"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.
Clinical Trial Experience
Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.
The safety of RELISTOR (methylnaltrexone bromide) was evaluated in two, double-blind, placebo-controlled trials in patients with advanced illness receiving palliative care: Study 1 included a single-dose, double-blind, placebo-controlled period, whereas Study 2 included a 14-day multiple dose, double-blind, placebo-controlled period [see Clinical Studies]. In both studies, patients had advanced illness with a life expectancy of less than 6 months and received care to control their symptoms. The majority of patients had a primary diagnosis of incurable cancer; other primary diagnoses included end-stage COPD/emphysema, cardiovascular disease/heart failure, Alzheimer's disease/dementia, HIV/AIDS, or other advanced illnesses. Patients were receiving opioid therapy (median daily baseline oral morphine equivalent dose =172 mg), and had opioid-induced constipation (either < 3 bowel movements in the preceding week or no bowel movement for 2 days). Both the methylnaltrexone bromide and placebo patients were on a stable laxative regimen for at least 3 days prior to study entry and continued on their regimen throughout the study.
The adverse reactions in patients receiving RELISTOR (methylnaltrexone bromide) are shown in table below.
Adverse Reactions from all Doses in Double-Blind, Placebo-Controlled
Clinical Studies of RELISTOR (methylnaltrexone bromide) *
|Adverse Reaction|| RELISTOR
|Abdominal Pain||47 (28.5%)||12 (9.8%)|
|Flatulence||22 (13.3%)||7 (5.7%)|
|Dizziness||12 (7.3%)||3 (2.4%)|
|Diarrhea||9 (5.5%)||3 (2.4%)|
|* Doses: 0.075, 0.15, and 0.30 mg/kg/dose 6.2 Postmarketing Experience|
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). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Read the Relistor (methylnaltrexone bromide) Side Effects Center for a complete guide to possible side effects »
Drugs Metabolized by Cytochrome P450 Isozymes
In in vitro drug metabolism studies methylnaltrexone bromide did not significantly inhibit the activity of cytochrome P450 (CYP) isozymes CYP1A2, CYP2A6, CYP2C9, CYP2C19 or CYP3A4, while it is a weak inhibitor of CYP2D6. In a clinical drug interaction study in healthy adult male subjects, a subcutaneous dose of 0.30 mg/kg of methylnaltrexone bromide did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate.
Drugs Renally Excreted
The potential for drug interactions between methylnaltrexone bromide and drugs that are actively secreted by the kidney has not been investigated in humans.
Drug Abuse And Dependence
Methylnaltrexone bromide is not a controlled substance.
RELISTOR (methylnaltrexone bromide) is a peripherally-acting mu-opioid receptor antagonist with no known risk of abuse.
RELISTOR (methylnaltrexone bromide) is a peripherally-acting mu-opioid receptor antagonist with no known risk of dependency.
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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