Mechanism of Action

Q: How does XENICAL work?
A: XENICAL acts locally in the GI tract to inhibit the fat-digesting action of lipases. Intact triglycerides pass through the intestines unabsorbed, creating a caloric deficit. XENICAL can block about 30% of dietary fat from being absorbed. It has no effect on other GI enzymes. Absorption of carbohydrates and proteins is not affected.

Q: How much of the drug is absorbed?
A: XENICAL is minimally absorbed. Its fat-blocking action takes place in the lumen of the stomach and small intestine.

Vitamin Supplementation

Q: Are vitamins affected by XENICAL treatment?
A: XENICAL has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene. Also, levels of vitamin D and beta-carotene may be low in obese patients compared with non-obese subjects.

Q: Is vitamin supplementation recommended?
A: Yes. Patients should be counseled to take a multivitamin supplement that contains fat-soluble vitamins to ensure adequate nutrition. The supplement should be taken once a day, at least 2 hours before or after the administration of XENICAL, such as at bedtime.

XENICAL Administration

Q: Which patients are appropriate candidates for XENICAL therapy?
A: XENICAL is indicated for obesity management, including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet, and for reduction of the risk of weight regain after prior weight loss. XENICAL is indicated for obese patients with an initial body mass index (BMI) of >30, or >27 in the presence of other risk factors (e.g., hypertension, diabetes, dyslipidemia). XENICAL is contraindicated in chronic malabsorption syndrome or cholestasis. Organic causes of obesity, such as hypothyroidism, should be excluded before prescribing XENICAL.

Q: What XENICAL doses are available?
A: XENICAL is available in 120-mg capsules.

Q: When should XENICAL be taken in relation to a meal?
A: XENICAL should be taken 3 times a day, with each main meal containing fat or up to 1 hour after the meal.

Q: Should XENICAL be taken more than 3 times a day?
A: XENICAL in doses higher than 120 mg 3 times a day has not been shown to produce greater weight loss.

Q: How long should patients take XENICAL?
A: XENICAL has been evaluated in seven long-term (up to 2 years) clinical studies of obesity management including weight loss, weight maintenance and minimizing the risk of weight regain. The safety and efficacy of XENICAL beyond 2 years have not been determined at this time.

Efficacy

Q: How much weight do patients lose with XENICAL treatment?
A: In clinical trials involving 1064 patients, 69% on XENICAL plus diet lost 3% or more of initial body weight within 3 months, with a mean loss of 13 lbs.¹⁸ In clinical trials, the overall mean weight loss from randomization to the end of 1 year in the intent-to-treat population was 13.4 lbs in patients treated with XENICAL plus diet versus 5.8 lbs in placebo-treated patients.

Q: How soon after XENICAL therapy is initiated does weight loss start?
A: Weight loss was observed within 2 weeks of initiation of therapy.

Q: Does XENICAL help maintain lost weight?
A: Across all studies, up to five times as many patients on XENICAL plus diet were able to maintain a weight loss of >10% of their body weight from randomization at year 2 versus those on placebo plus diet.

Q: Can XENICAL be taken with other prescription or over-the-counter weight-loss products?
A: Efficacy and safety studies regarding the combined use of XENICAL and other weight-loss products, whether prescription or OTC, have not been conducted.

Safety

Q: What are the most common adverse events seen with XENICAL?
A: The most commonly reported events (incidence of >5% and twice that of placebo) were oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation and fecal incontinence. These and other commonly observed events were generally mild and transient, and decreased markedly during the second year of treatment. Withdrawal rates due to these events in clinical studies were low. Patients should be educated to expect GI events when taking XENICAL.

Q: What was the dropout rate in clinical studies due to GI events?
A: Withdrawal rates due to treatment events were low. In controlled clinical trials, 8.8% of patients treated with XENICAL discontinued treatment due to adverse events, compared with 5.0% of placebo-treated patients. For XENICAL, the most common adverse events resulting in discontinuation of treatment were gastrointestinal.

Q: What is the timing of these GI events in relation to the start of XENICAL treatment?
A: In clinical trials, almost half of patients experiencing a GI event had the first occurrence within the first week of treatment. GI events are usually temporary and lessen or disappear as patients continue treatment and adhere to their reduced-calorie diet containing no more than 30% of calories from fat. Most GI events resolved within 4 weeks, and half resolved within 1 week. However, in some individuals these events occurred over a longer period.

Q: When can these GI events be expected to occur in relation to when XENICAL is taken with a meal?
A: Timing of a GI event reflects the normal transit time of a particular patient. (Transit time is the time food takes to pass completely through the body.) Normal transit time may be 12 to 36 hours. Based on fecal fat measurements, the effect of XENICAL may be seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pretreatment levels within 48 to 72 hours.

Q: How are GI events linked to fat intake?
A: The mechanism of action of XENICAL results in undigested fat clearance. If XENICAL is taken with any one meal very high in fat, the possibility of GI events increases.

Q: What can physicians do about GI events?
A: Physicians can inform patients before treatment begins about expected GI events, and advise them to manage such events by following a reduced-calorie diet consisting of no more than 30% of calories from fat. The daily intake of fat should be distributed over three main meals.

Q: Can XENICAL be prescribed to patients with GI disease?
A: XENICAL is contraindicated in chronic malabsorption syndrome or cholestasis.

Q: Does XENICAL interfere with the absorption of other fat-soluble drugs?
A: XENICAL shows no interaction with commonly prescribed drugs that were tested, including some fat-soluble drugs.