving HCTZ alone, dofetilide AUC increased by 27% and Cmax by 21%. However, the pharmacodynamic effect increased by 197% (QTc increase over time) and by 95% (maximum QTc increase). However, the pharmacodynamic effect increased by 190% (QTc increase over time) and by 84% (Maximum QTc increase). The pharmacodynamic effects can be explained by a combination of the increase in dofetilide exposure and the reductions in serum potassium. In the DIAMOND trials, 1252 patients were treated with TIKOSYN and diuretics concomitantly of whom 493 died compared to 508 deaths among the 1248 patients receiving placebo and diuretics. Of the 229 patients who had potassium depleting diuretics added to their concomitant medications in the DIAMOND trials, the patients on TIKOSYN had a non-significantly reduced relative risk for death of 0.68 (95% CI 0.376, 1.230). Potential Drug Interactions Dofetilide is eliminated in the kidney by cationic secretion. Inhibitors of renal cationic secretion are contraindicated with TIKOSYN. In addition, drugs that are actively secreted via this route (e.g., triamterene, metformin and amiloride) should be co-administered with care as they might increase dofetilide levels. Dofetilide is metabolized to a small extent by the CYP3A4 isoenzyme of the cytochrome P450 system. Inhibitors of the CYP3A4 isoenzyme could increase systemic dofetilide exposure. Inhibitors of this isoenzyme (e.g., macrolide antibiotics, azole antifungal agents, protease inhibitors, serotonin reuptake inhibitors, amiodarone, cannabinoids, diltiazem, grapefruit juice, nefazadone, norfloxacin, quinine, zafirlukast) should be cautiously coadministered with TIKOSYN as they can potentially increase dofetilide levels. Dofetilide is not an inhibitor of CYP3A4 nor of other cytochrome P450 isoenzymes (e.g., CYP2C9, CYP2D6) and is not expected to increase levels of drugs metabolized by CYP3A4. Other Drug Interaction Information Digoxin: Studies in healthy volunteers have shown that TIKOSYN does not affect the pharmacokinetics of digoxin. In patients, the concomitant administration of digoxin with dofetilide was associated with a higher occurrence of torsade de pointes. It is not clear whether this represents an interaction with TIKOSYN or the presence of more severe structural heart disease in patients on digoxin; structural heart disease is a known risk factor for arrhythmia. No increase in mortality was observed in patients taking digoxin as concomitant medication. Other Drugs: In healthy volunteers, amlodipine, phenytoin, glyburide, ranitidine, omeprazole, hormone replacement therapy (a combination of conjugated estrogens and medroxyprogesterone), antacid (aluminum and magnesium hydroxides) and theophylline did not affect the pharmacokinetics of TIKOSYN. In addition, studies in healthy volunteers have shown that TIKOSYN does not affect the pharmacokinetics or pharmacodynamics of warfarin, or the pharmacokinetics of propranolol (40 mg twice daily), phenytoin, theophylline, or oral contraceptives. Population pharmacokinetic analyses were conducted on plasma concentration data from 1445 patients in clinical trials to examine the effects of concomitant medications on clearance or volume of distribution of dofetilide. Concomitant medications were grouped as ACE inhibitors, oral anticoagulants, calcium channel blockers, beta blockers, cardiac glycosides, inducers of CYP3A4, substrates and inhibitors of CYP3A4, substrates and inhibitors of P-glycoprotein, nitrates, sulphonylureas, loop diuretics, potassium sparing diuretics, thiazide diuretics, substrates and inhibitors of tubular organic cation transport, and QTc-prolonging drugs. Differences in clearance between patients on these medications (at any occasion in the study) and those off medications varied between -16% and +3%. The mean clearances of dofetilide were 16% and 15% lower in patients on thiazide diuretics and inhibitors of tubular organic cation transport, respectively." ], "offsets": [ [ 0, 5960 ] ] } ]

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"BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 513, 520 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T10", "type": "GROUP", "text": [ "anti-ulcer" ], "offsets": [ [ 525, 535 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T11", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 566, 576 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T12", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 578, 588 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T13", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 593, 601 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T14", "type": "DRUG", "text": [ "aluminum", "hydroxide" ], "offsets": [ [ 603, 611 ], [ 626, 635 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T15", "type": "DRUG", "text": [ "magnesium hydroxide" ], "offsets": [ [ 616, 635 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T16", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 665, 675 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T17", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 742, 749 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T18", "type": "DRUG", "text": [ "Verapamil" ], "offsets": [ [ 751, 760 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T19", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 781, 790 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T20", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 832, 839 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T21", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 845, 854 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T22", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 880, 890 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T23", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 947, 957 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T24", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 1108, 1117 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T25", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 1123, 1133 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T26", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 1197, 1209 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T27", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 1230, 1242 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T28", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 1263, 1275 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T29", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 1354, 1361 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T30", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 1414, 1424 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T31", "type": "DRUG", "text": [ "Trimethoprim" ], "offsets": [ [ 1510, 1522 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T32", "type": "DRUG", "text": [ "Sulfamethoxazole" ], "offsets": [ [ 1552, 1568 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T33", "type": "DRUG", "text": [ "trimethoprim" ], "offsets": [ [ 1589, 1601 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T34", "type": "DRUG", "text": [ "sulfamethoxazole" ], "offsets": [ [ 1631, 1647 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T35", "type": "DRUG", "text": [ "Hydrochlorothiazide" ], "offsets": [ [ 1668, 1687 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T36", "type": "DRUG", "text": [ "HCTZ" ], "offsets": [ [ 1689, 1693 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T37", "type": "DRUG", "text": [ "Triamterene" ], "offsets": [ [ 1724, 1735 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T38", "type": "DRUG", "text": [ "HCTZ" ], "offsets": [ [ 1756, 1760 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T39", "type": "DRUG", "text": [ "triamterene" ], "offsets": [ [ 1790, 1801 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T40", "type": "DRUG", "text": [ "HCTZ" ], "offsets": [ [ 1822, 1826 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T41", "type": "DRUG", "text": [ "HCTZ" ], "offsets": [ [ 1839, 1843 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T42", "type": "DRUG", "text": [ "triamterene" ], "offsets": [ [ 1844, 1855 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T43", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 1894, 1901 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T44", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 1948, 1956 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T45", "type": "DRUG", "text": [ "HCTZ" ], "offsets": [ [ 1998, 2002 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T46", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 2010, 2020 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T47", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 2368, 2378 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T48", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 2482, 2489 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T49", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 2494, 2503 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T50", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 2604, 2613 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T51", "type": "GROUP", "text": [ "potassium depleting diuretics" ], "offsets": [ [ 2643, 2672 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T52", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 2751, 2758 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T53", "type": "DRUG", "text": [ "Dofetilide" ], "offsets": [ [ 2874, 2884 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T54", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 3000, 3007 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T55", "type": "DRUG", "text": [ "triamterene" ], "offsets": [ [ 3077, 3088 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T56", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 3090, 3099 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T57", "type": "DRUG", "text": [ "amiloride" ], "offsets": [ [ 3104, 3113 ] ], "normalized": [] 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"offsets": [ [ 3508, 3518 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T66", "type": "GROUP", "text": [ "cannabinoids" ], "offsets": [ [ 3520, 3532 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T67", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 3534, 3543 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T68", "type": "DRUG", "text": [ "nefazadone" ], "offsets": [ [ 3563, 3573 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T69", "type": "DRUG", "text": [ "norfloxacin" ], "offsets": [ [ 3575, 3586 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T70", "type": "DRUG", "text": [ "quinine" ], "offsets": [ [ 3588, 3595 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T71", "type": "DRUG", "text": [ "zafirlukast" ], "offsets": [ [ 3597, 3608 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T72", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 3651, 3658 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T73", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 3692, 3702 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T74", "type": "DRUG", "text": [ "Dofetilide" ], "offsets": [ [ 3711, 3721 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T75", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 3921, 3928 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T76", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 3976, 3983 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T77", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 4024, 4031 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T78", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 4080, 4087 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T79", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 4093, 4103 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T80", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 4227, 4234 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T81", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 4306, 4313 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T82", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 4436, 4443 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T83", "type": "DRUG", "text": [ "amlodipine" ], "offsets": [ [ 4507, 4517 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T84", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 4519, 4528 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T85", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 4530, 4539 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T86", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 4541, 4551 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T87", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 4553, 4563 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T88", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 4622, 4631 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T89", "type": "DRUG", "text": [ "medroxyprogesterone" ], "offsets": [ [ 4636, 4655 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T90", "type": "GROUP", "text": [ "antacid" ], "offsets": [ [ 4658, 4665 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T91", "type": "DRUG", "text": [ "aluminum", "hydroxide" ], "offsets": [ [ 4667, 4675 ], [ 4690, 4699 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T92", "type": "DRUG", "text": [ "magnesium hydroxide" ], "offsets": [ [ 4680, 4699 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T93", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 4706, 4718 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T94", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 4758, 4765 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T95", "type": "BRAND", "text": [ "TIKOSYN" ], "offsets": [ [ 4826, 4833 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T96", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4894, 4902 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T97", "type": "DRUG", "text": [ "propranolol" ], "offsets": [ [ 4931, 4942 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T98", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 4964, 4973 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T99", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 4975, 4987 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T100", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 4997, 5011 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T101", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 5223, 5233 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T102", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 5275, 5289 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T103", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 5296, 5310 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T104", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 5312, 5336 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T105", "type": "GROUP", "text": [ "beta blockers" ], "offsets": [ [ 5338, 5351 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T106", "type": "GROUP", "text": [ "cardiac glycosides" ], "offsets": [ [ 5353, 5371 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T107", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 5475, 5483 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T108", "type": "GROUP", "text": [ "sulphonylureas" ], "offsets": [ [ 5485, 5499 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T109", "type": "GROUP", "text": [ "loop diuretics" ], "offsets": [ [ 5501, 5515 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T110", "type": "GROUP", "text": [ "potassium sparing diuretics" ], "offsets": [ [ 5517, 5544 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T111", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 5546, 5564 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T112", "type": "DRUG", "text": [ "dofetilide" ], "offsets": [ [ 5827, 5837 ] ], "normalized": [] }, { "id": "Dofetilide_ddi_T113", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 5876, 5894 ] ], "normalized": [] } ]

[]

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[ { "id": "Dofetilide_ddi_R1", "type": "MECHANISM", "arg1_id": "Dofetilide_ddi_T3", "arg2_id": "Dofetilide_ddi_T4", "normalized": [] }, { "id": "Dofetilide_ddi_R2", "type": "MECHANISM", "arg1_id": "Dofetilide_ddi_T6", "arg2_id": "Dofetilide_ddi_T7", "normalized": [] }, { "id": "Dofetilide_ddi_R3", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T9", "arg2_id": "Dofetilide_ddi_T16", "normalized": [] }, { "id": "Dofetilide_ddi_R4", "type": "MECHANISM", "arg1_id": "Dofetilide_ddi_T20", "arg2_id": "Dofetilide_ddi_T21", "normalized": [] }, { "id": "Dofetilide_ddi_R5", "type": "EFFECT", "arg1_id": "Dofetilide_ddi_T24", "arg2_id": "Dofetilide_ddi_T25", "normalized": [] }, { "id": "Dofetilide_ddi_R6", "type": "MECHANISM", "arg1_id": "Dofetilide_ddi_T28", "arg2_id": "Dofetilide_ddi_T29", "normalized": [] }, { "id": "Dofetilide_ddi_R7", "type": "MECHANISM", "arg1_id": "Dofetilide_ddi_T45", "arg2_id": "Dofetilide_ddi_T46", "normalized": [] }, { "id": "Dofetilide_ddi_R8", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T55", "arg2_id": "Dofetilide_ddi_T58", "normalized": [] }, { "id": "Dofetilide_ddi_R9", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T56", "arg2_id": "Dofetilide_ddi_T58", "normalized": [] }, { "id": "Dofetilide_ddi_R10", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T57", "arg2_id": "Dofetilide_ddi_T58", "normalized": [] }, { "id": "Dofetilide_ddi_R11", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T61", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R12", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T62", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R13", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T63", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R14", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T64", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R15", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T65", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R16", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T66", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R17", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T67", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R18", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T68", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R19", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T69", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R20", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T70", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R21", "type": "ADVISE", "arg1_id": "Dofetilide_ddi_T71", "arg2_id": "Dofetilide_ddi_T72", "normalized": [] }, { "id": "Dofetilide_ddi_R22", "type": "EFFECT", "arg1_id": "Dofetilide_ddi_T78", "arg2_id": "Dofetilide_ddi_T79", "normalized": [] }, { "id": "Dofetilide_ddi_R23", "type": "MECHANISM", "arg1_id": "Dofetilide_ddi_T112", "arg2_id": "Dofetilide_ddi_T113", "normalized": [] } ]

[ { "id": "Docetaxel_ddi__text", "type": "abstract", "text": [ "There have been no formal clinical studies to evaluate the drug interactions of TAXOTERE with other medications. In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4, such as cyclosporine, terfenadine, ketoconazole, erythromycin, and troleandomycin. Caution should be exercised with these drugs when treating patients receiving TAXOTERE as there is a potential for a significant interaction." ], "offsets": [ [ 0, 526 ] ] } ]

[ { "id": "Docetaxel_ddi_T1", "type": "BRAND", "text": [ "TAXOTERE" ], "offsets": [ [ 80, 88 ] ], "normalized": [] }, { "id": "Docetaxel_ddi_T2", "type": "DRUG", "text": [ "docetaxel" ], "offsets": [ [ 164, 173 ] ], "normalized": [] }, { "id": "Docetaxel_ddi_T3", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 310, 322 ] ], "normalized": [] }, { "id": "Docetaxel_ddi_T4", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 324, 335 ] ], "normalized": [] }, { "id": "Docetaxel_ddi_T5", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 337, 349 ] ], "normalized": [] }, { "id": "Docetaxel_ddi_T6", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 351, 363 ] ], "normalized": [] }, { "id": "Docetaxel_ddi_T7", "type": "DRUG", "text": [ "troleandomycin" ], "offsets": [ [ 369, 383 ] ], "normalized": [] }, { "id": "Docetaxel_ddi_T8", "type": "BRAND", "text": [ "TAXOTERE" ], "offsets": [ [ 463, 471 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Docetaxel_ddi_R1", "type": "MECHANISM", "arg1_id": "Docetaxel_ddi_T2", "arg2_id": "Docetaxel_ddi_T3", "normalized": [] }, { "id": "Docetaxel_ddi_R2", "type": "MECHANISM", "arg1_id": "Docetaxel_ddi_T2", "arg2_id": "Docetaxel_ddi_T4", "normalized": [] }, { "id": "Docetaxel_ddi_R3", "type": "MECHANISM", "arg1_id": "Docetaxel_ddi_T2", "arg2_id": "Docetaxel_ddi_T5", "normalized": [] }, { "id": "Docetaxel_ddi_R4", "type": "MECHANISM", "arg1_id": "Docetaxel_ddi_T2", "arg2_id": "Docetaxel_ddi_T6", "normalized": [] }, { "id": "Docetaxel_ddi_R5", "type": "MECHANISM", "arg1_id": "Docetaxel_ddi_T2", "arg2_id": "Docetaxel_ddi_T7", "normalized": [] } ]

[ { "id": "Icodextrin_ddi__text", "type": "abstract", "text": [ "General No clinical drug interaction studies were performed. No evaluation of EXTRANEALs effects on the cytochrome P450 system was conducted. As with other dialysis solutions, blood concentrations of dialyzable drugs may be reduced by dialysis. Dosage adjustment of concomitant medications may be necessary. In patients using cardiac glycosides (digoxin and others), plasma levels of calcium, potassium and magnesium must be carefully monitored. Insulin: A clinical study in 6 insulin-dependent diabetic patients demonstrated no effect of EXTRANEAL on insulin absorption from the peritoneal cavity or on insulins ability to control blood glucose when insulin was administered intraperitoneally with EXTRANEAL. However, appropriate monitoring of blood glucose should be performed when initiating EXTRANEAL in diabetic patients and insulin dosage should be adjusted if needed. Heparin: No human drug interaction studies with heparin were conducted. In vitro studies demonstrated no evidence of incompatibility of heparin with EXTRANEAL. Antibiotics: No human drug interaction studies with antibiotics were conducted. In vitro studies evaluating the minimum inhibitory concentration (MIC) of vancomycin, cefazolin, ampicillin, ampicillin/flucoxacillin, ceftazidime, gentamicin, and amphotericin demonstrated no evidence of incompatibility of these antibiotics with EXTRANEAL. Drug/Laboratory Test Interactions Blood Glucose Blood glucose measurement must be done with a glucose-specific method to prevent maltose interference with test results. Since falsely elevated glucose levels have been observed with blood glucose monitoring devices and test strips that use glucose dehydrogenase pyrroloquinolinequinone (GDH PQQ)-based methods, GDH PQQ-based methods should not be used to measure glucose levels in patients administered EXTRANEAL.. Serum Amylase An apparent decrease in serum amylase activity has been observed in patients administered EXTRANEAL. Preliminary investigations indicate that icodextrin and its metabolites interfere with enzymatic-based amylase assays, resulting in inaccurately low values. This should be taken into account when evaluating serum amylase levels for diagnosis or monitoring of pancreatitis in patients using EXTRANEAL." ], "offsets": [ [ 0, 2252 ] ] } ]

[ { "id": "Icodextrin_ddi_T1", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 78, 87 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T2", "type": "GROUP", "text": [ "dialysis solutions" ], "offsets": [ [ 156, 174 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T3", "type": "GROUP", "text": [ "cardiac glycosides" ], "offsets": [ [ 326, 344 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T4", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 346, 353 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T5", "type": "DRUG", "text": [ "Insulin" ], "offsets": [ [ 446, 453 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T6", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 539, 548 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T7", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 552, 559 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T8", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 604, 611 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T9", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 651, 658 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T10", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 699, 708 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T11", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 795, 804 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T12", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 830, 837 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T13", "type": "DRUG", "text": [ "Heparin" ], "offsets": [ [ 875, 882 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T14", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 923, 930 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T15", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 1011, 1018 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T16", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 1024, 1033 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T17", "type": "GROUP", "text": [ "Antibiotics" ], "offsets": [ [ 1035, 1046 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T18", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 1087, 1098 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T19", "type": "DRUG", "text": [ "vancomycin" ], "offsets": [ [ 1189, 1199 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T20", "type": "DRUG", "text": [ "cefazolin" ], "offsets": [ [ 1201, 1210 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T21", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 1212, 1222 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T22", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 1224, 1234 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T23", "type": "DRUG", "text": [ "ceftazidime" ], "offsets": [ [ 1250, 1261 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T24", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 1263, 1273 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T25", "type": "DRUG", "text": [ "amphotericin" ], "offsets": [ [ 1279, 1291 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T26", "type": "GROUP", "text": [ "antibiotics" ], "offsets": [ [ 1345, 1356 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T27", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 1362, 1371 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T28", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 1825, 1834 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T29", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 1941, 1950 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T30", "type": "DRUG", "text": [ "icodextrin" ], "offsets": [ [ 1993, 2003 ] ], "normalized": [] }, { "id": "Icodextrin_ddi_T31", "type": "BRAND", "text": [ "EXTRANEAL" ], "offsets": [ [ 2242, 2251 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Icodextrin_ddi_R1", "type": "ADVISE", "arg1_id": "Icodextrin_ddi_T11", "arg2_id": "Icodextrin_ddi_T12", "normalized": [] } ]

[ { "id": "Gabapentin_ddi__text", "type": "abstract", "text": [ "In vitro studies were conducted to investigate the potential of gabapentin to inhibit the major cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) that mediate drug and xenobiotic metabolism using isoform selective marker substrates and human liver microsomal preparations. Only at the highest concentration tested (171 g/mL; 1 mM) was a slight degree of inhibition (14%-30%) of isoform CYP2A6 observed. No inhibition of any of the other isoforms tested was observed at gabapentin concentrations up to 171 mg/mL (approximately 15 times the Cmax at 3600 mg/day). Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly coadministered antiepileptic drugs. The drug interaction data described in this section were obtained from studies involving healthy adults and adult patients with epilepsy. Phenytoin: In a single (400 mg) and multiple dose (400 mg TID) study of Neurontin in epileptic patients (N=8) maintained on phenytoin monotherapy for at least 2 months, gabapentin had no effect on the steady-state trough plasma concentrations of phenytoin and phenytoin had no effect on gabapentin pharmacokinetics. Carbamazepine: Steady-state trough plasma carbamazepine and carbamazepine 10, 11 epoxide concentrations were not affected by concomitant gabapentin (400 mg TID; N=12) administration. Likewise, gabapentin pharmacokinetics were unaltered by carbamazepine administration. Valproic Acid: The mean steady-state trough serum valproic acid concentrations prior to and during concomitant gabapentin administration (400 mg TID; N=17) were not different and neither were gabapentin pharmacokinetic parameters affected by valproic acid. Phenobarbital: Estimates of steady-state pharmacokinetic parameters for phenobarbital or gabapentin (300 mg TID; N=12) are identical whether the drugs are administered alone or together. Naproxen: Coadministration (N=18) of naproxen sodium capsules (250 mg) with Neurontin (125 mg) appears to increase the amount of gabapentin absorbed by 12% to 15%. Gabapentin had no effect on naproxen pharmacokinetic parameters. These doses are lower than the therapeutic doses for both drugs. The magnitude of interaction within the recommended dose ranges of either drug is not known. Hydrocodone: Coadministration of Neurontin (125 to 500 mg; N=48) decreases hydrocodone (10 mg; N=50) Cmax and AUC values in a dose-dependent manner relative to administration of hydrocodone alone; Cmax and AUC values are 3% to 4% lower, respectively, after administration of 125 mg Neurontin and 21% to 22% lower, respectively, after administration of 500 mg Neurontin . The mechanism for this interaction is unknown. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other doses is not known. Morphine: A literature article reported that when a 60-mg controlled-release morphine capsule was administered 2 hours prior to a 600-mg Neurontin capsule (N=12), mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Morphine pharmacokinetic parameter values were not affected by administration of Neurontin 2 hours after morphine. The magnitude of interaction at other doses is not known. Cimetidine: In the presence of cimetidine at 300 mg QID (N=12) the mean apparent oral clearance of gabapentin fell by 14% and creatinine clearance fell by 10%. Thus cimetidine appeared to alter the renal excretion of both gabapentin and creatinine, an endogenous marker of renal function. This small decrease in excretion of gabapentin by cimetidine is not expected to be of clinical importance. The effect of gabapentin on cimetidine was not evaluated. Oral Contraceptive: Based on AUC and half-life, multiple-dose pharmacokinetic profiles of norethindrone and ethinyl estradiol following administration of tablets containing 2.5 mg of norethindrone acetate and 50 mcg of ethinyl estradiol were similar with and without coadministration of gabapentin (400 mg TID; N=13). The Cmax of norethindrone was 13% higher when it was coadministered with gabapentin; this interaction is not expected to be of clinical importance. Antacid (Maalox ): Maalox reduced the bioavailability of gabapentin (N=16) by about 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after Maalox. It is recommended that gabapentin be taken at least 2 hours following Maalox administration. Effect of Probenecid: Probenecid is a blocker of renal tubular secretion. Gabapentin pharmacokinetic parameters without and with probenecid were comparable. This indicates that gabapentin does not undergo renal tubular secretion by the pathway that is blocked by probenecid. Drug/Laboratory Tests Interactions Because false positive readings were reported with the Ames N-Multistix SG dipstick test for urinary protein when gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein ." ], "offsets": [ [ 0, 5041 ] ] } ]

[ { "id": "Gabapentin_ddi_T1", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 64, 74 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T2", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 505, 515 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T3", "type": "DRUG", "text": [ "Gabapentin" ], "offsets": [ [ 597, 607 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T4", "type": "GROUP", "text": [ "antiepileptic drugs" ], "offsets": [ [ 708, 727 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T5", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 867, 876 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T6", "type": "BRAND", "text": [ "Neurontin" ], "offsets": [ [ 939, 948 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T7", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 991, 1000 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T8", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 1036, 1046 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T9", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1113, 1122 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T10", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1127, 1136 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T11", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 1154, 1164 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T12", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 1183, 1196 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T13", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1225, 1238 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T14", "type": "DRUG_N", "text": [ "carbamazepine 10, 11 epoxide" ], "offsets": [ [ 1243, 1271 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T15", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 1320, 1330 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T16", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 1376, 1386 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T17", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1422, 1435 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T18", "type": "DRUG", "text": [ "Valproic Acid" ], "offsets": [ [ 1452, 1465 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T19", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 1502, 1515 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T20", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 1563, 1573 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T21", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 1644, 1654 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T22", "type": "DRUG", "text": [ "valproic acid" ], "offsets": [ [ 1694, 1707 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T23", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 1709, 1722 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T24", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 1781, 1794 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T25", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 1798, 1808 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T26", "type": "DRUG", "text": [ "Naproxen" ], "offsets": [ [ 1896, 1904 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T27", "type": "DRUG", "text": [ "naproxen sodium" ], "offsets": [ [ 1933, 1948 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T28", "type": "BRAND", "text": [ "Neurontin" ], "offsets": [ [ 1972, 1981 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T29", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 2025, 2035 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T30", "type": "DRUG", "text": [ "Gabapentin" ], "offsets": [ [ 2060, 2070 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T31", "type": "DRUG", "text": [ "naproxen" ], "offsets": [ [ 2088, 2096 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T32", "type": "DRUG", "text": [ "Hydrocodone" ], "offsets": [ [ 2283, 2294 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T33", "type": "BRAND", "text": [ "Neurontin" ], "offsets": [ [ 2316, 2325 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T34", "type": "DRUG", "text": [ "hydrocodone" ], "offsets": [ [ 2359, 2370 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T35", "type": "DRUG", "text": [ "hydrocodone" ], "offsets": [ [ 2462, 2473 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T36", "type": "BRAND", "text": [ "Neurontin" ], "offsets": [ [ 2566, 2575 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T37", "type": "BRAND", "text": [ "Neurontin" ], "offsets": [ [ 2644, 2653 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T38", "type": "DRUG", "text": [ "Hydrocodone" ], "offsets": [ [ 2703, 2714 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T39", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 2725, 2735 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T40", "type": "DRUG", "text": [ "Morphine" ], "offsets": [ [ 2813, 2821 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T41", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 2890, 2898 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T42", "type": "BRAND", "text": [ "Neurontin" ], "offsets": [ [ 2950, 2959 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T43", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 2982, 2992 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T44", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 3026, 3036 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T45", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 3058, 3066 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T46", "type": "DRUG", "text": [ "Morphine" ], "offsets": [ [ 3068, 3076 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T47", "type": "BRAND", "text": [ "Neurontin" ], "offsets": [ [ 3149, 3158 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T48", "type": "DRUG", "text": [ "morphine" ], "offsets": [ [ 3174, 3182 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T49", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 3242, 3252 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T50", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3273, 3283 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T51", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 3341, 3351 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T52", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3407, 3417 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T53", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 3464, 3474 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T54", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 3567, 3577 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T55", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3581, 3591 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T56", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 3652, 3662 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T57", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3666, 3676 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T58", "type": "GROUP", "text": [ "Contraceptive" ], "offsets": [ [ 3701, 3714 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T59", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 3786, 3799 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T60", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 3804, 3821 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T61", "type": "DRUG", "text": [ "norethindrone acetate" ], "offsets": [ [ 3879, 3900 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T62", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 3915, 3932 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T63", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 3983, 3993 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T64", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 4026, 4039 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T65", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 4087, 4097 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T66", "type": "GROUP", "text": [ "Antacid" ], "offsets": [ [ 4162, 4169 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T67", "type": "BRAND", "text": [ "Maalox" ], "offsets": [ [ 4171, 4177 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T68", "type": "BRAND", "text": [ "Maalox" ], "offsets": [ [ 4181, 4187 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T69", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 4219, 4229 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T70", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 4302, 4312 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T71", "type": "BRAND", "text": [ "Maalox" ], "offsets": [ [ 4344, 4350 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T72", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 4375, 4385 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T73", "type": "BRAND", "text": [ "Maalox" ], "offsets": [ [ 4422, 4428 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T74", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 4455, 4465 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T75", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 4467, 4477 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T76", "type": "DRUG", "text": [ "Gabapentin" ], "offsets": [ [ 4519, 4529 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T77", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 4574, 4584 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T78", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 4622, 4632 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T79", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 4708, 4718 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T80", "type": "DRUG", "text": [ "gabapentin" ], "offsets": [ [ 4869, 4879 ] ], "normalized": [] }, { "id": "Gabapentin_ddi_T81", "type": "GROUP", "text": [ "antiepileptic drugs" ], "offsets": [ [ 4899, 4918 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Gabapentin_ddi_R1", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T27", "arg2_id": "Gabapentin_ddi_T28", "normalized": [] }, { "id": "Gabapentin_ddi_R2", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T38", "arg2_id": "Gabapentin_ddi_T39", "normalized": [] }, { "id": "Gabapentin_ddi_R3", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T41", "arg2_id": "Gabapentin_ddi_T42", "normalized": [] }, { "id": "Gabapentin_ddi_R4", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T50", "arg2_id": "Gabapentin_ddi_T51", "normalized": [] }, { "id": "Gabapentin_ddi_R5", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T52", "arg2_id": "Gabapentin_ddi_T53", "normalized": [] }, { "id": "Gabapentin_ddi_R6", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T54", "arg2_id": "Gabapentin_ddi_T55", "normalized": [] }, { "id": "Gabapentin_ddi_R7", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T64", "arg2_id": "Gabapentin_ddi_T65", "normalized": [] }, { "id": "Gabapentin_ddi_R8", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T68", "arg2_id": "Gabapentin_ddi_T69", "normalized": [] }, { "id": "Gabapentin_ddi_R9", "type": "MECHANISM", "arg1_id": "Gabapentin_ddi_T70", "arg2_id": "Gabapentin_ddi_T71", "normalized": [] }, { "id": "Gabapentin_ddi_R10", "type": "ADVISE", "arg1_id": "Gabapentin_ddi_T72", "arg2_id": "Gabapentin_ddi_T73", "normalized": [] } ]

