preloder

Loperamide Hydrochloride


Loperamide Hydrochloride

is indicated for the control and symptomatic relief of acute nonspecific

diarrhea

and of chronic

diarrhea

associated with inflammatory bowel disease.

Loperamide

is also indicated for reducing the volume of discharge from ileostomies.
Dosing
Adult dosing:
  • 4 mg

    ORALLY followed by

    2 mg

    after each

    loose stool

    up to a maximum of

    16 mg

    /day

  • Diarrhea, chronic – Irritable bowel syndrome:
    Initial:
  • 4 mg

    ORALLY followed by

    2 mg

    after each

    loose stool

    up to a maximum of

    16 mg

    /day

  • Maintenance:
  • Titrate to individual’s need, average daily dosage

    4 mg

    to 8 mg ORALLY up to a maximum of

    16 mg

    /day, may be taken as a single dose or in divided
    doses

  • High output ileostomy:
    Dose used in some trials:
  • 4 mg

    twice daily for 4 days, may then be increased to 12 mg daily for the remaining 3 days (total duration of therapy studied: 7 days)

  • Traveler’s

    diarrhea

    :

  • 4 mg

    ORALLY followed by

    2 mg

    after each

    loose stool

    up to a maximum of 8 mg/day

  • Pediatric dosing:
    Diarrhea, acute:
    First day dosage:
  • 2 to 5 years, 13 to 20 kg:

    1 mg

    ORALLY 3 times daily
  • 6 to 8 years, 20 to 30 kg:

    2 mg

    ORALLY twice daily
  • 8 to 12 years, greater than 30 kg:

    2 mg

    ORALLY 3 times daily

  • Subsequent daily dosage:
    2 to 12 years:
  • 1 mg

    /10 kg of body weight ORALLY only after a

    loose stool

    , total daily dose should not exceed dosages for the first day

  • Diarrhea, chronic – Irritable bowel syndrome:
  • Therapeutic dose in children has not been established; 0.08 to 0.24 milligram/kilogram/day in 2 to 3 divided
    doses
    have been used

  • Traveler’s

    diarrhea

    :

    2 to 5 years, 11 to 21.9 kg:
  • 1 mg

    ORALLY followed by

    1 mg

    after each

    loose stool

    up to a maximum of 3 mg/day

  • 6 to 8 years, 22 to 26.9 kg:
  • 2 mg

    ORALLY followed by

    1 mg

    after each

    loose stool

    up to a maximum of

    4 mg

    /day

  • 9 to 11 years, 27 to 43 kg:
  • 2 mg

    ORALLY followed by

    1 mg

    after each

    loose stool

    up to a maximum of 6 mg/day

  • 12 years and older:
  • 4 mg

    ORALLY followed by

    2 mg

    after each

    loose stool

    up to a maximum of 8 mg/day

  • Indications
    FDA-Labeled Indications:
  • Diarrhea

    , acute
  • Diarrhea

    , chronic – Irritable bowel syndrome
  • High output ileostomy
  • Traveler’s

    diarrhea


  • Non-FDA Labeled Indications:
  • Diarrhea

    , chronic
  • Proctocolectomy

  • Mechanism of Action
  • In vitro and animal studies show that Loperamide acts by slowing intestinal motility and by affecting water and electrolyte movement through the bowel. Loperamide binds to the opiate receptor in the gut wall. Consequently, it inhibits the release of acetylcholine and prostaglandins, thereby reducing propulsive peristalsis, and increasing intestinal transit time. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency.
  • Adverse Effect
    Common:
    Endocrine metabolic:
  • Hyperglycemia

  • Gastrointestinal:
  • Abdominal pain

  • Nausea
  • Vomiting
  • Xerostomia

  • Neurologic:
  • Dizziness
  • Somnolence

  • Other:
  • Fatigue

  • Serious:
    Gastrointestinal:
  • Necrotizing enterocolitis in fetus OR newborn (rare)
  • Contraindication
  • Abdominal pain

    in the absence of

    diarrhea

  • Bacterial enterocolitis, caused by invasive organisms including Salmonella, Shigella, and Campylobacter; do not

    use

    as primary therapy
  • Dysentery, acute; do not

    use

    as primary therapy
  • Hypersensitivity to loperamide or to any of the excipients
  • Infants below 24 months of age
  • Pseudomembranous colitis, associated with the

    use

    of broad spectrum

    antibiotics

    ; do not

    use

    as primary therapy
  • Ulcerative colitis, acute; do not

    use

    as primary therapy
  • Interaction
    Effects of Other Drugs on Loperamide:
  • Concomitant

    use

    of Loperamide with
    inhibitors
    of CYP3A4 (e.g.,

    itraconazole

    ) or CYP2C8 (e.g., Gemfibrozil) or
    inhibitors
    of P-glycoprotein (e.g., quinidine, ritonavir) can increase exposure to loperamide. The increased systemic exposure to loperamide may increase a risk for cardiac adverse reactions especially in patients who are taking multiple CYP enzyme
    inhibitors
    , or in patients with underlying cardiac conditions. Monitor patients for cardiac adverse reactions.

  • CYP3A4 Inhibitors:
    Itraconazole:
  • Concomitant administration of multiple
    doses
    of 100 mg

    itraconazole

    twice daily, an inhibitor of both CYP3A4 and P-glycoprotein, with a single 4-mg dose of loperamide hydrochloride increased the peak plasma concentration and the systemic exposure to loperamide by 2.9-fold and 3.8-fold, respectively.

