Imotil Plus

It is indicated for the symptomatic treatment of acute diarrhea in adults and adolescents over 12 years when acute diarrhea is associated with gas-related abdominal discomfort including bloating, cramping or flatulence.

Loperamide binds to the opiate receptor in the gut wall, reducing propulsive peristalsis increasing intestinal transit time and enhancing resorption of water and electrolytes. Loperamide increases the tone of the anal sphincter Simethicone is a surface-active agent with anti-foaming properties thereby potentially relieving gas related symptoms associated with diarrhea. Most ingested Loperamide is absorbed from the gut. But due to significant first pass metabolism systemic bioavailability is approximately 0.3% Simethicone is not absorbed The plasma protein binding of Loperamide is 95% Loperamide is almost completely extracted by the liver, where it is predominantly metabolized, conjugated and excreted via the bile. The half-life of Loperamide is about 11 hours. Excretion of the unchanged Loperamide and the metabolites mainly occur through the faeces.

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.

The safety of Loperamide-Simethicone was evaluated in 2040 patients in five clinical trials. The most commonly reported (i.e. 21% incidence) ADRs: dysgeusia (2.6%) & nausea (1.6%).

Safety in human pregnancy has not been established. Animal studies show no indications of teratogenic or embryotoxic properties. It should not be given during pregnancy, especially during the first trimester, unless clinically justified. Small amounts of Loperamide may appear in human breast milk. Therefore, it is not recommended during breast feeding.

Treatment of diarrhea with Loperamide-Simethicone is only symptomatic. Whenever an underlying etiology can be determined, specific treatment should be given. If clinical improvement is not observed within 48 hours, the administration of Loperamide-Simethicone must be discontinued. This medicine must be used with caution in patients with hepatic impairment as it may result in a relative overdose leading to central nervous system (CNS) toxicity. Loperamide-Simethicone should be used under medical supervision in patients with severe hepatic dysfunction. Cardiac events including OT interval and QRS complex prolongation. have been reported in association with overdose.

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