Loperamide (Imodium) inhibits peristalsis and increase the transit time of intestines by acting as mu-opioid receptor agonist. It is used in patients with non-infectious causes of diarrhea.

Indications of Loperamide (Imodium):

• Diarrhea:

  • Rx labeling: Control and symptomatic relief of chronic diarrhea associated with inflammatory bowel disease in adults.
  • Acute nonspecific diarrhea in patients 2 years of age or more
  • To reduce the volume of ileostomy discharge
  • OTC labeling: Control of symptoms of diarrhea, including the Traveler's diarrhea.

• Off Label Use of Loperamide in Adults:

  • Cancer treatment-induced diarrhea
  • Traveler’s diarrhea

Loperamide (Imodium) dose in adults:

Loperamide (Imodium) dose in the treatment of acute diarrhea: 

• Initial: 4 mg per oral followed by 2 mg after each loose stool
• The maximum dose: 16 mg/day.

Loperamide (Imodium) dose in the treatment of chronic diarrhea: 

• Initial: 4 mg per oral, followed by 2 mg after each loose stool.
• The maximum dose: 16 mg/day.
• The maintenance dose should be slowly titrated downward to the minimum required to control symptoms (usual: 4 to 8 mg/day as a single dose or in divided doses;
• The maximum dose: 16 mg/day).
• If there is no improvement despite 10 days of treatment with 16 mg/day, further therapy is unlikely to control symptoms.
• If diarrhea cannot be adequately controlled with diet or other therapy, the treatment can be continued.

Loperamide (Imodium) dose in the treatment of Traveler's diarrhea:

• Initial: 4 mg per oral after first loose stool, followed by 2 mg after each subsequent stool.
• The maximum dose is 16 mg/day [OTC: 8 mg/day]) (duration of therapy should not exceed 48 hours).
• Loperamide should be given as adjunct therapy with antibiotics to reduce the duration of diarrhea in patients with moderate-to-severe illness.
• However, the acquisition of extended-spectrum-beta-lactamase-producing pathogens may be more common when loperamide and antibiotics are given together.
• Loperamide use is not recommended in cases of dysentery.

Loperamide (Imodium) Dose in the Cancer treatment-induced diarrhea (off-label):

• 4 mg per oral followed by 2 mg every 2 to 4 hours or after each loose stool (more persistent diarrhea will require the higher frequency).
• doses >16 mg/day may not provide benefit
• Maximum: 16 mg/day
• or alternately 4 mg followed by 2 mg every 2 hours (may utilize 4 mg every 4 hours at night) until 12 hours have passed without a loose bowel movement.

loperamide (Imodium) dose for the prophylaxis of Neratinib-induced diarrhea (off-label):

• Oral: 4 mg 3 times daily (days 1 to 14 of neratinib therapy), followed by 4 mg twice daily (days 15 to 56 of neratinib therapy), followed by 4 mg as needed up to a maximum of 16 mg/day (days 57 to 365 of neratinib therapy).
• Note:
  • Antidiarrheal prophylaxis is recommended during the first 2 cycles of neratinib therapy and should be started with the first neratinib dose.
  • Titrate to 1 to 2 bowel movements/day.
  • In the case of loperamide refractory diarrhea, additional antidiarrheal medication might be needed.

Loperamide (Imodium) dose in the treatment of Irinotecan-induced delayed diarrhea (off-label):

• 4 mg per oral after first loose or frequent bowel movement, then 2 mg every 2 hours (4 mg every 4 hours at night) until 12 hours have passed without a bowel movement.

loperamide (Imodium) dose in children:

loperamide (Imodium) dose in the treatment of acute diarrhea:

Note: Loperamide is not recommended for the management of infectious diarrhea in pediatric patients. The dose should be given according to weight for patients who are small for chronological age. The lowest effective dose for the shortest duration is recommended.

• Children 2 to <12 years:

  • 2 to 5 years weighing 13 to <21 kg:
    • Initial: 1 mg per oral with first loose stool followed by 1 mg/dose after each subsequent loose stool.
    • maximum daily dose: 3 mg/day.
  • 6 to 8 years weighing 21 to 27 kg:
    • Initial: 2 mg with first loose stool followed by 1 mg/dose after each subsequent loose stool.
    • maximum daily dose: 4 mg/day.
  • 9 to 11 years weighing 27.1 to 43 kg:
    • Initial: 2 mg with first loose stool followed by 1 mg/dose after each subsequent loose stool.
    • maximum daily dose: 6 mg/day.