[ { "id": "Formoterol_ddi__text", "type": "abstract", "text": [ "Short-Acting beta2-agonists: Aerosol bronchodilators of the short-acting adrenergic stimulant type may be used for relief of breakthrough symptoms while using formoterol. However, increasing use of such preparations to control symptoms indicates deterioration of asthma control and the need to reassess the patient s therapy. Concomitant administration of other sympathomimetic agents may potentiate the undesirable effects of FORADIL. Monoamine Oxidase Inhibitors and Tricyclic Antidepressants: FORADIL should be administered with extreme caution in patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants because the action of formoterol on the cardiovascular system may be potentiated by these agents. Corticosteroids, Methylxanthines and Diuretics: Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate a possible hypokalemic effect of beta2-agonists. Hypokalemia may increase susceptibility to cardiac arrhythmias in patients treated with digitalis. -adrenergic Blockers: -adrenergic blockers may weaken or antagonise the effect of FORADIL. Therefore FORADIL should not be given together with -adrenergic blockers (including eye drops) unless there are compelling reasons for their use. Other Drugs:Drugs such as quinidine, disopyramide, procainamide, phenothiazines, antihistamines, and tricyclic antidepressants may be associated with QT-interval prolongation and an increased risk of ventricular arrhythmia. INFORMATION TO BE PROVIDED TO THE PATIENT OR GUARDIAN See illustrated Information For The Patient or Guardian section. It is important that patients understand how to use FORADIL (formoterol fumarate) capsules with the supplied AerolizerTM inhalation device and how it should be used in relation to other asthma or COPD medications they are taking. Patients/Guardians should be given the following information: i. The recommended dosage (one or two capsules twice daily, morning and evening) should not be exceeded. ii. FORADIL is not meant to relieve acute asthma or COPD symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with a short-acting, inhaled beta2-agonist such as salbutamol (the physician should provide the patient with such medication and instruct the patient in how it should be used). iii. The physician should be notified immediately if any of the following situations occur, which may be a sign of seriously worsening asthma: Decreased effectiveness of short-acting, inhaled beta2-agonists; Need for more inhalations than usual of short-acting, inhaled beta2-agonists. iv. FORADIL should not be used as a substitute for oral or inhaled corticosteroids. The dosage of these medications should not be changed and they should not be stopped without consulting the physician, even if the patient feels better after initiating treatment with FORADIL. v. Patients should be cautioned regarding potential adverse cardiovascular effects, such as palpitations or chest pain. vi. In patients receiving FORADIL, other inhaled medications should be used only as directed by the physician. vii. Guardians of children who have been prescribed FORADIL should be alerted to the general concern regarding asthma therapy compliance, especially neglect of anti-inflammatory therapy and overuse of short-acting beta2-agonists." ], "offsets": [ [ 0, 3355 ] ] } ]

[ { "id": "Formoterol_ddi_T1", "type": "GROUP", "text": [ "Short-Acting beta2-agonists" ], "offsets": [ [ 0, 27 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T2", "type": "GROUP", "text": [ "bronchodilators" ], "offsets": [ [ 37, 52 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T3", "type": "DRUG", "text": [ "formoterol" ], "offsets": [ [ 159, 169 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T4", "type": "GROUP", "text": [ "sympathomimetic agents" ], "offsets": [ [ 362, 384 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T5", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 427, 434 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T6", "type": "GROUP", "text": [ "Monoamine Oxidase Inhibitors" ], "offsets": [ [ 436, 464 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T7", "type": "GROUP", "text": [ "Tricyclic Antidepressants" ], "offsets": [ [ 469, 494 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T8", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 496, 503 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T9", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 579, 607 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T10", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 611, 636 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T11", "type": "DRUG", "text": [ "formoterol" ], "offsets": [ [ 659, 669 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T12", "type": "GROUP", "text": [ "Corticosteroids" ], "offsets": [ [ 735, 750 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T13", "type": "GROUP", "text": [ "Methylxanthines" ], "offsets": [ [ 752, 767 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T14", "type": "GROUP", "text": [ "Diuretics" ], "offsets": [ [ 772, 781 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T15", "type": "GROUP", "text": [ "xanthine derivatives" ], "offsets": [ [ 810, 830 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T16", "type": "GROUP", "text": [ "steroids" ], "offsets": [ [ 832, 840 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T17", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 845, 854 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T18", "type": "GROUP", "text": [ "beta2-agonists." ], "offsets": [ [ 904, 919 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T19", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 1008, 1017 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T20", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 1102, 1109 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T21", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 1121, 1128 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T22", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1284, 1293 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T23", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 1295, 1307 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T24", "type": "DRUG", "text": [ "procainamide" ], "offsets": [ [ 1309, 1321 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T25", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 1323, 1337 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T26", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 1339, 1353 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T27", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 1359, 1384 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T28", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 1653, 1660 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T29", "type": "DRUG", "text": [ "formoterol fumarate" ], "offsets": [ [ 1663, 1682 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T30", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 2003, 2010 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T31", "type": "GROUP", "text": [ "beta2-agonist" ], "offsets": [ [ 2181, 2194 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T32", "type": "DRUG", "text": [ "salbutamol" ], "offsets": [ [ 2203, 2213 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T33", "type": "GROUP", "text": [ "short-acting, inhaled beta2-agonists" ], "offsets": [ [ 2501, 2537 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T34", "type": "GROUP", "text": [ "short-acting, inhaled beta2-agonists" ], "offsets": [ [ 2579, 2615 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T35", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 2621, 2628 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T36", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 2684, 2699 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T37", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 2885, 2892 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T38", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 3040, 3047 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T39", "type": "BRAND", "text": [ "FORADIL" ], "offsets": [ [ 3177, 3184 ] ], "normalized": [] }, { "id": "Formoterol_ddi_T40", "type": "GROUP", "text": [ "short-acting beta2-agonists" ], "offsets": [ [ 3326, 3354 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Formoterol_ddi_R1", "type": "EFFECT", "arg1_id": "Formoterol_ddi_T4", "arg2_id": "Formoterol_ddi_T5", "normalized": [] }, { "id": "Formoterol_ddi_R2", "type": "ADVISE", "arg1_id": "Formoterol_ddi_T8", "arg2_id": "Formoterol_ddi_T9", "normalized": [] }, { "id": "Formoterol_ddi_R3", "type": "ADVISE", "arg1_id": "Formoterol_ddi_T8", "arg2_id": "Formoterol_ddi_T10", "normalized": [] }, { "id": "Formoterol_ddi_R4", "type": "EFFECT", "arg1_id": "Formoterol_ddi_T15", "arg2_id": "Formoterol_ddi_T18", "normalized": [] }, { "id": "Formoterol_ddi_R5", "type": "EFFECT", "arg1_id": "Formoterol_ddi_T16", "arg2_id": "Formoterol_ddi_T18", "normalized": [] }, { "id": "Formoterol_ddi_R6", "type": "EFFECT", "arg1_id": "Formoterol_ddi_T17", "arg2_id": "Formoterol_ddi_T18", "normalized": [] } ]

[ { "id": "Nadolol_ddi__text", "type": "abstract", "text": [ "When administered concurrently, the following drugs may interact with beta-adrenergic receptor blocking agents: Anesthetics, general: exaggeration of the hypotension induced by general anesthetics. Antidiabetic drugs (oral agents and insulin): hypoglycemia or hyperglycemia; adjust dosage of antidiabetic drug accordingly. Catecholamine-depleting drugs (e.g., reserpine): additive effect; monitor closely for evidence of hypotension and/or excessive bradycardia (e.g., vertigo, syncope, postural hypotension). Response to Treatment for Anaphylactic Reaction: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction." ], "offsets": [ [ 0, 860 ] ] } ]

[ { "id": "Nadolol_ddi_T1", "type": "GROUP", "text": [ "beta-adrenergic receptor blocking agents" ], "offsets": [ [ 70, 110 ] ], "normalized": [] }, { "id": "Nadolol_ddi_T2", "type": "GROUP", "text": [ "Anesthetics" ], "offsets": [ [ 112, 123 ] ], "normalized": [] }, { "id": "Nadolol_ddi_T3", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 185, 196 ] ], "normalized": [] }, { "id": "Nadolol_ddi_T4", "type": "GROUP", "text": [ "Antidiabetic drugs" ], "offsets": [ [ 198, 216 ] ], "normalized": [] }, { "id": "Nadolol_ddi_T5", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 234, 241 ] ], "normalized": [] }, { "id": "Nadolol_ddi_T6", "type": "GROUP", "text": [ "antidiabetic drug" ], "offsets": [ [ 292, 309 ] ], "normalized": [] }, { "id": "Nadolol_ddi_T7", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 360, 369 ] ], "normalized": [] }, { "id": "Nadolol_ddi_T8", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 572, 585 ] ], "normalized": [] }, { "id": "Nadolol_ddi_T9", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 816, 827 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Nadolol_ddi_R1", "type": "INT", "arg1_id": "Nadolol_ddi_T1", "arg2_id": "Nadolol_ddi_T2", "normalized": [] } ]

[ { "id": "Nitroglycerin_ddi__text", "type": "abstract", "text": [ "The vasodilating effects of nitroglycerin may be additive with those of other vasodilators. Alcohol, in particular, has been found to exhibit additive effects of this variety. Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination. Dose adjustments of either class of agents may be necessary." ], "offsets": [ [ 0, 374 ] ] } ]

[ { "id": "Nitroglycerin_ddi_T1", "type": "DRUG", "text": [ "nitroglycerin" ], "offsets": [ [ 28, 41 ] ], "normalized": [] }, { "id": "Nitroglycerin_ddi_T2", "type": "GROUP", "text": [ "vasodilators" ], "offsets": [ [ 78, 90 ] ], "normalized": [] }, { "id": "Nitroglycerin_ddi_T3", "type": "DRUG", "text": [ "Alcohol" ], "offsets": [ [ 92, 99 ] ], "normalized": [] }, { "id": "Nitroglycerin_ddi_T4", "type": "GROUP", "text": [ "calcium channel blockers" ], "offsets": [ [ 242, 266 ] ], "normalized": [] }, { "id": "Nitroglycerin_ddi_T5", "type": "GROUP", "text": [ "nitrates" ], "offsets": [ [ 279, 287 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Nitroglycerin_ddi_R1", "type": "EFFECT", "arg1_id": "Nitroglycerin_ddi_T1", "arg2_id": "Nitroglycerin_ddi_T2", "normalized": [] }, { "id": "Nitroglycerin_ddi_R2", "type": "EFFECT", "arg1_id": "Nitroglycerin_ddi_T4", "arg2_id": "Nitroglycerin_ddi_T5", "normalized": [] } ]

[ { "id": "Chloroquine_ddi__text", "type": "abstract", "text": [ "Antacids and kaolin: Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed. Cimetidine: Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level. Concomitant use of cimetidine should be avoided. Ampicillin: In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin. An interval of at least two hours between intake of this agent and chloroquine should be observed. Cyclosporin: After introduction of chloroquine (oral form), a sudden increase in serum cyclosporin level has been reported. Therefore, close monitoring of serum cyclosporin level is recommended and, if necessary, chloroquine should be discontinued." ], "offsets": [ [ 0, 784 ] ] } ]

[ { "id": "Chloroquine_ddi_T1", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T2", "type": "DRUG", "text": [ "kaolin" ], "offsets": [ [ 13, 19 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T3", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 21, 29 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T4", "type": "DRUG", "text": [ "kaolin" ], "offsets": [ [ 34, 40 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T5", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 66, 77 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T6", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 146, 157 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T7", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 178, 188 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T8", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 190, 200 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T9", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 231, 242 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T10", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 292, 302 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T11", "type": "DRUG", "text": [ "Ampicillin" ], "offsets": [ [ 322, 332 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T12", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 368, 379 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T13", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 425, 435 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T14", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 504, 515 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T15", "type": "DRUG", "text": [ "Cyclosporin" ], "offsets": [ [ 536, 547 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T16", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 571, 582 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T17", "type": "DRUG", "text": [ "cyclosporin" ], "offsets": [ [ 623, 634 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T18", "type": "DRUG", "text": [ "cyclosporin" ], "offsets": [ [ 697, 708 ] ], "normalized": [] }, { "id": "Chloroquine_ddi_T19", "type": "DRUG", "text": [ "chloroquine" ], "offsets": [ [ 749, 760 ] ], "normalized": [] } ]

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[ { "id": "Chloroquine_ddi_R1", "type": "MECHANISM", "arg1_id": "Chloroquine_ddi_T3", "arg2_id": "Chloroquine_ddi_T5", "normalized": [] }, { "id": "Chloroquine_ddi_R2", "type": "MECHANISM", "arg1_id": "Chloroquine_ddi_T4", "arg2_id": "Chloroquine_ddi_T5", "normalized": [] }, { "id": "Chloroquine_ddi_R3", "type": "MECHANISM", "arg1_id": "Chloroquine_ddi_T8", "arg2_id": "Chloroquine_ddi_T9", "normalized": [] }, { "id": "Chloroquine_ddi_R4", "type": "MECHANISM", "arg1_id": "Chloroquine_ddi_T12", "arg2_id": "Chloroquine_ddi_T13", "normalized": [] }, { "id": "Chloroquine_ddi_R5", "type": "MECHANISM", "arg1_id": "Chloroquine_ddi_T16", "arg2_id": "Chloroquine_ddi_T17", "normalized": [] } ]

[ { "id": "Beclomethasone_ddi__text", "type": "abstract", "text": [ "Albuterol, Antihistamines, antidiabetic drugs, diuretics, digitalis." ], "offsets": [ [ 0, 68 ] ] } ]

[ { "id": "Beclomethasone_ddi_T1", "type": "DRUG", "text": [ "Albuterol" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Beclomethasone_ddi_T2", "type": "GROUP", "text": [ "Antihistamines" ], "offsets": [ [ 11, 25 ] ], "normalized": [] }, { "id": "Beclomethasone_ddi_T3", "type": "GROUP", "text": [ "antidiabetic drugs" ], "offsets": [ [ 27, 45 ] ], "normalized": [] }, { "id": "Beclomethasone_ddi_T4", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 47, 56 ] ], "normalized": [] }, { "id": "Beclomethasone_ddi_T5", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 58, 67 ] ], "normalized": [] } ]

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[ { "id": "Apraclonidine_ddi__text", "type": "abstract", "text": [ "Apraclonidine should not be used in patients receiving MAO inhibitors.. Although no specific drug interactions with topical glaucoma drugs or systemic medications were identified in clinical studies of IOPIDINE 0.5% Ophthalmic Solution, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, anesthetics) should be considered. Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with apraclonidine can lead to a reduction in IOP lowering effect. No data on the level of circulating catecholamines after apraclonidine withdrawal are available. Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines. An additive hypotensive effect has been reported with the combination of systemic clonidine and neuroleptic therapy. Systemic clonidine may inhibit the production of catecholamines in response to insulin-induced hypoglycemia and mask the signs and symptoms of hypoglycemia. Since apraclonidine may reduce pulse and blood pressure, caution in using drugs such as beta-blockers (ophthalmic and systemic), antihypertensives, and cardiac glycosides is advised. Patients using cardiovascular drugs concurrently with IOPIDINE 0.5% Ophthalmic Solution should have pulse and blood pressures frequently monitored. Caution should be exercised with simultaneous use of clonidine and other similar pharmacologic agents ." ], "offsets": [ [ 0, 1562 ] ] } ]

[ { "id": "Apraclonidine_ddi_T1", "type": "DRUG", "text": [ "Apraclonidine" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T2", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 55, 69 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T3", "type": "BRAND", "text": [ "IOPIDINE" ], "offsets": [ [ 202, 210 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T4", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 296, 311 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T5", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 313, 320 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T6", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 322, 334 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T7", "type": "GROUP", "text": [ "opiates" ], "offsets": [ [ 336, 343 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T8", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 345, 354 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T9", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 356, 367 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T10", "type": "GROUP", "text": [ "Tricyclic antidepressants" ], "offsets": [ [ 391, 416 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T11", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 480, 489 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T12", "type": "DRUG", "text": [ "apraclonidine" ], "offsets": [ [ 555, 568 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T13", "type": "DRUG", "text": [ "apraclonidine" ], "offsets": [ [ 674, 687 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T14", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 762, 787 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T15", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 936, 945 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T16", "type": "GROUP", "text": [ "neuroleptic" ], "offsets": [ [ 950, 961 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T17", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 980, 989 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T18", "type": "DRUG", "text": [ "apraclonidine" ], "offsets": [ [ 1134, 1147 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T19", "type": "GROUP", "text": [ "beta-blockers" ], "offsets": [ [ 1216, 1229 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T20", "type": "GROUP", "text": [ "antihypertensives" ], "offsets": [ [ 1257, 1274 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T21", "type": "GROUP", "text": [ "cardiac glycosides" ], "offsets": [ [ 1280, 1298 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T22", "type": "BRAND", "text": [ "IOPIDINE" ], "offsets": [ [ 1365, 1373 ] ], "normalized": [] }, { "id": "Apraclonidine_ddi_T23", "type": "DRUG", "text": [ "clonidine" ], "offsets": [ [ 1512, 1521 ] ], "normalized": [] } ]

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[ { "id": "Apraclonidine_ddi_R1", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T1", "arg2_id": "Apraclonidine_ddi_T2", "normalized": [] }, { "id": "Apraclonidine_ddi_R2", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T3", "arg2_id": "Apraclonidine_ddi_T4", "normalized": [] }, { "id": "Apraclonidine_ddi_R3", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T3", "arg2_id": "Apraclonidine_ddi_T5", "normalized": [] }, { "id": "Apraclonidine_ddi_R4", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T3", "arg2_id": "Apraclonidine_ddi_T6", "normalized": [] }, { "id": "Apraclonidine_ddi_R5", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T3", "arg2_id": "Apraclonidine_ddi_T7", "normalized": [] }, { "id": "Apraclonidine_ddi_R6", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T3", "arg2_id": "Apraclonidine_ddi_T8", "normalized": [] }, { "id": "Apraclonidine_ddi_R7", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T3", "arg2_id": "Apraclonidine_ddi_T9", "normalized": [] }, { "id": "Apraclonidine_ddi_R8", "type": "EFFECT", "arg1_id": "Apraclonidine_ddi_T10", "arg2_id": "Apraclonidine_ddi_T11", "normalized": [] }, { "id": "Apraclonidine_ddi_R9", "type": "EFFECT", "arg1_id": "Apraclonidine_ddi_T15", "arg2_id": "Apraclonidine_ddi_T16", "normalized": [] }, { "id": "Apraclonidine_ddi_R10", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T18", "arg2_id": "Apraclonidine_ddi_T19", "normalized": [] }, { "id": "Apraclonidine_ddi_R11", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T18", "arg2_id": "Apraclonidine_ddi_T20", "normalized": [] }, { "id": "Apraclonidine_ddi_R12", "type": "ADVISE", "arg1_id": "Apraclonidine_ddi_T18", "arg2_id": "Apraclonidine_ddi_T21", "normalized": [] } ]

[ { "id": "Dienestrol_ddi__text", "type": "abstract", "text": [ "Drug/ Laboratory Test Interactions Certain endocrine and liver function tests may be affected by estrogen-containing oral contraceptives. The following similar changes may be expected with larger doses of estrogen: - Increased sulfobromophthalein retention . - Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability . - Increased thyroid-binding globulin (TBG) leading to in-creased circulating total thyroid hormone; as measured by PBI, T4 by column, or T4 by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered . - Impaired glucose tolerance . - Decreased pregnanediol excretion . - Reduced response to metyrapone test . - Reduced serum folate concentration . - Increased serum triglyceride and phospholipid concentration." ], "offsets": [ [ 0, 872 ] ] } ]

[ { "id": "Dienestrol_ddi_T1", "type": "GROUP", "text": [ "estrogen" ], "offsets": [ [ 97, 105 ] ], "normalized": [] }, { "id": "Dienestrol_ddi_T2", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 122, 136 ] ], "normalized": [] }, { "id": "Dienestrol_ddi_T3", "type": "GROUP", "text": [ "estrogen" ], "offsets": [ [ 205, 213 ] ], "normalized": [] }, { "id": "Dienestrol_ddi_T4", "type": "DRUG", "text": [ "antithrombin 3" ], "offsets": [ [ 327, 341 ] ], "normalized": [] } ]

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[ { "id": "Floxuridine_ddi__text", "type": "abstract", "text": [ "Combination Therapy: Any form of therapy which adds to the stress of the patient, interferes with nutrition or depresses bone marrow function will increase the toxicity of Floxuridine." ], "offsets": [ [ 0, 184 ] ] } ]

[ { "id": "Floxuridine_ddi_T1", "type": "DRUG", "text": [ "Floxuridine" ], "offsets": [ [ 172, 183 ] ], "normalized": [] } ]

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[ { "id": "Hyoscyamine_ddi__text", "type": "abstract", "text": [ "Additive adverse effects resulting from cholinergic blockade may occur when LEVSIN is administered concomitantly with other antimuscarinics, amantadine, haloperidol, phenothiazines, monoamine oxidase (MAO) inhibitors, tricyclic antidepressants or some antihistamines. Antacids may interfere with the absorption of LEVSIN. Administer LEVSIN before meals; antacids after meals." ], "offsets": [ [ 0, 375 ] ] } ]

[ { "id": "Hyoscyamine_ddi_T1", "type": "BRAND", "text": [ "LEVSIN" ], "offsets": [ [ 76, 82 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T2", "type": "GROUP", "text": [ "antimuscarinics" ], "offsets": [ [ 124, 139 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T3", "type": "DRUG", "text": [ "amantadine" ], "offsets": [ [ 141, 151 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T4", "type": "DRUG", "text": [ "haloperidol" ], "offsets": [ [ 153, 164 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T5", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 166, 180 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T6", "type": "GROUP", "text": [ "monoamine oxidase (MAO) inhibitors" ], "offsets": [ [ 182, 216 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T7", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 218, 243 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T8", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 252, 266 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T9", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 268, 276 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T10", "type": "BRAND", "text": [ "LEVSIN" ], "offsets": [ [ 314, 320 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T11", "type": "BRAND", "text": [ "LEVSIN" ], "offsets": [ [ 333, 339 ] ], "normalized": [] }, { "id": "Hyoscyamine_ddi_T12", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 354, 362 ] ], "normalized": [] } ]

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[ { "id": "Hyoscyamine_ddi_R1", "type": "EFFECT", "arg1_id": "Hyoscyamine_ddi_T1", "arg2_id": "Hyoscyamine_ddi_T2", "normalized": [] }, { "id": "Hyoscyamine_ddi_R2", "type": "EFFECT", "arg1_id": "Hyoscyamine_ddi_T1", "arg2_id": "Hyoscyamine_ddi_T3", "normalized": [] }, { "id": "Hyoscyamine_ddi_R3", "type": "EFFECT", "arg1_id": "Hyoscyamine_ddi_T1", "arg2_id": "Hyoscyamine_ddi_T4", "normalized": [] }, { "id": "Hyoscyamine_ddi_R4", "type": "EFFECT", "arg1_id": "Hyoscyamine_ddi_T1", "arg2_id": "Hyoscyamine_ddi_T5", "normalized": [] }, { "id": "Hyoscyamine_ddi_R5", "type": "EFFECT", "arg1_id": "Hyoscyamine_ddi_T1", "arg2_id": "Hyoscyamine_ddi_T6", "normalized": [] }, { "id": "Hyoscyamine_ddi_R6", "type": "EFFECT", "arg1_id": "Hyoscyamine_ddi_T1", "arg2_id": "Hyoscyamine_ddi_T7", "normalized": [] }, { "id": "Hyoscyamine_ddi_R7", "type": "EFFECT", "arg1_id": "Hyoscyamine_ddi_T1", "arg2_id": "Hyoscyamine_ddi_T8", "normalized": [] }, { "id": "Hyoscyamine_ddi_R8", "type": "MECHANISM", "arg1_id": "Hyoscyamine_ddi_T9", "arg2_id": "Hyoscyamine_ddi_T10", "normalized": [] } ]

[ { "id": "Aminoglutethimide_ddi__text", "type": "abstract", "text": [ "Cytadren accelerates the metabolism of dexamethasone; therefore, if glucocorticoid replacement is needed, hydrocortisone should be prescribed. Aminoglutethimide diminishes the effect of coumarin and warfarin." ], "offsets": [ [ 0, 208 ] ] } ]

[ { "id": "Aminoglutethimide_ddi_T1", "type": "BRAND", "text": [ "Cytadren" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Aminoglutethimide_ddi_T2", "type": "DRUG", "text": [ "dexamethasone" ], "offsets": [ [ 39, 52 ] ], "normalized": [] }, { "id": "Aminoglutethimide_ddi_T3", "type": "GROUP", "text": [ "glucocorticoid" ], "offsets": [ [ 68, 82 ] ], "normalized": [] }, { "id": "Aminoglutethimide_ddi_T4", "type": "DRUG", "text": [ "hydrocortisone" ], "offsets": [ [ 106, 120 ] ], "normalized": [] }, { "id": "Aminoglutethimide_ddi_T5", "type": "DRUG", "text": [ "Aminoglutethimide" ], "offsets": [ [ 143, 160 ] ], "normalized": [] }, { "id": "Aminoglutethimide_ddi_T6", "type": "GROUP", "text": [ "coumarin" ], "offsets": [ [ 186, 194 ] ], "normalized": [] }, { "id": "Aminoglutethimide_ddi_T7", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 199, 207 ] ], "normalized": [] } ]

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[ { "id": "Aminoglutethimide_ddi_R1", "type": "MECHANISM", "arg1_id": "Aminoglutethimide_ddi_T1", "arg2_id": "Aminoglutethimide_ddi_T2", "normalized": [] }, { "id": "Aminoglutethimide_ddi_R2", "type": "EFFECT", "arg1_id": "Aminoglutethimide_ddi_T5", "arg2_id": "Aminoglutethimide_ddi_T6", "normalized": [] }, { "id": "Aminoglutethimide_ddi_R3", "type": "EFFECT", "arg1_id": "Aminoglutethimide_ddi_T5", "arg2_id": "Aminoglutethimide_ddi_T7", "normalized": [] } ]

[ { "id": "Bivalirudin_ddi__text", "type": "abstract", "text": [ "Angiomax does not exhibit binding to plasma proteins (other than thrombin) or red blood cells. In clinical trials in patients undergoing PTCA/PCI, co-administration of Angiomax with heparin, warfarin, thrombolytics or glycoprotein IIb/IIIa inhibitors was associated with increased risks of major bleeding events compared to patients not receiving these concomitant medications. There is no experience with co-administration of Angiomax and plasma expanders such as dextran. Angiomax should be used with caution in patients with disease states associated with an increased risk of bleeding. Immunogenicity/Re-exposure: In in vitro studies, Angiomax exhibited no platelet aggregation response against sera from patients with a history of HIT/HITTS. Among 494 subjects who received Angiomax in clinical trials and were tested for antibodies, 2 subjects had treatment-emergent positive bivalirudin antibody tests. Neither subject demonstrated clinical evidence of allergic or anaphylactic reactions and repeat testing was not performed. Nine additional patients who had initial positive tests were negative on repeat testing." ], "offsets": [ [ 0, 1121 ] ] } ]

[ { "id": "Bivalirudin_ddi_T1", "type": "BRAND", "text": [ "Angiomax" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T2", "type": "BRAND", "text": [ "Angiomax" ], "offsets": [ [ 168, 176 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T3", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 182, 189 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T4", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 191, 199 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T5", "type": "GROUP", "text": [ "thrombolytics" ], "offsets": [ [ 201, 214 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T6", "type": "BRAND", "text": [ "Angiomax" ], "offsets": [ [ 427, 435 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T7", "type": "DRUG", "text": [ "dextran" ], "offsets": [ [ 465, 472 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T8", "type": "BRAND", "text": [ "Angiomax" ], "offsets": [ [ 474, 482 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T9", "type": "BRAND", "text": [ "Angiomax" ], "offsets": [ [ 639, 647 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T10", "type": "BRAND", "text": [ "Angiomax" ], "offsets": [ [ 779, 787 ] ], "normalized": [] }, { "id": "Bivalirudin_ddi_T11", "type": "DRUG", "text": [ "bivalirudin" ], "offsets": [ [ 882, 893 ] ], "normalized": [] } ]

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[ { "id": "Bivalirudin_ddi_R1", "type": "EFFECT", "arg1_id": "Bivalirudin_ddi_T2", "arg2_id": "Bivalirudin_ddi_T3", "normalized": [] }, { "id": "Bivalirudin_ddi_R2", "type": "EFFECT", "arg1_id": "Bivalirudin_ddi_T2", "arg2_id": "Bivalirudin_ddi_T4", "normalized": [] }, { "id": "Bivalirudin_ddi_R3", "type": "EFFECT", "arg1_id": "Bivalirudin_ddi_T2", "arg2_id": "Bivalirudin_ddi_T5", "normalized": [] } ]

[ { "id": "Cefoxitin_ddi__text", "type": "abstract", "text": [ "Increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics. Drug/Laboratory Test Interactions As with cephalothin, high concentrations of cefoxitin ( 100 micrograms/mL) may interfere with measurement of serum and urine creatinine levels by the Jaff reaction, and produce false increases of modest degree in the levels of creatinine reported. Serum samples from patients treated with cefoxitin should not be analyzed for creatinine if withdrawn within 2 hours of drug administration. High concentrations of cefoxitin in the urine may interfere with measurement of urinary 17-hydroxy-corticosteroids by the Porter-Silber reaction, and produce false increases of modest degree in the levels reported. A false-positive reaction for glucose in the urine may occur. This has been observed with CLINITEST reagent tablets . Registered trademark of Ames Company, Division of Miles Laboratories, Inc." ], "offsets": [ [ 0, 962 ] ] } ]

[ { "id": "Cefoxitin_ddi_T1", "type": "GROUP", "text": [ "cephalosporins" ], "offsets": [ [ 83, 97 ] ], "normalized": [] }, { "id": "Cefoxitin_ddi_T2", "type": "GROUP", "text": [ "aminoglycoside antibiotics" ], "offsets": [ [ 102, 128 ] ], "normalized": [] }, { "id": "Cefoxitin_ddi_T3", "type": "DRUG", "text": [ "cephalothin" ], "offsets": [ [ 172, 183 ] ], "normalized": [] }, { "id": "Cefoxitin_ddi_T4", "type": "DRUG", "text": [ "cefoxitin" ], "offsets": [ [ 208, 217 ] ], "normalized": [] }, { "id": "Cefoxitin_ddi_T5", "type": "DRUG", "text": [ "cefoxitin" ], "offsets": [ [ 454, 463 ] ], "normalized": [] }, { "id": "Cefoxitin_ddi_T6", "type": "DRUG", "text": [ "cefoxitin" ], "offsets": [ [ 577, 586 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cefoxitin_ddi_R1", "type": "EFFECT", "arg1_id": "Cefoxitin_ddi_T1", "arg2_id": "Cefoxitin_ddi_T2", "normalized": [] } ]

