"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
Severe or Persistent Diarrhea
If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR (methylnaltrexone bromide) and consult their physician.
Rare cases of gastrointestinal (GI) perforation have been reported in advanced illness patients with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the GI tract (i.e., cancer, peptic ulcer, Ogilvie's syndrome). Perforations have involved varying regions of the GI tract: (e.g., stomach, duodenum, colon).
Use RELISTOR (methylnaltrexone bromide) with caution in patients with known or suspected lesions of the GI tract. Advise patients to discontinue therapy with RELISTOR (methylnaltrexone bromide) and promptly notify their physician if they develop severe, persistent, and/or worsening abdominal symptoms.
Use of RELISTOR (methylnaltrexone bromide) has not been studied in patients with peritoneal catheters.
Patient Counseling Information
[See FDA-approved PATIENT INFORMATION]
Instruct patients that the usual schedule is one dose every other day, as needed, but no more frequently than one dose in a 24-hour period.
In approximately 30% of patients in clinical trials, laxation was reported within 30 minutes of a dose of RELISTOR (methylnaltrexone bromide) ; therefore, advise patients to be within close proximity to toilet facilities once the drug is administered.
Instruct patients not to continue taking RELISTOR (methylnaltrexone bromide) if they experience severe or persistent diarrhea. Instruct patients that common side effects of RELISTOR (methylnaltrexone bromide) include transient abdominal pain, nausea and vomiting.
Instruct patients not to continue taking RELISTOR (methylnaltrexone bromide) and to promptly notify their physician if they experience severe, persistent, and/or worsening abdominal symptoms because these could be symptoms of intestinal perforation [see WARNINGS AND PRECAUTIONS].
Instruct patients to discontinue RELISTOR (methylnaltrexone bromide) if they stop taking their opioid pain medication.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of methylnaltrexone bromide.
Methylnaltrexone bromide was negative in the Ames test, chromosome aberration tests in Chinese hamster ovary cells and human lymphocytes, in the mouse lymphoma cell forward mutation tests and in the in vivo mouse micronucleus test.
Impairment of Fertility
Methylnaltrexone bromide at subcutaneous doses up to 150 mg/kg/day (about 81 times the recommended maximum human subcutaneous dose based on the body surface area) was found to have no adverse effect on fertility and reproductive performance of male and female rats.
Use In Specific Populations
Pregnancy Category B
Reproduction studies have been performed in pregnant rats at intravenous doses up to about 14 times the recommended maximum human subcutaneous dose of 0.3 mg/kg based on the body surface area and in pregnant rabbits at intravenous doses up to about 17 times the recommended maximum human subcutaneous dose based on the body surface area and have revealed no evidence of impaired fertility or harm to the fetus due to methylnaltrexone bromide. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, methylnaltrexone bromide should be used during pregnancy only if clearly needed.
Labor and Delivery
Effects of RELISTOR (methylnaltrexone bromide) on mother, fetus, duration of labor, and delivery are unknown. There were no effects on the mother, labor, delivery, or on offspring survival and growth in rats following subcutaneous injection of methylnaltrexone bromide at dosages up to 25 mg/kg/day.
Results from an animal study using [3H]-labeled methylnaltrexone bromide indicate that methylnaltrexone bromide is excreted via the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when RELISTOR (methylnaltrexone bromide) is administered to a nursing woman.
Safety and efficacy of RELISTOR (methylnaltrexone bromide) have not been established in pediatric patients.
In the phase 2 and 3 double-blind studies, a total of 77 (24%) patients aged 65-74 years (54 methylnaltrexone bromide, 23 placebo) and a total of 100 (31.2%) patients aged 75 years or older (61 methylnaltrexone bromide, 39 placebo) were enrolled. There was no difference in the efficacy or safety profile of these elderly patients when compared to younger patients. Therefore, no dose adjustment is recommended based on age.
No dose adjustment is required in patients with mild or moderate renal impairment. Dose-reduction by one-half is recommended in patients with severe renal impairment (creatinine clearance less than 30 mL/min). In a study of volunteers with varying degrees of renal impairment receiving a single dose of 0.30 mg/kg methylnaltrexone bromide, renal impairment had a marked effect on the renal excretion of methylnaltrexone bromide. Severe renal impairment decreased the renal clearance of methylnaltrexone bromide by 8- to 9-fold and resulted in a 2-fold increase in total methylnaltrexone bromide exposure (AUC). Cmax was not significantly changed. No studies were performed in patients with end-stage renal impairment requiring dialysis.
No dose adjustment is required for patients with mild or moderate hepatic impairment. The effect of mild and moderate hepatic impairment on the systemic exposure to methylnaltrexone bromide has been studied in 8 subjects each, with Child-Pugh Class A and B, compared to healthy subjects. Results showed no meaningful effect of hepatic impairment on the AUC or Cmax of methylnaltrexone bromide. The effect of severe hepatic impairment on the pharmacokinetics of methylnaltrexone bromide has not been studied.
Last reviewed on RxList: 8/13/2010
This monograph has been modified to include the generic and brand name in many instances.
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