• Children ≥12 years and Adolescents:

  • Initial: 4 mg per ora with first loose stool followed by 2 mg/dose after each subsequent loose stool.
  • maximum daily dose: 8 mg/day.

loperamide (Imodium) dose in the treatment of chronic diarrhea secondary to intestinal failure, short-bowel syndrome, or other noninfectious causes:

• Infants ≥2 months and Children:

  • Oral: 0.08 to 0.24 mg/kg/day divided 2 to 3 times/day was reported in a case series of 10 pediatric patients (age range: 2 to 52 months).
  • In a case series of six infants and young children, higher dosing was described:
  • Initial: 1 to 1.5 mg/kg/day in 4 divided doses with subsequent dose decreased as stool output and diet tolerance improved and patient weight increased.
  • The reported final dose range of 0.25 to 0.5 mg/kg/day in 2 divided doses was used the long term until the patient achieved target weight and dietary goals;
  • The reported duration of therapy: 6 months to ~2 years.
  • The maximum single dose: 2 mg.

Loperamide (Imodium) dose in the treatment of Irinotecan-induced (delayed) diarrhea:

• Fixed dosing (Children's Oncology Group 2009):

  • Children ≥2 to 12 years:

    • <13 kg:
      • Initial: 0.5 mg after the first loose bowel movement, followed by 0.5 mg every 3 hours while awake; during the night, may administer every 4 hours.
      • The maximum daily dose: 4 mg/day.
    • 13 kg to <20 kg:
      • Initial: 1 mg after the first loose bowel movement, followed by 1 mg every 4 hours.
      • The maximum daily dose: 6 mg/day.
    • 20 kg to <30 kg:
      • Initial: 2 mg after the first loose bowel movement, followed by 1 mg every 3 hours while awake;
      • during the night, may administer every 4 hours.
      • The maximum daily dose: 8 mg/day.
    • 30 kg to <43 kg:
      • Initial: 2 mg after the first loose bowel movement, followed by 1 mg every 2 hours while awake;
      • during the night, may administer every 4 hours.
      • The maximum daily dose: 12 mg/day.

  • Adolescents weighing ≥43 kg:

    • Initial: 4 mg after the first loose bowel movement, followed by 2 mg after each loose stool.
    • The maximum daily dose: 16 mg/day.

• Weight-directed dosing:

  • Children and Adolescents 2 to <15 years:

    • Grade 1 or 2:
      • 0.03 mg/kg/dose every 4 hours.
    • Grade 3 or 4:
      • 0.06 mg/kg/dose every 4 hours.
    • Maximum single dose dependent upon weight:
      • <13 kg:
        • 0.5 mg.
      • 13 to <20 kg:
        • 1 mg.
      • 20 to <43 kg:
        • Initial: 2 mg;
        • subsequent doses: 1 mg.
      • ≥43 kg:
        • Initial: 4 mg;
        • subsequent doses: 2 mg.

Pregnancy Risk Factor C

• Animal reproduction studies did not reveal adverse outcomes.
• There is not much information available on loperamide use during pregnancy. Data is inconsistent.
• Acute diarrhea is best treated with oral rehydration during pregnancy.
• A small amount of loperamide may be tolerated in the event of severe symptoms.

Loperamide use during breastfeeding:

• Breast milk may contain Loperamide.
• There haven't been any studies that evaluated the milk concentrations of loperamide after maternal use.
• The available information is based upon studies using loperamide dioxide, the prodrug for loperamide.
• Six women were given two doses of oral loperamide oxide at 12 and 47 hours, respectively.
• Breast milk Loperamide levels ranged from not detectable (0.1ng/mL) and 0.61ng/mL.
• This compares to maternal plasma concentrations ranging from 0.2ng/mL up to 1.71ng/mL.
• Lloperamide is not recommended for children younger than 2 years old.
• According to the manufacturer, breastfeeding should not be done.

Dose adjustment in renal disease:

No dosage adjustment is necessary.

loperamide (Imodium) Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer's labeling; Use with caution.

Side Effects of loperamide (Imodium):

• Central nervous system:

  • Dizziness

• Gastrointestinal:

  • Constipation
  • Abdominal cramps
  • Nausea

Contraindications to loperamide (Imodium):

• Hypersensitivity to loperamide and any other component of the formulation
• Children under 2 years
• Acute dysentery
• Acute ulcerative colitis
• Bacterial enterocolitis caused by Salmonella and Shigella.
• Associated with broad-spectrum antibiotic use, pseudodomembranous colitis.
• Abdominal pain with or without diarrhea

Canadian labeling: Additional contraindications not in the US labeling

• It is best to avoid constipation
• Avoid using the inhibition of peristalsis if you are concerned about its possible side effects

OTC labelingIf the stool is black or bloody, it should not be used as self-medication.

