Antidiarrhoeal (peripheral opioid agonist)
Loperamide is a medicine used for the symptomatic relief of acute diarrhoea (in adults and children ≥2 years) and of chronic diarrhoea associated with inflammatory bowel disease, and to reduce ileostomy output. It works by slowing bowel movements and reducing water and salt loss.
Also known as: Imodium, loperamide
Clarithromycin may raise loperamide concentrations, potentiating CNS-depressant and cardiac effects.
Loperamide is a substrate of CYP3A4 and P-glycoprotein; clarithromycin inhibits both pathways and can substantially raise its concentrations, potentiating CNS depression (drowsiness, severe constipation) and QT prolongation (high loperamide doses). Use the lowest effective dose, avoid high doses and monitor drowsiness, constipation and palpitations during the combination.
Loperamide + clarithromycin: clarithromycin raises loperamide levels (CYP3A4/P-gp inhibition), with risk of CNS and QT effects. Use the lowest effective dose.
CYP3A4 inhibition by clarithromycin increases loperamide exposure.
Monitor drowsiness, constipation, palpitations and rhythm changes.
Loperamide toxicity (CNS, QT).
Use the lowest effective dose and monitor adverse effects; avoid high doses.
DailyMed (FDA) — approved Loperamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=568064c9-139d-7233-e063-6294a90a10d4 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol potentiates the CNS depression associated with loperamide.
Avoid alcohol during treatment.
EMC-UK (MHRA) — approved Loperamide SmPC: https://www.medicines.org.uk/emc/product/2986/smpc
Loperamide undergoes first-pass metabolism; severe hepatic impairment carries a risk of accumulation and CNS toxicity.
Do not use in severe hepatic impairment.
EMC-UK (MHRA) — approved Loperamide SmPC: https://www.medicines.org.uk/emc/product/2986/smpc
Loperamide may precipitate toxic megacolon in acute ulcerative colitis.
Do not use in acute ulcerative colitis or antibiotic-associated colitis.
EMC-UK (MHRA) — approved Loperamide SmPC: https://www.medicines.org.uk/emc/product/2986/smpc
Loperamide should be avoided in pregnancy, especially in the 1st trimester, unless medically indicated.
Use only if strictly necessary and for the shortest time.
Excreted into breast milk in small amounts; occasional use is probably compatible.
No specific additional contraception.
EMC-UK (MHRA) — approved Loperamide SmPC: https://www.medicines.org.uk/emc/product/2986/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Peripheral opioid antidiarrhoeal agonist (does not cross the blood-brain barrier under normal conditions — P-glycoprotein substrate); reduces peristalsis and fluid loss; no central analgesic effect.
Binds opioid receptors in the gut wall, inhibiting acetylcholine and prostaglandin release: reduces propulsive peristalsis, increases transit time, anal sphincter tone and water/electrolyte reabsorption.
Low systemic absorption: plasma concentrations <2 ng/mL after 2 mg orally; plasma peak ~5 h (capsule); ~95% protein binding; P-glycoprotein substrate (intestinal efflux limits CNS entry).
Extensive hepatic metabolism by oxidative N-demethylation (CYP2C8 and CYP3A4, with minor roles of CYP2B6/CYP2D6); predominantly faecal excretion of the drug and metabolites, with minor urinary excretion.
Apparent elimination half-life ~10.8 h (9.1-14.4 h); the antidiarrhoeal effect lasts ~12-24 h with the usual dose.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
