Drug reference

Methylnaltrexone

Peripherally-acting mu-opioid receptor antagonist (PAMORA) · Opioid-Induced Constipation Treatment

Also known as Relistor, Methylnaltrexone bromide

START

SC 8 mg (<62 kg) or 12 mg (62–114 kg) every other day; or PO 450 mg/d fasting

TYPICAL MAX

Once-daily SC if needed; PO 450 mg/day

STOP IF

GI perforation signs (severe abdominal pain), or severe withdrawal

WATCH

Laxation response, GI symptoms, gut-wall integrity history

CDSCO approvedSchedule HATC A06AH01

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 15min · absorption
PEAK: 30min · SC Tmax
t½: 8h · t½
DURATION: 2d · alt-day SC

EXCRETION

Renal (~50% unchanged); some faecal

route + CYP

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Limited data; use only if benefit outweighs risk; may precipitate fetal withdrawal.

FDA category + note

Top interactionssee all 12 →

AcetaminophenSevereTextbookHarrison 22e · p98-99
AlprazolamSevereTextbookG&G 14e
BarbituratesSevereTextbookKDT 7e · p401
BenzodiazepinesSevereTextbookKDT 7e · p383

Mechanism

Quaternary amine derivative of naltrexone that does NOT cross the blood-brain barrier — peripheral μ-opioid antagonism blocks opioid-induced gut motility suppression while preserving central analgesia.

Indications

Opioid-induced constipation in adults with advanced illness (palliative care)OIC in adults with non-cancer chronic pain

Dosing

Adult: SC: 8 mg (<62 kg) or 12 mg (62–114 kg) every other day as needed (up to once daily). PO: 450 mg once daily fasting.
Pediatric: Not established.
Renal adjustment: CrCl <30: reduce SC dose by 50%. PO 450 mg → 150 mg.
Hepatic adjustment: Severe impairment: reduce dose / monitor.
Geriatric: No specific adjustment.
Max dose: Once-daily dosing (SC every other day standard; PO 450 mg daily)

Pharmacokinetics

Onset

Laxation within 30 min – 4 h

Peak effect

SC ~30 min; PO ~1.5 h

Duration

Per dose; redose every other day

Half-life

~8 h

Bioavailability

SC ~82%; PO ~3% (fasting)

Protein binding

Low

Metabolism

Minimal hepatic

Excretion

Renal (~50% unchanged); some faecal

Contraindications

Known or suspected mechanical GI obstruction
Hypersensitivity
Caution: severe disturbances of gut wall (Crohn's, diverticulitis, malignancy)

Side effects

Common

Abdominal painFlatulenceNauseaDizzinessDiarrhoeaHyperhidrosis

Serious

GI perforation (rare; in patients with gut-wall disease)
Severe opioid withdrawal (if BBB disrupted)
Severe diarrhoea / dehydration

Pregnancy & lactation

Pregnancy

Limited data; use only if benefit outweighs risk; may precipitate fetal withdrawal.

Lactation

Limited data; weigh benefit/risk.

Drug interactions

Acetaminophen

Severe

Textbook

Acetaminophen-related hepatotoxicity, a significant cause for liver failure.

Many practitioners have moved away from opioid-acetaminophen combination analgesics to avoid the risk of excessive acetaminophen exposure.

Source: Harrison 22e · p98-99

Alprazolam

Severe

Textbook

Increased rates of accidental overdose and death.

Caution is advised, especially for patients with a history of drug abuse.

Source: G&G 14e

Barbiturates

Severe

Textbook

Exaggerated CNS depression.

Source: KDT 7e · p401

Benzodiazepines

Severe

Textbook

Marked depression of respiration, cardiac contractility, and blood pressure.

Carefully monitor respiratory and cardiovascular functions when co-administering benzodiazepines with opioids due to increased risk of severe depression of vital signs.

Source: KDT 7e · p383

Chloral Hydrate

Severe

Textbook

Increased rates of accidental overdose and death.

Caution is advised, especially for patients with a history of drug abuse.

Source: G&G 14e

Chlordiazepoxide Hydrochloride

Severe

Textbook

Increased rates of accidental overdose and death.

Caution is advised, especially for patients with a history of drug abuse.