Pharmacotherapeutic group: anti-propulsive. ATC code: A07DA03.
Pharmacology: Mechanism of Action: In vitro and animal studies show that IMODIUM (loperamide hydrochloride) 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 peristalsis, and increasing intestinal transit time. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency.
IMODIUM (loperamide hydrochloride) is indicated for the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease; also indicated for reducing the volume of discharge from ileostomies in adult patient (≥18 yr).
Patients should receive appropriate fluid and electrolyte replacement as needed. For adults only (≥18 yr).
Acute Diarrhea: The recommended initial dose is 4 mg (2 tabs) followed by 2 mg (1 tab) after each unformed stool. Daily dose should not exceed 16 mg (8 tabs). Clinical improvement is usually observed within 48 hours.
Chronic Diarrhea: The recommended initial dose is 4 mg (2 tabs) followed by 2 mg (1 tab) after each unformed stool until diarrhea is controlled. When the optimal daily dosage has been established, average daily maintenance dosage in clinical trials was 2 to 12 mg (1 to 6 tabs). Daily dose should not exceed 16 mg (8 tabs).
Patients with hepatic impairment: Although no pharmacokinetic data are available in patients with hepatic impairment, IMODIUM (loperamide HCl) should be used with caution in this patients because of reduced first pass metabolism.
In cases of overdosing (including in patients with impaired liver function), CNS depression, urinary retention and ileus can occur.
In patients who intentionally consumed high-dose loperamide HCl (reported doses of 40 to 792 mg daily), the complex extension of QT interval and QRS and/or serious ventricular arrhythmias, including Torsades de pointes might occur. Some fatal cases have also been reported.
Treatment: In overdose case, ECG monitoring to determine the extension of the QT interval should be done. If symptoms of overdose occur, naloxone can be given as an antidote. In view of the prolonged action of loperamide and the short duration (one to three hours) of naloxone, the patient must be monitored closely and treated repeatedly with naloxone as indicated. Therefore it must be closely monitored for at least 48 hours to observe/detect possible effects of central nervous system depression.
IMODIUM (loperamide HCl) is contraindicated in patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients; patients with abdominal pain in the absence of diarrhea; infants below 24 months of age. IMODIUM (loperamide HCl) should not be used as the primary therapy in patients with acute dysentery, which is characterized by blood in stools and high fever; acute ulcerative colitis; patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella, and Campylobacter, and in patients with pseudomembranous colitis associated with the use of broad-spectrum antibiotics.
Generally, IMODIUM should not be used if peristaltic resistance occurs. This should be avoided because of the possibility of significant risks including ileus, megacolon and toxic megacolon. IMODIUM must be stopped immediately if there is constipation, abdominal distension or the presence of signs of ileus.
Acquired immune deficiency syndrome (AIDS): People with AIDS should stop taking loperamide and contact their doctor if they experience abdominal swelling or distention.
Constipation: If the patient develops constipation, stop taking this medication and contact a doctor.
Drowsiness or dizziness: Loperamide may cause drowsiness or dizziness. Do not drive or operate machinery until the patient know how loperamide affects him/her.
Fluids and electrolytes: The loss of fluids and electrolytes (e.g., chloride, sodium) can occur if the patient has diarrhea. Loperamide helps with the symptoms of diarrhea but will not correct any fluid or electrolyte problems caused by diarrhea. Talk to a doctor or pharmacist about whether the patient need fluid and electrolyte replacement, also referred to as oral rehydration therapy.
Improvement in diarrhea: If diarrhea has not improved after 48 hours of treatment with loperamide, stop taking it and contact a doctor.
Liver function: Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects. If the patient has liver problems, discuss with the doctor how this medication may affect the medical condition, how the medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.
Medical conditions: Loperamide should not be used by people with intestinal infections such as dysentery, which is often associated with severe diarrhea, fever, and blood in the stool, and other infections of the gut. More serious problem of the bowel may develop if loperamide is used by some people with acute ulcerative colitis or a serious form of diarrhea associated with antibiotic use.
Use in Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. If the patient become pregnant while taking this medication, contact the doctor immediately.
Use in Lactation: This medication passes into breast milk. If the patient is a breast-feeding mother and taking loperamide, it may affect the baby. Talk to the doctor about whether the patient should continue breast-feeding.
Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. If the patient become pregnant while taking this medication, contact the doctor immediately.
Breast-feeding: This medication passes into breast milk. If the patient is a breast-feeding mother and taking loperamide, it may affect the baby. Talk to the doctor about whether the patient should continue breast-feeding.
Skin and subcutaneous tissue disorders:
Rash, pruritus, urticaria, and angioedema and extremely rare cases bullous eruption including erythema multiforme, Stevens-Johnson syndrome and Toxic Epidermal Necrolysis have been reported with use of IMODIUM.
Immune system disorders:
Isolated occurrences of allergic reactions and in some cases severe hypersensitivity reactions including anaphylactic shock and anaphylactoid reactions have been reported with the use of IMODIUM.
Dry mouth, abdominal pain, distention or discomfort, upper abdominal pain, nausea, vomiting, flatulence, dyspepsia, constipation, paralytic ileus, megacolon including toxic megacolon, glossodynia.
Renal and urinary disorders:
Nervous system disorders:
Drowsiness, dizziness, abnormal coordination, depressed level of consciousness, hypertonia, decreased consciousness, stupor.
General disorders and administrative site conditions:
Concomitant use of IMODIUM 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.
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 IMODIUM is administered at the recommended dosages (2 mg, up to 16 mg maximum daily dose) with P-glycoprotein inhibitors.
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 IMODIUM is given with saquinavir, the therapeutic efficacy of saquinavir should be closely monitored.
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.
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.
Store in the temperature 30°C.
A07DA03 - loperamide ; Belongs to the class of antipropulsives. Used in the treatment of diarrhea.