[ { "id": "Ceftibuten_ddi__text", "type": "abstract", "text": [ "Theophylline: Twelve healthy male volunteers were administered one 200-mg ceftibuten capsule twice daily for 6 days. With the morning dose of ceftibuten on day 6, each volunteer received a single intravenous infusion of theophylline (4 mg/kg). The pharmacokinetics of theophylline were not altered. The effect of ceftibuten on the pharmacokinetics of theophylline administered orally has not been investigated. Antacids or H 2 -receptor antagonists: The effect of increased gastric pH on the bioavailability of ceftibuten was evaluated in 18 healthy adult volunteers. Each volunteer was administered one 400-mg ceftibuten capsule. A single dose of liquid antacid did not affect the C max or AUC of ceftibuten; however, 150 mg of ranitidine q12h for 3 days increased the ceftibuten C max by 23% and ceftibuten AUC by 16%. The clinical relevance of these increases is not known. Drug/Laboratory Test Interactions: There have been no chemical or laboratory test interactions with ceftibuten noted to date. False-positive direct Coombs tests have been reported during treatment with other cephalosporins. Therefore, it should be recognized that a positive Coombs test could be due to the drug. The results of assays using red cells from healthy subjects to determine whether ceftibuten would cause direct Coombs reactions in vitro showed no positive reaction at ceftibuten concentrations as high as 40 g/mL." ], "offsets": [ [ 0, 1404 ] ] } ]

[ { "id": "Ceftibuten_ddi_T1", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T2", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 74, 84 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T3", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 142, 152 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T4", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 220, 232 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T5", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 268, 280 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T6", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 313, 323 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T7", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 351, 363 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T8", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 411, 419 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T9", "type": "GROUP", "text": [ "H 2 -receptor antagonists" ], "offsets": [ [ 423, 448 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T10", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 511, 521 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T11", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 611, 621 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T12", "type": "GROUP", "text": [ "antacid" ], "offsets": [ [ 655, 662 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T13", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 698, 708 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T14", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 729, 739 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T15", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 770, 780 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T16", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 798, 808 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T17", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 977, 987 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T18", "type": "GROUP", "text": [ "cephalosporins" ], "offsets": [ [ 1085, 1099 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T19", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 1271, 1281 ] ], "normalized": [] }, { "id": "Ceftibuten_ddi_T20", "type": "DRUG", "text": [ "ceftibuten" ], "offsets": [ [ 1358, 1368 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ceftibuten_ddi_R1", "type": "MECHANISM", "arg1_id": "Ceftibuten_ddi_T14", "arg2_id": "Ceftibuten_ddi_T15", "normalized": [] }, { "id": "Ceftibuten_ddi_R2", "type": "MECHANISM", "arg1_id": "Ceftibuten_ddi_T14", "arg2_id": "Ceftibuten_ddi_T16", "normalized": [] } ]

[ { "id": "Chlorotrianisene_ddi__text", "type": "abstract", "text": [ "Chlorotrianisene may interact with antidepressants, aspirin, barbiturates, bromocriptine, calcium supplements, corticosteroids, corticotropin, cyclosporine, dantrolene, nicotine, somatropin, tamoxifen, and warfarin." ], "offsets": [ [ 0, 215 ] ] } ]

[ { "id": "Chlorotrianisene_ddi_T1", "type": "DRUG", "text": [ "Chlorotrianisene" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T2", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 35, 50 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T3", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 52, 59 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T4", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 61, 73 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T5", "type": "DRUG", "text": [ "bromocriptine" ], "offsets": [ [ 75, 88 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T6", "type": "DRUG", "text": [ "calcium" ], "offsets": [ [ 90, 97 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T7", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 111, 126 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T8", "type": "DRUG", "text": [ "corticotropin" ], "offsets": [ [ 128, 141 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T9", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 143, 155 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T10", "type": "DRUG", "text": [ "dantrolene" ], "offsets": [ [ 157, 167 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T11", "type": "DRUG", "text": [ "nicotine" ], "offsets": [ [ 169, 177 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T12", "type": "DRUG", "text": [ "somatropin" ], "offsets": [ [ 179, 189 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T13", "type": "DRUG", "text": [ "tamoxifen" ], "offsets": [ [ 191, 200 ] ], "normalized": [] }, { "id": "Chlorotrianisene_ddi_T14", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 206, 214 ] ], "normalized": [] } ]

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[ { "id": "Chlorotrianisene_ddi_R1", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T2", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R2", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T3", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R3", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T4", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R4", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T5", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R5", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T6", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R6", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T7", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R7", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T8", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R8", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T9", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R9", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T10", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R10", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T11", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R11", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T12", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R12", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T13", "normalized": [] }, { "id": "Chlorotrianisene_ddi_R13", "type": "INT", "arg1_id": "Chlorotrianisene_ddi_T1", "arg2_id": "Chlorotrianisene_ddi_T14", "normalized": [] } ]

[ { "id": "Carbimazole_ddi__text", "type": "abstract", "text": [ "Iodine or iodine excess may decrease the effect of Carbimazole, and an iodine deficiency can increase the effect of Carbimazole. Serum concentration of digoxin and digitoxin may increase when patients take antithyroid agents. A decrease of the dosage may be necessary when patient becomes euthyroid. Antithyroid agents may decrease thyroidal uptake of sodium iodide I131, a rebound in uptake may occur up to 5 days after sudden withdrawal of Carbimazole. Patients response to oral anticoagulants may be affected by his/her thyroid and metabolic status. An evaluation of prothrombin time and an adjustment of anticoagulant dosage are recommended" ], "offsets": [ [ 0, 644 ] ] } ]

[ { "id": "Carbimazole_ddi_T1", "type": "DRUG", "text": [ "Iodine" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T2", "type": "DRUG", "text": [ "iodine" ], "offsets": [ [ 10, 16 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T3", "type": "DRUG", "text": [ "Carbimazole" ], "offsets": [ [ 51, 62 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T4", "type": "DRUG", "text": [ "iodine" ], "offsets": [ [ 71, 77 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T5", "type": "DRUG", "text": [ "Carbimazole" ], "offsets": [ [ 116, 127 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T6", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 152, 159 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T7", "type": "DRUG", "text": [ "digitoxin" ], "offsets": [ [ 164, 173 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T8", "type": "GROUP", "text": [ "antithyroid agents" ], "offsets": [ [ 206, 224 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T9", "type": "GROUP", "text": [ "Antithyroid agents" ], "offsets": [ [ 300, 318 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T10", "type": "DRUG", "text": [ "sodium iodide I131" ], "offsets": [ [ 352, 370 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T11", "type": "DRUG", "text": [ "Carbimazole" ], "offsets": [ [ 442, 453 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T12", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 481, 495 ] ], "normalized": [] }, { "id": "Carbimazole_ddi_T13", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 608, 621 ] ], "normalized": [] } ]

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[ { "id": "Carbimazole_ddi_R1", "type": "EFFECT", "arg1_id": "Carbimazole_ddi_T1", "arg2_id": "Carbimazole_ddi_T3", "normalized": [] }, { "id": "Carbimazole_ddi_R2", "type": "EFFECT", "arg1_id": "Carbimazole_ddi_T4", "arg2_id": "Carbimazole_ddi_T5", "normalized": [] }, { "id": "Carbimazole_ddi_R3", "type": "MECHANISM", "arg1_id": "Carbimazole_ddi_T6", "arg2_id": "Carbimazole_ddi_T8", "normalized": [] }, { "id": "Carbimazole_ddi_R4", "type": "MECHANISM", "arg1_id": "Carbimazole_ddi_T7", "arg2_id": "Carbimazole_ddi_T8", "normalized": [] }, { "id": "Carbimazole_ddi_R5", "type": "EFFECT", "arg1_id": "Carbimazole_ddi_T9", "arg2_id": "Carbimazole_ddi_T10", "normalized": [] } ]

[ { "id": "Fluoxymesterone_ddi__text", "type": "abstract", "text": [ "Androgens may increase sensitivity to oral anticoagulahts. Dosage of the anticoagulant may require reduction in order to maintain satisfactory therapeutic hypoprothrombinemia. Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and therefore, insulin requirements." ], "offsets": [ [ 0, 411 ] ] } ]

[ { "id": "Fluoxymesterone_ddi_T1", "type": "GROUP", "text": [ "Androgens" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Fluoxymesterone_ddi_T2", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 73, 86 ] ], "normalized": [] }, { "id": "Fluoxymesterone_ddi_T3", "type": "DRUG", "text": [ "oxyphenbutazone" ], "offsets": [ [ 205, 220 ] ], "normalized": [] }, { "id": "Fluoxymesterone_ddi_T4", "type": "GROUP", "text": [ "androgens" ], "offsets": [ [ 225, 234 ] ], "normalized": [] }, { "id": "Fluoxymesterone_ddi_T5", "type": "DRUG", "text": [ "oxyphenbutazone" ], "offsets": [ [ 274, 289 ] ], "normalized": [] }, { "id": "Fluoxymesterone_ddi_T6", "type": "GROUP", "text": [ "androgens" ], "offsets": [ [ 338, 347 ] ], "normalized": [] }, { "id": "Fluoxymesterone_ddi_T7", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 390, 397 ] ], "normalized": [] } ]

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[ { "id": "Fluoxymesterone_ddi_R1", "type": "MECHANISM", "arg1_id": "Fluoxymesterone_ddi_T3", "arg2_id": "Fluoxymesterone_ddi_T4", "normalized": [] }, { "id": "Fluoxymesterone_ddi_R2", "type": "EFFECT", "arg1_id": "Fluoxymesterone_ddi_T6", "arg2_id": "Fluoxymesterone_ddi_T7", "normalized": [] } ]

[ { "id": "Clobazam_ddi__text", "type": "abstract", "text": [ "Alcohol (increases bioavailability by 50%), cimetidine, and valproates." ], "offsets": [ [ 0, 71 ] ] } ]

[ { "id": "Clobazam_ddi_T1", "type": "DRUG", "text": [ "Alcohol" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Clobazam_ddi_T2", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 44, 54 ] ], "normalized": [] } ]

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[ { "id": "L-Methionine_ddi__text", "type": "abstract", "text": [ "Acetaminophen and methotrexate - L-methionine may decrease hepatic toxicity in those with acetaminophen overdosage or in those taking methotrexate. Theoretically, it may decrease hepatic toxicity in the case of other potential hepatotoxic drugs, as well. Gentamicin - Methionine may protect against the ototoxic effects of gentamicin." ], "offsets": [ [ 0, 334 ] ] } ]

[ { "id": "L-Methionine_ddi_T1", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "L-Methionine_ddi_T2", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 18, 30 ] ], "normalized": [] }, { "id": "L-Methionine_ddi_T3", "type": "DRUG", "text": [ "L-methionine" ], "offsets": [ [ 33, 45 ] ], "normalized": [] }, { "id": "L-Methionine_ddi_T4", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 90, 103 ] ], "normalized": [] }, { "id": "L-Methionine_ddi_T5", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 134, 146 ] ], "normalized": [] }, { "id": "L-Methionine_ddi_T6", "type": "DRUG", "text": [ "Gentamicin" ], "offsets": [ [ 255, 265 ] ], "normalized": [] }, { "id": "L-Methionine_ddi_T7", "type": "DRUG", "text": [ "Methionine" ], "offsets": [ [ 268, 278 ] ], "normalized": [] }, { "id": "L-Methionine_ddi_T8", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 323, 333 ] ], "normalized": [] } ]

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[]

[ { "id": "L-Methionine_ddi_R1", "type": "EFFECT", "arg1_id": "L-Methionine_ddi_T3", "arg2_id": "L-Methionine_ddi_T4", "normalized": [] }, { "id": "L-Methionine_ddi_R2", "type": "EFFECT", "arg1_id": "L-Methionine_ddi_T3", "arg2_id": "L-Methionine_ddi_T5", "normalized": [] }, { "id": "L-Methionine_ddi_R3", "type": "EFFECT", "arg1_id": "L-Methionine_ddi_T7", "arg2_id": "L-Methionine_ddi_T8", "normalized": [] } ]

[ { "id": "Nicotine_ddi__text", "type": "abstract", "text": [ "Physiological changes resulting from smoking cessation, with or without nicotine replacement, may alter the pharmacokinetics of certain concomitant medications, such as tricyclic antidepressants and theophylline. Doses of these and perhaps other medications may need to be adjusted in patients who successfully quit smoking." ], "offsets": [ [ 0, 324 ] ] } ]

[ { "id": "Nicotine_ddi_T1", "type": "DRUG", "text": [ "nicotine" ], "offsets": [ [ 72, 80 ] ], "normalized": [] }, { "id": "Nicotine_ddi_T2", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 169, 194 ] ], "normalized": [] }, { "id": "Nicotine_ddi_T3", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 199, 211 ] ], "normalized": [] } ]

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[ { "id": "Diphenhydramine_ddi__text", "type": "abstract", "text": [ "Diphenhydramine hydrochloride has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc). MAO inhibitors prolong and intensify the anticholinergic (drying) effects of antihistamines." ], "offsets": [ [ 0, 226 ] ] } ]

[ { "id": "Diphenhydramine_ddi_T1", "type": "DRUG", "text": [ "Diphenhydramine hydrochloride" ], "offsets": [ [ 0, 29 ] ], "normalized": [] }, { "id": "Diphenhydramine_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 56, 63 ] ], "normalized": [] }, { "id": "Diphenhydramine_ddi_T3", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 74, 89 ] ], "normalized": [] }, { "id": "Diphenhydramine_ddi_T4", "type": "GROUP", "text": [ "hypnotics" ], "offsets": [ [ 91, 100 ] ], "normalized": [] }, { "id": "Diphenhydramine_ddi_T5", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 102, 111 ] ], "normalized": [] }, { "id": "Diphenhydramine_ddi_T6", "type": "GROUP", "text": [ "tranquilizers" ], "offsets": [ [ 113, 126 ] ], "normalized": [] }, { "id": "Diphenhydramine_ddi_T7", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 134, 148 ] ], "normalized": [] }, { "id": "Diphenhydramine_ddi_T8", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 211, 225 ] ], "normalized": [] } ]

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[ { "id": "Diphenhydramine_ddi_R1", "type": "EFFECT", "arg1_id": "Diphenhydramine_ddi_T1", "arg2_id": "Diphenhydramine_ddi_T2", "normalized": [] }, { "id": "Diphenhydramine_ddi_R2", "type": "EFFECT", "arg1_id": "Diphenhydramine_ddi_T1", "arg2_id": "Diphenhydramine_ddi_T3", "normalized": [] }, { "id": "Diphenhydramine_ddi_R3", "type": "EFFECT", "arg1_id": "Diphenhydramine_ddi_T1", "arg2_id": "Diphenhydramine_ddi_T4", "normalized": [] }, { "id": "Diphenhydramine_ddi_R4", "type": "EFFECT", "arg1_id": "Diphenhydramine_ddi_T1", "arg2_id": "Diphenhydramine_ddi_T5", "normalized": [] }, { "id": "Diphenhydramine_ddi_R5", "type": "EFFECT", "arg1_id": "Diphenhydramine_ddi_T1", "arg2_id": "Diphenhydramine_ddi_T6", "normalized": [] }, { "id": "Diphenhydramine_ddi_R6", "type": "EFFECT", "arg1_id": "Diphenhydramine_ddi_T7", "arg2_id": "Diphenhydramine_ddi_T8", "normalized": [] } ]

[ { "id": "Dezocine_ddi__text", "type": "abstract", "text": [ "Additive depressant effect when used with general anesthetics, sedatives, antianxiety drugs, hypnotics, alcohol, and other opiate analgesics." ], "offsets": [ [ 0, 141 ] ] } ]

[ { "id": "Dezocine_ddi_T1", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 50, 61 ] ], "normalized": [] }, { "id": "Dezocine_ddi_T2", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 63, 72 ] ], "normalized": [] }, { "id": "Dezocine_ddi_T3", "type": "GROUP", "text": [ "antianxiety drugs" ], "offsets": [ [ 74, 91 ] ], "normalized": [] }, { "id": "Dezocine_ddi_T4", "type": "GROUP", "text": [ "hypnotics" ], "offsets": [ [ 93, 102 ] ], "normalized": [] }, { "id": "Dezocine_ddi_T5", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 104, 111 ] ], "normalized": [] }, { "id": "Dezocine_ddi_T6", "type": "GROUP", "text": [ "opiate analgesics" ], "offsets": [ [ 123, 140 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Lomefloxacin_ddi__text", "type": "abstract", "text": [ "Theophylline: In three pharmacokinetic studies including 46 normal, healthy subjects, theophylline clearance and concentration were not significantly altered by the addition of lomefloxacin. In clinical studies where patients were on chronic theophylline therapy, lomefloxacin had no measurable effect on the mean distribution of theophylline concentrations or the mean estimates of theophylline clearance. Though individual theophylline levels fluctuated, there were no clinically significant symptoms of drug inter-action. Antacids and sucralfate: Sucralfate and antacids containing magnesium or aluminum, as well as formulations containing divalent and trivalent cations such as Videx (didanosine), chewable/buffered tablets or the pediatric powder for oral solution can form chelation complexes with lomefloxacin and interfere with its bioavailability. Sucralfate administered 2 hours before lomefloxacin resulted in a slower absorption (mean C max decreased by 30% and mean T max increased by 1 hour) and a lesser extent of absorption (mean AUC decreased by approximately 25%). Magnesium- and aluminum-containing antacids, administered concomitantly with lomefloxacin, significantly decreased the bioavailability (48%) of lomefloxacin. Separating the doses of antacid and lomefloxacin minimizes this decrease in bioavailability; therefore, administration of these agents should precede lomefloxacin dosing by 4 hours or follow lomefloxacin dosing by at least 2 hours. Caffeine: Two hundred mg of caffeine (equivalent to 1 to 3 cups of American coffee) was administered to 16 normal, healthy volunteers who had achieved steady-state blood concentrations of lomefloxacin after being dosed at 400 mg qd. This did not result in any statistically or clinically relevant changes in the pharmacokinetic parameters of either caffeine or its major metabolite, paraxanthine. No data are available on potential interactions in individuals who consume greater than 200 mg of caffeine per day or in those, such as the geriatric population, who are generally believed to be more susceptible to the development of drug-induced CNS-related adverse effects. Other quinolones have demonstrated moderate to marked interference with the metabolism of caffeine, resulting in a reduced clearance, a prolongation of plasma half-life, and an increase in symptoms that accompany high levels of caffeine. Cimetidine: Cimetidine has been demonstrated to interfere with the elimination of other quinolones. This interference has resulted in significant increases in half-life and AUC. The interaction between lomefloxacin and cimetidine has not been studied. Cyclosporine: Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with other members of the quinolone class. Interaction between lomefloxacin and cyclosporine has not been studied. Omeprazole: No clinically significant changes in lomefloxacin pharmacokinetics (AUC, C max , or T max ) were observed when a single dose of lomefloxacin 400 mg was given after multiple doses of omeprazole (20 mg qd) in 13 healthy volunteers. Changes in omeprazole pharmacokinetics were not studied. Phenytoin: No significant differences were observed in mean phenytoin AUC, C max , C min or T max (although C max increased by 11%) when extended phenytoin sodium capsules (100 mg tid) were coadministered with lomefloxacin (400 mg qd) for five days in 15 healthy males. Lomefloxacin is unlikely to have a significant effect on phenytoin metabolism. Probenecid: Probenecid slows the renal elimination of lome-floxacin. An increase of 63% in the mean AUC and increases of 50% and 4%, respectively, in the mean T max and mean C max were noted in 1 study of 6 individuals. Terfenadine: No clinically significant changes occurred in heart rate or corrected QT intervals, or in terfenadine metabolite or lomefloxacin pharmacokinetics, during concurrent administration of lomefloxacin and terfenadine at steady-state in 28 healthy males. Warfarin: Quinolones may enhance the effects of the oral anticoagulant, warfarin, or its derivatives. When these products are administered concomitantly, prothrombin or other suitable coagulation tests should be monitored closely. However, no clinically or statistically significant differences in prothrombin time ratio or warfarin enantiomer pharmacokinetics were observed in a small study of 7 healthy males who received both warfarin and lomefloxacin under steady-state conditions." ], "offsets": [ [ 0, 4475 ] ] } ]

[ { "id": "Lomefloxacin_ddi_T1", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T2", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 86, 98 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T3", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 177, 189 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T4", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 242, 254 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T5", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 264, 276 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T6", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 330, 342 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T7", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 383, 395 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T8", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 425, 437 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T9", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 525, 533 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T10", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 538, 548 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T11", "type": "DRUG", "text": [ "Sucralfate" ], "offsets": [ [ 550, 560 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T12", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 565, 573 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T13", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 585, 594 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T14", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 598, 606 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T15", "type": "BRAND", "text": [ "Videx" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T16", "type": "DRUG", "text": [ "didanosine" ], "offsets": [ [ 690, 700 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T17", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 805, 817 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T18", "type": "DRUG", "text": [ "Sucralfate" ], "offsets": [ [ 858, 868 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T19", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 897, 909 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T20", "type": "DRUG", "text": [ "Magnesium" ], "offsets": [ [ 1084, 1093 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T21", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 1099, 1107 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T22", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 1119, 1127 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T23", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 1161, 1173 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T24", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 1228, 1240 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T25", "type": "GROUP", "text": [ "antacid" ], "offsets": [ [ 1266, 1273 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T26", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 1278, 1290 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T27", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 1392, 1404 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T28", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 1433, 1445 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T29", "type": "DRUG", "text": [ "Caffeine" ], "offsets": [ [ 1474, 1482 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T30", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 1502, 1510 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T31", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 1662, 1674 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T32", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 1823, 1831 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T33", "type": "DRUG_N", "text": [ "paraxanthine" ], "offsets": [ [ 1857, 1869 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T34", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 1969, 1977 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T35", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 2153, 2163 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T36", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 2237, 2245 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T37", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 2375, 2383 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T38", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 2385, 2395 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T39", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 2397, 2407 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T40", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 2473, 2483 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T41", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 2587, 2599 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T42", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 2604, 2614 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T43", "type": "DRUG", "text": [ "Cyclosporine" ], "offsets": [ [ 2637, 2649 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T44", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2676, 2688 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T45", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2732, 2744 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T46", "type": "GROUP", "text": [ "quinolone class" ], "offsets": [ [ 2771, 2786 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T47", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 2808, 2820 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T48", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 2825, 2837 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T49", "type": "DRUG", "text": [ "Omeprazole" ], "offsets": [ [ 2860, 2870 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T50", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 2909, 2921 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T51", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 3000, 3012 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T52", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 3054, 3064 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T53", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 3113, 3123 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T54", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 3159, 3168 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T55", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3219, 3228 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T56", "type": "DRUG", "text": [ "phenytoin sodium" ], "offsets": [ [ 3305, 3321 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T57", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 3369, 3381 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T58", "type": "DRUG", "text": [ "Lomefloxacin" ], "offsets": [ [ 3429, 3441 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T59", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3486, 3495 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T60", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 3508, 3518 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T61", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 3520, 3530 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T62", "type": "DRUG", "text": [ "Terfenadine" ], "offsets": [ [ 3728, 3739 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T63", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 3831, 3842 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T64", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 3857, 3869 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T65", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 3924, 3936 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T66", "type": "DRUG", "text": [ "terfenadine" ], "offsets": [ [ 3941, 3952 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T67", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 3990, 3998 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T68", "type": "GROUP", "text": [ "Quinolones" ], "offsets": [ [ 4000, 4010 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T69", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 4047, 4060 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T70", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4062, 4070 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T71", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4314, 4322 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T72", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4419, 4427 ] ], "normalized": [] }, { "id": "Lomefloxacin_ddi_T73", "type": "DRUG", "text": [ "lomefloxacin" ], "offsets": [ [ 4432, 4444 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Lomefloxacin_ddi_R1", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T11", "arg2_id": "Lomefloxacin_ddi_T17", "normalized": [] }, { "id": "Lomefloxacin_ddi_R2", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T13", "arg2_id": "Lomefloxacin_ddi_T17", "normalized": [] }, { "id": "Lomefloxacin_ddi_R3", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T14", "arg2_id": "Lomefloxacin_ddi_T17", "normalized": [] }, { "id": "Lomefloxacin_ddi_R4", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T15", "arg2_id": "Lomefloxacin_ddi_T17", "normalized": [] }, { "id": "Lomefloxacin_ddi_R5", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T16", "arg2_id": "Lomefloxacin_ddi_T17", "normalized": [] }, { "id": "Lomefloxacin_ddi_R6", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T18", "arg2_id": "Lomefloxacin_ddi_T19", "normalized": [] }, { "id": "Lomefloxacin_ddi_R7", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T20", "arg2_id": "Lomefloxacin_ddi_T23", "normalized": [] }, { "id": "Lomefloxacin_ddi_R8", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T21", "arg2_id": "Lomefloxacin_ddi_T23", "normalized": [] }, { "id": "Lomefloxacin_ddi_R9", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T22", "arg2_id": "Lomefloxacin_ddi_T23", "normalized": [] }, { "id": "Lomefloxacin_ddi_R10", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T25", "arg2_id": "Lomefloxacin_ddi_T26", "normalized": [] }, { "id": "Lomefloxacin_ddi_R11", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T35", "arg2_id": "Lomefloxacin_ddi_T36", "normalized": [] }, { "id": "Lomefloxacin_ddi_R12", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T39", "arg2_id": "Lomefloxacin_ddi_T40", "normalized": [] }, { "id": "Lomefloxacin_ddi_R13", "type": "MECHANISM", "arg1_id": "Lomefloxacin_ddi_T45", "arg2_id": "Lomefloxacin_ddi_T46", "normalized": [] }, { "id": "Lomefloxacin_ddi_R14", "type": "EFFECT", "arg1_id": "Lomefloxacin_ddi_T68", "arg2_id": "Lomefloxacin_ddi_T69", "normalized": [] }, { "id": "Lomefloxacin_ddi_R15", "type": "EFFECT", "arg1_id": "Lomefloxacin_ddi_T68", "arg2_id": "Lomefloxacin_ddi_T70", "normalized": [] } ]

[ { "id": "Duloxetine_ddi__text", "type": "abstract", "text": [ "Potential for Other Drugs to Affect Duloxetine: Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism. Inhibitors of CYP1A2: Concomitant use of duloxetine with fluvoxamine, an inhibitor of CYP1A2, results in approximately a 6-fold increase in AUC and about a 2.5-fold increase in Cmax of duloxetine. Some quinolone antibiotics would be expected to have similar effects and these combinations should be avoided. Inhibitors of CYP2D6: Because CYP2D6 is involved in duloxetine metabolism, concomitant use of duloxetine with potent inhibitors of CYP2D6 may result in higher concentrations of duloxetine. Paroxetine (20 mg QD) increased the concentration of duloxetine (40 mg QD) by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine. Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine). Potential for Duloxetine to Affect Other Drugs: Drugs Metabolized by CYP1A2: In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity, and it is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates. Drugs Metabolized by CYP2D6: Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered (at a dose of 60 mg BID) in conjunction with a single 50-mg dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold. Therefore, co-administration of Duloxetine with other drugs that are extensively metabolized by this isozyme and which have a narrow therapeutic index, including certain antidepressants (tricyclic antidepressants [TCAs], such as nortriptyline, amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution. Plasma TCA concentrations may need to be monitored and the dose of the TCA may need to be reduced if a TCA is co-administered with Duloxetine. Because of the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, Duloxetine and thioridazine should not be co-administered. Drugs Metabolized by CYP3A: Results of in vitro studies demonstrate that duloxetine does not inhibit or induce CYP3A activity. Duloxetine May Have a Clinically Important Interaction with the Following Other Drugs: Alcohol: When Duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, Duloxetine did not increase the impairment of mental and motor skills caused by alcohol. In the Duloxetine clinical trials database, three Duloxetine-treated patients had liver injury as manifested by ALT and total bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, and this may have contributed to the abnormalities seen. CNS Acting Drugs: Given the primary CNS effects of Duloxetine, it should be used with caution when it is taken in combination with or substituted for other centrally acting drugs, including those with a similar mechanism of action. Potential for Interaction with Drugs that Affect Gastric Acidity: Duloxetine has an enteric coating that resists dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. In extremely acidic conditions, Duloxetine, unprotected by the enteric coating, may undergo hydrolysis to form naphthol. Caution is advised in using Duloxetine in patients with conditions that may slow gastric emptying (e.g., some diabetics). Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine. However, co-administration of Duloxetine with aluminum- and magnesium-containing antacids (51 mEq) or Duloxetine with famotidine, had no significant effect on the rate or extent of duloxetine absorption after administration of a 40-mg oral dose. It is unknown whether the concomitant administration of proton pump inhibitors affects duloxetine absorption." ], "offsets": [ [ 0, 3992 ] ] } ]

