Loperamide + Simethicone

Diarrhea may be defined as a failure or imbalance of one or a combination of activities in the gut which include secretion, absorption and motility. Loperamide hydrochloride has been shown to act on all of these functions via cholinergic, non-cholinergic, opiate and non-opiate receptor-mediated mechanisms. In this way, loperamide HCl effectively reduces fecal output and frequency, improves stool consistency and relieves symptoms of abdominal cramping and fecal incontinence.

Loperamide binds to the opiate receptor in the gut wall. Consequently, it inhibits the release of acetylcholine and prostaglandins, thereby reducing propulsive peristalsis, increasing intestinal transit time and enhancing resorption of water and electrolytes. Loperamide does not change the physiological flora. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency. Loperamide does not act centrally. Loperamide has a high affinity for the gut wall and is extensively metabolized on first-pass through the liver. Therefore, loperamide hardly reaches the systemic circulation. Simethicone is an inert surface-active agent with anti-foaming properties which relieves symptoms associated with diarrhea, particularly flatulence, abdominal discomfort, bloating and cramping.

Adults and children 12 years of age and older: 2 Tablets after the first loose bowel movement and one tablet or caplet after each subsequent loose bowel movement, up to a maximum of 4 tablets or caplets a day for no more than 2 days.

Children 6-11 years of age: This is not recommended for children under 12 years of age except on the advice of a physician.

The proposed dose that may be used: 1 Tablet after the first loose bowel movement and 1/2 tablet or caplet after each subsequent loose bowel movement, up to a maximum 3 tablets or caplets (for ages 9-11 years) or maximum 2 tablets or caplets (for ages 6-8 years) per day, for no longer than 2 days.

Children under 12 years of age: This tablet should be used with special caution in children under 12 years of age because of greater variability of response and possible difficulty of swallowing.

Geriatrics (> 65 years of age): No dose adjustments are required for the elderly.

Renal Impairment: No dosage adjustment necessary in renal impairment.

Hepatic Impairment: Although no pharmacokinetic data are available in patients with hepatic impairment, this tablet should be used with caution in such patients because of reduced first pass metabolism.

Administration: This tablet should be taken by mouth and can be taken at any time of day. The caplets should be taken with a full (250 mL) glass of water. The chewable tablets should be chewed fully and then swallowed. Drink plenty of clear fluids to help prevent dehydration which may accompany diarrhea. Take only on an empty stomach (1 hour before or 2 hours after a meal).

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 central nervous system (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.

Since simethicone is not absorbed from the gastrointestinal tract, no relevant interactions between simethicone and other drugs are expected.

Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.

Loperamide hydrochloride/Simethicone is contraindicated for use in children under 2 years of age.

Loperamide hydrochloride/Simethicone is contraindicated in those in whom constipation must be avoided.

Loperamide hydrochloride/Simethicone should not be used in the case of acute dysentery that is characterized by blood in stools and elevated temperature. Fluid and electrolyte depletion may occur in patients who have diarrhea. The use of Loperamide hydrochloride/Simethicone does not preclude the administration of appropriate fluid and electrolyte therapy.

Loperamide hydrochloride/Simethicone should not be used in patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella, and Campylobacter.

Loperamide hydrochloride/Simethicone must not be used in patients with acute ulcerative colitis or pseudomembranous colitis associated with broad-spectrum antibiotics. In such patients, agents which inhibit intestinal motility or delay intestinal transit time have increased the possible risk of significant sequelae including ileus, megacolon and toxic megacolon . Loperamide hydrochloride/Simethicone therapy should be discontinued promptly if abdominal distention occurs or if untoward symptoms develop. In general, Loperamide hydrochloride/Simethicone should not be used when the inhibition of peristalsis is to be avoided.

With use of loperamide hydrochloride, occasional hypersensitivity reactions have been reported, such as skin rash and urticaria, and extremely rare cases of anaphylactic reaction (including anaphylactic shock) and bullous eruption including Toxic Epidermal Necrolysis. In the majority of these cases, the patients were on other medications which may have caused or contributed to the events.

The adverse effects reported in adults during clinical trials with Loperamide hydrochloride/Simethicone Chewable Tablets were generally of a minor and self-limiting nature and infrequent: nausea, altered taste (<2%); headache, chills, dry mouth, cough, skin rash (<1%); constipation (<1%) and/or abdominal distension have also been reported. In some very rare cases, particularly in which the treatment information had not been respected, these latter effects have been associated with ileus (including paralytic ileus). Urinary retention has been reported rarely.

Pregnant Women: Safe use of Loperamide hydrochloride/Simethicone during pregnancy has not been established. Reproduction studies performed with loperamide hydrochloride in the rat and the rabbit revealed no evidence of impaired fertility or harm to the fetus at dosage levels up to 30-fold the therapeutic dose for man. Therefore, Loperamide hydrochloride / Simethicone should be used in pregnant women only when, in the opinion of the physician, the potential benefits outweigh the potential risks. Although there are no indications that loperamide or simethicone possess teratogenic or embryotoxic properties, the anticipated therapeutic benefits should be weighed against potential hazards before Loperamide hydrochloride/Simethicone is given during pregnancy, especially during the first trimester.

Nursing Women: Small amounts of loperamide may appear in human breast milk. Therefore, Loperamide hydrochloride/ Simethicone is not recommended during breast-feeding.

If clinical improvement is not observed within 48 hours, the administration of Loperamide hydrochloride/ Simethicone should be discontinued and patients should be advised to consult their physician. The use of higher than the recommended doses for control of the diarrhea may lead to abnormal heart rhythms and serious cardiac events leading to death. Tiredness, dizziness, or drowsiness may occur in the setting of diarrheal symptoms treated with loperamide. Therefore, it is advisable to use caution when driving a car or operating machinery. Abuse and misuse, as an opioid substitute, have been described in individuals with opioid addiction.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.