"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.
Serious and important adverse reactions described elsewhere in labeling include:
- Gastrointestinal perforation [see WARNINGS AND PRECAUTIONS]
- Severe or persistent diarrhea [see WARNINGS AND PRECAUTIONS]
- Opioid withdrawal [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain
The safety of RELISTOR was evaluated in a double-blind, placebo-controlled trial in adult patients with opioid-induced constipation and chronic non-cancer pain receiving opioid analgesia. This study (Study 1) included a 4-week, double-blind, placebocontrolled period in which adult patients were randomized to receive RELISTOR 12 mg once daily (150 patients) or placebo (162 patients) [see Clinical Studies]. After 4 weeks of double-blind treatment, patients began an 8-week open-label treatment period during which RELISTOR 12 mg was administered less frequently than the recommended dosage regimen of 12 mg once daily.
Adverse reactions in adult patients with opioid-induced constipation and chronic noncancer pain receiving RELISTOR are shown in Table 2. The adverse reactions in the table below may reflect symptoms of opioid withdrawal.
Table 2: Adverse Reactions* in 4-Week Double-Blind,
Placebo-Controlled Period of Clinical Study of RELISTOR in Adult Patients with
Opioid-Induced Constipation and Chronic Non-Cancer Pain
|Adverse Reaction||RELISTOR 12 mg once daily
n = 150
n = 162
|* Adverse reactions occurring in ≥ 1 % of patients receiving RELISTOR 12 mg once daily and at an incidence greater than placebo.|
During the 4-week double-blind period, in patients with opioid-induced constipation and chronic non-cancer pain that received RELISTOR 12 mg every other day, there was a higher incidence of adverse reactions, including nausea (12%), diarrhea (12%), vomiting (7%), tremor (3%), feeling of body temperature change (3%), piloerection (3%), and chills (2%) as compared to daily Relistor dosing. Use of RELISTOR 12 mg every other day is not recommended in patients with OIC and chronic non-cancer pain [see DOSAGE AND ADMINISTRATION]. The rates of discontinuation due to adverse reactions during the double-blind period (Study 1) were higher in the RELISTOR once daily (7%) than the placebo group (3%). Abdominal pain was the most common adverse reaction resulting in discontinuation from the double-blind period in the RELISTOR once daily group (2%).
The safety of RELISTOR was also evaluated in a 48-week, open-label, uncontrolled trial in 1034 adult patients with opioid-induced constipation and chronic non-cancer pain (Study 2). Patients were allowed to administer RELISTOR 12 mg less frequently than the recommended dosage regimen of 12 mg once daily, and took a median of 6 doses per week. A total of 624 patients (60%) completed at least 24 weeks of treatment and 477 (46%) completed the 48-week study. The adverse reactions seen in this study were similar to those observed during the 4-week double-blind period of Study 1. Additionally, in Study 2, investigators reported 4 myocardial infarctions (1 fatal), 1 stroke (fatal), 1 fatal cardiac arrest and 1 sudden death. It is not possible to establish a relationship between these events and RELISTOR.
Opioid-Induced Constipation in Adult Patients with Advanced Illness
The safety of RELISTOR was evaluated in two, double-blind, placebo-controlled trials in adult patients with opioid-induced constipation and advanced illness receiving palliative care: Study 3 included a single-dose, double-blind, placebo-controlled period, whereas Study 4 included a 14-day multiple dose, double-blind, placebo-controlled period [see Clinical Studies].
The most common ( ≥ 5%) adverse reactions in adult patients with opioid-induced constipation and advanced illness receiving RELISTOR are shown in Table 3 below.
Table 3: Adverse Reactions from all Doses in
Double-Blind, Placebo-Controlled Clinical Studies of RELISTOR in Adult Patients
with Opioid-Induced Constipation and Advanced Illness*
n = 165
n = 123
|* Adverse reactions occurring in ≥ 5 % of patients receiving all doses of RELISTOR (0.075, 0.15, and 0.30 mg/kg/dose) and at an incidence greater than placebo.|
The rates of discontinuation due to adverse events during the double-blind placebo controlled clinical trials (Study 3 and Study 4) were comparable between RELISTOR (1%) and placebo (2%).
The following adverse reactions have been identified during post-approval use of RELISTOR. Because they 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.
Perforation, cramping, vomiting
General Disorders and Administrative Site Disorders
Read the Relistor (methylnaltrexone bromide) Side Effects Center for a complete guide to possible side effects
Other Opioid Antagonists
Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Drugs Metabolized By Cytochrome P450 Isozymes
Last reviewed on RxList: 10/20/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Relistor Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Chronic Pain/Back Pain
Find tips and advances in treatment.