[ { "id": "Duloxetine_ddi_T1", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 36, 46 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T2", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 91, 101 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T3", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 155, 165 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T4", "type": "DRUG", "text": [ "fluvoxamine" ], "offsets": [ [ 171, 182 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T5", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 299, 309 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T6", "type": "GROUP", "text": [ "quinolone antibiotics" ], "offsets": [ [ 316, 337 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T7", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 474, 484 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T8", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 516, 526 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T9", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 599, 609 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T10", "type": "DRUG", "text": [ "Paroxetine" ], "offsets": [ [ 611, 621 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T11", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 664, 674 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T12", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 768, 778 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T13", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 857, 867 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T14", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 869, 878 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T15", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 895, 905 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T16", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 1009, 1019 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T17", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 1181, 1191 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T18", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 1232, 1242 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T19", "type": "DRUG", "text": [ "desipramine" ], "offsets": [ [ 1328, 1339 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T20", "type": "DRUG", "text": [ "desipramine" ], "offsets": [ [ 1372, 1383 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T21", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 1434, 1444 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T22", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 1572, 1587 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T23", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 1589, 1614 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T24", "type": "GROUP", "text": [ "TCAs" ], "offsets": [ [ 1616, 1620 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T25", "type": "DRUG", "text": [ "nortriptyline" ], "offsets": [ [ 1631, 1644 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T26", "type": "DRUG", "text": [ "amitriptyline" ], "offsets": [ [ 1646, 1659 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T27", "type": "DRUG", "text": [ "imipramine" ], "offsets": [ [ 1665, 1675 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T28", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 1678, 1692 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T29", "type": "GROUP", "text": [ "Type 1C antiarrhythmics" ], "offsets": [ [ 1697, 1720 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T30", "type": "DRUG", "text": [ "propafenone" ], "offsets": [ [ 1728, 1739 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T31", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1741, 1751 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T32", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 1796, 1799 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T33", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 1860, 1863 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T34", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 1892, 1895 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T35", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 1920, 1930 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T36", "type": "DRUG", "text": [ "thioridazine" ], "offsets": [ [ 2058, 2070 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T37", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 2072, 2082 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T38", "type": "DRUG", "text": [ "thioridazine" ], "offsets": [ [ 2087, 2099 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T39", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 2204, 2214 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T40", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 2258, 2268 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T41", "type": "DRUG", "text": [ "Alcohol" ], "offsets": [ [ 2345, 2352 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T42", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 2359, 2369 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T43", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 2374, 2381 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T44", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 2472, 2482 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T45", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 2552, 2559 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T46", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 2568, 2578 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T47", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 2611, 2621 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T48", "type": "DRUG", "text": [ "ethanol" ], "offsets": [ [ 2764, 2771 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T49", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 2920, 2930 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T50", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 3167, 3177 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T51", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 3339, 3349 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T52", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 3456, 3466 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T53", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 3625, 3635 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T54", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 3667, 3677 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T55", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 3683, 3691 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T56", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 3697, 3706 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T57", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 3718, 3726 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T58", "type": "DRUG", "text": [ "Duloxetine" ], "offsets": [ [ 3739, 3749 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T59", "type": "DRUG", "text": [ "famotidine" ], "offsets": [ [ 3755, 3765 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T60", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 3818, 3828 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T61", "type": "GROUP", "text": [ "proton pump inhibitors" ], "offsets": [ [ 3939, 3961 ] ], "normalized": [] }, { "id": "Duloxetine_ddi_T62", "type": "DRUG", "text": [ "duloxetine" ], "offsets": [ [ 3970, 3980 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Duloxetine_ddi_R1", "type": "MECHANISM", "arg1_id": "Duloxetine_ddi_T3", "arg2_id": "Duloxetine_ddi_T4", "normalized": [] }, { "id": "Duloxetine_ddi_R2", "type": "MECHANISM", "arg1_id": "Duloxetine_ddi_T10", "arg2_id": "Duloxetine_ddi_T11", "normalized": [] }, { "id": "Duloxetine_ddi_R3", "type": "MECHANISM", "arg1_id": "Duloxetine_ddi_T18", "arg2_id": "Duloxetine_ddi_T19", "normalized": [] }, { "id": "Duloxetine_ddi_R4", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T22", "normalized": [] }, { "id": "Duloxetine_ddi_R5", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T23", "normalized": [] }, { "id": "Duloxetine_ddi_R6", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T24", "normalized": [] }, { "id": "Duloxetine_ddi_R7", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T25", "normalized": [] }, { "id": "Duloxetine_ddi_R8", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T26", "normalized": [] }, { "id": "Duloxetine_ddi_R9", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T27", "normalized": [] }, { "id": "Duloxetine_ddi_R10", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T28", "normalized": [] }, { "id": "Duloxetine_ddi_R11", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T29", "normalized": [] }, { "id": "Duloxetine_ddi_R12", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T30", "normalized": [] }, { "id": "Duloxetine_ddi_R13", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T21", "arg2_id": "Duloxetine_ddi_T31", "normalized": [] }, { "id": "Duloxetine_ddi_R14", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T34", "arg2_id": "Duloxetine_ddi_T35", "normalized": [] }, { "id": "Duloxetine_ddi_R15", "type": "ADVISE", "arg1_id": "Duloxetine_ddi_T37", "arg2_id": "Duloxetine_ddi_T38", "normalized": [] } ]

[ { "id": "Bentoquatam_ddi__text", "type": "abstract", "text": [ "May interact with other creams, lotions, or skin medicines when placed on the same areas of your skin that you are using bentoquatam." ], "offsets": [ [ 0, 133 ] ] } ]

[ { "id": "Bentoquatam_ddi_T1", "type": "DRUG_N", "text": [ "bentoquatam" ], "offsets": [ [ 121, 132 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Gemtuzumab ozogamicin_ddi__text", "type": "abstract", "text": [ "There have been no formal drug-interaction studies performed with Mylotarg. The potential for drug-drug interaction with drugs affected by cytochrome P450 enzymes may not be ruled out. Laboratory Test Interactions Mylotarg is not known to interfere with any routine diagnostic tests." ], "offsets": [ [ 0, 283 ] ] } ]

[ { "id": "Gemtuzumab ozogamicin_ddi_T1", "type": "BRAND", "text": [ "Mylotarg" ], "offsets": [ [ 66, 74 ] ], "normalized": [] }, { "id": "Gemtuzumab ozogamicin_ddi_T2", "type": "BRAND", "text": [ "Mylotarg" ], "offsets": [ [ 214, 222 ] ], "normalized": [] } ]

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[ { "id": "Glipizide_ddi__text", "type": "abstract", "text": [ "Immediate and Extended Release Tablets The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving glipizide, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving glipizide, the patient should be observed closely for loss of control. In vitro binding studies with human serum proteins indicate that glipizide binds differently than tolbutamide and does not interact with salicylate or dicumarol. However, caution must be exercised in extrapolating these findings to the clinical situation and in the use of glipizide with these drugs. Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving glipizide, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving glipizide, the patient should be observed closely for hypoglycemia. A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known. The effect of concomitant administration of fluconazole and glipizide has been demonstrated in a placebo-controlled crossover study in normal volunteers. All subjects received glipizide alone and following treatment with 100 mg of fluconazole as a single daily oral dose for seven days. The mean percentage increase in the glipizide AUC after fluconazole administration was 56.9% (range: 35 to 81)." ], "offsets": [ [ 0, 2111 ] ] } ]

[ { "id": "Glipizide_ddi_T1", "type": "GROUP", "text": [ "sulfonylureas" ], "offsets": [ [ 66, 79 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T2", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 126, 163 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T3", "type": "GROUP", "text": [ "azoles" ], "offsets": [ [ 170, 176 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T4", "type": "GROUP", "text": [ "salicylates" ], "offsets": [ [ 224, 235 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T5", "type": "GROUP", "text": [ "sulfonamides" ], "offsets": [ [ 237, 249 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T6", "type": "DRUG", "text": [ "chloramphenicol" ], "offsets": [ [ 251, 266 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T7", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 268, 278 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T8", "type": "GROUP", "text": [ "coumarins" ], "offsets": [ [ 280, 289 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T9", "type": "GROUP", "text": [ "monoamine oxidase inhibitors" ], "offsets": [ [ 291, 319 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T10", "type": "GROUP", "text": [ "beta adrenergic blocking agents" ], "offsets": [ [ 325, 356 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T11", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 414, 423 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T12", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 537, 546 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T13", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 673, 682 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T14", "type": "DRUG", "text": [ "tolbutamide" ], "offsets": [ [ 706, 717 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T15", "type": "GROUP", "text": [ "salicylate" ], "offsets": [ [ 745, 755 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T16", "type": "DRUG", "text": [ "dicumarol" ], "offsets": [ [ 759, 768 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T17", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 881, 890 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T18", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 1010, 1019 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T19", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 1030, 1039 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T20", "type": "GROUP", "text": [ "corticosteroids" ], "offsets": [ [ 1041, 1056 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T21", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 1058, 1072 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T22", "type": "GROUP", "text": [ "thyroid products" ], "offsets": [ [ 1074, 1090 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T23", "type": "GROUP", "text": [ "estrogens" ], "offsets": [ [ 1092, 1101 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T24", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 1108, 1122 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T25", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T26", "type": "DRUG", "text": [ "nicotinic acid" ], "offsets": [ [ 1135, 1149 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T27", "type": "GROUP", "text": [ "sympathomimetics" ], "offsets": [ [ 1151, 1167 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T28", "type": "GROUP", "text": [ "calcium channel blocking drugs" ], "offsets": [ [ 1169, 1199 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T29", "type": "DRUG", "text": [ "isoniazid" ], "offsets": [ [ 1205, 1214 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T30", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 1272, 1281 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T31", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 1398, 1407 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T32", "type": "DRUG", "text": [ "miconazole" ], "offsets": [ [ 1503, 1513 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T33", "type": "GROUP", "text": [ "hypoglycemic agents" ], "offsets": [ [ 1523, 1542 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T34", "type": "DRUG", "text": [ "miconazole" ], "offsets": [ [ 1688, 1698 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T35", "type": "DRUG", "text": [ "fluconazole" ], "offsets": [ [ 1757, 1768 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T36", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 1773, 1782 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T37", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 1889, 1898 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T38", "type": "DRUG", "text": [ "fluconazole" ], "offsets": [ [ 1944, 1955 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T39", "type": "DRUG", "text": [ "glipizide" ], "offsets": [ [ 2036, 2045 ] ], "normalized": [] }, { "id": "Glipizide_ddi_T40", "type": "DRUG", "text": [ "fluconazole" ], "offsets": [ [ 2056, 2067 ] ], "normalized": [] } ]

[]

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[ { "id": "Glipizide_ddi_R1", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T2", "normalized": [] }, { "id": "Glipizide_ddi_R2", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T3", "normalized": [] }, { "id": "Glipizide_ddi_R3", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T4", "normalized": [] }, { "id": "Glipizide_ddi_R4", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T5", "normalized": [] }, { "id": "Glipizide_ddi_R5", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T6", "normalized": [] }, { "id": "Glipizide_ddi_R6", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T7", "normalized": [] }, { "id": "Glipizide_ddi_R7", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T8", "normalized": [] }, { "id": "Glipizide_ddi_R8", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T9", "normalized": [] }, { "id": "Glipizide_ddi_R9", "type": "EFFECT", "arg1_id": "Glipizide_ddi_T1", "arg2_id": "Glipizide_ddi_T10", "normalized": [] }, { "id": "Glipizide_ddi_R10", "type": "INT", "arg1_id": "Glipizide_ddi_T32", "arg2_id": "Glipizide_ddi_T33", "normalized": [] }, { "id": "Glipizide_ddi_R11", "type": "INT", "arg1_id": "Glipizide_ddi_T35", "arg2_id": "Glipizide_ddi_T36", "normalized": [] }, { "id": "Glipizide_ddi_R12", "type": "MECHANISM", "arg1_id": "Glipizide_ddi_T39", "arg2_id": "Glipizide_ddi_T40", "normalized": [] } ]

[ { "id": "Cevimeline_ddi__text", "type": "abstract", "text": [ "Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Drugs with parasympathomimetic effects administered concurrently with cevimeline can be expected to have additive effects. Cevimeline might interfere with desirable antimuscarinic effects of drugs used concomitantly. Drugs which inhibit CYP2D6 and CYP3A3/4 also inhibit the metabolism of cevimeline. Cevimeline should be used with caution in individuals known or suspected to be deficient in CYP2D6 activity, based on previous experience, as they may be at a higher risk of adverse events. In an in vitro study, cytochrome P450 isozymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 were not inhibited by exposure to cevimeline." ], "offsets": [ [ 0, 771 ] ] } ]

[ { "id": "Cevimeline_ddi_T1", "type": "DRUG", "text": [ "Cevimeline" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Cevimeline_ddi_T2", "type": "GROUP", "text": [ "beta adrenergic antagonists" ], "offsets": [ [ 66, 93 ] ], "normalized": [] }, { "id": "Cevimeline_ddi_T3", "type": "DRUG", "text": [ "cevimeline" ], "offsets": [ [ 220, 230 ] ], "normalized": [] }, { "id": "Cevimeline_ddi_T4", "type": "DRUG", "text": [ "Cevimeline" ], "offsets": [ [ 273, 283 ] ], "normalized": [] }, { "id": "Cevimeline_ddi_T5", "type": "DRUG", "text": [ "cevimeline" ], "offsets": [ [ 438, 448 ] ], "normalized": [] }, { "id": "Cevimeline_ddi_T6", "type": "DRUG", "text": [ "Cevimeline" ], "offsets": [ [ 450, 460 ] ], "normalized": [] }, { "id": "Cevimeline_ddi_T7", "type": "DRUG", "text": [ "cevimeline" ], "offsets": [ [ 760, 770 ] ], "normalized": [] } ]

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[ { "id": "Cevimeline_ddi_R1", "type": "ADVISE", "arg1_id": "Cevimeline_ddi_T1", "arg2_id": "Cevimeline_ddi_T2", "normalized": [] } ]

[ { "id": "Guanfacine_ddi__text", "type": "abstract", "text": [ "The potential for increased sedation when guanfacine is given with other CNS-depressant drug should be appreciated. The administration of guanfacine concomitantly with known microsomal enzyme inducer (phenobarbital or phenytoin) to two patients with renal impairment reportedly resulted in significant reductions in elimination half-life and plasma concentration. In such cases, therefore, more frequent dosing may be required to achieve or maintain the desired hypotensive response. Further, if guanfacine is to be discontinued in such patients, careful tapering of the dosage may be necessary in order to avoid rebound phenomena. TCAs decrease the hypotensive effect of guanfacine. Noncardioselective beta-blockers (nadolol,porpranolol,timolol) may exacerbate rebound hypertension when guanfacine is withdrawn. The beta-blocker should be withdrawn first. The gradual withdrawal of guafacine or a cardioselective beta-blocker could be substituted. Anticoagulants: Ten patients who were stabilized on oral anticoagulants were given guanfacine, 1-2 mg/day, for 4 weeks. No changes were observed in the degree of anticoagulation. In several well-controlled studies, guanfacine was administered together with diuretics with no drug interactions reported. In the long-term safety studies, guanfacine was given concomitantly with many drugs without evidence of any interactions. The principal drugs given (number of patients in parentheses) were: cardiac glycosides (115), sedatives and hypnotics (103), coronary vasodilators (52), oral hypoglycemics (45), cough and cold preparations (45), NSAIDs (38), antihyperlipidemics (29), antigout drugs (24), oral contraceptives (18), bronchodilators (13), insulin (10), and beta blockers (10). Laboratory Test In clinical trials, no clinically relevant laboratory test abnormalities were identified as causally related to drug during short-term treatment with guanfacine. Drug/Laboratory Test Interactions No laboratory test abnormalities related to the use of guanfacine have been identified." ], "offsets": [ [ 0, 2031 ] ] } ]

[ { "id": "Guanfacine_ddi_T1", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 42, 52 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T2", "type": "GROUP", "text": [ "CNS-depressant drug" ], "offsets": [ [ 73, 92 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T3", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 138, 148 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T4", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 201, 214 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T5", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 218, 227 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T6", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 496, 506 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T7", "type": "GROUP", "text": [ "TCAs" ], "offsets": [ [ 632, 636 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T8", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 672, 682 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T9", "type": "GROUP", "text": [ "Noncardioselective beta-blockers" ], "offsets": [ [ 684, 716 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T10", "type": "DRUG", "text": [ "nadolol" ], "offsets": [ [ 718, 725 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T11", "type": "DRUG", "text": [ "timolol" ], "offsets": [ [ 738, 745 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T12", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 788, 798 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T13", "type": "GROUP", "text": [ "beta-blocker" ], "offsets": [ [ 817, 829 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T14", "type": "DRUG", "text": [ "guafacine" ], "offsets": [ [ 883, 892 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T15", "type": "GROUP", "text": [ "cardioselective beta-blocker" ], "offsets": [ [ 898, 926 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T16", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 949, 963 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T17", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1006, 1020 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T18", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 1032, 1042 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T19", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 1164, 1174 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T20", "type": "GROUP", "text": [ "diuretics" ], "offsets": [ [ 1206, 1215 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T21", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 1285, 1295 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T22", "type": "GROUP", "text": [ "cardiac glycosides" ], "offsets": [ [ 1442, 1460 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T23", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 1468, 1477 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T24", "type": "GROUP", "text": [ "hypnotics" ], "offsets": [ [ 1482, 1491 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T25", "type": "GROUP", "text": [ "coronary vasodilators" ], "offsets": [ [ 1499, 1520 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T26", "type": "GROUP", "text": [ "hypoglycemics" ], "offsets": [ [ 1532, 1545 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T27", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1586, 1592 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T28", "type": "GROUP", "text": [ "antihyperlipidemics" ], "offsets": [ [ 1599, 1618 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T29", "type": "GROUP", "text": [ "antigout drugs" ], "offsets": [ [ 1625, 1639 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T30", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 1651, 1665 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T31", "type": "GROUP", "text": [ "bronchodilators" ], "offsets": [ [ 1672, 1687 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T32", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 1694, 1701 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T33", "type": "GROUP", "text": [ "beta blockers" ], "offsets": [ [ 1712, 1725 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T34", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 1898, 1908 ] ], "normalized": [] }, { "id": "Guanfacine_ddi_T35", "type": "DRUG", "text": [ "guanfacine" ], "offsets": [ [ 1999, 2009 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Guanfacine_ddi_R1", "type": "EFFECT", "arg1_id": "Guanfacine_ddi_T1", "arg2_id": "Guanfacine_ddi_T2", "normalized": [] }, { "id": "Guanfacine_ddi_R2", "type": "MECHANISM", "arg1_id": "Guanfacine_ddi_T3", "arg2_id": "Guanfacine_ddi_T4", "normalized": [] }, { "id": "Guanfacine_ddi_R3", "type": "MECHANISM", "arg1_id": "Guanfacine_ddi_T3", "arg2_id": "Guanfacine_ddi_T5", "normalized": [] }, { "id": "Guanfacine_ddi_R4", "type": "EFFECT", "arg1_id": "Guanfacine_ddi_T7", "arg2_id": "Guanfacine_ddi_T8", "normalized": [] }, { "id": "Guanfacine_ddi_R5", "type": "EFFECT", "arg1_id": "Guanfacine_ddi_T9", "arg2_id": "Guanfacine_ddi_T12", "normalized": [] }, { "id": "Guanfacine_ddi_R6", "type": "EFFECT", "arg1_id": "Guanfacine_ddi_T10", "arg2_id": "Guanfacine_ddi_T12", "normalized": [] }, { "id": "Guanfacine_ddi_R7", "type": "EFFECT", "arg1_id": "Guanfacine_ddi_T11", "arg2_id": "Guanfacine_ddi_T12", "normalized": [] } ]

[ { "id": "Levobunolol_ddi__text", "type": "abstract", "text": [ "Although BETAGAN used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with BETAGAN and epinephrine may occur. Close observation of the patient is recommended when a beta-blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may produce vertigo, syncope or postural hypotension. Patients receiving beta-adrenergic blocking agents along with either oral or intravenous calcium antagonists should be monitored for possible atrioventricular conduction disturbances, left ventricular failure and hypotension. In patients with impaired cardiac function, simultaneous use should be avoided altogether. The concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects on prolonging atrioventricular conduction time. Phenothiazine-related compounds and beta-adrenergic blocking agents may have additive hypotensite effects due to the inhibition of each other s metabolism." ], "offsets": [ [ 0, 1105 ] ] } ]

[ { "id": "Levobunolol_ddi_T1", "type": "BRAND", "text": [ "BETAGAN" ], "offsets": [ [ 9, 16 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T2", "type": "BRAND", "text": [ "BETAGAN" ], "offsets": [ [ 117, 124 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T3", "type": "DRUG", "text": [ "epinephrine" ], "offsets": [ [ 129, 140 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T4", "type": "GROUP", "text": [ "beta-blocker" ], "offsets": [ [ 207, 219 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T5", "type": "DRUG", "text": [ "reserpine" ], "offsets": [ [ 296, 305 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T6", "type": "GROUP", "text": [ "beta-adrenergic blocking agents" ], "offsets": [ [ 484, 515 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T7", "type": "GROUP", "text": [ "calcium antagonists" ], "offsets": [ [ 554, 573 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T8", "type": "GROUP", "text": [ "beta-adrenergic blocking agents" ], "offsets": [ [ 805, 836 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T9", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 842, 851 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T10", "type": "GROUP", "text": [ "calcium antagonist" ], "offsets": [ [ 856, 874 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T11", "type": "GROUP", "text": [ "Phenothiazine-related compounds" ], "offsets": [ [ 950, 981 ] ], "normalized": [] }, { "id": "Levobunolol_ddi_T12", "type": "GROUP", "text": [ "beta-adrenergic blocking agents" ], "offsets": [ [ 986, 1017 ] ], "normalized": [] } ]

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[]

[ { "id": "Levobunolol_ddi_R1", "type": "EFFECT", "arg1_id": "Levobunolol_ddi_T2", "arg2_id": "Levobunolol_ddi_T3", "normalized": [] }, { "id": "Levobunolol_ddi_R2", "type": "ADVISE", "arg1_id": "Levobunolol_ddi_T4", "arg2_id": "Levobunolol_ddi_T5", "normalized": [] }, { "id": "Levobunolol_ddi_R3", "type": "ADVISE", "arg1_id": "Levobunolol_ddi_T6", "arg2_id": "Levobunolol_ddi_T7", "normalized": [] }, { "id": "Levobunolol_ddi_R4", "type": "EFFECT", "arg1_id": "Levobunolol_ddi_T8", "arg2_id": "Levobunolol_ddi_T9", "normalized": [] }, { "id": "Levobunolol_ddi_R5", "type": "EFFECT", "arg1_id": "Levobunolol_ddi_T8", "arg2_id": "Levobunolol_ddi_T10", "normalized": [] }, { "id": "Levobunolol_ddi_R6", "type": "MECHANISM", "arg1_id": "Levobunolol_ddi_T11", "arg2_id": "Levobunolol_ddi_T12", "normalized": [] } ]

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

[ { "id": "Dexbrompheniramine_ddi_T1", "type": "DRUG", "text": [ "Dexbrompheniramine" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "Dexbrompheniramine_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 37, 44 ] ], "normalized": [] }, { "id": "Dexbrompheniramine_ddi_T3", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 54, 69 ] ], "normalized": [] }, { "id": "Dexbrompheniramine_ddi_T4", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 144, 158 ] ], "normalized": [] }, { "id": "Dexbrompheniramine_ddi_T5", "type": "GROUP", "text": [ "anticholinergics" ], "offsets": [ [ 161, 177 ] ], "normalized": [] }, { "id": "Dexbrompheniramine_ddi_T6", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 323, 337 ] ], "normalized": [] }, { "id": "Dexbrompheniramine_ddi_T7", "type": "GROUP", "text": [ "monoamine oxidase (MAO) inhibitors" ], "offsets": [ [ 344, 378 ] ], "normalized": [] }, { "id": "Dexbrompheniramine_ddi_T8", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 400, 414 ] ], "normalized": [] }, { "id": "Dexbrompheniramine_ddi_T9", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 491, 505 ] ], "normalized": [] } ]

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[ { "id": "Dexbrompheniramine_ddi_R1", "type": "INT", "arg1_id": "Dexbrompheniramine_ddi_T1", "arg2_id": "Dexbrompheniramine_ddi_T2", "normalized": [] }, { "id": "Dexbrompheniramine_ddi_R2", "type": "INT", "arg1_id": "Dexbrompheniramine_ddi_T1", "arg2_id": "Dexbrompheniramine_ddi_T3", "normalized": [] }, { "id": "Dexbrompheniramine_ddi_R3", "type": "INT", "arg1_id": "Dexbrompheniramine_ddi_T1", "arg2_id": "Dexbrompheniramine_ddi_T5", "normalized": [] }, { "id": "Dexbrompheniramine_ddi_R4", "type": "INT", "arg1_id": "Dexbrompheniramine_ddi_T1", "arg2_id": "Dexbrompheniramine_ddi_T7", "normalized": [] } ]

[ { "id": "Desipramine_ddi__text", "type": "abstract", "text": [ "1. Drugs Metabolized by P450 2D6: The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of caucasians are so called poor metabolizers); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the traction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble p.o. metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythrnics propatenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, seriraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of T.A. with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6. 2. Close supervision and careful adjustment of dosage are required when this drug is given concomitantly with anticholinergic or sympathomimetic drugs. 3. Clinical experience in the concurrent administration of ECT and antidepressant drugs is limited. Thus, if such treatment is essential, the possibility of increased risk relative to benefits should be considered. 4. If desipramine hydrochloride is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of desipramine and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive. Both the sedative and anticholinergic effects of the major tranquilizers are also additive to those of desipramine. 5. Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma levels of the tricyclic antidepressants. Conversely, decreases in plasma levels of the tricyclic antidepressants have been reported upon discontinuation of cimetidine which may result in the loss of the therapeutic efficacy of the tricyclic antidepressant 6. There have been greater than two-fold increases of previously stable plasma levels of tricyclic antidepressants when fluoxetine has been administered in combination with these agents." ], "offsets": [ [ 0, 3780 ] ] } ]

[ { "id": "Desipramine_ddi_T1", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 462, 487 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T2", "type": "GROUP", "text": [ "TCAs" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T3", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 682, 685 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T4", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 856, 859 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T5", "type": "DRUG", "text": [ "quinidine" ], "offsets": [ [ 1047, 1056 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T6", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1058, 1068 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T7", "type": "GROUP", "text": [ "antidepressants" ], "offsets": [ [ 1124, 1139 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T8", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 1141, 1155 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T9", "type": "DRUG", "text": [ "flecainide" ], "offsets": [ [ 1206, 1216 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T10", "type": "GROUP", "text": [ "selective serotonin reuptake inhibitors" ], "offsets": [ [ 1233, 1272 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T11", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 1274, 1279 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T12", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1288, 1298 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T13", "type": "DRUG", "text": [ "paroxetine" ], "offsets": [ [ 1316, 1326 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T14", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 1409, 1413 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T15", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 1414, 1417 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T16", "type": "GROUP", "text": [ "SSRI" ], "offsets": [ [ 1530, 1534 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T17", "type": "GROUP", "text": [ "T.A." ], "offsets": [ [ 1608, 1612 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T18", "type": "GROUP", "text": [ "SSRIs" ], "offsets": [ [ 1629, 1634 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T19", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 1806, 1816 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T20", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 1935, 1960 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T21", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 2072, 2096 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T22", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 2214, 2238 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T23", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 2283, 2286 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T24", "type": "GROUP", "text": [ "TCA" ], "offsets": [ [ 2312, 2315 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T25", "type": "GROUP", "text": [ "anticholinergic" ], "offsets": [ [ 2513, 2528 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T26", "type": "GROUP", "text": [ "sympathomimetic drugs" ], "offsets": [ [ 2532, 2553 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T27", "type": "GROUP", "text": [ "antidepressant drugs" ], "offsets": [ [ 2622, 2642 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T28", "type": "DRUG", "text": [ "desipramine hydrochloride" ], "offsets": [ [ 2776, 2801 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T29", "type": "GROUP", "text": [ "psychotropic agents" ], "offsets": [ [ 2831, 2850 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T30", "type": "GROUP", "text": [ "tranquilizers" ], "offsets": [ [ 2859, 2872 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T31", "type": "GROUP", "text": [ "sedative" ], "offsets": [ [ 2876, 2884 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T32", "type": "GROUP", "text": [ "hypnotics" ], "offsets": [ [ 2885, 2894 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T33", "type": "DRUG", "text": [ "desipramine" ], "offsets": [ [ 3007, 3018 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T34", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 3023, 3038 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T35", "type": "DRUG", "text": [ "chlordiazepoxide" ], "offsets": [ [ 3046, 3062 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T36", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 3066, 3074 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T37", "type": "GROUP", "text": [ "major tranquilizers" ], "offsets": [ [ 3143, 3162 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T38", "type": "DRUG", "text": [ "desipramine" ], "offsets": [ [ 3193, 3204 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T39", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3238, 3248 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T40", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3253, 3278 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T41", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3352, 3377 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T42", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3425, 3450 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T43", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 3494, 3504 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T44", "type": "GROUP", "text": [ "tricyclic antidepressant" ], "offsets": [ [ 3569, 3593 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T45", "type": "GROUP", "text": [ "tricyclic antidepressants" ], "offsets": [ [ 3683, 3708 ] ], "normalized": [] }, { "id": "Desipramine_ddi_T46", "type": "DRUG", "text": [ "fluoxetine" ], "offsets": [ [ 3714, 3724 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Desipramine_ddi_R1", "type": "INT", "arg1_id": "Desipramine_ddi_T14", "arg2_id": "Desipramine_ddi_T15", "normalized": [] }, { "id": "Desipramine_ddi_R2", "type": "ADVISE", "arg1_id": "Desipramine_ddi_T17", "arg2_id": "Desipramine_ddi_T18", "normalized": [] }, { "id": "Desipramine_ddi_R3", "type": "EFFECT", "arg1_id": "Desipramine_ddi_T28", "arg2_id": "Desipramine_ddi_T29", "normalized": [] }, { "id": "Desipramine_ddi_R4", "type": "EFFECT", "arg1_id": "Desipramine_ddi_T28", "arg2_id": "Desipramine_ddi_T30", "normalized": [] }, { "id": "Desipramine_ddi_R5", "type": "EFFECT", "arg1_id": "Desipramine_ddi_T28", "arg2_id": "Desipramine_ddi_T31", "normalized": [] }, { "id": "Desipramine_ddi_R6", "type": "EFFECT", "arg1_id": "Desipramine_ddi_T28", "arg2_id": "Desipramine_ddi_T32", "normalized": [] }, { "id": "Desipramine_ddi_R7", "type": "EFFECT", "arg1_id": "Desipramine_ddi_T33", "arg2_id": "Desipramine_ddi_T34", "normalized": [] }, { "id": "Desipramine_ddi_R8", "type": "EFFECT", "arg1_id": "Desipramine_ddi_T33", "arg2_id": "Desipramine_ddi_T35", "normalized": [] }, { "id": "Desipramine_ddi_R9", "type": "EFFECT", "arg1_id": "Desipramine_ddi_T33", "arg2_id": "Desipramine_ddi_T36", "normalized": [] }, { "id": "Desipramine_ddi_R10", "type": "EFFECT", "arg1_id": "Desipramine_ddi_T37", "arg2_id": "Desipramine_ddi_T38", "normalized": [] }, { "id": "Desipramine_ddi_R11", "type": "MECHANISM", "arg1_id": "Desipramine_ddi_T39", "arg2_id": "Desipramine_ddi_T40", "normalized": [] }, { "id": "Desipramine_ddi_R12", "type": "MECHANISM", "arg1_id": "Desipramine_ddi_T42", "arg2_id": "Desipramine_ddi_T43", "normalized": [] }, { "id": "Desipramine_ddi_R13", "type": "MECHANISM", "arg1_id": "Desipramine_ddi_T45", "arg2_id": "Desipramine_ddi_T46", "normalized": [] } ]