• There is not much evidence of antidiarrheal allergenic cross-reactivity. 
• Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Allergy reactions:

  • Anaphylaxis or anaphylactic shock can rarely be caused by Loperamide.

• CNS effects

  • Loperamide may cause dizziness or drowsiness, which can lead to impairment of physical and mental abilities.
  • It is important to warn patients about driving or operating machinery.

• GI effects

  • Constipation, bloody stool, and abdominal pain/distension can all occur.
  • Peristalsis inhibition is not recommended. This is due to the possibility of ileus, megacolon and/or toxic megacolon.

• Torsades of pointes, sudden death and Torsades de Pointes: [US Boxed Warn]

  • Higher doses can cause torsades, cardiac arrest and even death.
  • QT prolongation can be increased in patients with congenital long QT Syndrome, elderly, electrolyte abnormalities and patients with cardiac arrhythmias.
  • Patients aged >=2 years should avoid higher doses due to the possibility of serious cardiac adverse effects.
  • Syncope or ventricular tachycardia can result from taking the recommended doses.
  • Children under 2 years old can experience syncope, cardiac arrest and respiratory depression.

• AIDS patients:

  • Therapy should be stopped as soon as there is abdominal distension.
  • Toxic megacolon in HIV patients can be caused by loperamide.

• Hepatic impairment

  • Patients with impaired liver function should not use it.
  • It is important to monitor for signs and symptoms of CNS toxicities.

Loperamide: Drug Interaction

Monitoring parameters:

Signs of CNS toxicity in patients with hepatic impairment.

How to administer loperamide (Imodium)?

It should be taken orally with plenty of clear fluids to prevent dehydration. Oral solution: Shake well before administering the dose.

Cancer treatment-induced diarrhea:

• The dose should be taken 30 minutes before eating 4 times daily to slow gastrocolic reflex.

Mechanism of action of loperamide (Imodium):

• Through the opioid receptor, Loperamide directly affects the circular and longitudinal inner muscles.
• This results in inhibition of peristalsis as well as prolonged transit time.
• It can also cause a reduction in fecal volume, viscosity, and electrolytes.
• It has antisecretory properties and increased the tone in the anal sphincter.

Absorption:

• Poor.

Distribution:

• Poor penetration into the brain.

Metabolism:

• It is metabolized in the liver via oxidative N-demethylation; CYP2C8 and CYP3A4 (major) and CYP2B6 and CYP2D6 (minor) role in N-demethylation.

Half-life elimination:

• 9.1 to 14.4 hours.

Time to peak plasma concentration:

• Liquid: 2.5 hours;
• Capsule: about 5 hours.

Excretion:

• Feces.

International Brands of Loperamide:

• Anti-Diarrheal
• Diamode
• Imodium A-D
• Loperamide A-D
• Abydium
• Albutil
• Arret
• Beamodium
• Betaperamide
• Binaldan
• Blotasime
• Cicamin
• Colidium
• Colifilm
• Coliper
• Colodium
• Contem
• D-Stop-ratiopharm
• Degortkap
• Diadium
• Diamide
• Diaperol
• Diarlop
• Diarodil
• Diatabs
• Diatrol
• Dissenten
• Donafan
• Donamed F
• Dyspagon
• Elcoman
• Fortasec
• Gastro-Stop
• Gastron
• Good Sense Anti-Diarrheal
• Harmonise
• Hocular
• Hrindeks
• Imodium
• Imodonil
• Imonox
• Imosec
• Imosen
• Imossel
• Imotil
• Inamid
• Lenide-T
• Lockit
• Lodia
• Lomedium
• Lomid
• Lomotil
• Loniper
• Lopamid
• Lopamide
• Lopedin
• Lopedium
• Lopemid
• Loper
• Loperamid-ratiopharm
• Loperamide-Eurogenerics
• LoperamideGenerics
• Loperamil
• Loperhoe
• Loperium
• Lopermid
• Lopermide
• Lopicare
• Lopide
• Lopmin
• Loprid
• Lopron
• Loramide
• Lordiar
• Lorid
• Luobaomai
• Motilex
• NT-Diorea
• Pangetan NF
• Paradoxone
• Perasian
• Permid
• Ramide
• Regulane
• Rexamide
• Reximide
• Rhomuz
• Safe
• Salvacolina
• Sanpo
• Seldiar
• Stoperan
• Stopit
• Stoprrhea
• Suprasec
• Tarmin
• Toban
• Toban F
• Undiarrhea
• Vacontil
• Vancotil
• Velaral

Loperamide Brands in Pakistan: