XENICAL Capsule

In conjunction with a mildly hypocaloric diet, is indicated for treatment of obese patients or overweight patients with associated comorbidities.

Dosage and Administration

120mg with each main meal (during or up to 1 hour after the meal). If a meal is missed or contains so fat, the dose may be omitted.

The patient should be on a nutritionally balanced, mildly hypocaloric diet that contains approximately 30% of calories from fat.

The daily intake of fat, carbohydrate and protein should be distributed over three main meals.

Doses above 120mg 3 times daily have not been shown to provide additional benefit.

Clinical investigations in patient with hepatic and/or renal impairment and children under the age of 12 have not been undertaken.

See the package insert about the details: Renal/Hepatic impairment

In patients with chronic malabsorption syndrome, cholestasis and in patients with known hypersensitivity to Orlistat or any of the other components contained in the medical product.

Adverse reactions to Xenical are largely gastrointestinal in nature and related to the pharmacologic effect of the drug on preventing the absorption of ingested fat. Commonly observed events are oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation and fecal incontinence. The incidence of these increases the higher the fat content of the diet. Patients should be counselled as to the possibility of gastrointestinal effects occurring and how best to handle them such as reinforcing the diet, particularly the percentage of fat it contains.

Consumption of a diet low in fat will decrease the likelihood of experiencing adverse gastrointestinal events and this may help patients monitor and regulate their fat intake.

These adverse gastrointestinal reactions are generally mild and transient. They occurred early in treatment (within 3 months) and most patients experienced only one episode.

Treatment-emergent GI-adverse events that occurred commonly among patients treated with Xenical were: abdominal pain/discomfort, flatulence, lipid stools, stools, soft stools, rectal pain/discomfort, tooth disorder, gingival disorder.

Other events observed rarely were: upper respiratory infection, lower respiratory infection; influenza; headache; menstrual irregularity; anxiety; fatigue; urinary tract infection.

Unique treatment adverse events observed in obese type 2 diabetic patients were hypoglycemia (very common) and abdominal distension (common). Weight loss induced by Xenical is accompanied by improved metabolic control in type 2 diabetics which might allow or require reduction in the dose of hypoglycemic medication.

In a 4-year clinical trial, the general pattern of adverse event distribution was similar to that reported for the 1 and 2 year studies with the total incidence of gastrointestinal related adverse events occurring in year 1 decreasing year on year over the 4-year period.

Decreases in the absorption of vitamin D, E and beta-carotene have been observed when co-administered with Xenical. If a multivitamin supplements is recommended, it should be taken at least 2 hours after the administration of Xenical or at bedtime.

A reduction in cyclosporin plasma levels has been observed when Xenical is co-administered. Therefore it is recommended to monitor more frequently than usual the cyclosporin plasma levels when Xenical is co-administered.

In a PK study, oral administration of amiodarone reduction in the systemic exposure to amiodarone during orlistat treatment demonstrated a 25-30% reduction in the systemic exposure to amiodarone and desethylamiodarone. Due to the complex pharmacokinetics of amiodarone, the clinical effect of this is unclear. The effect of commencing orlistat treatment in patients on stable amiodarone therapy has not been studied. A reduced therapeutic effect of amiodarone is possible.

Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic drugs. A causal relationship has not been established; however, patients should be monitored for possible changes in the frequency and/or severity of convulsions.

No interactions based on specific drug-drug interaction studies with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, oral contraceptives, phentermine, pravastatin, warfarin, nifedipine, Gastrointestinal Therapeutic System, nifedipine slow release, sibutramine or alcohol have been reported.

However, when warfarin or other oral anticoagulants are given in combination with orlistat, international normalised ration (INR) values should be monitored.

See the package insert about the details below:

Pregnancy

Not recommended for use during pregnancy in the absence of clinical data.

Lactation

Should not be taken during breast-feeding.

General

A reduction in cyclosporine plasma levels has been observed when Xenical is co-administered. Therefore it is recommended to monitor more frequently than usual the cyclosporine plasma levels when Xenical is co-administered.

The majority of patients in long-term studies of up to 4 years of treatment had vitamin A, D, E and K and beta-carotene levels within normal range. In order to ensure adequate nutrition, the use of a multivitamin supplement should be considered.

Patients should be advised to adhere to dietary guidelines. The possibility of experiencing gastrointestinal events may increase when Xenical is taken with a diet high in fat (e.g. i a 2000kcak/day diet, >30% of calories from fat equates to >67 of fat). The daily intake of fat should be distributed over three main meals.

If Xenical is taken with any one meal very high in fat, the possibility of gastrointestinal effects may increase. Weight loss induced by Xenical is accompanied by improved metabolic control in type 2 diabetics which might allow or require reduction in the dose of hypoglycemic medication (e.g. sulfonylureas).

Xenical is a potent, specific and reversible long-act in inhibitor of gastrointestinal lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the serine residue of the active site of gastric and pancreatic lipases. The inactivated enzyme is thus unable to hydrolyse dietary fat, in the form of triglycerides, into absorbable free fatty acids and monoglycerides.

As undigested triglycerides are not absorbed, the resulting caloric deficit has a positive effect on weight control.

Based on fecal fat measurements, the effect of Xenical is seen as soon as 24-48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pre-treatment levels, within 48-72 hours.