Tegaserod (Zelnorm) Interactions
Antimuscarinics
Tegaserod (Zelnorm) Interactions
In-vitro drug interaction data with tegaserod indicate the drug does not inhibit the cytochrome P450 isoenzymes CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4. In human liver studies in-vitro, inhibition of hepatic microsomal CYP450 enzymes 1A2 and 2D6 could not be ruled out. However, in-vivo studies evaluating the prototype substrates theophylline (CYP1A2) and dextromethorphan (CYP2D6) show no significant drug interactions. Additionally, warfarin and oral contraceptives have not been shown to interact pharmacokinetically with tegaserod.
Drugs that exert significant anticholinergic properties such as antimuscarinics may pharmacodynamically oppose the effects of prokinetic agents such as tegaserod. Avoid administering antimuscarinics along with tegaserod under most circumstances. Inhaled respiratory antimuscarinics, such as ipratropium, are unlikely to interact with tegaserod. Ophthalmic anticholinergics may interact if sufficient systemic absorption of the eye medication occurs.
The co-administration of dextromethorphan (a CYP2D6 substrate) and tegaserod did not significantly change the pharmacokinetics of either compound. Dose adjustment of either drug is not needed when co-administered. Based on this data, in theory tegaserod should not alter the pharmacokinetics of other drugs metabolized by CYP2D6 (e.g., captopril, fluoxetine, omeprazole, phenothiazines).
Dose adjustment of theophylline (a CYP1A2 substrate) is not needed when co-administered with tegaserod. Therefore, theoretically, tegaserod is not expected to alter the pharmacokinetics of other drugs metabolized by CYP1A2 (e.g., estradiol, omeprazole).
When digoxin is combined with tegaserod, a 15% reduction in digoxin peak plasma concentration occurs. Digoxin dose adjustments are unlikely to be required when combined with tegaserod. Until further clinical use is gained with tegaserod, use caution and consider monitoring digoxin levels more frequently if combined with tegaserod.
Tegaserod (Zelnorm) can enhance gastric emptying. Exenatide (which is an injectable) has been shown to slow gastric emptying. The clinical effects of these competing mechanisms, if exenatide were to be prescribed with tegaserod, is not known. Blood glucose should be closely monitored and exenatide adjusted accordingly in this situation.
[ Last revised: 6/14/2005 4:38:00 PM ]
References
. Camilleri M. Review article: Tegaserod (Zelnorm). Aliment Pharmacol Ther 2001;15:277 - 89.
. Zelnorm® (tegaserod maleate) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2004 April.
. Hoffman BB, Lefkowitz RJ. Atropine, scopolamine, and related antimuscarinic drugs. Gilman AG, Rall TW, Nies AS, Taylor P, (eds.) In: Goodman and Gilman’s Pharmacological Basis of Therapeutics. 8th ed., New York, Pergamon Press. 1990. 150 - 61.
. Byetta™ (exenatide) package insert. San Diego, CA: Amylin Pharmaceuticals, Inc.; 2005 Apr.
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