RELISTOR SIDE EFFECTS
- Generic Name: methylnaltrexone bromide injection
- Brand Name:Relistor
- Drug Class: Peripherally-Acting Mu-Opioid Receptor Antagonists (PAMORA)
SIDE EFFECTS
Serious and important adverse reactions described elsewhere in the labeling include:
- Gastrointestinal perforation
- Severe or persistent diarrhea
- Opioid withdrawal
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 tablets was evaluated in a double-blind, placebo-controlled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 1) included a 12-week, double-blind, placebo-controlled period in which adult patients were randomized to receive RELISTOR tablets 450 mg orally (200 patients) or placebo (201 patients) After 4 weeks of double-blind treatment administered once daily, patients continued 8 weeks of double-blind treatment on an as needed basis (but not more than once daily).
The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR tablets are shown in Table 1. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.
Table 1: Adverse Reactions* in 4,-Week Double-Blind, Placebo-Controlled Period of Clinical Study of RELISTOR Tablets in Adult Patients with OIC and Chronic Non-Cancer Pain (Study 1)
| Adverse Reaction | RELISTOR Tablets n = 200 |
Placebo n = 201 |
| Abdominal Pain ** | 14% | 10% |
| Diarrhea | 5% | 2% |
| Headache | 4% | 3% |
| Abdominal Distention | 4% | 2% |
| Vomiting | 3% | 2% |
| Hyperhidrosis | 3% | 1% |
| Anxiety | 2% | 1% |
| Muscle Spasms | 2% | 1% |
| Rhinorrhea | 2% | 1% |
| Chills | 2% | 0% |
| * Adverse reactions occurring in at least 2% of patients receiving RELISTOR tablets 450 mg once daily and at an incidence greater than placebo. ** Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness |
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The safety of RELISTOR injection was evaluated in a double-blind, placebo-controlled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 2) included a 4-week, double-blind, placebo-controlled period in which adult patients were randomized to receive RELISTOR injection 12 mg subcutaneously once daily (150 patients) or placebo (162 patients. After 4 weeks of double-blind treatment, patients began an 8-week open-label treatment period during which RELISTOR injection 12 mg subcutaneously was administered less frequently than the recommended dosage regimen of 12 mg once daily.
The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR injection 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 Injection in Adult Patients with OIC and Chronic Non-Cancer Pain (Study 2)
| Adverse Reaction | RELISTOR Injection n = 150 |
Placebo n = 162 |
| Abdominal Pain** | 21% | 7% |
| Nausea | 9% | 6% |
| Diarrhea | 6% | 4% |
| Hyperhidrosis | 6% | 1% |
| Hot Flush | 3% | 2% |
| Tremor | 1% | <1% |
| Chills | 1% | 0% |
| * Adverse reactions occurring in at least 1% of patients receiving RELISTOR injection 12 mg subcutaneously once daily and at an incidence greater than placebo. ** Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness |
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During the 4-week double-blind period, in patients with OIC and chronic non-cancer pain that received RELISTOR 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 injection 12 mg subcutaneously every other day is not recommended in patients with OIC and chronic non-cancer pain. The rates of discontinuation due to adverse reactions during the double-blind period (Study 2) 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 injection was also evaluated in a 48-week, open-label, uncontrolled trial in 1034 adult patients with OIC and chronic non-cancer pain (Study 3). Patients were allowed to administer RELISTOR injection 12 mg subcutaneously 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 2. Additionally, in Study 3, 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 injection was evaluated in two, double-blind, placebo-controlled trials in adult patients with OIC and advanced illness receiving palliative care: Study 4 included a single-dose, double-blind, placebo-controlled period, whereas Study 5 included a 14-day multiple dose, double-blind, placebo-controlled period.
The most common adverse reactions in adult patients with OIC and advanced illness receiving RELISTOR injection are shown in Table 3below.
Table 3: Adverse Reactions from All Doses in Double-Blind, Placebo-Controlled Clinical Studies of RELISTOR Injection in Adult Patients with OIC and Advanced Illness* (Studies 4 and 5)
| Adverse Reaction | RELISTOR Injection n = 165 |
Placebo n = 123 |
| Abdominal Pain ** | 29% | 10% |
| Flatulence | 13% | 6% |
| Nausea | 12% | 5% |
| Dizziness | 7% | 2% |
| Diarrhea | 6% | 2% |
| * Adverse reactions occurring in at least 5% of patients receiving all doses of RELISTOR injection (0.075, 0.15, and 0.3 mg/kg) and at an incidence greater than placebo ** Includes: abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort and abdominal tenderness |
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The rates of discontinuation due to adverse reactions during the double-blind, placebo-controlled clinical trials (Study 4 and Study 5) were comparable between RELISTOR (1%) and placebo (2%).
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of RELISTOR injection. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Gastrointestinal
Perforation, cramping, vomiting
General Disorders And Administration Site Disorders
Diaphoresis, flushing, malaise, pain. Cases of opioid withdrawal have been reported.
SRC: NLM .