methylnaltrexone

me-thil-nal-TREX-one

Therapeutic Classification: laxatives

Pharmacologic Classification: opioid antagonists

REMS

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.

Therapeutic effects:

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

Absorption: Rapidly absorbed after SUBQ 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)

ROUTE	ONSET	PEAK	DURATION
SUBQ	rapid	0.5 hr	24–48 hr
PO	rapid	1.5 hr	unknown

Contraindicated in:

Known/suspected mechanical GI obstruction;
Lactation: Lactation.

Use Cautiously in:

Known/suspected lesions of GI tract (↑ risk for GI perforation);
Moderate or severe renal impairment (dose ↓ required);
Moderate or severe hepatic impairment (dose ↓ may be required);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children.

Derm: ↑sweating

GI: abdominal pain, flatulence, nausea, diarrhea

Neuro: dizziness

Misc: opioid withdrawal

Drug-drug:

None reported.

Opioid-Induced Constipation in Patients with Advanced Illness

SC (Adults >114 kg): 0.15 mg/kg every other day, as needed (not to exceed 1 dose every 24 hr).

Renal Impairment

(Adults ): CCr <60 mL/min: use 50% of recommended dose based on weight.
SC (Adults 62–114 kg): 12 mg every other day, as needed (not to exceed 1 dose every 24 hr).
SC (Adults 38–62 kg): 8 mg every other day, as needed (not to exceed 1 dose every 24 hr).
SC (Adults <38 kg): 0.15 mg/kg every other day, as needed (not to exceed 1 dose every 24 hr).

Renal Impairment

SC (Adults >114 kg): CCr <60 mL/min: 0.075 mg/kg every other day, as needed (not to exceed 1 dose every 24 hr).

Renal Impairment

SC (Adults 62–114 kg): CCr <60 mL/min: 6 mg every other day, as needed (not to exceed 1 dose every 24 hr).

Renal Impairment

SC (Adults 38–<62 kg): CCr <60 mL/min: 4 mg every other day, as needed (not to exceed 1 dose every 24 hr).

Renal Impairment

SC (Adults <38 kg): CCr <60 mL/min: 0.15 mg/kg every other day, as needed (not to exceed 1 dose every 24 hr).

Opioid-Induced Constipation in Patients with Non-Cancer Pain

SC (Adults ): 12 mg once daily.
PO (Adults ): 450 mg once daily.

Renal Impairment

SC (Adults ): CCr <60 mL/min: 6 mg once daily.

Renal Impairment

PO (Adults ): CCr <60 mL/min: 150 mg once daily.

Hepatic Impairment

SC (Adults >114 kg): Severe hepatic impairment: 0.075 mg/kg once daily.

Hepatic Impairment

SC (Adults 62–114 kg): Severe hepatic impairment: 6 mg once daily.

Hepatic Impairment

SC (Adults 38–<62 kg): Severe hepatic impairment: 4 mg once daily.

Hepatic Impairment

SC (Adults <38 kg): Severe hepatic impairment: 0.075 mg/kg once daily.

Hepatic Impairment

PO (Adults ): Moderate or severe hepatic impairment: 150 mg once daily.

Tablets: 150 mg
Solution for injection (prefilled syringes): 8 mg/0.4 mL; 12 mg/0.6 mL
Solution for injection (single-use vials): 12 mg/0.6 mL

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 SUBQ 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.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Laxation and relief of OIC.

Relistor

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Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