[ { "id": "Cetrorelix_ddi__text", "type": "abstract", "text": [ "No formal drug interaction studies have been performed with Cetrotide ." ], "offsets": [ [ 0, 71 ] ] } ]

[ { "id": "Cetrorelix_ddi_T1", "type": "BRAND", "text": [ "Cetrotide" ], "offsets": [ [ 60, 69 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "Cephalexin_ddi__text", "type": "abstract", "text": [ "Metformin: In healthy subjects given single 500 mg doses of cephalexin and metformin, plasma metformin mean cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%. No information is available about the interaction of cephalexin and metformin following multiple doses of either drug. Although not observed in this study, adverse effects could potentially arise from co-administration of cephalexin and metformin by inhibition of tubular secretion via organic cationic transporter systems. Accordingly, careful patient monitoring and dose adjustment of metformin is recommended in patients concomitantly taking cephalexin and metformin. Probenecid: As with other b-lactams, the renal excretion of cephalexin is inhibited by probenecid. Drug / Laboratory Test Interactions As a result of administration of Keflex, a false-positive reaction for glucose in the urine may occur. This has been observed with Benedict s and Fehling s solutions and also with Clinitest tablets." ], "offsets": [ [ 0, 1033 ] ] } ]

[ { "id": "Cephalexin_ddi_T1", "type": "DRUG", "text": [ "Metformin" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T2", "type": "DRUG", "text": [ "cephalexin" ], "offsets": [ [ 60, 70 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T3", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 75, 84 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T4", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 93, 102 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T5", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 179, 188 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T6", "type": "DRUG", "text": [ "cephalexin" ], "offsets": [ [ 281, 291 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T7", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 296, 305 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T8", "type": "DRUG", "text": [ "cephalexin" ], "offsets": [ [ 450, 460 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T9", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 465, 474 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T10", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 615, 624 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T11", "type": "DRUG", "text": [ "cephalexin" ], "offsets": [ [ 673, 683 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T12", "type": "DRUG", "text": [ "metformin" ], "offsets": [ [ 688, 697 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T13", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 699, 709 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T14", "type": "GROUP", "text": [ "b-lactams" ], "offsets": [ [ 725, 734 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T15", "type": "DRUG", "text": [ "cephalexin" ], "offsets": [ [ 759, 769 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T16", "type": "DRUG", "text": [ "probenecid" ], "offsets": [ [ 786, 796 ] ], "normalized": [] }, { "id": "Cephalexin_ddi_T17", "type": "BRAND", "text": [ "Keflex" ], "offsets": [ [ 867, 873 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Cephalexin_ddi_R1", "type": "MECHANISM", "arg1_id": "Cephalexin_ddi_T2", "arg2_id": "Cephalexin_ddi_T3", "normalized": [] }, { "id": "Cephalexin_ddi_R2", "type": "MECHANISM", "arg1_id": "Cephalexin_ddi_T8", "arg2_id": "Cephalexin_ddi_T9", "normalized": [] }, { "id": "Cephalexin_ddi_R3", "type": "ADVISE", "arg1_id": "Cephalexin_ddi_T11", "arg2_id": "Cephalexin_ddi_T12", "normalized": [] }, { "id": "Cephalexin_ddi_R4", "type": "MECHANISM", "arg1_id": "Cephalexin_ddi_T15", "arg2_id": "Cephalexin_ddi_T16", "normalized": [] } ]

[ { "id": "Aldesleukin_ddi__text", "type": "abstract", "text": [ "PROLEUKIN may affect central nervous function. Therefore, interactions could occur following concomitant administration of psychotropic drugs (e.g., narcotics, analgesics, antiemetics, sedatives, tranquilizers). Concurrent administration of drugs possessing nephrotoxic (e.g., aminoglycosides, indomethacin), myelotoxic (e.g., cytotoxic chemotherapy), cardiotoxic (e.g., doxorubicin) or hepatotoxic (e.g., methotrexate, asparaginase) effects with PROLEUKIN may increase toxicity in these organ systems. The safety and efficacy of PROLEUKIN in combination with any antineoplastic agents have not been established. In addition, reduced kidney and liver function secondary to PROLEUKIN treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. Hypersensitivity reactions have been reported in patients receiving combination regimens containing sequential high dose PROLEUKIN and antineoplastic agents, specifically, dacarbazine, cis-platinum, tamoxifen and interferon-alfa. These reactions consisted of erythema, pruritus, and hypotension and occurred within hours of administration of chemotherapy. These events required medical intervention in some patients. Myocardial injury, including myocardial infarction, myocarditis, ventricular hypokinesia, and severe rhabdomyolysis appear to be increased in patients receiving PROLEUKIN and interferon-alfa concurrently. Exacerbation or the initial presentation of a number of autoimmune and inflammatory disorders has been observed following concurrent use of interferon-alfa and PROLEUKIN, including crescentic IgA glomerulonephritis, oculo-bulbar myasthenia gravis, inflammatory arthritis, thyroiditis, bullous pemphigoid, and Stevens-Johnson syndrome. Although glucocorticoids have been shown to reduce PROLEUKIN-induced side effects including fever, renal insufficiency, hyperbilirubinemia, confusion, and dyspnea, concomitant administration of these agents with PROLEUKIN may reduce the antitumor effectiveness of PROLEUKIN and thus should be avoided. 12 Beta-blockers and other antihypertensives may potentiate the hypotension seen with PROLEUKIN. Delayed Adverse Reactions to Iodinated Contrast Media: A review of the literature revealed that 12.6% (range 11-28%) of 501 patients treated with various interleukin-2 containing regimens who were subsequently administered radiographic iodinated contrast media experienced acute, atypical adverse reactions. The onset of symptoms usually occurred within hours (most commonly 1 to 4 hours) following the administration of contrast media. These reactions include fever, chills, nausea, vomiting, pruritus, rash, diarrhea, hypotension, edema, and oliguria. Some clinicians have noted that these reactions resemble the immediate side effects caused by interleukin-2 administration, however the cause of contrast reactions after interleukin-2 therapy is unknown. Most events were reported to occur when contrast media was given within 4 weeks after the last dose of interleukin-2. These events were also reported to occur when contrast media was given several months after interleukin-2 treatment." ], "offsets": [ [ 0, 3148 ] ] } ]

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"Aldesleukin_ddi_T9", "type": "DRUG", "text": [ "indomethacin" ], "offsets": [ [ 294, 306 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T10", "type": "GROUP", "text": [ "cytotoxic" ], "offsets": [ [ 327, 336 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T11", "type": "DRUG", "text": [ "doxorubicin" ], "offsets": [ [ 371, 382 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T12", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 406, 418 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T13", "type": "DRUG", "text": [ "asparaginase" ], "offsets": [ [ 420, 432 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T14", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 447, 456 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T15", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 530, 539 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T16", "type": "GROUP", "text": [ "antineoplastic agents" ], "offsets": [ [ 564, 585 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T17", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 673, 682 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T18", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 921, 930 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T19", "type": "GROUP", "text": [ "antineoplastic agents" ], "offsets": [ [ 935, 956 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T20", "type": "DRUG", "text": [ "dacarbazine" ], "offsets": [ [ 972, 983 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T21", "type": "DRUG", "text": [ "cis-platinum" ], "offsets": [ [ 985, 997 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T22", "type": "DRUG", "text": [ "tamoxifen" ], "offsets": [ [ 999, 1008 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T23", "type": "DRUG", "text": [ "interferon-alfa" ], "offsets": [ [ 1013, 1028 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T24", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 1378, 1387 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T25", "type": "DRUG", "text": [ "interferon-alfa" ], "offsets": [ [ 1392, 1407 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T26", "type": "DRUG", "text": [ "interferon-alfa" ], "offsets": [ [ 1562, 1577 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T27", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 1582, 1591 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T28", "type": "GROUP", "text": [ "glucocorticoids" ], "offsets": [ [ 1766, 1781 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T29", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 1808, 1817 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T30", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 1969, 1978 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T31", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 2021, 2030 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T32", "type": "GROUP", "text": [ "Beta-blockers" ], "offsets": [ [ 2062, 2075 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T33", "type": "GROUP", "text": [ "antihypertensives" ], "offsets": [ [ 2086, 2103 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T34", "type": "BRAND", "text": [ "PROLEUKIN" ], "offsets": [ [ 2145, 2154 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T35", "type": "GROUP", "text": [ "Iodinated Contrast Media" ], "offsets": [ [ 2185, 2209 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T36", "type": "DRUG", "text": [ "interleukin-2" ], "offsets": [ [ 2310, 2323 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T37", "type": "GROUP", "text": [ "radiographic iodinated contrast media" ], "offsets": [ [ 2379, 2416 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T38", "type": "DRUG", "text": [ "interleukin-2" ], "offsets": [ [ 2804, 2817 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T39", "type": "DRUG", "text": [ "interleukin-2" ], "offsets": [ [ 3017, 3030 ] ], "normalized": [] }, { "id": "Aldesleukin_ddi_T40", "type": "DRUG", "text": [ "interleukin-2" ], "offsets": [ [ 3124, 3137 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Aldesleukin_ddi_R1", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T8", "arg2_id": "Aldesleukin_ddi_T14", "normalized": [] }, { "id": "Aldesleukin_ddi_R2", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T9", "arg2_id": "Aldesleukin_ddi_T14", "normalized": [] }, { "id": "Aldesleukin_ddi_R3", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T10", "arg2_id": "Aldesleukin_ddi_T14", "normalized": [] }, { "id": "Aldesleukin_ddi_R4", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T11", "arg2_id": "Aldesleukin_ddi_T14", "normalized": [] }, { "id": "Aldesleukin_ddi_R5", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T12", "arg2_id": "Aldesleukin_ddi_T14", "normalized": [] }, { "id": "Aldesleukin_ddi_R6", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T13", "arg2_id": "Aldesleukin_ddi_T14", "normalized": [] }, { "id": "Aldesleukin_ddi_R7", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T18", "arg2_id": "Aldesleukin_ddi_T19", "normalized": [] }, { "id": "Aldesleukin_ddi_R8", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T18", "arg2_id": "Aldesleukin_ddi_T20", "normalized": [] }, { "id": "Aldesleukin_ddi_R9", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T18", "arg2_id": "Aldesleukin_ddi_T21", "normalized": [] }, { "id": "Aldesleukin_ddi_R10", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T18", "arg2_id": "Aldesleukin_ddi_T22", "normalized": [] }, { "id": "Aldesleukin_ddi_R11", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T18", "arg2_id": "Aldesleukin_ddi_T23", "normalized": [] }, { "id": "Aldesleukin_ddi_R12", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T24", "arg2_id": "Aldesleukin_ddi_T25", "normalized": [] }, { "id": "Aldesleukin_ddi_R13", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T26", "arg2_id": "Aldesleukin_ddi_T27", "normalized": [] }, { "id": "Aldesleukin_ddi_R14", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T28", "arg2_id": "Aldesleukin_ddi_T29", "normalized": [] }, { "id": "Aldesleukin_ddi_R15", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T32", "arg2_id": "Aldesleukin_ddi_T34", "normalized": [] }, { "id": "Aldesleukin_ddi_R16", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T33", "arg2_id": "Aldesleukin_ddi_T34", "normalized": [] }, { "id": "Aldesleukin_ddi_R17", "type": "EFFECT", "arg1_id": "Aldesleukin_ddi_T36", "arg2_id": "Aldesleukin_ddi_T37", "normalized": [] } ]

[ { "id": "Ethchlorvynol_ddi__text", "type": "abstract", "text": [ "Dicumarol and warfarin may decrease hypoprothrombinemic effect. Other depressasnts such as alcohol, barbiturates, and MAOIs may enhance CNS depression when administered with ethchlorvynol." ], "offsets": [ [ 0, 188 ] ] } ]

[ { "id": "Ethchlorvynol_ddi_T1", "type": "DRUG", "text": [ "Dicumarol" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "Ethchlorvynol_ddi_T2", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 14, 22 ] ], "normalized": [] }, { "id": "Ethchlorvynol_ddi_T3", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 91, 98 ] ], "normalized": [] }, { "id": "Ethchlorvynol_ddi_T4", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 100, 112 ] ], "normalized": [] }, { "id": "Ethchlorvynol_ddi_T5", "type": "GROUP", "text": [ "MAOIs" ], "offsets": [ [ 118, 123 ] ], "normalized": [] }, { "id": "Ethchlorvynol_ddi_T6", "type": "DRUG", "text": [ "ethchlorvynol" ], "offsets": [ [ 174, 187 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ethchlorvynol_ddi_R1", "type": "EFFECT", "arg1_id": "Ethchlorvynol_ddi_T3", "arg2_id": "Ethchlorvynol_ddi_T6", "normalized": [] }, { "id": "Ethchlorvynol_ddi_R2", "type": "EFFECT", "arg1_id": "Ethchlorvynol_ddi_T4", "arg2_id": "Ethchlorvynol_ddi_T6", "normalized": [] }, { "id": "Ethchlorvynol_ddi_R3", "type": "EFFECT", "arg1_id": "Ethchlorvynol_ddi_T5", "arg2_id": "Ethchlorvynol_ddi_T6", "normalized": [] } ]

[ { "id": "Azlocillin_ddi__text", "type": "abstract", "text": [ "Azlocillin should not be administered concomitantly with amikacin, ciprofloxacin, gentamicin, netilmicin, or tobramycin." ], "offsets": [ [ 0, 120 ] ] } ]

[ { "id": "Azlocillin_ddi_T1", "type": "DRUG", "text": [ "Azlocillin" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "Azlocillin_ddi_T2", "type": "DRUG", "text": [ "amikacin" ], "offsets": [ [ 57, 65 ] ], "normalized": [] }, { "id": "Azlocillin_ddi_T3", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 67, 80 ] ], "normalized": [] }, { "id": "Azlocillin_ddi_T4", "type": "DRUG", "text": [ "gentamicin" ], "offsets": [ [ 82, 92 ] ], "normalized": [] }, { "id": "Azlocillin_ddi_T5", "type": "DRUG", "text": [ "netilmicin" ], "offsets": [ [ 94, 104 ] ], "normalized": [] }, { "id": "Azlocillin_ddi_T6", "type": "DRUG", "text": [ "tobramycin" ], "offsets": [ [ 109, 119 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Azlocillin_ddi_R1", "type": "ADVISE", "arg1_id": "Azlocillin_ddi_T1", "arg2_id": "Azlocillin_ddi_T2", "normalized": [] }, { "id": "Azlocillin_ddi_R2", "type": "ADVISE", "arg1_id": "Azlocillin_ddi_T1", "arg2_id": "Azlocillin_ddi_T3", "normalized": [] }, { "id": "Azlocillin_ddi_R3", "type": "ADVISE", "arg1_id": "Azlocillin_ddi_T1", "arg2_id": "Azlocillin_ddi_T4", "normalized": [] }, { "id": "Azlocillin_ddi_R4", "type": "ADVISE", "arg1_id": "Azlocillin_ddi_T1", "arg2_id": "Azlocillin_ddi_T5", "normalized": [] }, { "id": "Azlocillin_ddi_R5", "type": "ADVISE", "arg1_id": "Azlocillin_ddi_T1", "arg2_id": "Azlocillin_ddi_T6", "normalized": [] } ]

[ { "id": "Eculizumab_ddi__text", "type": "abstract", "text": [ "Drug interaction studies have not been performed with Soliris." ], "offsets": [ [ 0, 62 ] ] } ]

[ { "id": "Eculizumab_ddi_T1", "type": "BRAND", "text": [ "Soliris" ], "offsets": [ [ 54, 61 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Diphenylpyraline_ddi__text", "type": "abstract", "text": [ "This drug may interact with alcohol or other CNS depressants (may potentiate the CNS depressant effects of either these medications or antihistamines), anticholinergics or other medications with anticholinergic activity (anticholinergic effects may be potentiated when these medications are used concurrently with antihistamines), and monoamine oxidase (MAO) inhibitors (concurrent use with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines)." ], "offsets": [ [ 0, 498 ] ] } ]

[ { "id": "Diphenylpyraline_ddi_T1", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 28, 35 ] ], "normalized": [] }, { "id": "Diphenylpyraline_ddi_T2", "type": "GROUP", "text": [ "CNS depressants" ], "offsets": [ [ 45, 60 ] ], "normalized": [] }, { "id": "Diphenylpyraline_ddi_T3", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 135, 149 ] ], "normalized": [] }, { "id": "Diphenylpyraline_ddi_T4", "type": "GROUP", "text": [ "anticholinergics" ], "offsets": [ [ 152, 168 ] ], "normalized": [] }, { "id": "Diphenylpyraline_ddi_T5", "type": "GROUP", "text": [ "antihistamines" ], "offsets": [ [ 314, 328 ] ], "normalized": [] }, { "id": "Diphenylpyraline_ddi_T6", "type": "GROUP", "text": [ "monoamine oxidase (MAO) inhibitors" ], "offsets": [ [ 335, 369 ] ], "normalized": [] }, { "id": "Diphenylpyraline_ddi_T7", "type": "DRUG", "text": [ "antihistamines" ], "offsets": [ [ 391, 405 ] ], "normalized": [] }, { "id": "Diphenylpyraline_ddi_T8", "type": "DRUG", "text": [ "antihistamines" ], "offsets": [ [ 482, 496 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Butenafine_ddi__text", "type": "abstract", "text": [ "Potential drug interactions between Mentax (butenafine HCl cream) Cream, 1%, and other drugs have not been systematically evaluated." ], "offsets": [ [ 0, 132 ] ] } ]

[ { "id": "Butenafine_ddi_T1", "type": "BRAND", "text": [ "Mentax" ], "offsets": [ [ 36, 42 ] ], "normalized": [] }, { "id": "Butenafine_ddi_T2", "type": "DRUG", "text": [ "butenafine HCl" ], "offsets": [ [ 44, 58 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Clofazimine_ddi__text", "type": "abstract", "text": [ "Preliminary data which suggest that dapsone may inhibit the anti-inflammatory activity of Lamprene have not been confirmed. If leprosy-associated inflammatory reactions develop in patients being treated with dapsone and clofazimine, it is still advisable to continue treatment with both drugs." ], "offsets": [ [ 0, 293 ] ] } ]

[ { "id": "Clofazimine_ddi_T1", "type": "DRUG", "text": [ "dapsone" ], "offsets": [ [ 36, 43 ] ], "normalized": [] }, { "id": "Clofazimine_ddi_T2", "type": "BRAND", "text": [ "Lamprene" ], "offsets": [ [ 90, 98 ] ], "normalized": [] }, { "id": "Clofazimine_ddi_T3", "type": "DRUG", "text": [ "dapsone" ], "offsets": [ [ 208, 215 ] ], "normalized": [] }, { "id": "Clofazimine_ddi_T4", "type": "DRUG", "text": [ "clofazimine" ], "offsets": [ [ 220, 231 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Clofazimine_ddi_R1", "type": "EFFECT", "arg1_id": "Clofazimine_ddi_T1", "arg2_id": "Clofazimine_ddi_T2", "normalized": [] }, { "id": "Clofazimine_ddi_R2", "type": "ADVISE", "arg1_id": "Clofazimine_ddi_T3", "arg2_id": "Clofazimine_ddi_T4", "normalized": [] } ]

[ { "id": "Ergocalciferol_ddi__text", "type": "abstract", "text": [ "Mineral oil interferes with the absorption of fat-soluble vitamins, including vitamin D preparations. Administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with ergocalciferol may cause hypercalcemia." ], "offsets": [ [ 0, 246 ] ] } ]

[ { "id": "Ergocalciferol_ddi_T1", "type": "DRUG", "text": [ "Mineral oil" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "Ergocalciferol_ddi_T2", "type": "GROUP", "text": [ "fat-soluble vitamins" ], "offsets": [ [ 46, 66 ] ], "normalized": [] }, { "id": "Ergocalciferol_ddi_T3", "type": "GROUP", "text": [ "vitamin D preparations" ], "offsets": [ [ 78, 100 ] ], "normalized": [] }, { "id": "Ergocalciferol_ddi_T4", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 120, 138 ] ], "normalized": [] }, { "id": "Ergocalciferol_ddi_T5", "type": "DRUG", "text": [ "ergocalciferol" ], "offsets": [ [ 207, 221 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ergocalciferol_ddi_R1", "type": "MECHANISM", "arg1_id": "Ergocalciferol_ddi_T1", "arg2_id": "Ergocalciferol_ddi_T2", "normalized": [] }, { "id": "Ergocalciferol_ddi_R2", "type": "MECHANISM", "arg1_id": "Ergocalciferol_ddi_T1", "arg2_id": "Ergocalciferol_ddi_T3", "normalized": [] }, { "id": "Ergocalciferol_ddi_R3", "type": "EFFECT", "arg1_id": "Ergocalciferol_ddi_T4", "arg2_id": "Ergocalciferol_ddi_T5", "normalized": [] } ]

[ { "id": "Hydroflumethiazide_ddi__text", "type": "abstract", "text": [ "Anticoagulants, oral (Effects may be decreased when used concurrently with thiazide diuretics; dosage adjustments may be necessary.) Antigout medications (Thiazide diuretics may raise the level of blood uric acid; dosage adjustment of antigout medications may be necessary to control hyperuricemia and gout.) Antihypertensive medications, other, especially diazoxide, or preanesthetic and anesthetic agents used in surgery or skeletal-muscle relaxants, nondepolarizing, used in surgery (Effects may be potentiated when used concurrently with thiazide diuretics; dosage adjustments may be necessary.) Amphotericin B or Corticosteroids or Corticotropin (ACTH) (Concurrent use with thiazide diuretics may intensify electrolyte imbalance, particularly hypokalemia.) Cardiac glycosides (Concurrent use with thiazide diuretics may enhance the possibility of digitalis toxicity associated with hypokalemia.) Colestipol (May inhibit gastrointestinal absorption of the thiazide diuretics; administration 1 hour before or 4 hours after colestipol is recommended.) Hypoglycemics (Thiazide diuretics may raise blood glucose levels; for adult-onset diabetics, dosage adjustment of hypoglycemic medications may be necessary during and after thiazide diuretic therapy; insulin requirements may be increased, decreased, or unchanged.) Lithium salts (Concurrent use with thiazide diuretics is not recommended, as they may provoke lithium toxicity because of reduced renal clearance.) Methenamine (Effectiveness may be decreased when used concurrently with thiazide diuretics because of alkalinization of the urine.) Nonsteroidal anti-inflammatory agents (In some patients, the steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium sparing, and thiazide diuretics. Therefore, when hydroflumethiazide and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.) Norepinephrine (Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.) Tubocurarine (Thiazide drugs may increase the responsiveness to tubocurarine.) DIAGNOSTIC INTERFERENCE With expected physiologic effects: Blood and urine glucose levels (usually only in patients with a predisposition for glucose intolerance) and Serum bilirubin levels (by displacement from albumin binding) and Serum calcium levels (thiazide diuretics should be discontinued before parathyroid-function tests are carried out) and Serum uric acid levels (may be increased) Serum magnesium, potassium, and sodium levels (may be decreased; serum magnesium levels may increase in uremic patients) Serum protein-bound iodine (PBI) levels (may be decreased) Thiazides should be discontinued before carrying out tests for parathyroid function." ], "offsets": [ [ 0, 2940 ] ] } ]

[ { "id": "Hydroflumethiazide_ddi_T1", "type": "GROUP", "text": [ "Anticoagulants" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T2", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 75, 93 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T3", "type": "GROUP", "text": [ "Antigout medications" ], "offsets": [ [ 133, 153 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T4", "type": "GROUP", "text": [ "Thiazide diuretics" ], "offsets": [ [ 155, 173 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T5", "type": "GROUP", "text": [ "antigout medications" ], "offsets": [ [ 235, 255 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T6", "type": "GROUP", "text": [ "Antihypertensive medications" ], "offsets": [ [ 309, 337 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T7", "type": "DRUG", "text": [ "diazoxide" ], "offsets": [ [ 357, 366 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T8", "type": "GROUP", "text": [ "anesthetic" ], "offsets": [ [ 374, 384 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T9", "type": "GROUP", "text": [ "skeletal-muscle relaxants" ], "offsets": [ [ 426, 451 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T10", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 542, 560 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T11", "type": "DRUG", "text": [ "Amphotericin B" ], "offsets": [ [ 600, 614 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T12", "type": "GROUP", "text": [ "Corticosteroids" ], "offsets": [ [ 618, 633 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T13", "type": "DRUG", "text": [ "Corticotropin" ], "offsets": [ [ 637, 650 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T14", "type": "DRUG", "text": [ "ACTH" ], "offsets": [ [ 652, 656 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T15", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 679, 697 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T16", "type": "GROUP", "text": [ "Cardiac glycosides" ], "offsets": [ [ 762, 780 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T17", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 802, 820 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T18", "type": "GROUP", "text": [ "digitalis" ], "offsets": [ [ 852, 861 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T19", "type": "DRUG", "text": [ "Colestipol" ], "offsets": [ [ 901, 911 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T20", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 960, 978 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T21", "type": "DRUG", "text": [ "colestipol" ], "offsets": [ [ 1026, 1036 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T22", "type": "GROUP", "text": [ "Hypoglycemics" ], "offsets": [ [ 1054, 1067 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T23", "type": "GROUP", "text": [ "Thiazide diuretics" ], "offsets": [ [ 1069, 1087 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T24", "type": "GROUP", "text": [ "hypoglycemic medications" ], "offsets": [ [ 1168, 1192 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T25", "type": "GROUP", "text": [ "thiazide diuretic" ], "offsets": [ [ 1227, 1244 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T26", "type": "DRUG", "text": [ "insulin" ], "offsets": [ [ 1254, 1261 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T27", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 1319, 1326 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T28", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 1354, 1372 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T29", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 1413, 1420 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T30", "type": "DRUG", "text": [ "Methenamine" ], "offsets": [ [ 1467, 1478 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T31", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 1539, 1557 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T32", "type": "GROUP", "text": [ "Nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 1599, 1636 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T33", "type": "GROUP", "text": [ "steroidal anti-inflammatory agent" ], "offsets": [ [ 1660, 1693 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T34", "type": "GROUP", "text": [ "loop", "diuretics" ], "offsets": [ [ 1764, 1768 ], [ 1802, 1811 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T35", "type": "GROUP", "text": [ "potassium sparing", "diuretics" ], "offsets": [ [ 1770, 1787 ], [ 1802, 1811 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T36", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 1793, 1811 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T37", "type": "DRUG", "text": [ "hydroflumethiazide" ], "offsets": [ [ 1829, 1847 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T38", "type": "GROUP", "text": [ "nonsteroidal anti-inflammatory agents" ], "offsets": [ [ 1852, 1889 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T39", "type": "GROUP", "text": [ "diuretic" ], "offsets": [ [ 1995, 2003 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T40", "type": "DRUG", "text": [ "Norepinephrine" ], "offsets": [ [ 2018, 2032 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T41", "type": "GROUP", "text": [ "Thiazides" ], "offsets": [ [ 2034, 2043 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T42", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 2084, 2098 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T43", "type": "DRUG", "text": [ "Tubocurarine" ], "offsets": [ [ 2203, 2215 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T44", "type": "GROUP", "text": [ "Thiazide drugs" ], "offsets": [ [ 2217, 2231 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T45", "type": "DRUG", "text": [ "tubocurarine" ], "offsets": [ [ 2267, 2279 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T46", "type": "GROUP", "text": [ "thiazide diuretics" ], "offsets": [ [ 2537, 2555 ] ], "normalized": [] }, { "id": "Hydroflumethiazide_ddi_T47", "type": "GROUP", "text": [ "Thiazides" ], "offsets": [ [ 2856, 2865 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Hydroflumethiazide_ddi_R1", "type": "EFFECT", "arg1_id": "Hydroflumethiazide_ddi_T17", "arg2_id": "Hydroflumethiazide_ddi_T18", "normalized": [] }, { "id": "Hydroflumethiazide_ddi_R2", "type": "ADVISE", "arg1_id": "Hydroflumethiazide_ddi_T24", "arg2_id": "Hydroflumethiazide_ddi_T25", "normalized": [] }, { "id": "Hydroflumethiazide_ddi_R3", "type": "EFFECT", "arg1_id": "Hydroflumethiazide_ddi_T33", "arg2_id": "Hydroflumethiazide_ddi_T34", "normalized": [] }, { "id": "Hydroflumethiazide_ddi_R4", "type": "EFFECT", "arg1_id": "Hydroflumethiazide_ddi_T33", "arg2_id": "Hydroflumethiazide_ddi_T35", "normalized": [] }, { "id": "Hydroflumethiazide_ddi_R5", "type": "EFFECT", "arg1_id": "Hydroflumethiazide_ddi_T33", "arg2_id": "Hydroflumethiazide_ddi_T36", "normalized": [] }, { "id": "Hydroflumethiazide_ddi_R6", "type": "ADVISE", "arg1_id": "Hydroflumethiazide_ddi_T37", "arg2_id": "Hydroflumethiazide_ddi_T38", "normalized": [] }, { "id": "Hydroflumethiazide_ddi_R7", "type": "EFFECT", "arg1_id": "Hydroflumethiazide_ddi_T41", "arg2_id": "Hydroflumethiazide_ddi_T42", "normalized": [] }, { "id": "Hydroflumethiazide_ddi_R8", "type": "EFFECT", "arg1_id": "Hydroflumethiazide_ddi_T44", "arg2_id": "Hydroflumethiazide_ddi_T45", "normalized": [] } ]

