Tegaserod (Zelnorm) Contraindications and Precautions
- abdominal pain
- breast-feeding
- colitis
- gallbladder disease
- hypotension
- renal failure
- syncope
- cardiac disease
- children
- diarrhea
- GI bleeding
- GI disease
- hepatic disease
- hypovolemia
- myocardial infarction
- ovarian cyst
- pregnancy
- renal disease
- renal impairment
Tegaserod (Zelnorm) Contraindications and Precautions
Tegaserod (Zelnorm) is contraindicated in any patient with a known hypersensitivity to the drug or any of its excipients. Tegaserod (Zelnorm) is also contraindicated in patients with moderate or severe hepatic impairment or hepatic disease, cirrhosis, severe renal impairment, renal failure, or renal disease, a history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, or abdominal adhesions. Tegaserod (Zelnorm) should not be initiated in any patient who is currently experiencing or frequently experiences diarrhea.
The effect of tegaserod in patients with gastrointestinal (GI) disease, other than IBS, is not known. Diarrhea, which is a common adverse effect of tegaserod, may aggravate certain GI disease. Serious consequences of diarrhea, including hypovolemia, hypotension and syncope have been reported with tegaserod treatment, in some instances requiring hospitalization for rehydration. Tegaserod (Zelnorm) should be discontinued immediately in any patient who develops hypotension or syncope. Any undiagnosed rectal or GI bleeding should be evaluated prior to therapy with tegaserod. Additionally, although diarrhea appears to be a transient adverse effect of tegaserod, extended diarrhea may put a patient at risk for dehydration and electrolyte imbalance. Tegaserod (Zelnorm) should be discontinued immediately in patients with new or worsening abdominal pain. Patients should consult with their prescriber if they experience severe diarrhea, or if the diarrhea is accompanied by severe cramping, abdominal pain, or dizziness. Ischemic colitis has been reported in post-marketing reports submitted to the FDA, although causality has not been determined. Clinical trials (n=7000) over a 3 month period did not result in any cases of ischemic colitis. Tegaserod (Zelnorm) should be discontinued immediately in any patient who develops bloody diarrhea, rectal bleeding or new or worsening abdominal pain. The patient should be evaluated and tegaserod should not be reinitiated in any patient with symptoms consistent with ischemic colitis.
Ovarian cyst development has been noted in tegaserod clinical trials, but a causal relationship has not been determined. It is not known if women with a history of ovarian cysts are at greater risk for further development of cysts while receiving tegaserod.
Tegaserod (Zelnorm) is classified in FDA pregnancy risk category B. Although limited, the human pregnancy experience suggests a low risk. However, it has been suggested that if a woman requires tegaserod therapy in pregnancy, avoid use during the first trimester as data are insufficient to determine the true risk to the developing fetus. Animal studies at tegaserod doses 15 to 51 times the normal human dose of 6 mg two times a day have revealed no evidence of impaired fertility or harm to the fetus.
Tegaserod (Zelnorm) should be avoided in lactating women. Studies in animals have detected tegaserod milk levels are 3 times higher than plasma levels. Although the clinical effects are not known, data suggest that a breast-feeding infant might ingest a significant dose of tegaserod. It is not known whether tegaserod is excreted in human milk. Based on the tumorigenicity data shown for tegaserod in the mouse carcinogenicity study and other potential significant exposure, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother.
Tegaserod (Zelnorm) has not been formally studied in a pediatric population with IBS. The safety and effectiveness of tegaserod in children below the age of 18 years have not been established.
Carcinogenic effects in rats have not been seen at doses up to 111 times the normal human dose of tegaserod (6 mg PO bid). In mice, dietary administration of tegaserod for 104 weeks produced mucosal hyperplasia and adenocarcinoma of the small intestines at 600 mg/kg/day (83 - 110 times the normal human dose). There was no evidence of carcinogenicity at a lower dose of 200 mg/kg/day (24 - 35 times the normal human dose) or 60 mg/kg/day (3 - 4 times the normal human dose).
Use tegaserod with caution in patients with significant cardiac disease or a history of myocardial infarction. In a single case report, a myocardial infarction is described in a man who received 2 doses of 6 mg tegaserod. Causality with tegaserod cannot be made; however, tegaserod has partial 5HT-1 agonist activity and theoretically may lead to cardiac events similar to the potent 5HT-1 agonists (i.e. sumatriptan) used for migraine headaches (see Adverse Reactions).
[ Last revised: 1/19/2006 3:56:00 PM ]
References
. Camilleri M. Review article: Tegaserod. Aliment Pharmacol Ther 2001;15:277 - 89.
. Wooltorton E. Tegaserod (Zelnorm) for irritable bowel syndrome: reports of serious diarrhea and intestinal ischemia. CMAJ. 2004;170:1908.
. Busti AJ, Murillo JR Jr, Cryer B. Tegaserod-induced myocardial infarction: case report and hypothesis. Pharmacotherapy. 2004;24:526 - 31.
. Briggs, Freeman, Yaffee. Tegaserod. Update, Drugs in Pregnancy and Lactation. 2005:18;30 - 31.
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