Drug reference

Naldemedine

Antidote · Treatment of Opioid-Induced Constipation

Also known as Naldemedine tosylate, Rizmoic

AntidoteTreatment of Opioid-Induced ConstipationATC A06AH03

CDSCO approvedSchedule HATC A06AH03

EXCRETION

—

not curated

INTERACTIONS

11 major

SEVERE in our sources

PREGNANCY

Manufacturer advises avoid unless potential benefit outweighs risk— animal studies do not indicate toxicity; risk of opioid withdrawal in fetus.

FDA category + note

Top interactionssee all 11 →

ApalutamideSevereDatabaseDDInter
CarbamazepineSevereDatabaseDDInter
EnzalutamideSevereDatabaseDDInter
FosphenytoinSevereDatabaseDDInter

Mechanism

Naldemedine is a peripherally acting opioid receptor antagonist. It decreases the constipating effects of opioids without altering their central analgesic effects. Its principal mechanism for the selective therapeutic effect is peripheral enteric μ-receptor antagonism with minimal CNS penetration.

Indications

Opioid-induced constipation [previous treatment with a laxative]Constipation in patients with opioid-induced constipation (OIC) with chronic noncancer pain and late-stage advanced illnessOpioid-induced constipation (in adult patients with chronic noncancer pain)

Dosing

Adult: 200 micrograms once daily
Renal adjustment: If eGFR less than 30 mL/minute/1.73 m2, reduce dose as follows: body-weight under 62 kg, 75 micrograms/kg on alternate days; body-weight 62–114 kg, 8 mg on alternate days; body-weight over 114 kg, 75 micrograms/kg on alternate days.
Hepatic adjustment: Manufacturer advises avoid in severe impairment (no information available)
Geriatric: Treatment initiation in patients aged 75 years and over (limited information available)

Pharmacokinetics

Peak effect

Approximately 45 min (fasted state); ~2.5 h (with food)

Half-life

11 h

Metabolism

Hepatic CYP3A

Excretion

57% in urine, 35% in feces

Contraindications

Increased risk of recurrent obstruction (risk of gastro-intestinal perforation)
Known or suspected gastro-intestinal obstruction (risk of gastro-intestinal perforation)
Known or suspected obstruction of the GI tract

Side effects

Common

Abdominal painDiarrheaNauseaVomitingGastroenteritis

Serious

Gastro-intestinal perforation
Severe, persistent or worsening gastro-intestinal effects (such as abdominal pain)
Opioid withdrawal syndrome
Opioid withdrawal (may be precipitated)