Loperamide (Imodium)

Antidiarrhealoral · inferred

Peripheral mu-opioid receptor agonist that reduces intestinal motility without crossing the blood-brain barrier at therapeutic doses — the P-gp efflux transporter actively pumps loperamide out of the CNS. This peripheral selectivity makes it the safest opioid for diarrhea with minimal abuse potential at standard doses. However, at supratherapeutic doses (60-800 mg — 15-200x normal), P-gp saturation and inhibition allows CNS penetration → euphoria and severe respiratory depression. P-gp inhibitors (quinidine, ritonavir, itraconazole) increase CNS effects. CYP3A4 and CYP2C8 substrate with extensive first-pass metabolism. FDA issued warnings about cardiac events (Torsades de Pointes) from hERG channel blockade at high doses.

Projected serum levels — 4 mg, as needed (shown daily)

Loperamide (Imodium)
Loperamide (Imodium) modeled serum levels, 4 mg as needed (shown daily) over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 2 days. 0 0.25 0.50 0.75 1 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 2
Loperamide (Imodium) modeled serum levels with a loading dose of 5.3 mg, then 4 mg as needed (shown daily) The first dose is larger so levels approach steady state faster. 0 0.25 0.50 0.75 1 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule

Maintenance schedule: 4 mg as needed (shown daily) (oral).

Loading schedule: 5.3 mg on day 1, then 4 mg as needed (shown daily) — reaching therapeutic levels sooner.

Modeled steady state after ~2 days: peak ≈ 0.21 mg, trough ≈ 0.069 mg body load. Population-based estimate over 15 days for a 4 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Antidiarrheal
Route modeled
Oral
Model confidence
inferred
Half-life
11 h
Common dose
4 mg
Suggested maximum
16 mg/day
Reference dose range
2–16 mg (single dose)
Suggested cadence
as needed (shown daily)
Validated against
4 mg oral — Cmax 0.002 mg/L at 5 h

Documented interactions

  • danger
    Carbamazepine (Tegretol) + Loperamide (Imodium) CYP induction

    Carbamazepine (Tegretol) inducer of CYP3A4 predicted to change Loperamide (Imodium) AUC by ~0.33x

  • danger
    Efavirenz (Sustiva) + Loperamide (Imodium) CYP induction

    Efavirenz (Sustiva) inducer of CYP3A4 predicted to change Loperamide (Imodium) AUC by ~0.22x

  • danger
    Levothyroxine (Synthroid) + Loperamide (Imodium) Protein binding

    Loperamide (Imodium) may displace Levothyroxine (Synthroid) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic index; free…

  • danger
    Methadone + Loperamide (Imodium) Stacked effects

    Loperamide (Imodium) and Methadone both push the delta opioid, herg, and mu opioid in the same direction.

  • danger
    Phenobarbital + Loperamide (Imodium) CYP induction

    Phenobarbital inducer of CYP3A4 predicted to change Loperamide (Imodium) AUC by ~0.50x

  • danger
    Phenytoin (Dilantin) + Loperamide (Imodium) CYP induction

    Phenytoin (Dilantin) inducer of CYP3A4 predicted to change Loperamide (Imodium) AUC by ~0.50x

Serum checks 283 modeled interaction pairings for loperamide (imodium) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. Loperamide: a pharmacological review Baker DE · Reviews in Gastroenterological Disorders, 2007

    Comprehensive pharmacological review establishing loperamide as the preferred antidiarrheal due to P-gp-mediated peripheral mu-opioid selectivity, superior to diphenoxylate (which contains atropine to deter abuse), with…

  2. Loperamide misuse and abuse: a growing concern Daniulaityte R et al. · Journal of the American Pharmacists Association, 2017 DOI

    Review documenting emerging loperamide abuse at supratherapeutic doses (70-800 mg/day) for opioid withdrawal self-treatment and euphoria, with FDA adverse event reports showing 48 cases of serious cardiac events…

2 published studies referenced in the app, each with a plain-language summary.