Drug Interactions between amitriptyline and Colestid

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

ADJUST DOSING INTERVAL: Bile acid sequestrants and the phosphate binder, sevelamer, can decrease the absorption of fat-soluble vitamins A, D, E, and K. By binding bile acids, these agents may interfere with normal fat digestion and absorption, thereby preventing the absorption of fat-soluble vitamins. When 8 grams of cholestyramine was administered simultaneously with a normal meal containing 250,000 units of vitamin A acetate in four healthy young adult subjects, plasma vitamin A levels were significantly reduced during a 9-hour postprandial period compared to the values obtained with the control meal. Coadministration with 4 grams of cholestyramine had no significant effect. In a crossover study involving healthy subjects, coadministration of sevelamer with calcitriol resulted in a significant reduction in bioavailability for calcitriol (calcitriol with sevelamer vs calcitriol alone: AUC 137 pg*h/mL vs 318 pg*h/mL and Cmax 40.1 pg/mL vs 49.7 pg/mL, respectively). Chronic use of bile acid sequestrants has been rarely associated with an increased bleeding tendency due to hypoprothrombinemia resulting from vitamin K deficiency. Isolated cases of Vitamin A (including one case of night blindness) and D deficiencies have also been reported with chronic cholestyramine therapy.

MANAGEMENT: When bile acid sequestrants are given for prolonged periods, some manufacturers recommend that concomitant supplementation with water-miscible or parenteral forms of fat-soluble vitamins be considered. If oral vitamin supplements are used with cholestyramine or colestipol, advise patients to take them at least 1 hour before or 4 to 6 hours after the bile acid sequestrant to minimize the potential impact on their absorption. No recommendations are available for sevelamer, but it may be advisable to follow the same precautions.

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.