[ { "id": "Felbamate_ddi__text", "type": "abstract", "text": [ "The drug interaction data described in this section were obtained from controlled clinical trials and studies involving otherwise healthy adults with epilepsy. Use in Conjunction with Other Antiepileptic Drugs: The addition of Felbatol to antiepileptic drugs (AEDs) affects the steady-state plasma concentrations of AEDs. The net effect of these interactions is summarized in the following table: AED AED Felbatol Coadministered Concentration Concentration Phenytoin Valproate ** Carbamazepine (CBZ) *CBZ epoxide Phenobarbital *Not administered, but an active metabolite of carbamazepine. **No significant effect. Specific Effects of Felbatol on Other Antiepileptic Drugs Phenytoin: Felbatol causes an increase in steady-state phenytoin plasma concentrations. In 10 otherwise healthy subjects with epilepsy ingesting phenytoin, the steadystate trough (Cmin) phenytoin plasma concentration was 17 5 micrograms/mL. The steady-state Cmin increased to 21 5 micrograms/mL when 1200 mg/day of felbamate was coadministered. Increasing the felbamate dose to 1800 mg/day in six of these subjects increased the steady-state phenytoin Cmin to 25 7 micrograms/mL. In order to maintain phenytoin levels, limit adverse experiences, and achieve the felbamate dose of 3600 mg/day, a phenytoin dose reduction of approximately 40% was necessary for eight of these 10 subjects. In a controlled clinical trial, a 20% reduction of the phenytoin dose at the initiation of Felbatol therapy resulted in phenytoin levels comparable to those prior to Felbatol administration. Carbamazepine: Felbatol causes a decrease in the steady-state carbamazepine plasma concentrations and an increase in the steady-state carbamazepine epoxide plasma concentration. In nine otherwise healthy subjects with epilepsy ingesting carbamazepine, the steady-state trough (Cmin) carbamazepine concentration was 8 2 micrograms/mL. The carbamazepine steady-state Cmin decreased 31% to 5 1 micrograms/mL when felbamate (3000 mg/day, divided into three doses) was coadministered. Carbamazepine epoxide steady-state Cmin concentrations increased 57% from 1.0 0.3 to 1.6 0.4 micrograms/mL with the addition of felbamate. In clinical trials, similar changes in carbamazepine and carbamazepine epoxide were seen. Valproate: Felbatol causes an increase in steady-state valproate concentrations. In four subjects with epilepsy ingesting valproate, the steady-state trough (Cmin) valproate plasma concentration was 63 16 micrograms/mL. The steady-state Cmin increased to 78 14 micrograms/mL when 1200 mg/day of felbamate was coadministered. Increasing the felbamate dose to 2400 mg/day increased the steadystate valproate Cmin to 96 25 micrograms/mL. Corresponding values for free valproate Cmin concentrations were 7 3, 9 4, and 11 6 micrograms/mL for 0, 1200, and 2400 mg/day Felbatol , respectively. The ratios of the AUCs of unbound valproate to the AUCs of the total valproate were 11.1 %, 13.0%, and 11.5%, with coadministration of 0, 1200, and 2400 mg/day of Felbatol , respectively. Phenobarbital: Coadministration of felbamate with phenobarbital causes an increase in phenobarbital plasma concentrations, In 12 otherwise healthy male volunteers ingesting phenobarbital, the steady-state trough (Cmin) phenobarbital concentration was 14.2 micrograms/mL. The steady-state Cmin concentration increased to 17.8 micrograms/mL when 2400 mg/day of felbamate was coadministered for one week. Effects of Other Antiepileptic Drugs on Felbatol Phenytoin: Phenytoin causes an approximate doubling of the clearance of Felbatol (felbamate) at steady state and, therefore, the addition of phenytoin causes an approximate 45% decrease in the steady-state trough concentrations of Felbatol as compared to the same dose of Felbatol given as monotherapy. Carbamazepine: Carbamazepine causes an approximate 50% increase in the clearance of Felbatol at steady state and, therefore, the addition of carbamazepine results in an approximate 40% decrease in the steady-state trough concentrations of Felbatol as compared to the same dose of Felbatol given as monotherapy. Valproate: Available data suggest that there is no significant effect of valproate on the clearance of Felbatol at steady state, Therefore, the addition of valproate is not expected to cause a clinically important effect on Felbatol (felbamate) plasma concentrations. Phenobarbital: It appears that phenobarbital may reduce plasma felbamate concentrations. Steady-state plasma felbamate concentrations were found to be 29% lower than the mean concentrations of a group of newly diagnosed subjects with epilepsy also receiving 2400 mg of felbamate a day. Effects of Antacids on Felbatol The rate and extent of absorption of a 2400 mg dose of Felbatol as monotherapy given as tablets was not affected when coadministered with antacids. Effects of Erythromycin on Felbatol The coadministration of erythromycin (1000 mg/day) for 10 days did not alter the pharmacokinetic parameters of Cmax, Cmin, AUC, CI/kg or tmax at felbamate daily doses of 3000 or 3600 mg/day in 10 otherwise healthy subjects with epilepsy. Effects of Felbatol on Low-Dose Combination Oral Contraceptives A group of 24 nonsmoking, healthy white female volunteers established on an oral contraceptive regimen containing 30 mg ethinyl estradiol and 75 mg gestodene for at least 3 months received 2400 mg/day of felbamate from midcycle (day 15) to midcycle (day 14) of two consecutive oral contraceptive cycles. Felbamate treatment resulted in a 42% decrease in the gestodene AUC 0-24, but no clinically relevant effect was observed on the pharmacokinetic parameters of ethinyl estradiol. No volunteer showed hormonal evidence of ovulation, but one volunteer reported intermenstrual bleeding during felbamate treatment." ], "offsets": [ [ 0, 5805 ] ] } ]

[ { "id": "Felbamate_ddi_T1", "type": "GROUP", "text": [ "Antiepileptic Drugs" ], "offsets": [ [ 190, 209 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T2", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 227, 235 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T3", "type": "GROUP", "text": [ "antiepileptic drugs" ], "offsets": [ [ 240, 259 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T4", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 261, 265 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T5", "type": "GROUP", "text": [ "AEDs" ], "offsets": [ [ 317, 321 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T6", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 398, 401 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T7", "type": "GROUP", "text": [ "AED" ], "offsets": [ [ 402, 405 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T8", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 406, 414 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T9", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 458, 467 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T10", "type": "DRUG", "text": [ "Valproate" ], "offsets": [ [ 468, 477 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T11", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 484, 497 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T12", "type": "DRUG", "text": [ "CBZ" ], "offsets": [ [ 499, 502 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T13", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 517, 530 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T14", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 578, 591 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T15", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 638, 646 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T16", "type": "GROUP", "text": [ "Antiepileptic Drugs" ], "offsets": [ [ 657, 676 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T17", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 677, 686 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T18", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 688, 696 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T19", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 733, 742 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T20", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 823, 832 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T21", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 864, 873 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T22", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 993, 1002 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T23", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 1038, 1047 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T24", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1120, 1129 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T25", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1179, 1188 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T26", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 1240, 1249 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T27", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1273, 1282 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T28", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1420, 1429 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T29", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 1456, 1464 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T30", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1486, 1495 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T31", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 1532, 1540 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T32", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 1558, 1571 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T33", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 1573, 1581 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T34", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1621, 1634 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T35", "type": "DRUG_N", "text": [ "carbamazepine epoxide" ], "offsets": [ [ 1693, 1714 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T36", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1796, 1809 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T37", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1842, 1855 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T38", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 1897, 1910 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T39", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 1969, 1978 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T40", "type": "DRUG_N", "text": [ "Carbamazepine epoxide" ], "offsets": [ [ 2039, 2060 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T41", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 2167, 2176 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T42", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 2217, 2230 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T43", "type": "DRUG_N", "text": [ "carbamazepine epoxide" ], "offsets": [ [ 2235, 2256 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T44", "type": "DRUG", "text": [ "Valproate" ], "offsets": [ [ 2268, 2277 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T45", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 2279, 2287 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T46", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2324, 2333 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T47", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2391, 2400 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T48", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2433, 2442 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T49", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 2564, 2573 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T50", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 2609, 2618 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T51", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2665, 2674 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T52", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2734, 2743 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T53", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 2831, 2839 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T54", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2890, 2899 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T55", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 2925, 2934 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T56", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 3019, 3027 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T57", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 3044, 3057 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T58", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 3079, 3088 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T59", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 3094, 3107 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T60", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 3130, 3143 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T61", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 3217, 3230 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T62", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 3263, 3276 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T63", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 3403, 3412 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T64", "type": "GROUP", "text": [ "Antiepileptic Drugs" ], "offsets": [ [ 3463, 3482 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T65", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 3486, 3494 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T66", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 3496, 3505 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T67", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 3507, 3516 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T68", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 3568, 3576 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T69", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 3579, 3588 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T70", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 3638, 3647 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T71", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 3728, 3736 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T72", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 3770, 3778 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T73", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 3802, 3815 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T74", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 3817, 3830 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T75", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 3886, 3894 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T76", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 3944, 3957 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T77", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 4042, 4050 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T78", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 4084, 4092 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T79", "type": "DRUG", "text": [ "Valproate" ], "offsets": [ [ 4116, 4125 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T80", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 4189, 4198 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T81", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 4219, 4227 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T82", "type": "DRUG", "text": [ "valproate" ], "offsets": [ [ 4273, 4282 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T83", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 4341, 4349 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T84", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 4352, 4361 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T85", "type": "DRUG", "text": [ "Phenobarbital" ], "offsets": [ [ 4386, 4399 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T86", "type": "DRUG", "text": [ "phenobarbital" ], "offsets": [ [ 4417, 4430 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T87", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 4449, 4458 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T88", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 4495, 4504 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T89", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 4655, 4664 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T90", "type": "GROUP", "text": [ "Antacids" ], "offsets": [ [ 4683, 4691 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T91", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 4695, 4703 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T92", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 4760, 4768 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T93", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 4844, 4852 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T94", "type": "DRUG", "text": [ "Erythromycin" ], "offsets": [ [ 4865, 4877 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T95", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 4881, 4889 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T96", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 4915, 4927 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T97", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 5036, 5045 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T98", "type": "BRAND", "text": [ "Felbatol" ], "offsets": [ [ 5140, 5148 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T99", "type": "GROUP", "text": [ "Combination Oral Contraceptives" ], "offsets": [ [ 5162, 5193 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T100", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 5275, 5288 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T101", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 5314, 5331 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T102", "type": "DRUG", "text": [ "gestodene" ], "offsets": [ [ 5342, 5351 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T103", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 5398, 5407 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T104", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 5476, 5489 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T105", "type": "DRUG", "text": [ "Felbamate" ], "offsets": [ [ 5498, 5507 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T106", "type": "DRUG", "text": [ "gestodene" ], "offsets": [ [ 5552, 5561 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T107", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 5656, 5673 ] ], "normalized": [] }, { "id": "Felbamate_ddi_T108", "type": "DRUG", "text": [ "felbamate" ], "offsets": [ [ 5785, 5794 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Felbamate_ddi_R1", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T2", "arg2_id": "Felbamate_ddi_T3", "normalized": [] }, { "id": "Felbamate_ddi_R2", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T2", "arg2_id": "Felbamate_ddi_T4", "normalized": [] }, { "id": "Felbamate_ddi_R3", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T18", "arg2_id": "Felbamate_ddi_T19", "normalized": [] }, { "id": "Felbamate_ddi_R4", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T23", "arg2_id": "Felbamate_ddi_T24", "normalized": [] }, { "id": "Felbamate_ddi_R5", "type": "ADVISE", "arg1_id": "Felbamate_ddi_T26", "arg2_id": "Felbamate_ddi_T27", "normalized": [] }, { "id": "Felbamate_ddi_R6", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T33", "arg2_id": "Felbamate_ddi_T34", "normalized": [] }, { "id": "Felbamate_ddi_R7", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T38", "arg2_id": "Felbamate_ddi_T39", "normalized": [] }, { "id": "Felbamate_ddi_R8", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T45", "arg2_id": "Felbamate_ddi_T46", "normalized": [] }, { "id": "Felbamate_ddi_R9", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T50", "arg2_id": "Felbamate_ddi_T51", "normalized": [] }, { "id": "Felbamate_ddi_R10", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T58", "arg2_id": "Felbamate_ddi_T59", "normalized": [] }, { "id": "Felbamate_ddi_R11", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T67", "arg2_id": "Felbamate_ddi_T68", "normalized": [] }, { "id": "Felbamate_ddi_R12", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T67", "arg2_id": "Felbamate_ddi_T69", "normalized": [] }, { "id": "Felbamate_ddi_R13", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T70", "arg2_id": "Felbamate_ddi_T71", "normalized": [] }, { "id": "Felbamate_ddi_R14", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T74", "arg2_id": "Felbamate_ddi_T75", "normalized": [] }, { "id": "Felbamate_ddi_R15", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T76", "arg2_id": "Felbamate_ddi_T77", "normalized": [] }, { "id": "Felbamate_ddi_R16", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T86", "arg2_id": "Felbamate_ddi_T87", "normalized": [] }, { "id": "Felbamate_ddi_R17", "type": "MECHANISM", "arg1_id": "Felbamate_ddi_T105", "arg2_id": "Felbamate_ddi_T106", "normalized": [] } ]

[ { "id": "Argatroban_ddi__text", "type": "abstract", "text": [ "Heparin: Since heparin is contraindicated in patients with heparin-induced thrombocytopenia, the co-administration of Argatroban and heparin is unlikely for this indication. However, if Argatroban is to be initiated after cessation of heparin therapy, allow sufficient time for heparins effect on the aPTT to decrease prior to initiation of Argatroban therapy. Aspirin/Acetaminophen: Pharmacokinetic or pharmacodynamic drug-drug interactions have not been demonstrated between Argatroban and concomitantly administered aspirin (162.5 mg orally given 26 and 2 hours prior to initiation of Argatroban 1 g/kg/min. over 4 hours) or acetaminophen (1000 mg orally given 12, 6 and 0 hours prior to, and 6 and 12 hours subsequent to, initiation of Argatroban 1.5 g/kg/min. over 18 hours). Oral anticoagulant agents: Pharmacokinetic drug-drug interactions between Argatroban and warfarin (7.5 mg single oral dose) have not been demonstrated. However, the concomitant use of Argatroban and warfarin (5-7.5 mg initial oral dose followed by 2.5-6 mg/day orally for 6-10 days) results in prolongation of the prothrombin time (PT) and International Normalized Ratio (INR). Thrombolytic agents: The safety and effectiveness of Argatroban with thrombolytic agents have not been established. Co-administration: Concomitant use of Argatroban with antiplatelet agents, thrombolytics, and other anticoagulants may increase the risk of bleeding. Drug-drug interactions have not been observed between Argatroban and digoxin or erythromycin." ], "offsets": [ [ 0, 1520 ] ] } ]

[ { "id": "Argatroban_ddi_T1", "type": "DRUG", "text": [ "Heparin" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T2", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 15, 22 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T3", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 59, 66 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T4", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 118, 128 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T5", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 133, 140 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T6", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 186, 196 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T7", "type": "DRUG", "text": [ "heparin" ], "offsets": [ [ 235, 242 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T8", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 341, 351 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T9", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 361, 368 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T10", "type": "DRUG", "text": [ "Acetaminophen" ], "offsets": [ [ 369, 382 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T11", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 477, 487 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T12", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 519, 526 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T13", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 588, 598 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T14", "type": "DRUG", "text": [ "acetaminophen" ], "offsets": [ [ 629, 642 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T15", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 741, 751 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T16", "type": "GROUP", "text": [ "anticoagulant agents" ], "offsets": [ [ 788, 808 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T17", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 857, 867 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T18", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 872, 880 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T19", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 967, 977 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T20", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 982, 990 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T21", "type": "GROUP", "text": [ "Thrombolytic agents" ], "offsets": [ [ 1161, 1180 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T22", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 1214, 1224 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T23", "type": "GROUP", "text": [ "thrombolytic agents" ], "offsets": [ [ 1230, 1249 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T24", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 1315, 1325 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T25", "type": "GROUP", "text": [ "antiplatelet agents" ], "offsets": [ [ 1331, 1350 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T26", "type": "GROUP", "text": [ "thrombolytics" ], "offsets": [ [ 1352, 1365 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T27", "type": "GROUP", "text": [ "anticoagulants" ], "offsets": [ [ 1377, 1391 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T28", "type": "DRUG", "text": [ "Argatroban" ], "offsets": [ [ 1481, 1491 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T29", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 1496, 1503 ] ], "normalized": [] }, { "id": "Argatroban_ddi_T30", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 1507, 1519 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Argatroban_ddi_R1", "type": "EFFECT", "arg1_id": "Argatroban_ddi_T19", "arg2_id": "Argatroban_ddi_T20", "normalized": [] }, { "id": "Argatroban_ddi_R2", "type": "EFFECT", "arg1_id": "Argatroban_ddi_T24", "arg2_id": "Argatroban_ddi_T25", "normalized": [] }, { "id": "Argatroban_ddi_R3", "type": "EFFECT", "arg1_id": "Argatroban_ddi_T24", "arg2_id": "Argatroban_ddi_T26", "normalized": [] }, { "id": "Argatroban_ddi_R4", "type": "EFFECT", "arg1_id": "Argatroban_ddi_T24", "arg2_id": "Argatroban_ddi_T27", "normalized": [] } ]

[ { "id": "L-Aspartic Acid_ddi__text", "type": "abstract", "text": [ "No drug, nutritional supplement, food or herb interactions are known." ], "offsets": [ [ 0, 69 ] ] } ]

[]

[]

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[ { "id": "Fentanyl_ddi__text", "type": "abstract", "text": [ "Agents Affecting Cytochrome P450 3A4 Isoenzyme System Fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential interactions may occur when DURAGESIC is given concurrently with agents that affect CYP3A4 activity. Coadminstration with agents that induce 3A4 activity may reduce the efficacy of DURAGESIC . The concomitant use of transdermal fentanyl with ritonavir or other potent 3A4 inhibitors such as ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, and nefazadone may result in an increase in fentanyl plasma concentrations. The concomitant use of other CYP3A4 inhibitors such as diltiazem and erythromycin with transdermal fentanyl may also result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause serious respiratory depression. In this situation, special patient care and observation are appropriate. Central Nervous System Depressants: The concomitant use of DURAGESIC (fentanyl transdermal system) with other central nervous system depressants, including but not limited to other opioids, sedatives, hypnotics, tranquilizers (e.g., benzodiazepines), general anesthetics, phenothiazines, skeletal muscle relaxants, and alcohol, may cause respiratory depression, hypotension, and profound sedation, or potentially result in coma or death. When such combined therapy is contemplated, the dose of one or both agents should be significantly reduced. MAO Inhibitors: DURAGESIC is not recommended for use in patients who have received MAOI within 14 days because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics ." ], "offsets": [ [ 0, 1709 ] ] } ]

[ { "id": "Fentanyl_ddi_T1", "type": "DRUG", "text": [ "Fentanyl" ], "offsets": [ [ 54, 62 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T2", "type": "BRAND", "text": [ "DURAGESIC" ], "offsets": [ [ 194, 203 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T3", "type": "BRAND", "text": [ "DURAGESIC" ], "offsets": [ [ 348, 357 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T4", "type": "DRUG", "text": [ "fentanyl" ], "offsets": [ [ 395, 403 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T5", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 409, 418 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T6", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 458, 470 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T7", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 472, 484 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T8", "type": "DRUG", "text": [ "troleandomycin" ], "offsets": [ [ 486, 500 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T9", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 502, 516 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T10", "type": "DRUG", "text": [ "nelfinavir" ], "offsets": [ [ 518, 528 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T11", "type": "DRUG", "text": [ "fentanyl" ], "offsets": [ [ 574, 582 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T12", "type": "DRUG", "text": [ "diltiazem" ], "offsets": [ [ 661, 670 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T13", "type": "DRUG", "text": [ "erythromycin" ], "offsets": [ [ 675, 687 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T14", "type": "DRUG", "text": [ "fentanyl" ], "offsets": [ [ 705, 713 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T15", "type": "DRUG", "text": [ "fentanyl" ], "offsets": [ [ 748, 756 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T16", "type": "GROUP", "text": [ "Central Nervous System Depressants" ], "offsets": [ [ 952, 986 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T17", "type": "BRAND", "text": [ "DURAGESIC" ], "offsets": [ [ 1011, 1020 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T18", "type": "DRUG", "text": [ "fentanyl" ], "offsets": [ [ 1023, 1031 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T19", "type": "GROUP", "text": [ "central nervous system depressants" ], "offsets": [ [ 1063, 1097 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T20", "type": "GROUP", "text": [ "opioids" ], "offsets": [ [ 1134, 1141 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T21", "type": "GROUP", "text": [ "sedatives" ], "offsets": [ [ 1143, 1152 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T22", "type": "GROUP", "text": [ "hypnotics" ], "offsets": [ [ 1154, 1163 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T23", "type": "GROUP", "text": [ "tranquilizers" ], "offsets": [ [ 1165, 1178 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T24", "type": "GROUP", "text": [ "benzodiazepines" ], "offsets": [ [ 1186, 1201 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T25", "type": "GROUP", "text": [ "anesthetics" ], "offsets": [ [ 1212, 1223 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T26", "type": "GROUP", "text": [ "phenothiazines" ], "offsets": [ [ 1225, 1239 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T27", "type": "GROUP", "text": [ "skeletal muscle relaxants" ], "offsets": [ [ 1241, 1266 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T28", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 1272, 1279 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T29", "type": "GROUP", "text": [ "MAO Inhibitors" ], "offsets": [ [ 1499, 1513 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T30", "type": "BRAND", "text": [ "DURAGESIC" ], "offsets": [ [ 1515, 1524 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T31", "type": "GROUP", "text": [ "MAOI" ], "offsets": [ [ 1583, 1587 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T32", "type": "GROUP", "text": [ "MAO inhibitors" ], "offsets": [ [ 1652, 1666 ] ], "normalized": [] }, { "id": "Fentanyl_ddi_T33", "type": "GROUP", "text": [ "opioid analgesics" ], "offsets": [ [ 1690, 1707 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Fentanyl_ddi_R1", "type": "MECHANISM", "arg1_id": "Fentanyl_ddi_T4", "arg2_id": "Fentanyl_ddi_T5", "normalized": [] }, { "id": "Fentanyl_ddi_R2", "type": "MECHANISM", "arg1_id": "Fentanyl_ddi_T4", "arg2_id": "Fentanyl_ddi_T6", "normalized": [] }, { "id": "Fentanyl_ddi_R3", "type": "MECHANISM", "arg1_id": "Fentanyl_ddi_T4", "arg2_id": "Fentanyl_ddi_T7", "normalized": [] }, { "id": "Fentanyl_ddi_R4", "type": "MECHANISM", "arg1_id": "Fentanyl_ddi_T4", "arg2_id": "Fentanyl_ddi_T8", "normalized": [] }, { "id": "Fentanyl_ddi_R5", "type": "MECHANISM", "arg1_id": "Fentanyl_ddi_T4", "arg2_id": "Fentanyl_ddi_T9", "normalized": [] }, { "id": "Fentanyl_ddi_R6", "type": "MECHANISM", "arg1_id": "Fentanyl_ddi_T4", "arg2_id": "Fentanyl_ddi_T10", "normalized": [] }, { "id": "Fentanyl_ddi_R7", "type": "MECHANISM", "arg1_id": "Fentanyl_ddi_T12", "arg2_id": "Fentanyl_ddi_T14", "normalized": [] }, { "id": "Fentanyl_ddi_R8", "type": "MECHANISM", "arg1_id": "Fentanyl_ddi_T13", "arg2_id": "Fentanyl_ddi_T14", "normalized": [] }, { "id": "Fentanyl_ddi_R9", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T19", "normalized": [] }, { "id": "Fentanyl_ddi_R10", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T20", "normalized": [] }, { "id": "Fentanyl_ddi_R11", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T21", "normalized": [] }, { "id": "Fentanyl_ddi_R12", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T22", "normalized": [] }, { "id": "Fentanyl_ddi_R13", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T23", "normalized": [] }, { "id": "Fentanyl_ddi_R14", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T24", "normalized": [] }, { "id": "Fentanyl_ddi_R15", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T25", "normalized": [] }, { "id": "Fentanyl_ddi_R16", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T26", "normalized": [] }, { "id": "Fentanyl_ddi_R17", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T27", "normalized": [] }, { "id": "Fentanyl_ddi_R18", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T17", "arg2_id": "Fentanyl_ddi_T28", "normalized": [] }, { "id": "Fentanyl_ddi_R19", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T19", "normalized": [] }, { "id": "Fentanyl_ddi_R20", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T20", "normalized": [] }, { "id": "Fentanyl_ddi_R21", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T21", "normalized": [] }, { "id": "Fentanyl_ddi_R22", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T22", "normalized": [] }, { "id": "Fentanyl_ddi_R23", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T23", "normalized": [] }, { "id": "Fentanyl_ddi_R24", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T24", "normalized": [] }, { "id": "Fentanyl_ddi_R25", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T25", "normalized": [] }, { "id": "Fentanyl_ddi_R26", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T26", "normalized": [] }, { "id": "Fentanyl_ddi_R27", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T27", "normalized": [] }, { "id": "Fentanyl_ddi_R28", "type": "EFFECT", "arg1_id": "Fentanyl_ddi_T18", "arg2_id": "Fentanyl_ddi_T28", "normalized": [] }, { "id": "Fentanyl_ddi_R29", "type": "ADVISE", "arg1_id": "Fentanyl_ddi_T30", "arg2_id": "Fentanyl_ddi_T31", "normalized": [] }, { "id": "Fentanyl_ddi_R30", "type": "ADVISE", "arg1_id": "Fentanyl_ddi_T32", "arg2_id": "Fentanyl_ddi_T33", "normalized": [] } ]

[ { "id": "Ganciclovir_ddi__text", "type": "abstract", "text": [ "No drug interactions have been observed with the Vitrasert Implant. There is limited experience with use of retinal tamponades in conjunction with the Vitrasert Implant." ], "offsets": [ [ 0, 169 ] ] } ]

[ { "id": "Ganciclovir_ddi_T1", "type": "BRAND", "text": [ "Vitrasert" ], "offsets": [ [ 49, 58 ] ], "normalized": [] }, { "id": "Ganciclovir_ddi_T2", "type": "BRAND", "text": [ "Vitrasert" ], "offsets": [ [ 151, 160 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Desogestrel_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, phenyl-butazone, phenytoin sodium, carbamazepine and possibly with griseofulvin, ampicillin, and tetracyclines (72) ." ], "offsets": [ [ 0, 348 ] ] } ]

[ { "id": "Desogestrel_ddi_T1", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 140, 148 ] ], "normalized": [] }, { "id": "Desogestrel_ddi_T2", "type": "GROUP", "text": [ "barbiturates" ], "offsets": [ [ 217, 229 ] ], "normalized": [] }, { "id": "Desogestrel_ddi_T3", "type": "DRUG", "text": [ "phenytoin sodium" ], "offsets": [ [ 248, 264 ] ], "normalized": [] }, { "id": "Desogestrel_ddi_T4", "type": "DRUG", "text": [ "carbamazepine" ], "offsets": [ [ 266, 279 ] ], "normalized": [] }, { "id": "Desogestrel_ddi_T5", "type": "DRUG", "text": [ "griseofulvin" ], "offsets": [ [ 298, 310 ] ], "normalized": [] }, { "id": "Desogestrel_ddi_T6", "type": "DRUG", "text": [ "ampicillin" ], "offsets": [ [ 312, 322 ] ], "normalized": [] }, { "id": "Desogestrel_ddi_T7", "type": "GROUP", "text": [ "tetracyclines" ], "offsets": [ [ 328, 341 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "Rofecoxib_ddi__text", "type": "abstract", "text": [ "ACE inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of Angiotensin Converting Enzyme (ACE) inhibitors. In patients with mild to moderate hypertension, administration of 25 mg daily of VIOXX with the ACE inhibitor benazepril, 10 to 40 mg for 4 weeks, was associated with an average increase in mean arterial pressure of about 3 mm Hg compared to ACE inhibitor alone. This interaction should be given consideration in patients taking VIOXX concomitantly with ACE inhibitors. Aspirin: Concomitant administration of low-dose aspirin with VIOXX may result in an increased rate of GI ulceration or other complications, compared to use of VIOXX alone. In a 12-week endoscopy study conducted in OA patients there was no difference in the cumulative incidence of endoscopic gastroduodenal ulcers in patients taking low-dose (81 mg) enteric coated aspirin plus VIOXX 25 mg daily, as compared to those taking ibuprofen 2400 mg daily alone. Patients taking low-dose aspirin plus ibuprofen were not studied. At steady state, VIOXX 50 mg once daily had no effect on the anti-platelet activity of low-dose (81 mg once daily) aspirin, as assessed by ex vivo platelet aggregation and serum TXB2 generation in clotting blood. Because of its lack of platelet effects, VIOXX is not a substitute for aspirin for cardiovascular prophylaxis. Therefore, in patients taking VIOXX, antiplatelet therapies should not be discontinued and should be considered in patients with an indication for cardiovascular prophylaxis. Prospective, long-term studies on concomitant administration of VIOXX and aspirin have not been conducted. Cimetidine: Co-administration with high doses of cimetidine [800 mg twice daily] increased the Cmax of rofecoxib by 21%, the AUC0-120hr by 23% and the t1/2 by 15%. These small changes are not clinically significant and no dose adjustment is necessary. Digoxin: Rofecoxib 75 mg once daily for 11 days does not alter the plasma concentration profile or renal elimination of digoxin after a single 0.5 mg oral dose. Furosemide: Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. Ketoconazole: Ketoconazole 400 mg daily did not have any clinically important effect on the pharmacokinetics of rofecoxib. Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. In post-marketing experience there have been reports of increases in plasma lithium levels. Thus, when VIOXX and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. Methotrexate VIOXX 12.5, 25, and 50 mg, each dose administered once daily for 7 days, had no effect on the plasma concentration of methotrexate as measured by AUC0-24hr in patients receiving single weekly methotrexate doses of 7.5 to 20 mg for rheumatoid arthritis. At higher than recommended doses, VIOXX 75 mg administered once daily for 10 days increased plasma concentrations by 23% as measured by AUC0-24hr in patients receiving methotrexate 7.5 to 15 mg/week for rheumatoid arthritis. At 24 hours postdose, a similar proportion of patients treated with methotrexate alone (94%) and subsequently treated with methotrexate co-administered with 75 mg of rofecoxib (88%) had methotrexate plasma concentrations below the measurable limit (5 ng/mL). Standard monitoring of methotrexate-related toxicity should be continued if VIOXX and methotrexate are administered concomitantly. Oral Contraceptives Rofecoxib did not have any clinically important effect on the pharmacokinetics of ethinyl estradiol and norethindrone. Prednisone/prednisolone: Rofecoxib did not have any clinically important effect on the pharmacokinetics of prednisolone or prednisone. Rifampin: Co-administration of VIOXX with rifampin 600 mg daily, a potent inducer of hepatic metabolism, produced an approximate 50% decrease in rofecoxib plasma concentrations. Therefore, a starting daily dose of 25 mg of VIOXX should be considered for the treatment of osteoarthritis when VIOXX is co-administered with potent inducers of hepatic metabolism. Theophylline VIOXX 12.5, 25, and 50 mg administered once daily for 7 days increased plasma theophylline concentrations (AUC(0- )) by 38 to 60% in healthy subjects administered a single 300-mg dose of theophylline. Adequate monitoring of theophylline plasma concentrations should be considered when therapy with VIOXX is initiated or changed in patients receiving theophylline. These data suggest that rofecoxib may produce a modest inhibition of cytochrome P450 (CYP) 1A2. Therefore, there is a potential for an interaction with other drugs that are metabolized by CYP 1A2 (e.g., amitriptyline, tacrine, and zileuton). Warfarin: Anticoagulant activity should be monitored, particularly in the first few days after initiating or changing VIOXX therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding complications. In single and multiple dose studies in healthy subjects receiving both warfarin and rofecoxib, prothrombin time (measured as INR) was increased by approximately 8% to 11%. In post-marketing experience, bleeding events have been reported, predominantly in the elderly, in association with increases in prothrombin time in patients receiving VIOXX concurrently with warfarin." ], "offsets": [ [ 0, 5520 ] ] } ]

