methylnaltrexone: me-thil-nal-TREX-one

Therapeutic Classification: laxatives

Pharmacologic Classification: opioid antagonists

• SC: Treatment of opioid-induced constipation (OIC) in patients with advanced illness or pain caused by active cancer who require opioid dose escalation for palliative care.
• SC, PO: Treatment of OIC in patients with chronic, non-cancer pain, including those with chronic pain related to prior cancer or its treatment who do not require frequent (e.g. weekly) opioid dose escalation.

• Acts peripherally as mu-opioid receptor antagonist, blocking opioid effects on the GI tract.

• Blocks constipating effects of opioids on the GI tract without loss of analgesia.

Absorption: Rapidly absorbed after subcutaneous and oral administration; oral absorption delayed by high-fat meal by 2 hr.

Distribution: Moderate tissue distribution, does not cross the blood-brain barrier.

Metabolism/Excretion: Some metabolism; 85% excreted unchanged in urine.

Half-life: 15 hr (oral).

(plasma concentrations)

Contraindicated in:

• Known/suspected mechanical GI obstruction.

Use Cautiously in:

• Known/suspected lesions of GI tract (↑ risk for GI perforation)
• Moderate-severe renal impairment (dose ↓ required)
• Moderate-severe hepatic impairment (dose ↓ may be required)
• OB: Lactation: Use in pregnancy only if clearly needed; use cautiously during lactation
• Pedi: Safety and effectiveness not established.

CNS: dizziness.

Derm: hyperhidrosis.

GI: GI PERFORATION, abdominal pain, flatulence, nausea, diarrhea.

Misc: opioid withdrawal.

Drug-Drug:

• None noted.

OIC in Patients with Advanced Illness

• SC (Adults): 38–<62 kg — 8 mg every other day, not to exceed every 24 hr; 62–114 kg — 12 mg every other day, not to exceed every 24 hr; >114 kg — 0.15 mg/kg every other day, not to exceed every 24 hr.

OIC in Patients with Non-Cancer Pain

• SC (Adults): 12 mg once daily.

• Solution for injection (prefilled syringes): 8 mg/0.4 mL; 12 mg/0.6 mL;
  • Cost: All strengths; $71.46/syringe.
• Tablets: 150 mg;

• Assess bowel sounds and frequency, quantity, and consistency of stools periodically during therapy.
• Monitor pain intensity during therapy. Methylnaltrexone does not affect pain or effects of opioid analgesics on pain control.

• Maintenance laxative must be stopped prior to administration of methylnaltrexone. If response is not sufficient after 3 days, laxatives may be restarted.
• PO: Administer with water on an empty stomach at least 30 min before first meal of the day.
• SC: Pinch skin and administer in upper arm, abdomen, or thigh at a 45° angle using a 1-mL syringe with a 27-gauge needle inserted the full length of the needle. Do not rub the injection site. Solution is clear and colorless to pale yellow. Do not administer solutions that are discolored or contain a precipitate. Solution is stable for 24 hr at room temperature. Protect vials from light. Do not freeze. Do not use single-use vials for more than 1 dose.

• Instruct patient to take methylnaltrexone as directed and on correct technique for administration of methylnaltrexone and disposal of supplies. Usual schedule is one dose every other day, as needed, but no more than one dose in a 24-hr period. Advise patient to read the Patient Information prior to starting therapy and with each Rx refill in case of changes.
• Advise patient that laxation may occur within 30 min of subcut injection, so toilet facilities should be available following administration.
• Advise patient to discontinue all maintenance laxatives; can be added if inadequate response to methylnaltrexone.
• May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
• Advise patient to notify health care professional and discontinue therapy if severe or persistent diarrhea occurs or if abdominal pain, nausea, or vomiting persists or worsens.
• Instruct patient to stop taking methylnaltrexone if they stop taking opioid medications.
• Advise patient to consult health care professional prior to taking other Rx, OTC, or herbal products.
• Advise female patients to notify health care professional if pregnancy is planned or suspected, and to avoid breast feeding; may cause opioid withdrawal in infant.

• Laxation and relief of OIC.

Relistor

• Constipation (Indications).
• Diarrhea (Adverse Reactions).