Dosing and uses of Relistor (methylnaltrexone)
Adult dosage forms and strengths
injectable solution
- 8mg/0.4mL vial
- 12mg/0.6mL vial
tablet
- 150mg
Opioid-Induced Constipation (Advanced Illness Receiving Palliative Care)
Indicated for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has been insufficient
38-62 kg: 8 mg/dose SC every other day
62-114 kg: 12 mg/dose SC every other day
<38 kg or >114 kg: 0.15 mg/kg/dose SC every other day
Dosing considerations
- Usual dose is every other day; not to exceed 1 dose/24 hr
- Use beyond 4 months has not been studied in the advanced illness population
Opioid-Induced Constipation (Chronic Noncancer Pain)
Indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic noncancer pain
12 mg SC qDay, Or
450 mg PO qDay in morning
Also see Administration
Dosage modifications
Renal impairment
- Mild: No dose adjustment recommended
- Moderate-to-severe (CrCl <60 mL/min): Modified dosage shown by indication below according to indication and dosage form
- OIC with chronic noncancer pain
- Tablets: 150 mg PO qDay in morning
- SC injection: 6 mg SC qDay
- OIC with advanced illness receiving palliative care
- Every other day SC injection based on weight
- <38 kg: 0.075 mg/kg
- 38 to <62 kg: 4 mg
- 62-114 kg: 6 mg
- >114 kg: 0.075 mg/kg
Hepatic impairment
- Tablets
- Mild (Child-Pugh A): No dose adjustment recommended
- Moderate-to-severe (Child-Pugh B or C): 150 mg PO qDay in morning
- SC injection
- Every other day SC injection based on weight for severe hepatic impairment
- <38 kg: 0.075 mg/kg
- 38 to <62 kg: 4 mg
- 62-114 kg: 6 mg
- >114 kg: 0.075 mg/kg
Pediatric dosage forms and strengths
Safety and efficacy not established
Relistor (methylnaltrexone) adverse (side) effects
>10%
Abdominal pain (28.5%)
Flatulence (13.5%)
Nausea (11.5%)
1-10%
Dizziness (7.3%)
Hyperhidrosis (6.7%)
Diarrhea (5.5%)
Postmarketing Reports
Gastrointestinal: Cramping, perforation, vomiting
General disorders and administrative site disorders: Diaphoresis, flushing, malaise, pain
Warnings
Contraindications
Documented hypersensitivity
Known or suspected GI obstruction and patients at increased risk of recurrent obstruction; increases risk for GI perforation
Cautions
Severe renal impairment
Discontinue if severe/persistent diarrhea develops
GI perforation reported with other PAMORA in patients with conditions associated with reduced structural integrity in the wall of the GI tract (eg, PUD, Ogilvie syndrome, diverticular disease, infiltrative GI malignancies, peritoneal metastases, Crohn disease); monitor for development of severe, persistent, or worsening abdominal pain; discontinue naloxegol in patients who develop these symptoms
Symptoms consistent with opioid withdrawal (eg, hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, yawning) reported
Pregnancy and lactation
Pregnancy category: B
Lactation: Not known if distributed in breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Relistor (methylnaltrexone)
Mechanism of action
Peripheral mu-opioid receptor antagonist; limited ability to cross blood brain barrier so doesn't abolish opioid-induced analgesia nor cause withdrawal symptoms but decreases opioid-induced constipation
Absorption
Onset of action: Within 30-60 min
Peak plasma time: 0.5 hr
Peak plasma concentration: 117-392 ng/mL (dose dependent)
AUC: 175-582 ng·hr/mL (dose dependent)
Distribution
Protein bound: 11-15.3%
Vd: 1.1 L/kg
Metabolism
Metabolites: 5 distinct metabolite; methyl-6-naltrexol isomers (5% of total) and methylnaltrexone sulfate (1.3% of total) appear to be the primary pathways of metabolism
Elimination
Half-life elimination: 8 hr
Excretion: Urine (50%); feces (50%)
Administration
General Information
Be within close proximity to toilet facilities when administered
Shown to be efficacious in patients who have taken opioids for at least 4 weeks
Discontinue all maintenance laxative therapy prior to initiation; laxatives can be used prn if there is suboptimal response to methylnaltrexone after 3 days
Reevaluate the continued need for methylnaltrexone when the opioid regimen is changed to avoid adverse reactions
Discontinue if the opioid pain medication is also discontinued
SC Administration
Administer in upper arm, abdomen, or thigh (rotate injection site)
Oral Administration
Take with water on an empty stomach at least 30 minutes before the first meal of the day
Storage
Tablets or injection: Store at controlled room temperature up to 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)
Injection: Do not freeze and protect from light