[ { "id": "Rofecoxib_ddi_T1", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T2", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 37, 43 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T3", "type": "GROUP", "text": [ "Angiotensin Converting Enzyme (ACE) inhibitors" ], "offsets": [ [ 88, 134 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T4", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 217, 222 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T5", "type": "GROUP", "text": [ "ACE inhibitor" ], "offsets": [ [ 232, 245 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T6", "type": "DRUG", "text": [ "benazepril" ], "offsets": [ [ 246, 256 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T7", "type": "GROUP", "text": [ "ACE inhibitor" ], "offsets": [ [ 378, 391 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T8", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 465, 470 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T9", "type": "GROUP", "text": [ "ACE inhibitors" ], "offsets": [ [ 490, 504 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T10", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 506, 513 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T11", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 554, 561 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T12", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 567, 572 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T13", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 665, 670 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T14", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 871, 878 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T15", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 884, 889 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T16", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 931, 940 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T17", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 987, 994 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T18", "type": "DRUG", "text": [ "ibuprofen" ], "offsets": [ [ 1000, 1009 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T19", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 1045, 1050 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T20", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 1143, 1150 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T21", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 1282, 1287 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T22", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 1312, 1319 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T23", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T24", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 1591, 1596 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T25", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 1601, 1608 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T26", "type": "DRUG", "text": [ "Cimetidine" ], "offsets": [ [ 1634, 1644 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T27", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1683, 1693 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T28", "type": "DRUG", "text": [ "rofecoxib" ], "offsets": [ [ 1737, 1746 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T29", "type": "DRUG", "text": [ "Digoxin" ], "offsets": [ [ 1886, 1893 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T30", "type": "DRUG", "text": [ "Rofecoxib" ], "offsets": [ [ 1895, 1904 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T31", "type": "DRUG", "text": [ "digoxin" ], "offsets": [ [ 2006, 2013 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T32", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 2047, 2057 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T33", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2133, 2139 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T34", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 2177, 2187 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T35", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 2192, 2201 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T36", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 2302, 2314 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T37", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 2316, 2328 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T38", "type": "DRUG", "text": [ "rofecoxib" ], "offsets": [ [ 2414, 2423 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T39", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 2425, 2432 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T40", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 2434, 2440 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T41", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2478, 2485 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T42", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2518, 2525 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T43", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2613, 2620 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T44", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 2640, 2645 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T45", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2650, 2657 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T46", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 2740, 2747 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T47", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 2758, 2770 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T48", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 2771, 2776 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T49", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2889, 2901 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T50", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 2963, 2975 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T51", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 3058, 3063 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T52", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 3192, 3204 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T53", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 3317, 3329 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T54", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 3372, 3384 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T55", "type": "DRUG", "text": [ "rofecoxib" ], "offsets": [ [ 3415, 3424 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T56", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 3435, 3447 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T57", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 3531, 3543 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T58", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 3584, 3589 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T59", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 3594, 3606 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T60", "type": "GROUP", "text": [ "Contraceptives" ], "offsets": [ [ 3644, 3658 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T61", "type": "DRUG", "text": [ "Rofecoxib" ], "offsets": [ [ 3659, 3668 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T62", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 3741, 3758 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T63", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 3763, 3776 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T64", "type": "DRUG", "text": [ "Prednisone" ], "offsets": [ [ 3778, 3788 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T65", "type": "DRUG", "text": [ "prednisolone" ], "offsets": [ [ 3789, 3801 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T66", "type": "DRUG", "text": [ "Rofecoxib" ], "offsets": [ [ 3803, 3812 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T67", "type": "DRUG", "text": [ "prednisolone" ], "offsets": [ [ 3885, 3897 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T68", "type": "DRUG", "text": [ "prednisone" ], "offsets": [ [ 3901, 3911 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T69", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 3913, 3921 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T70", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 3944, 3949 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T71", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 3955, 3963 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T72", "type": "DRUG", "text": [ "rofecoxib" ], "offsets": [ [ 4058, 4067 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T73", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 4136, 4141 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T74", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 4204, 4209 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T75", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 4273, 4285 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T76", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 4286, 4291 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T77", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 4364, 4376 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T78", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 4473, 4485 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T79", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 4510, 4522 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T80", "type": "BRAND", "text": [ "VIOXX" ], "offsets": [ [ 4584, 4589 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T81", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 4636, 4648 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T82", "type": "DRUG", "text": [ "rofecoxib" ], "offsets": [ [ 4674, 4683 ] ], "normalized": [] }, { "id": "Rofecoxib_ddi_T83", 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[]

[]

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[ { "id": "Nevirapine_ddi__text", "type": "abstract", "text": [ "Nevirapine is principally metabolized by the liver via the cytochrome P450 isoenzymes, 3A4 and 2B6. Nevirapine is known to be an inducer of these enzymes. As a result, drugs that are metabolized by these enzyme systems may have lower than expected plasma levels when coadministered with nevirapine. The specific pharmacokinetic changes that occur with co-administration of nevirapine and other drugs are listed in CLINICAL PHARMACOLOGY, Table 1. Clinical comments about possible dosage modifications based on these pharmacokinetic changes are listed in Table 3. The data inTables 1 and 3 are based on the results of drug interaction studies conducted in HIV-1 seropositive subjects unless otherwise indicated. In addition to established drug interactions, there may be potential pharmacokinetic interactions between nevirapine and other drug classes that are metabolized by the cytochrome P450 system. These potential drug interactions are listed in Table 4. Although specific drug interaction studies in HIV-1 seropositive subjects have not been conducted for the classes of drugs listed in Table 4, additional clinical monitoring may be warranted when co-administering these drugs. The in vitro interaction between nevirapine and the antithrombotic agent warfarin is complex. As a result, when giving these drugs concomitantly, plasma warfarin levels may change with the potential for increases in coagulation time. When warfarin is co-administered with nevirapine, anticoagulation levels should be monitored frequently. Table 3 Established Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies Drug Name Effect on Concentration of Nevirapine or Concomitant Drug Clinical Comment Clarithromycin Clarithromycin 14OH- clarithromycin Clarithromycin exposure was significantly decreased by nevirapine; however, 14-OH metabolite concentrations were increased.Because clarithromycin active metabolite has reduced activity against Mycobacteriumavium-intracellulare complex, overallactivity against this pathogen may bealtered. Alternatives to clarithromycin,such as azithromycin, should be considered. Efavirenz Efavirenz Appropriate doses for this combination are not established. Ethinyl estradiol and Norethindrone Ethinyl estradiol Norethindrone Oral contraceptives and other hormonalmethods of birth control should not be usedas the sole method of contraception inwomen taking nevirapine, since nevirapinemay lower the plasma levels of thesemedications. An alternative or additional method of contraception is recommended. Fluconazole Nevirapine Because of the risk of increased exposure tonevirapine, caution should be used inconcomitant administration, and patients should be monitored closely for nevirapine-associated adverse events. Indinavir Indinavir Appropriate doses for this combination arenot established, but an increase in thedosage of indinavir may be required. Ketoconazole Ketoconazole Nevirapine and ketoconazole should not beadministered concomitantly becausedecreases in ketoconazole plasmaconcentrations may reduce the efficacy of the drug. Lopinavir/Ritonavir Lopinavir A dose increase of lopinavir/ritonavir to 533/133 mg twice daily with food isrecommended in combination with nevirapine. Methadone Methadonea Methadone levels may be decreased; increased dosages may be required to prevent symptoms of opiate withdrawal. Methadone maintained patients beginning nevirapine therapy should be monitored forevidence of withdrawal and methadone dose should be adjusted accordingly. Nelfinavir Nelfinavir M8 The appropriate dose for nelfinavir incombination with nevirapine, with respectto safety and efficacy, has not been established. Rifabutin Rifabutin Rifabutin and its metabolite concentrationswere moderately increased. Due to highintersubject variability, however, somepatients may experience large increases inrifabutin exposure and may be at higher riskfor rifabutin toxicity. Therefore, caution should be used in concomitant administration. Rifampin Nevirapine Nevirapine and rifampin should not beadministered concomitantly becausedecreases in nevirapine plasmaconcentrations may reduce the efficacy ofthe drug. Physicians needing to treatpatients co-infected with tuberculosis andusing a nevirapine containing regimen mayuse rifabutin instead. Saquinavir Saquinavir Appropriate doses for this combination arenot established, but an increase in thedosage of saquinavir may be required. aBased on reports of narcotic withdrawal syndrome in patients treated with nevirapine and methadone concurrently, and evidence of decreased plasma concentrations of methadone. Table 4 Potential Drug Interactions:Use With Caution, Dose Adjustment of Co-administered Drug May Be Needed due to Possible Decrease in Clinical Effect Examples of Drugs in Which Plasma Concentrations May Be Decreased By Co-administration With Nevirapine Drug Class Examples of Drugs Antiarrhythmics Amiodarone, disopyramide, lidocaine Anticonvulsants Carbamazepine, clonazepam, ethosuximide Antifungals Itraconazole Calcium channel blockers Diltiazem, nifedipine, verapamil Cancer chemotherapy Cyclophosphamide Ergot alkaloids Ergotamine Immunosuppressants Cyclosporin, tacrolimus, sirolimus Motility agents Cisapride Opiate agonists Fentanyl Examples of Drugs in Which Plasma Concentrations May Be Increased By Co-administration With Nevirapine Antithrombotics Warfarin Potential effect on anticoagulation. Monitoring of anticoagulation levels is recommended. Fat redistribution: Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established ." ], "offsets": [ [ 0, 5917 ] ] } ]

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"Nevirapine_ddi_T9", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1337, 1345 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T10", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 1423, 1431 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T11", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 1456, 1466 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T12", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 1682, 1692 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T13", "type": "DRUG", "text": [ "Clarithromycin" ], "offsets": [ [ 1730, 1744 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T14", "type": "DRUG", "text": [ "Clarithromycin" ], "offsets": [ [ 1745, 1759 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T15", "type": "DRUG", "text": [ "Clarithromycin" ], "offsets": [ [ 1782, 1796 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T16", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 1837, 1847 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T17", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 1913, 1927 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T18", "type": "DRUG", "text": [ "clarithromycin" ], "offsets": [ [ 2087, 2101 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T19", "type": "DRUG", "text": [ "azithromycin" ], "offsets": [ [ 2110, 2122 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T20", "type": "DRUG", "text": [ "Efavirenz" ], "offsets": [ [ 2146, 2155 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T21", "type": "DRUG", "text": [ "Efavirenz" ], "offsets": [ [ 2156, 2165 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T22", "type": "DRUG", "text": [ "Ethinyl estradiol" ], "offsets": [ [ 2226, 2243 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T23", "type": "DRUG", "text": [ "Norethindrone" ], "offsets": [ [ 2248, 2261 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T24", "type": "DRUG", "text": [ "Ethinyl estradiol" ], "offsets": [ [ 2262, 2279 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T25", "type": "DRUG", "text": [ "Norethindrone" ], "offsets": [ [ 2280, 2293 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T26", "type": "GROUP", "text": [ "contraceptives" ], "offsets": [ [ 2299, 2313 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T27", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 2426, 2436 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T28", "type": "DRUG", "text": [ "Fluconazole" ], "offsets": [ [ 2572, 2583 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T29", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 2584, 2594 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T30", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 2639, 2649 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T31", "type": "DRUG", "text": [ "Indinavir" ], "offsets": [ [ 2787, 2796 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T32", "type": "DRUG", "text": [ "Indinavir" ], "offsets": [ [ 2797, 2806 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T33", "type": "DRUG", "text": [ "indinavir" ], "offsets": [ [ 2898, 2907 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T34", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 2925, 2937 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T35", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 2938, 2950 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T36", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 2951, 2961 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T37", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 2966, 2978 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T38", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 3039, 3051 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T39", "type": "DRUG", "text": [ "Lopinavir" ], "offsets": [ [ 3110, 3119 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T40", "type": "DRUG", "text": [ "Ritonavir" ], "offsets": [ [ 3120, 3129 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T41", "type": "DRUG", "text": [ "Lopinavir" ], "offsets": [ [ 3130, 3139 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T42", "type": "DRUG", "text": [ "lopinavir" ], "offsets": [ [ 3159, 3168 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T43", "type": "DRUG", "text": [ "ritonavir" ], "offsets": [ [ 3169, 3178 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T44", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 3249, 3259 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T45", "type": "DRUG", "text": [ "Methadone" ], "offsets": [ [ 3261, 3270 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T46", "type": "DRUG", "text": [ "Methadone" ], "offsets": [ [ 3282, 3291 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T47", "type": "GROUP", "text": [ "opiate" ], "offsets": [ [ 3374, 3380 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T48", "type": "DRUG", "text": [ "Methadone" ], "offsets": [ [ 3393, 3402 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T49", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 3433, 3443 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T50", "type": "DRUG", "text": [ "methadone" ], "offsets": [ [ 3502, 3511 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T51", "type": "DRUG", "text": [ "Nelfinavir" ], "offsets": [ [ 3549, 3559 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T52", "type": "DRUG", "text": [ "Nelfinavir" ], "offsets": [ [ 3560, 3570 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T53", "type": "DRUG", "text": [ "nelfinavir" ], "offsets": [ [ 3599, 3609 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T54", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 3629, 3639 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T55", "type": "DRUG", "text": [ "Rifabutin" ], "offsets": [ [ 3703, 3712 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T56", "type": "DRUG", "text": [ "Rifabutin" ], "offsets": [ [ 3713, 3722 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T57", "type": "DRUG", "text": [ "Rifabutin" ], "offsets": [ [ 3723, 3732 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T58", "type": "DRUG", "text": [ "rifabutin" ], "offsets": [ [ 3885, 3894 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T59", "type": "DRUG", "text": [ "Rifampin" ], "offsets": [ [ 4018, 4026 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T60", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 4027, 4037 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T61", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 4038, 4048 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T62", "type": "DRUG", "text": [ "rifampin" ], "offsets": [ [ 4053, 4061 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T63", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 4122, 4132 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T64", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 4267, 4277 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T65", "type": "DRUG", "text": [ "rifabutin" ], "offsets": [ [ 4304, 4313 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T66", "type": "DRUG", "text": [ "Saquinavir" ], "offsets": [ [ 4323, 4333 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T67", "type": "DRUG", "text": [ "Saquinavir" ], "offsets": [ [ 4334, 4344 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T68", "type": "DRUG", "text": [ "saquinavir" ], "offsets": [ [ 4436, 4446 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T69", "type": "DRUG", "text": [ "nevirapine" ], "offsets": [ [ 4539, 4549 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T70", "type": "DRUG", "text": [ "methadone" ], "offsets": [ [ 4554, 4563 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T71", "type": "DRUG", "text": [ "methadone" ], "offsets": [ [ 4629, 4638 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T72", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 4891, 4901 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T73", "type": "GROUP", "text": [ "Antiarrhythmics" ], "offsets": [ [ 4931, 4946 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T74", "type": "DRUG", "text": [ "Amiodarone" ], "offsets": [ [ 4947, 4957 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T75", "type": "DRUG", "text": [ "disopyramide" ], "offsets": [ [ 4959, 4971 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T76", "type": "DRUG", "text": [ "lidocaine" ], "offsets": [ [ 4973, 4982 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T77", "type": "GROUP", "text": [ "Anticonvulsants" ], "offsets": [ [ 4983, 4998 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T78", "type": "DRUG", "text": [ "Carbamazepine" ], "offsets": [ [ 4999, 5012 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T79", "type": "DRUG", "text": [ "clonazepam" ], "offsets": [ [ 5014, 5024 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T80", "type": "DRUG", "text": [ "ethosuximide" ], "offsets": [ [ 5026, 5038 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T81", "type": "GROUP", "text": [ "Antifungals" ], "offsets": [ [ 5039, 5050 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T82", "type": "DRUG", "text": [ "Itraconazole" ], "offsets": [ [ 5051, 5063 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T83", "type": "GROUP", "text": [ "Calcium channel blockers" ], "offsets": [ [ 5064, 5088 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T84", "type": "DRUG", "text": [ "Diltiazem" ], "offsets": [ [ 5089, 5098 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T85", "type": "DRUG", "text": [ "nifedipine" ], "offsets": [ [ 5100, 5110 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T86", "type": "DRUG", "text": [ "verapamil" ], "offsets": [ [ 5112, 5121 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T87", "type": "DRUG", "text": [ "Cyclophosphamide" ], "offsets": [ [ 5142, 5158 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T88", "type": "GROUP", "text": [ "Ergot alkaloids" ], "offsets": [ [ 5159, 5174 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T89", "type": "DRUG", "text": [ "Ergotamine" ], "offsets": [ [ 5175, 5185 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T90", "type": "GROUP", "text": [ "Immunosuppressants" ], "offsets": [ [ 5186, 5204 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T91", "type": "DRUG", "text": [ "Cyclosporin" ], "offsets": [ [ 5205, 5216 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T92", "type": "DRUG", "text": [ "tacrolimus" ], "offsets": [ [ 5218, 5228 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T93", "type": "DRUG", "text": [ "sirolimus" ], "offsets": [ [ 5230, 5239 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T94", "type": "DRUG", "text": [ "Cisapride" ], "offsets": [ [ 5256, 5265 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T95", "type": "GROUP", "text": [ "Opiate agonists" ], "offsets": [ [ 5266, 5281 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T96", "type": "DRUG", "text": [ "Fentanyl" ], "offsets": [ [ 5282, 5290 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T97", "type": "DRUG", "text": [ "Nevirapine" ], "offsets": [ [ 5383, 5393 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T98", "type": "GROUP", "text": [ "Antithrombotics" ], "offsets": [ [ 5394, 5409 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T99", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 5410, 5418 ] ], "normalized": [] }, { "id": "Nevirapine_ddi_T100", "type": "GROUP", "text": [ "antiretroviral" ], "offsets": [ [ 5765, 5779 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Nevirapine_ddi_R1", "type": "INT", "arg1_id": "Nevirapine_ddi_T6", "arg2_id": "Nevirapine_ddi_T8", "normalized": [] }, { "id": "Nevirapine_ddi_R2", "type": "ADVISE", "arg1_id": "Nevirapine_ddi_T10", "arg2_id": "Nevirapine_ddi_T11", "normalized": [] }, { "id": "Nevirapine_ddi_R3", "type": "MECHANISM", "arg1_id": "Nevirapine_ddi_T15", "arg2_id": "Nevirapine_ddi_T16", "normalized": [] }, { "id": "Nevirapine_ddi_R4", "type": "ADVISE", "arg1_id": "Nevirapine_ddi_T26", "arg2_id": "Nevirapine_ddi_T27", "normalized": [] }, { "id": "Nevirapine_ddi_R5", "type": "ADVISE", "arg1_id": "Nevirapine_ddi_T36", "arg2_id": "Nevirapine_ddi_T37", "normalized": [] }, { "id": "Nevirapine_ddi_R6", "type": "ADVISE", "arg1_id": "Nevirapine_ddi_T42", "arg2_id": "Nevirapine_ddi_T44", "normalized": [] }, { "id": "Nevirapine_ddi_R7", "type": "ADVISE", "arg1_id": "Nevirapine_ddi_T43", "arg2_id": "Nevirapine_ddi_T44", "normalized": [] }, { "id": "Nevirapine_ddi_R8", "type": "ADVISE", "arg1_id": "Nevirapine_ddi_T48", "arg2_id": "Nevirapine_ddi_T49", "normalized": [] }, { "id": "Nevirapine_ddi_R9", "type": "ADVISE", "arg1_id": "Nevirapine_ddi_T61", "arg2_id": "Nevirapine_ddi_T62", "normalized": [] }, { "id": "Nevirapine_ddi_R10", "type": "EFFECT", "arg1_id": "Nevirapine_ddi_T69", "arg2_id": "Nevirapine_ddi_T70", "normalized": [] } ]

[ { "id": "Ciprofloxacin_ddi__text", "type": "abstract", "text": [ "Some quinolones, including ciprofloxacin, have also been shown to interfere with the metabolism of caffeine. This may lead to reduced clearance of caffeine and a prolongation of its serum half-life. Some quinolones, including ciprofloxacin, have been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly. Glyburide: The concomitant administration of ciprofloxacin with the sulfonylurea glyburide has, on rare occasions, resulted in severe hypoglycemia. Histamine H2-receptor antagonists: Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of ciprofloxacin. Methotrexate Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate. This might increase the risk of methotrexate toxic reactions. Therefore, patients under methotrexate therapy should be carefully monitored when concomitant ciprofloxacin therapy is indicated. Multivalent Cation-Containing Products: Concurrent administration of a quinolone, including ciprofloxacin, with multivalent cation-containing products such as magnesium or aluminum antacids, sucralfate, VIDEX chewable/buffered tablets or pediatric powder, or products containing calcium, iron, or zinc may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired. Proquin XR should be administered at least 4 hours before or 2 hours after these products. This time window is different than for other oral formulations of ciprofloxacin, which are usually administered 2 hours before or 6 hours after antacids. Non-steroidal anti-inflammatory drugs (but not aspirin): These drugs in combination with very high doses of quinolones have been shown to provoke convulsions in pre-clinical studies. Omeprazole: The rate and extent of absorption of ciprofloxacin was bioequivalent when Proquin XR was given alone or when Proquin XR was given 2 hours after omeprazole at the dose that maximally suppresses gastric acid secretion. Omeprazole should be taken as directed and Proquin XR should be taken with a main meal of the day, preferably the evening meal.. Phenytoin: Altered serum levels of phenytoin (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin. Probenecid: Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in serum. Theophylline: As with some other quinolones, concurrent administration of ciprofloxacin with theophylline may lead to elevated serum concentrations of theophylline and prolongation of its elimination half-life. This may result in increased risk of theophylline-related adverse reactions. If concomitant use cannot be avoided, serum levels of theophylline should be monitored and dosage adjustments made as appropriate. Warfarin: Quinolones have been reported to enhance the effects of the oral anticoagulant warfarin or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be monitored." ], "offsets": [ [ 0, 3190 ] ] } ]

[ { "id": "Ciprofloxacin_ddi_T1", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 5, 15 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T2", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 27, 40 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T3", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 99, 107 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T4", "type": "DRUG", "text": [ "caffeine" ], "offsets": [ [ 147, 155 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T5", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 204, 214 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T6", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 226, 239 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T7", "type": "DRUG", "text": [ "cyclosporine" ], "offsets": [ [ 330, 342 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T8", "type": "DRUG", "text": [ "Glyburide" ], "offsets": [ [ 358, 367 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T9", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 403, 416 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T10", "type": "GROUP", "text": [ "sulfonylurea" ], "offsets": [ [ 426, 438 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T11", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 439, 448 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T12", "type": "GROUP", "text": [ "Histamine H2-receptor antagonists" ], "offsets": [ [ 506, 539 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T13", "type": "GROUP", "text": [ "Histamine H2-receptor antagonists" ], "offsets": [ [ 541, 574 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T14", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 638, 651 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T15", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 653, 665 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T16", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 693, 705 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T17", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 756, 769 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T18", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 821, 833 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T19", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 867, 879 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T20", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 923, 935 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T21", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 991, 1004 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T22", "type": "GROUP", "text": [ "quinolone" ], "offsets": [ [ 1098, 1107 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T23", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 1119, 1132 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T24", "type": "DRUG", "text": [ "magnesium" ], "offsets": [ [ 1186, 1195 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T25", "type": "DRUG", "text": [ "aluminum" ], "offsets": [ [ 1199, 1207 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T26", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 1208, 1216 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T27", "type": "DRUG", "text": [ "sucralfate" ], "offsets": [ [ 1218, 1228 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T28", "type": "BRAND", "text": [ "VIDEX" ], "offsets": [ [ 1230, 1235 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T29", "type": "DRUG", "text": [ "calcium" ], "offsets": [ [ 1306, 1313 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T30", "type": "DRUG", "text": [ "iron" ], "offsets": [ [ 1315, 1319 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T31", "type": "DRUG", "text": [ "zinc" ], "offsets": [ [ 1324, 1328 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T32", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 1374, 1387 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T33", "type": "BRAND", "text": [ "Proquin XR" ], "offsets": [ [ 1458, 1468 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T34", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 1615, 1628 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T35", "type": "GROUP", "text": [ "antacids" ], "offsets": [ [ 1693, 1701 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T36", "type": "GROUP", "text": [ "Non-steroidal anti-inflammatory drugs" ], "offsets": [ [ 1703, 1740 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T37", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 1750, 1757 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T38", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 1811, 1821 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T39", "type": "DRUG", "text": [ "Omeprazole" ], "offsets": [ [ 1886, 1896 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T40", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 1935, 1948 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T41", "type": "BRAND", "text": [ "Proquin XR" ], "offsets": [ [ 1972, 1982 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T42", "type": "BRAND", "text": [ "Proquin XR" ], "offsets": [ [ 2007, 2017 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T43", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 2042, 2052 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T44", "type": "DRUG", "text": [ "Omeprazole" ], "offsets": [ [ 2115, 2125 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T45", "type": "BRAND", "text": [ "Proquin XR" ], "offsets": [ [ 2158, 2168 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T46", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 2244, 2253 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T47", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2279, 2288 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T48", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 2368, 2381 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T49", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 2383, 2393 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T50", "type": "DRUG", "text": [ "Probenecid" ], "offsets": [ [ 2395, 2405 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T51", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 2449, 2462 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T52", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 2504, 2517 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T53", "type": "DRUG", "text": [ "Theophylline" ], "offsets": [ [ 2528, 2540 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T54", "type": "GROUP", "text": [ "quinolones" ], "offsets": [ [ 2561, 2571 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T55", "type": "DRUG", "text": [ "ciprofloxacin" ], "offsets": [ [ 2602, 2615 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T56", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2621, 2633 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T57", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2679, 2691 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T58", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2776, 2788 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T59", "type": "DRUG", "text": [ "theophylline" ], "offsets": [ [ 2870, 2882 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T60", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 2947, 2955 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T61", "type": "GROUP", "text": [ "Quinolones" ], "offsets": [ [ 2957, 2967 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T62", "type": "GROUP", "text": [ "anticoagulant" ], "offsets": [ [ 3022, 3035 ] ], "normalized": [] }, { "id": "Ciprofloxacin_ddi_T63", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3036, 3044 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Ciprofloxacin_ddi_R1", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T1", "arg2_id": "Ciprofloxacin_ddi_T3", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R2", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T2", "arg2_id": "Ciprofloxacin_ddi_T3", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R3", "type": "EFFECT", "arg1_id": "Ciprofloxacin_ddi_T5", "arg2_id": "Ciprofloxacin_ddi_T7", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R4", "type": "EFFECT", "arg1_id": "Ciprofloxacin_ddi_T6", "arg2_id": "Ciprofloxacin_ddi_T7", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R5", "type": "EFFECT", "arg1_id": "Ciprofloxacin_ddi_T9", "arg2_id": "Ciprofloxacin_ddi_T10", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R6", "type": "EFFECT", "arg1_id": "Ciprofloxacin_ddi_T9", "arg2_id": "Ciprofloxacin_ddi_T11", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R7", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T16", "arg2_id": "Ciprofloxacin_ddi_T17", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R8", "type": "ADVISE", "arg1_id": "Ciprofloxacin_ddi_T20", "arg2_id": "Ciprofloxacin_ddi_T21", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R9", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T22", "arg2_id": "Ciprofloxacin_ddi_T24", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R10", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T22", "arg2_id": "Ciprofloxacin_ddi_T25", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R11", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T22", "arg2_id": "Ciprofloxacin_ddi_T26", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R12", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T22", "arg2_id": "Ciprofloxacin_ddi_T27", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R13", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T22", "arg2_id": "Ciprofloxacin_ddi_T28", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R14", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T22", "arg2_id": "Ciprofloxacin_ddi_T29", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R15", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T22", "arg2_id": "Ciprofloxacin_ddi_T30", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R16", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T22", "arg2_id": "Ciprofloxacin_ddi_T31", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R17", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T24", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R18", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T25", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R19", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T26", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R20", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T27", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R21", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T28", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R22", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T29", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R23", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T30", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R24", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T31", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R25", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T23", "arg2_id": "Ciprofloxacin_ddi_T32", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R26", "type": "ADVISE", "arg1_id": "Ciprofloxacin_ddi_T34", "arg2_id": "Ciprofloxacin_ddi_T35", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R27", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T47", "arg2_id": "Ciprofloxacin_ddi_T48", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R28", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T50", "arg2_id": "Ciprofloxacin_ddi_T51", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R29", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T50", "arg2_id": "Ciprofloxacin_ddi_T52", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R30", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T54", "arg2_id": "Ciprofloxacin_ddi_T56", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R31", "type": "MECHANISM", "arg1_id": "Ciprofloxacin_ddi_T55", "arg2_id": "Ciprofloxacin_ddi_T56", "normalized": [] }, { "id": "Ciprofloxacin_ddi_R32", "type": "EFFECT", "arg1_id": "Ciprofloxacin_ddi_T61", "arg2_id": "Ciprofloxacin_ddi_T63", "normalized": [] } ]

