methylnaltrexone (Rx)

>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

Contraindications

Documented hypersensitivity

Known or suspected GI obstruction and patients at increased risk of recurrent obstruction

Cautions

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; monitor for symptoms of withdrawal in such patients

Therapy administration for longer than four months not studied; discontinue therapy when opioid therapy has ended

Use with caution in hepatic or renal impairment; dosage adjustments necessary

Pregnancy

The limited available data with in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriages; there are clinical considerations when drug is used by pregnant women; advise pregnant women of potential risk to a fetus

Use during pregnancy may precipitate opioid withdrawal in a fetus due to immature fetal blood-brain barrier

Lactation

No information regarding presence of methylnaltrexone in human milk, effects on breastfed infant, or on milk production; methylnaltrexone is present in rat milk; because of potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment

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.

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%)

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