LOPERAMIDE

Imodium™
2 mg Capsule
Antimotility

Description of the Product
Loperamide HCl (Imodium™) is a white powder filled in capsules with green cap and dark gray body.

What Is in the Medicine?
Loperamide hydrochloride

Strength of the Medicine
Each capsule contains:
Loperamide (as HCl) ……………………………………………2 mg

What is the medicine used for?
Loperamide HCl (Imodium™) is indicated for the symptomatic control of acute and chronic diarrhea. In patients with an ileostomy it can be used to reduce the number and volume of stools and to harden their consistency.

How much and how often should you use this medicine?
Adults and pediatrics
Acute diarrhea
The initial dose is 2 capsules (4 mg) for adults and 1 capsule (2 mg) for children; followed by 1 capsule (2 mg) after every subsequent loose stool.
Chronic diarrhea
The initial dose is 2 capsules (4 mg) daily for adults and 1 capsule (2 mg) daily for children; this initial dose should be adjusted until 1-2 solid stools a day are obtained, which is usually achieved with a maintenance dose of 1-6 capsules (2 mg-12 mg) daily.
The maximum dose for acute and chronic diarrhea is 8 capsules (16 mg) daily for adults; in children it must be related to the body weight (3 capsules/20 kg) but should not exceed a maximum of 8 capsules per day.
Pediatrics (under 2 years of age)
Loperamide HCl should not be used in children under 2 years of age.
Elderly
No dose adjustment is required for the elderly.
Renal impairment
No dose adjustment is required for patients with renal impairment.
Hepatic impairment
Although no pharmacokinetic data are available in patients with hepatic impairment, loperamide HCl should be used with caution in such patients because of reduced first pass metabolism.
Administration
The capsules should be taken with liquid.

When should you not take this medicine?

• Loperamide HCl is contraindicated in patients with a known hypersensitivity to loperamide HCl or to any of the excipients.
• Loperamide HCl should not be used in children under 2 years of age.
• 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,
  • In patients with acute ulcerative colitis,
  • In patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella, and Campylobacter,
  • In patients with pseudomembranous colitis associated with the use of broad-spectrum antibiotics.

Loperamide HCl should not be used when inhibition of peristalsis is to be avoided due to the possible risk of significant sequelae including ileus, megacolon and toxic megacolon. Loperamide HCl must be discontinued promptly when constipation, abdominal distension or ileus develop.

Care that should be taken when taking this medicine?
Treatment of diarrhea with loperamide HCl is only symptomatic. Whenever an underlying etiology can be determined, specific treatment should be given when appropriate.
In patients with diarrhea, especially in children, fluid and electrolyte depletion may occur. In such cases administration of appropriate fluid and electrolyte replacement therapy is the most important measure. Loperamide HCl should not be given to children aged 2 to 6 years of age without medical prescription and supervision.
In acute diarrhea, if clinical improvement is not observed within 48 hours, the administration of loperamide HCl should be discontinued and patients should be advised to consult their physician.
Patients with AIDS treated with loperamide HCl for diarrhea should have therapy stopped at the earliest signs of abdominal distension. There have been isolated reports of obstipation with an increased risk for toxic megacolon in AIDS patients with infectious colitis from both viral and bacterial pathogens treated with loperamide HCl.
Although no pharmacokinetic data are available in patients with hepatic impairment, loperamide HCl should be used with caution in such patients because of reduced first pass metabolism. This medicine must be used with caution in patients with hepatic impairment as it may result in a relative overdose leading to CNS toxicity.
Abuse and misuse of loperamide, as an opioid substitute, have been described in individuals with opioid addiction
Pregnancy and Breast-feeding
It is not advisable to administer this medicine in pregnancy. Women who are pregnant or breast feeding should therefore be advised to consult their doctor for appropriate treatment.
Effects on Ability to Drive and Use Machines
Tiredness, dizziness, or drowsiness may occur in the setting of diarrheal syndromes treated with Loperamide HCl. Therefore, it is advisable to use caution when driving a car or operating machinery.