[ { "id": "Benzthiazide_ddi__text", "type": "abstract", "text": [ "Benzthiazide may interact with alcohol, blood thinners, decongestant drugs (allergy, cold, and sinus medicines), diabetic drugs, lithium, norepinephrine, NSAIDs like Aleve or Ibuprofen, and high blood pressure medications." ], "offsets": [ [ 0, 222 ] ] } ]

[ { "id": "Benzthiazide_ddi_T1", "type": "DRUG", "text": [ "Benzthiazide" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "Benzthiazide_ddi_T2", "type": "DRUG", "text": [ "alcohol" ], "offsets": [ [ 31, 38 ] ], "normalized": [] }, { "id": "Benzthiazide_ddi_T3", "type": "GROUP", "text": [ "blood thinner" ], "offsets": [ [ 40, 53 ] ], "normalized": [] }, { "id": "Benzthiazide_ddi_T4", "type": "GROUP", "text": [ "decongestant drugs" ], "offsets": [ [ 56, 74 ] ], "normalized": [] }, { "id": "Benzthiazide_ddi_T5", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 129, 136 ] ], "normalized": [] }, { "id": "Benzthiazide_ddi_T6", "type": "DRUG", "text": [ "norepinephrine" ], "offsets": [ [ 138, 152 ] ], "normalized": [] }, { "id": "Benzthiazide_ddi_T7", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 154, 160 ] ], "normalized": [] }, { "id": "Benzthiazide_ddi_T8", "type": "BRAND", "text": [ "Aleve" ], "offsets": [ [ 166, 171 ] ], "normalized": [] }, { "id": "Benzthiazide_ddi_T9", "type": "DRUG", "text": [ "Ibuprofen" ], "offsets": [ [ 175, 184 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Benzthiazide_ddi_R1", "type": "INT", "arg1_id": "Benzthiazide_ddi_T1", "arg2_id": "Benzthiazide_ddi_T2", "normalized": [] }, { "id": "Benzthiazide_ddi_R2", "type": "INT", "arg1_id": "Benzthiazide_ddi_T1", "arg2_id": "Benzthiazide_ddi_T3", "normalized": [] }, { "id": "Benzthiazide_ddi_R3", "type": "INT", "arg1_id": "Benzthiazide_ddi_T1", "arg2_id": "Benzthiazide_ddi_T4", "normalized": [] }, { "id": "Benzthiazide_ddi_R4", "type": "INT", "arg1_id": "Benzthiazide_ddi_T1", "arg2_id": "Benzthiazide_ddi_T5", "normalized": [] }, { "id": "Benzthiazide_ddi_R5", "type": "INT", "arg1_id": "Benzthiazide_ddi_T1", "arg2_id": "Benzthiazide_ddi_T6", "normalized": [] }, { "id": "Benzthiazide_ddi_R6", "type": "INT", "arg1_id": "Benzthiazide_ddi_T1", "arg2_id": "Benzthiazide_ddi_T7", "normalized": [] }, { "id": "Benzthiazide_ddi_R7", "type": "INT", "arg1_id": "Benzthiazide_ddi_T1", "arg2_id": "Benzthiazide_ddi_T8", "normalized": [] }, { "id": "Benzthiazide_ddi_R8", "type": "INT", "arg1_id": "Benzthiazide_ddi_T1", "arg2_id": "Benzthiazide_ddi_T9", "normalized": [] } ]

[ { "id": "Valdecoxib_ddi__text", "type": "abstract", "text": [ "The drug interaction studies with valdecoxib were performed both with valdecoxib and a rapidly hydrolyzed intravenous prodrug form. The results from trials using the intravenous prodrug are reported in this section as they relate to the role of valdecoxib in drug interactions. General: In humans, valdecoxib metabolism is predominantly mediated via CYP 3A4 and 2C9 with glucuronidation being a further (20%) route of metabolism. In vitro studies indicate that valdecoxib is a moderate inhibitor of CYP 2C19 (IC50 = 6 g/mL or 19 M) and 2C9 (IC50 = 13 g/mL or 41 M), and a weak inhibitor of CYP 2D6 (IC50 = 31 g/mL or 100 M) and 3A4 (IC50 = 44 g/mL or 141 M ).. Aspirin: Concomitant administration of aspirin with valdecoxib may result in an increased risk of GI ulceration and complications compared to valdecoxib alone. Because of its lack of anti-platelet effect valdecoxib is not a substitute for aspirin for cardiovascular prophylaxis. In a parallel group drug interaction study comparing the intravenous prodrug form of valdecoxib at 40 mg BID (n=10) vs placebo (n=9), valdecoxib had no effect on in vitro aspirin-mediated inhibition of arachidonate- or collagen-stimulated platelet aggregation. Methotrexate: Valdecoxib 10 mg BID did not show a significant effect on the plasma exposure or renal clearance of methotrexate. ACE-inhibitors:Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking BEXTRA concomitantly with ACE-inhibitors. Furosemide: Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. Anticonvulsants (Phenytoin): Steady state plasma exposure (AUC) of valdecoxib (40 mg BID for 12 days) was decreased by 27% when co-administered with multiple doses (300 mg QD for 12 days) of phenytoin (a CYP 3A4 inducer). Patients already stabilized on valdecoxib should be closely monitored for loss of symptom control with phenytoin coadministration. Valdecoxib did not have a statistically significant effect on the pharmacokinetics of phenytoin (a CYP 2C9 and CYP 2C19 substrate). Drug interaction studies with other anticonvulsants have not been conducted. Routine monitoring should be performed when therapy with BEXTRA is either initiated or discontinued in patients on anticonvulsant therapy. Dextromethorphan: Dextromethorphan is primarily metabolized by CYP 2D6 and to a lesser extent by 3A4. Coadministration with valdecoxib (40 mg BID for 7 days) resulted in a significant increase in dextromethorphan plasma levels suggesting that, at these doses, valdecoxib is a weak inhibitor of 2D6. Even so dextromethorphan plasma concentrations in the presence of high doses of valdecoxib were almost 5-fold lower than those seen in CYP 2D6 poor metabolizers suggesting that dose adjustment is not necessary. Lithium: Valdecoxib 40 mg BID for 7 days produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alone. Lithium serum concentrations should be monitored closely when initiating or changing therapy with BEXTRA in patients receiving lithium. Lithium carbonate (450 mg BID for 7 days) had no effect on valdecoxib pharmacokinetics. Warfarin: The effect of valdecoxib on the anticoagulant effect of warfarin (1 - 8 mg/day) was studied in healthy subjects by coadministration of BEXTRA 40 mg BID for 7 days. Valdecoxib caused a statistically significant increase in plasma exposures of R-warfarin and S-warfarin (12% and 15%, respectively), and in the pharmacodynamic effects (prothrombin time, measured as INR) of warfarin. While mean INR values were only slightly increased with coadministration of valdecoxib, the day-to-day variability in individual INR values was increased. Anticoagulant therapy should be monitored, particularly during the first few weeks, after initiating therapy with BEXTRA in patients receiving warfarin or similar agents. Fluconazole and Ketoconazole: Ketoconazole and fluconazole are predominantly CYP 3A4 and 2C9 inhibitors, respectively. Concomitant single dose administration of valdecoxib 20 mg with multiple doses of ketoconazole and fluconazole produced a significant increase in exposure of valdecoxib. Plasma exposure (AUC) to valdecoxib was increased 62% when coadministered with fluconazole and 38% when coadministered with ketoconazole. Glyburide: Glyburide is a CYP 2C9 substrate. Coadministration of valdecoxib (10 mg BID for 7 days) with glyburide (5 mg QD or 10 mg BID) did not affect the pharmacokinetics (exposure) of glyburide. Coadministration of valdecoxib (40 mg BID (day 1) and 40 mg QD (days 2-7)) with glyburide (5 mg QD) did not affect either the pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of glyburide. Coadministration of valdecoxib (40 mg BID (day 1) and 40 mg QD (days 2-7)) with glyburide (10 mg glyburide BID) resulted in 21% increase in glyburide AUC0-12 and a 16% increase in glyburide Cmax leading to a 16% decrease in glucose AUC0-24. Insulin parameters were not affected. Because changes in glucose concentrations with valdecoxib coadministration were within the normal variability and individual glucose concentrations were above or near 70 mg/dL, dose adjustment for glyburide (5 mg QD and 10 mg BID) with valdecoxib coadministration (up to 40 mg QD) is not indicated. Coadministration of glyburide with doses higher than 40 mg valdecoxib (e.g., 40 mg BID) have not been studied. Omeprazole: Omeprazole is a CYP 3A4 substrate and CYP 2C19 substrate and inhibitor. Valdecoxib steady state plasma concentrations (40 mg BID) were not affected significantly with multiple doses of omeprazole (40 mg QD). Coadministration with valdecoxib increased exposure of omeprazole (AUC) by 46%. Drugs whose absorption is sensitive to pH may be negatively impacted by concomitant administration of omeprazole and valdecoxib. However, because higher doses (up to 360 mg QD) of omeprazole are tolerated in Zollinger-Ellison (ZE) patients, no dose adjustment for omeprazole is recommended at current doses. Coadministration of valdecoxib with doses higher than 40 mg QD omeprazole has not been studied. Oral Contraceptives: Valdecoxib (40 mg BID) did not induce the metabolism of the combination oral contraceptive norethindrone/ethinyl estradiol (1 mg /35 mcg combination, Ortho-Novum 1/35 ). Coadministration of valdecoxib and Ortho-Novum 1/35 increased the exposure of norethindrone and ethinyl estradiol by 20% and 34%, respectively. Although there is little risk for loss of contraceptive efficacy, the clinical significance of these increased exposures in terms of safety is not known. These increased exposures of norethindrone and ethinyl estradiol should be taken into consideration when selecting an oral contraceptive for women taking valdecoxib. Diazepam: Diazepam (Valium) is a CYP 3A4 and CYP 2C19 substrate. Plasma exposure of diazepam (10 mg BID) was increased by 28% following administration of valdecoxib (40 mg BID) for 12 days, while plasma exposure of valdecoxib (40 mg BID) was not substantially increased following administration of diazepam (10 mg BID) for 12 days. Although the magnitude of changes in diazepam plasma exposure when coadministered with valdecoxib were not sufficient to warrant dosage adjustments, patients may experience enhanced sedative side effects caused by increased exposure of diazepam under this circumstance. Patients should be cautioned against engaging in hazardous activities requiring complete mental alertness such as operating machinery or driving a motor vehicle." ], "offsets": [ [ 0, 7810 ] ] } ]

[ { "id": "Valdecoxib_ddi_T1", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 34, 44 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T2", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 70, 80 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T3", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 245, 255 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T4", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 298, 308 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T5", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 461, 471 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T6", "type": "BRAND", "text": [ "Aspirin" ], "offsets": [ [ 669, 676 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T7", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 708, 715 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T8", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 721, 731 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T9", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 811, 821 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T10", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 873, 883 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T11", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 908, 915 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T12", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 1033, 1043 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T13", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 1082, 1092 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T14", "type": "BRAND", "text": [ "aspirin" ], "offsets": [ [ 1119, 1126 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T15", "type": "DRUG", "text": [ "Methotrexate" ], "offsets": [ [ 1209, 1221 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T16", "type": "DRUG", "text": [ "Valdecoxib 10 mg" ], "offsets": [ [ 1223, 1239 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T17", "type": "DRUG", "text": [ "methotrexate" ], "offsets": [ [ 1323, 1335 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T18", "type": "GROUP", "text": [ "ACE-inhibitors" ], "offsets": [ [ 1337, 1351 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T19", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1373, 1379 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T20", "type": "GROUP", "text": [ "ACE-inhibitors" ], "offsets": [ [ 1424, 1438 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T21", "type": "BRAND", "text": [ "BEXTRA" ], "offsets": [ [ 1506, 1512 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T22", "type": "GROUP", "text": [ "ACE-inhibitors" ], "offsets": [ [ 1532, 1546 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T23", "type": "DRUG", "text": [ "Furosemide" ], "offsets": [ [ 1548, 1558 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T24", "type": "GROUP", "text": [ "NSAIDs" ], "offsets": [ [ 1634, 1640 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T25", "type": "DRUG", "text": [ "furosemide" ], "offsets": [ [ 1678, 1688 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T26", "type": "GROUP", "text": [ "thiazides" ], "offsets": [ [ 1693, 1702 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T27", "type": "GROUP", "text": [ "Anticonvulsants" ], "offsets": [ [ 1803, 1818 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T28", "type": "DRUG", "text": [ "Phenytoin" ], "offsets": [ [ 1820, 1829 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T29", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 1870, 1880 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T30", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 1994, 2003 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T31", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 2056, 2066 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T32", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2128, 2137 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T33", "type": "DRUG", "text": [ "Valdecoxib" ], "offsets": [ [ 2156, 2166 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T34", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 2242, 2251 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T35", "type": "GROUP", "text": [ "anticonvulsants" ], "offsets": [ [ 2324, 2339 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T36", "type": "BRAND", "text": [ "BEXTRA" ], "offsets": [ [ 2422, 2428 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T37", "type": "DRUG", "text": [ "Dextromethorphan" ], "offsets": [ [ 2504, 2520 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T38", "type": "DRUG", "text": [ "Dextromethorphan" ], "offsets": [ [ 2522, 2538 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T39", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 2628, 2638 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T40", "type": "DRUG", "text": [ "dextromethorphan" ], "offsets": [ [ 2700, 2716 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T41", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 2764, 2774 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T42", "type": "DRUG", "text": [ "dextromethorphan" ], "offsets": [ [ 2811, 2827 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T43", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 2883, 2893 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T44", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 3014, 3021 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T45", "type": "DRUG", "text": [ "Valdecoxib" ], "offsets": [ [ 3023, 3033 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T46", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 3089, 3096 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T47", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 3190, 3197 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T48", "type": "DRUG", "text": [ "Lithium" ], "offsets": [ [ 3205, 3212 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T49", "type": "BRAND", "text": [ "BEXTRA" ], "offsets": [ [ 3303, 3309 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T50", "type": "DRUG", "text": [ "lithium" ], "offsets": [ [ 3332, 3339 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T51", "type": "DRUG", "text": [ "Lithium carbonate" ], "offsets": [ [ 3341, 3358 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T52", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 3400, 3410 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T53", "type": "DRUG", "text": [ "Warfarin" ], "offsets": [ [ 3429, 3437 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T54", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 3453, 3463 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T55", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3495, 3503 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T56", "type": "BRAND", "text": [ "BEXTRA" ], "offsets": [ [ 3574, 3580 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T57", "type": "DRUG", "text": [ "Valdecoxib" ], "offsets": [ [ 3603, 3613 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T58", "type": "DRUG", "text": [ "R-warfarin" ], "offsets": [ [ 3681, 3691 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T59", "type": "DRUG", "text": [ "S-warfarin" ], "offsets": [ [ 3696, 3706 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T60", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 3810, 3818 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T61", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 3896, 3906 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T62", "type": "BRAND", "text": [ "Anticoagulant" ], "offsets": [ [ 3975, 3988 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T63", "type": "BRAND", "text": [ "BEXTRA" ], "offsets": [ [ 4089, 4095 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T64", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 4118, 4126 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T65", "type": "DRUG", "text": [ "Fluconazole" ], "offsets": [ [ 4146, 4157 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T66", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 4162, 4174 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T67", "type": "DRUG", "text": [ "Ketoconazole" ], "offsets": [ [ 4176, 4188 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T68", "type": "DRUG", "text": [ "fluconazole" ], "offsets": [ [ 4193, 4204 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T69", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 4307, 4317 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T70", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 4347, 4359 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T71", "type": "DRUG", "text": [ "fluconazole" ], "offsets": [ [ 4364, 4375 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T72", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 4423, 4433 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T73", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 4460, 4470 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T74", "type": "DRUG", "text": [ "fluconazole" ], "offsets": [ [ 4514, 4525 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T75", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 4559, 4571 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T76", "type": "DRUG", "text": [ "Glyburide" ], "offsets": [ [ 4573, 4582 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T77", "type": "DRUG", "text": [ "Glyburide" ], "offsets": [ [ 4584, 4593 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T78", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 4638, 4648 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T79", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 4677, 4686 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T80", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 4760, 4769 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T81", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 4791, 4801 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T82", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 4851, 4860 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T83", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 4987, 4996 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T84", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 5018, 5028 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T85", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 5078, 5087 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T86", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 5095, 5104 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T87", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 5138, 5147 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T88", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 5178, 5187 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T89", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 5324, 5334 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T90", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 5474, 5483 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T91", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 5513, 5523 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T92", "type": "DRUG", "text": [ "glyburide" ], "offsets": [ [ 5596, 5605 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T93", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 5635, 5645 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T94", "type": "DRUG", "text": [ "Omeprazole" ], "offsets": [ [ 5687, 5697 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T95", "type": "DRUG", "text": [ "Omeprazole" ], "offsets": [ [ 5699, 5709 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T96", "type": "DRUG", "text": [ "Valdecoxib" ], "offsets": [ [ 5771, 5781 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T97", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 5884, 5894 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T98", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 5929, 5939 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T99", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 5962, 5972 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T100", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 6089, 6099 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T101", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 6104, 6114 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T102", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 6167, 6177 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T103", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 6251, 6261 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T104", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 6315, 6325 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T105", "type": "DRUG", "text": [ "omeprazole" ], "offsets": [ [ 6358, 6368 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T106", "type": "GROUP", "text": [ "Contraceptives" ], "offsets": [ [ 6396, 6410 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T107", "type": "DRUG", "text": [ "Valdecoxib" ], "offsets": [ [ 6412, 6422 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T108", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 6489, 6502 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T109", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 6503, 6516 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T110", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 6517, 6534 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T111", "type": "BRAND", "text": [ "Ortho-Novum" ], "offsets": [ [ 6562, 6573 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T112", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 6602, 6612 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T113", "type": "BRAND", "text": [ "Ortho-Novum" ], "offsets": [ [ 6617, 6628 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T114", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 6661, 6674 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T115", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 6679, 6696 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T116", "type": "DRUG", "text": [ "norethindrone" ], "offsets": [ [ 6910, 6923 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T117", "type": "DRUG", "text": [ "ethinyl estradiol" ], "offsets": [ [ 6928, 6945 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T118", "type": "GROUP", "text": [ "contraceptive" ], "offsets": [ [ 7004, 7017 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T119", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 7035, 7045 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T120", "type": "DRUG", "text": [ "Diazepam" ], "offsets": [ [ 7047, 7055 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T121", "type": "DRUG", "text": [ "Diazepam" ], "offsets": [ [ 7057, 7065 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T122", "type": "BRAND", "text": [ "Valium" ], "offsets": [ [ 7067, 7073 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T123", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 7131, 7139 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T124", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 7201, 7211 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T125", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 7262, 7272 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T126", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 7345, 7353 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T127", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 7416, 7424 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T128", "type": "DRUG", "text": [ "valdecoxib" ], "offsets": [ [ 7466, 7476 ] ], "normalized": [] }, { "id": "Valdecoxib_ddi_T129", "type": "DRUG", "text": [ "diazepam" ], "offsets": [ [ 7615, 7623 ] ], "normalized": [] } ]

[]

[]

[ { "id": "Valdecoxib_ddi_R1", "type": "EFFECT", "arg1_id": "Valdecoxib_ddi_T7", "arg2_id": "Valdecoxib_ddi_T8", "normalized": [] }, { "id": "Valdecoxib_ddi_R2", "type": "EFFECT", "arg1_id": "Valdecoxib_ddi_T19", "arg2_id": "Valdecoxib_ddi_T20", "normalized": [] }, { "id": "Valdecoxib_ddi_R3", "type": "ADVISE", "arg1_id": "Valdecoxib_ddi_T21", "arg2_id": "Valdecoxib_ddi_T22", "normalized": [] }, { "id": "Valdecoxib_ddi_R4", "type": "EFFECT", "arg1_id": "Valdecoxib_ddi_T24", "arg2_id": "Valdecoxib_ddi_T25", "normalized": [] }, { "id": "Valdecoxib_ddi_R5", "type": "EFFECT", "arg1_id": "Valdecoxib_ddi_T24", "arg2_id": "Valdecoxib_ddi_T26", "normalized": [] }, { "id": "Valdecoxib_ddi_R6", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T29", "arg2_id": "Valdecoxib_ddi_T30", "normalized": [] }, { "id": "Valdecoxib_ddi_R7", "type": "ADVISE", "arg1_id": "Valdecoxib_ddi_T31", "arg2_id": "Valdecoxib_ddi_T32", "normalized": [] }, { "id": "Valdecoxib_ddi_R8", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T39", "arg2_id": "Valdecoxib_ddi_T40", "normalized": [] }, { "id": "Valdecoxib_ddi_R9", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T42", "arg2_id": "Valdecoxib_ddi_T43", "normalized": [] }, { "id": "Valdecoxib_ddi_R10", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T45", "arg2_id": "Valdecoxib_ddi_T46", "normalized": [] }, { "id": "Valdecoxib_ddi_R11", "type": "ADVISE", "arg1_id": "Valdecoxib_ddi_T49", "arg2_id": "Valdecoxib_ddi_T50", "normalized": [] }, { "id": "Valdecoxib_ddi_R12", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T57", "arg2_id": "Valdecoxib_ddi_T58", "normalized": [] }, { "id": "Valdecoxib_ddi_R13", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T57", "arg2_id": "Valdecoxib_ddi_T59", "normalized": [] }, { "id": "Valdecoxib_ddi_R14", "type": "EFFECT", "arg1_id": "Valdecoxib_ddi_T57", "arg2_id": "Valdecoxib_ddi_T60", "normalized": [] }, { "id": "Valdecoxib_ddi_R15", "type": "ADVISE", "arg1_id": "Valdecoxib_ddi_T63", "arg2_id": "Valdecoxib_ddi_T64", "normalized": [] }, { "id": "Valdecoxib_ddi_R16", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T69", "arg2_id": "Valdecoxib_ddi_T70", "normalized": [] }, { "id": "Valdecoxib_ddi_R17", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T69", "arg2_id": "Valdecoxib_ddi_T71", "normalized": [] }, { "id": "Valdecoxib_ddi_R18", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T73", "arg2_id": "Valdecoxib_ddi_T74", "normalized": [] }, { "id": "Valdecoxib_ddi_R19", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T73", "arg2_id": "Valdecoxib_ddi_T75", "normalized": [] }, { "id": "Valdecoxib_ddi_R20", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T84", "arg2_id": "Valdecoxib_ddi_T85", "normalized": [] }, { "id": "Valdecoxib_ddi_R21", "type": "ADVISE", "arg1_id": "Valdecoxib_ddi_T90", "arg2_id": "Valdecoxib_ddi_T91", "normalized": [] }, { "id": "Valdecoxib_ddi_R22", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T98", "arg2_id": "Valdecoxib_ddi_T99", "normalized": [] }, { "id": "Valdecoxib_ddi_R23", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T112", "arg2_id": "Valdecoxib_ddi_T113", "normalized": [] }, { "id": "Valdecoxib_ddi_R24", "type": "ADVISE", "arg1_id": "Valdecoxib_ddi_T118", "arg2_id": "Valdecoxib_ddi_T119", "normalized": [] }, { "id": "Valdecoxib_ddi_R25", "type": "MECHANISM", "arg1_id": "Valdecoxib_ddi_T123", "arg2_id": "Valdecoxib_ddi_T124", "normalized": [] }, { "id": "Valdecoxib_ddi_R26", "type": "EFFECT", "arg1_id": "Valdecoxib_ddi_T128", "arg2_id": "Valdecoxib_ddi_T129", "normalized": [] } ]

[ { "id": "Gefitinib_ddi__text", "type": "abstract", "text": [ "Substances that are inducers of CYP3A4 activity increase the metabolism of gefitinib and decrease its plasma concentrations. In patients receiving a potent CYP3A4 inducer such as rifampicin or phenytoin, a dose increase to 500 mg daily should be considered in the absence of severe adverse drug reaction, and clinical response and adverse events should be carefully monitored (see CLINICAL PHARMACOLOGY-Pharmacokinetics-Drug-Drug Interactions and DOSAGE AND ADMINISTRATION-Dosage Adjustment sections). International Normalized Ratio (INR) elevations and/or bleeding events have been reported in some patients taking warfarin while on IRESSA therapy. Patients taking warfarin should be monitored regularly for changes in prothrombin time or INR. Substances that are potent inhibitors of CYP3A4 activity (eg, ketoconazole and itraconazole) decrease gefitinib metabolism and increase gefitinib plasma concentrations. This increase may be clinically relevant as adverse experiences are related to dose and exposure; therefore, caution should be used when administering CYP3A4 inhibitors with IRESSA. Drugs that cause significant sustained elevation in gastric pH (histamine H2-receptor antagonists such as ranitidine or cimetidine) may reduce plasma concentrations of IRESSA and therefore potentially may reduce efficacy. Phase II clinical trial data, where IRESSA and vinorelbine have been used concomitantly, indicate that IRESSA may exacerbate the neutropenic effect of vinorelbine." ], "offsets": [ [ 0, 1481 ] ] } ]

[ { "id": "Gefitinib_ddi_T1", "type": "DRUG", "text": [ "gefitinib" ], "offsets": [ [ 75, 84 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T2", "type": "DRUG", "text": [ "rifampicin" ], "offsets": [ [ 179, 189 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T3", "type": "DRUG", "text": [ "phenytoin" ], "offsets": [ [ 193, 202 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T4", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 616, 624 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T5", "type": "BRAND", "text": [ "IRESSA" ], "offsets": [ [ 634, 640 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T6", "type": "DRUG", "text": [ "warfarin" ], "offsets": [ [ 666, 674 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T7", "type": "DRUG", "text": [ "ketoconazole" ], "offsets": [ [ 807, 819 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T8", "type": "DRUG", "text": [ "itraconazole" ], "offsets": [ [ 824, 836 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T9", "type": "DRUG", "text": [ "gefitinib" ], "offsets": [ [ 847, 856 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T10", "type": "DRUG", "text": [ "gefitinib" ], "offsets": [ [ 881, 890 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T11", "type": "BRAND", "text": [ "IRESSA" ], "offsets": [ [ 1088, 1094 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T12", "type": "GROUP", "text": [ "histamine H2-receptor antagonists" ], "offsets": [ [ 1160, 1193 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T13", "type": "DRUG", "text": [ "ranitidine" ], "offsets": [ [ 1202, 1212 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T14", "type": "DRUG", "text": [ "cimetidine" ], "offsets": [ [ 1216, 1226 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T15", "type": "BRAND", "text": [ "IRESSA" ], "offsets": [ [ 1264, 1270 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T16", "type": "BRAND", "text": [ "IRESSA" ], "offsets": [ [ 1354, 1360 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T17", "type": "DRUG", "text": [ "vinorelbine" ], "offsets": [ [ 1365, 1376 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T18", "type": "BRAND", "text": [ "IRESSA" ], "offsets": [ [ 1421, 1427 ] ], "normalized": [] }, { "id": "Gefitinib_ddi_T19", "type": "DRUG", "text": [ "vinorelbine" ], "offsets": [ [ 1469, 1480 ] ], "normalized": [] } ]

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[ { "id": "Gefitinib_ddi_R1", "type": "EFFECT", "arg1_id": "Gefitinib_ddi_T4", "arg2_id": "Gefitinib_ddi_T5", "normalized": [] }, { "id": "Gefitinib_ddi_R2", "type": "MECHANISM", "arg1_id": "Gefitinib_ddi_T7", "arg2_id": "Gefitinib_ddi_T9", "normalized": [] }, { "id": "Gefitinib_ddi_R3", "type": "MECHANISM", "arg1_id": "Gefitinib_ddi_T7", "arg2_id": "Gefitinib_ddi_T10", "normalized": [] }, { "id": "Gefitinib_ddi_R4", "type": "MECHANISM", "arg1_id": "Gefitinib_ddi_T8", "arg2_id": "Gefitinib_ddi_T9", "normalized": [] }, { "id": "Gefitinib_ddi_R5", "type": "MECHANISM", "arg1_id": "Gefitinib_ddi_T8", "arg2_id": "Gefitinib_ddi_T10", "normalized": [] }, { "id": "Gefitinib_ddi_R6", "type": "MECHANISM", "arg1_id": "Gefitinib_ddi_T12", "arg2_id": "Gefitinib_ddi_T15", "normalized": [] }, { "id": "Gefitinib_ddi_R7", "type": "MECHANISM", "arg1_id": "Gefitinib_ddi_T13", "arg2_id": "Gefitinib_ddi_T15", "normalized": [] }, { "id": "Gefitinib_ddi_R8", "type": "MECHANISM", "arg1_id": "Gefitinib_ddi_T14", "arg2_id": "Gefitinib_ddi_T15", "normalized": [] }, { "id": "Gefitinib_ddi_R9", "type": "EFFECT", "arg1_id": "Gefitinib_ddi_T18", "arg2_id": "Gefitinib_ddi_T19", "normalized": [] } ]

[ { "id": "Cefadroxil_ddi__text", "type": "abstract", "text": [ "Drug/Laboratory Test Interactions Positive direct Coombs tests have been reported during treatment with the cephalosporin antibiotics. In hematologic studies or in transfusion cross-matching procedures when anti-globulin tests are performed on the minor side or in Coombs testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs test may be due to the drug." ], "offsets": [ [ 0, 444 ] ] } ]

[ { "id": "Cefadroxil_ddi_T1", "type": "GROUP", "text": [ "cephalosporin antibiotics" ], "offsets": [ [ 109, 134 ] ], "normalized": [] }, { "id": "Cefadroxil_ddi_T2", "type": "GROUP", "text": [ "cephalosporin antibiotics" ], "offsets": [ [ 322, 347 ] ], "normalized": [] } ]

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