"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.
- Patient Information:
Details with Side Effects
Cases of gastrointestinal (GI) perforation have been reported in adult patients with opioid-induced constipation and advanced illness 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, or colon).
Use RELISTOR with caution in patients with known or suspected lesions of the GI tract. Advise patients to discontinue therapy with RELISTOR and promptly notify their physician if they develop severe, persistent, or worsening abdominal symptoms.
Severe or Persistent Diarrhea
If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their physician.
Patient Counseling Information
See FDA-approved patient labeling (Patient Information and Instructions for Use)
- Instruct patients not to continue taking RELISTOR and to promptly notify their physician if they experience severe, persistent, or worsening abdominal symptoms because these could be symptoms of gastrointestinal perforation [see WARNINGS AND PRECAUTIONS].
- Instruct patients not to continue taking RELISTOR if they experience severe or persistent diarrhea. Inform patients that common side effects of RELISTOR include abdominal pain, flatulence, nausea, dizziness, and diarrhea.
- Advise patients to be within close proximity to toilet facilities once the drug is administered.
- Instruct patients with opioid-induced constipation and advanced illness to administer one dose subcutaneously every other day, as needed, but no more frequently than one dose in a 24-hour period.
- Instruct patients to discontinue RELISTOR if they stop taking their opioid pain medication.
- Instruct patients to use the RELISTOR single-use vial with a 27 gauge x ½-inch needle and 1 mL syringe
Carcinogenesis, Mutagenesis, Impairment of Fertility
Two-year oral carcinogenicity studies have been conducted with methylnaltrexone in CD-1 mice at doses up to 200 mg/kg/day (about 108 times the recommended human dose of 0.15 mg/kg based on body surface area) in males and 400 mg/kg/day (about 216 times the recommended human dose of 0.15 mg/kg based on body surface area) in females and in Sprague Dawley rats at oral doses up to 300 mg/kg/day (about 324 times the recommended human dose of 0.15 mg/kg based on body surface area). Oral administration of methylnaltrexone for 104 weeks did not produce tumors in mice and rats.
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 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 is administered to a nursing woman.
Safety and effectiveness of RELISTOR 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. Pharmacokinetics of methylnaltrexone was similar between the elderly (mean age 72 years old) and young adults (mean age 30 years old). No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Based on pharmacokinetic data, and safety and efficacy data from controlled clinical trials, no dose adjustment based on age is recommended.
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 as estimated by Cockcroft-Gault).
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 severe hepatic impairment on the pharmacokinetics of methylnaltrexone has not been studied.
Last reviewed on RxList: 9/19/2013
This monograph has been modified to include the generic and brand name in many instances.
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