Zytrim (Orlistat)

Uses

Zytrim (Orlistat) is used for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet. Zytrim (Orlistat) is also used for the reduction of the risk of weight regain after prior weight loss. Zytrim (Orlistat) 120 mg is used for obese patients with an initial body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia) and Zytrim (Orlistat) 60 mg is used for overweight & obese patients with an initial body mass index (BMI) ≥25 kg/m2.

Zytrim (Orlistat) is also used to associated treatment for these conditions: Weight Gain, Weight Reduction

How Zytrim (Orlistat) works

Zytrim (Orlistat) is a potent and selective inhibitor of various lipase enzymes responsible for the metabolism of fat. It acts in the gastrointestinal (GI) tract via covalent binding to the serine residues located on the active site of both gastric and pancreatic lipase. When orlistat is taken with food containing fat, it partially inhibits the hydrolysis of triglycerides. This decreases absorption of monoaclglycerides and free fatty acids, contributing to weight maintenance and weight loss.

Dosage

Zytrim (Orlistat) dosage

The recommended dose of Zytrim (Orlistat) is one 60 mg or 120 mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal). The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat. The daily intake of fat, carbohydrate, and protein should be distributed over three main meals. If a meal is occasionally missed or contains no fat, the dose of Zytrim (Orlistat) can be omitted.

Because Zytrim (Orlistat) has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamin to ensure adequate nutrition. The vitamin supplement should be taken at least 2 hours before or after the administration of Zytrim (Orlistat), such as at bedtime.

Side Effects

Commonly-observed adverse events associated with the use of Zytrim (Orlistat) include oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation, fecal incontinence.

Toxicity

The oral LD50 of orlistat is >5000 mg/kg in rats. Single orlistat doses of 800 mg and multiple doses of up to 400 mg three times a day for 15 days have been administered to healthy weight and obese subjects without clinically significant adverse findings. In addition, doses of 240 mg three times a day have been given to obese patients for 6 months without a significant adverse effects. Post-marketing reports of overdoses cases indicate no adverse events or adverse events that are similar to those reported with the recommended dose. If a significant overdose with orlistat occurs, the patient should be observed for at least 24 hours. Based on the results of clinical studies, systemic effects caused by orlistat are likely to be rapidly reversible.

Precaution

Patients should be advised to adhere to dietary guidelines. gastrointestinal events may increase when orlistat is taken with a diet high in fat (>30% of calories from fat). The daily intake of fat should be distributed over three main meals. If a meal is missed, the dose of orlistat may be omitted.

Interaction

May reduce the absorption of iodine salts and/or levothyroxine, fat-soluble vit (A, D, E, K) and beta carotene. May decrease plasma levels of ciclosporin and amiodarone. May decrease the efficacy of antiepileptic drugs (e.g. valproate, lamotrigine), antiretrovirals, antidepressants, antipsychotics (including lithium). Additive effect on glycaemic control with antidiabetics. May cause hormonal contraceptive failure. May enhance the anticoagulant effect of warfarin.

Food Interaction

• Take with food. Take with meals or up to 1 hour after a meal. Doses may be skipped for missed meals or fat-free meals.

Zytrim (Orlistat) multivitamins interaction

[Minor] Zytrim (Orlistat) decreases the absorption of fat-soluble vitamins.

Studies have shown a 30% reduction in beta-carotene absorption and a 60% reduction in tocopherol acetate absorption when coadministered with orlistat.

Vitamin supplements should be taken at least two hours before or after orlistat administration.

Zytrim (Orlistat) Drug Interaction

Moderate: lamotrigine, levothyroxineMinor: cholecalciferolUnknown: amphetamine / dextroamphetamine, zolpidem, aspirin, lorazepam, celecoxib, duloxetine, omega-3 polyunsaturated fatty acids, fluticasone nasal, clonazepam, atorvastatin, pregabalin, acetaminophen, cyanocobalamin, ascorbic acid, alprazolam, sertraline, cetirizine

Zytrim (Orlistat) Disease Interaction

Major: malabsorptionModerate: diabetics, (fat soluble) vitamin deficiency, nephrolithiasis

Volume of Distribution

Volume of distribution cannot be obtained because the absorption of orlistat is minimal. Zytrim (Orlistat) is minimally distributed to erythrocytes and is primarily bound to proteins.

Elimination Route

The systemic absorption and exposure of orlistat is low, however, systemic absorption of the drug is not required for orlistat activity. After an oral dose with 360 mg of radiolabeled orlistat, plasma radioactivity achieved a peak at about 8 hours. Plasma concentrations of unchanged parent drug were close to the lower end of detection limits (15

Half Life

The half-life of orlistat of the small amount of absorbed orlistat ranges between 1-2 hours.

Elimination Route

After single oral dose of radiolabled orlistat in both normal weight and obese volunteers fecal excretion of the unabsorbed drug was found to be the major route of elimination with 11,20 Fecal elimination of orlistat is estimated between 95-97%. Complete excretion by both routes occurs within in 3 to 5 days.

Pregnancy & Breastfeeding use

Pregnancy Category X. Zytrim (Orlistat) is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm.

It is not known whether Zytrim (Orlistat) is present in human milk or not. Caution should be exercised when Zytrim (Orlistat) is administered to a nursing woman.

Contraindication

Zytrim (Orlistat) is contraindicated in Pregnancy, Patients with chronic malabsorption syndrome, Patients with cholestasis, Patients with known hypersensitivity to Zytrim (Orlistat) or to any component of this product.

Special Warning

Pediatric use: Safety and effectiveness in pediatric patients below the age of 12 have not been established.

Acute Overdose

Single doses of 800 mg and multiple doses of up to 400 mg three times a day for 15 days have been studied in normal weight and obese subjects without significant adverse findings. If a significant overdose of orlistat occur, it is recommended that the patient be observed for 24 hours. Based on human and animal studies, any systemic effects attributable to the lipase inhibiting properties of orlistat should be rapidly reversible

Storage Condition

Store below 25°C; excursions permitted to 15° to 30°C. Keep the medicine out of reach of children.

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