  • CYP2C8 Inhibitors:
    Gemfibrozil:
  • When a single 4-mg dose of loperamide hydrochloride was co-administered with

    600 mg

    Gemfibrozil, a strong inhibitor of CYP2C8, on day 3 of a 5-day treatment with Gemfibrozil twice daily, the mean peak plasma concentration and the systemic exposure to loperamide was increased by 1.6-fold and 2.2-fold, respectively.

  • CYP3A4 and CYP2C8 Inhibitors:
  • When multiple
    doses
    of both 100 mg itraconazole and

    600 mg

    Gemfibrozil twice daily were administered with a single 4-mg dose of loperamide hydrochloride, the mean peak plasma concentration and the systemic exposure to loperamide was increased by 4.2-fold and 12.6-fold, respectively.

  • P-glycoprotein Inhibitors:
  • Concomitant administration of a

    16 mg

    single dose of loperamide hydrochloride with a

    600 mg

    single dose of quinidine or ritonavir, both of which are P-glycoprotein
    inhibitors
    , resulted in a 2- to 3-fold increase in loperamide plasma concentrations. Due to the potential for enhanced CNS adverse reactions when loperamide is co-administered with quinidine and with ritonavir, caution should be exercised when Loperamide is administered at the recommended dosages (

    2 mg

    , up to

    16 mg

    maximum daily dose) with P-glycoprotein
    inhibitors
    .

  • Effects of Loperamide on Other Drugs:
    Saquinavir:
  • When a single 16-mg dose of loperamide hydrochloride is co administered with a

    600 mg

    single dose of saquinavir, loperamide decreased saquinavir exposure by 54%, which may be of clinical relevance due to reduction of therapeutic efficacy of saquinavir. The effect of saquinavir on Loperamide is of less clinical significance. Therefore, when Loperamide is given with saquinavir, the therapeutic efficacy of saquinavir should be closely monitored.

  • Precaution
  • AIDS patients, stop therapy at earliest signs of abdominal distension; isolated reports of toxic megacolon with infectious colitis from both viral and bacterial pathogens
  • Anaphylaxis
  • Dehydration in younger children
  • Discontinue

    use

    if no clinical improvement is observed within 48 hours in patients with acute

    diarrhea

  • Fluid and electrolyte depletion
  • Hepatic impairment; reduced first pass metabolism
  • When inhibition of peristalsis is to be avoided; possible risk of significant sequelae including ileus, megacolon and toxic megacolon, should be discontinued promptly when constipation, abdominal distension or ileus develop
  • Pregnancy Category
  • C (FDA)
  • B3 (AUS)
  • Breast Feeding
  • Infant risk cannot be ruled out.
  • Monitoring
  • Improvement in stool frequency and consistency
  • Periodic fluid and electrolyte status determinations in long term therapy
  • Abdominal pain

    , nausea or constipation
  • CNS toxicity in patients with hepatic impairment
  • Dosage Form
    Oral Capsule:
  • 2 mg


  • Oral Capsule, Liquid Filled:
  • 2 mg


  • Oral Liquid:
  • 1 mg

    /5 ML

  • Oral Solution:
  • 1 mg

    /7.5 ML
  • 1 mg

    /5 ML

  • Oral Suspension:
  • 1 mg

    /7.5 ML

  • Oral Tablet:
  • 2 mg


  • Treatment
    Management of Mild to Moderate Toxicity:
  • Supportive care is the mainstay of treatment. Administer naloxone for CNS or respiratory depression.

  • Management of Severe Toxicity:
  • Supportive care is the mainstay of treatment. Administer oxygen and monitor for respiratory and CNS depression. Administer naloxone to reverse respiratory or significant CNS depression. Treat dystonic reactions with benztropine (1 to

    4 mg

    IV or orally, maximum 6mg/day) or diphenhydramine. Assisted ventilation may be needed. Cardiac dysrhythmias (e.g., prolonged QRS and QT intervals, monomorphic and polymorphic ventricular dysrhythmias) developed in 5 patients with a history of loperamide abuse (
    doses
    : 70 mg to 792 mg daily). Treatment with standard anti-arrhythmic agents was ineffective; however, electrical overdrive pacing or isoproterenol continuous infusion was effective in treating dysrhythmias and preventing further episodes of torsades de pointes.
  • Toxicology
    Infants:
  • Six deaths were reported following complications secondary to misuse of loperamide in infants less than 6.5 months of age.

  • Adults:
  • Two fatalities have been reported after loperamide abuse. Both patients had significantly high loperamide concentrations (77 ng/mL and 140 ng/mL, respectively). Even in therapeutic
    doses
    , patients may experience mild to more severe toxicity, including paralytic ileus. Repeated low
    doses
    (0.12 mg/kg for 3
    doses
    in an infant, 0.27 mg/kg/day in a neonate) have caused CNS and respiratory depression. Cardiac dysrhythmias (e.g., prolonged QRS and QT intervals, monomorphic and polymorphic [torsades de pointes] ventricular dysrhythmias) developed in 5 patients with a history of loperamide abuse (
    doses
    : 70 mg to 792 mg daily). All patients recovered following supportive care.

  • Patient Counselling or Clinical Teaching
  • Inform patient not to

    use

    for

    abdominal pain

    in the absence of

    diarrhea

    .
  • Patient should avoid activities requiring mental alertness or coordination until drug effects are realized.
  • This drug may cause hyperglycemia, nausea, vomiting, xerostomia, dizziness, somnolence, or fatigue.
  • Patients with acute

    diarrhea

    should notify healthcare professional if no clinical improvement is observed within the first 48 hours.
  • Instruct AIDS patients to stop therapy and call healthcare professional at the first sign of abdominal distension.
  • Patient should maintain adequate hydration during treatment.
  • Advise patient not to take more than

    16 mg

    in a 24-hours period.












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