Undesirable effects of this medicine
Clinical trial data
Adults and pediatrics
Acute diarrhea
Adverse effects associated with the use of Loperamide HCl are headache, constipation, flatulence, nausea, dizziness, dry mouth, abdominal pain, abdominal discomfort, abdominal pain upper, abdominal distention, rash, vomiting and somnolence.
Chronic diarrhea
Adverse effects associated with the use of Loperamide HCl are dizziness, flatulence, constipation, nausea, headache, abdominal pain, dry mouth, abdominal discomfort and dyspepsia.
Post-Marketing Data
Adverse effects associated with the use of Loperamide HCl are Hypersensitivity reaction, Anaphylactic reaction (including Anaphylactic shock) and Anaphylactoid reaction, Coordination abnormality, Depressed level of consciousness, Hypertonia, Loss of consciousness, Somnolence, Stupor, Miosis, Ileus (including paralytic ileus), Megacolon (including toxic megacolon), angioedema, bullous eruption (including Steven- Johnson syndrome, Toxic epidermal necrolysis and Erythema multiforme), Pruritus, Urticaria, Urinary retention and fatigue.

What other medicine or food should be avoided while taking this medicine?
Non-clinical data have shown that loperamide is a P glycoprotein substrate. Concomitant administration of loperamide (16 mg single dose) with quinidine, or ritonavir, which are both P glycoprotein inhibitors, resulted in a 2 to 3-fold increase in loperamide plasma levels. The clinical relevance of this pharmacokinetic interaction with P glycoprotein inhibitors, when loperamide is given at recommended dosages, is unknown.
The concomitant administration of loperamide (4 mg single dose) and itraconazole, an inhibitor of CYP3A4 and P glycoprotein, resulted in a 3 to 4 fold increase in loperamide plasma concentrations. In the same study a CYP2C8 inhibitor, gemfibrozil, increased loperamide by approximately 2 fold. The combination of itraconazole and gemfibrozil resulted in a 4 fold increase in peak plasma levels of loperamide and a 13 fold increase in total plasma exposure. These increases were not associated with CNS effects as measured by psychomotor tests (i.e., subjective drowsiness and the Digit Symbol Substitution Test).
The concomitant administration of loperamide (16 mg single dose) and ketoconazole, an inhibitor of CYP3A4 and P glycoprotein, resulted in a 5 fold increase in loperamide plasma concentrations. This increase was not associated with increased pharmacodynamic effects as measured by pupillometry.
Concomitant treatment with oral desmopressin resulted in a 3 fold increase of desmopressin plasma concentrations, presumably due to slower gastrointestinal motility.
It is expected that drugs with similar pharmacological properties may potentiate loperamide’s effect and that drugs that accelerate gastrointestinal transit may decrease its effect.

What should you do if you miss a dose?
Continue medication based on dosage and/or consult your doctor.

Signs and Symptoms of Overdose
Signs and symptoms
In case of overdose (including relative overdose due to hepatic dysfunction), CNS depression (stupor, coordination abnormality, somnolence, miosis, muscular hypertonia, and respiratory depression), urinary retention and ileus may occur. Children may be more sensitive to CNS effects than adults.
In individuals who have intentionally ingested overdoses (reported in doses from 40 mg up to 792 mg per day) of loperamide HCl, QT interval and QRS complex prolongation and/or serious ventricular arrhythmias, including Torsade de Pointes, have been observed (see Warnings and Precautions). Fatal cases have also been reported. Abuse, misuse and/or overdose with excessively large doses of loperamide, may unmask Brugada syndrome.
Treatment
In cases of overdose, ECG monitoring for QT interval prolongation should be initiated.
If CNS symptoms of overdose occur, naloxone can be given as an antidote. Since the duration of action of loperamide is longer than that of naloxone (1 to 3 hours), repeated treatment with naloxone might be indicated. Therefore, the patient should be monitored closely for at least 48 hours in order to detect possible CNS depression.

What to do when you have taken more than the recommended dosage?
Consult your doctor if you have taken more than the recommended dosage.

How should you keep this medicine?
Store at temperatures not exceeding 30°C.

When should you consult your doctor?
If symptoms persist or worsen, or if new symptoms occur, stop use and consult your doctor.

Manufactured by:
Interphil Laboratories, Inc.
Canlubang Industrial Estate, Bo. Pittland, Cabuyao, Laguna

Distributed by:
JNTL Consumer Health (Philippines) Inc.
KM 14 Edison Road, Merville, Paranaque City

Patient must seek medical attention immediately at the first sign of any adverse drug reaction. For suspected adverse drug reaction, report to the FDA: www.fda.gov.ph.

Registration number: DR-XY14916
Version: 17 September 2018