Xenical Adverse Reactions



Commonly Observed (based on first year and second year data -- Xenical 120 mg three times a day versus placebo):

Gastrointestinal (GI) symptoms were the most commonly observed treatment-emergent adverse events associated with the use of Xenical in double-blind, placebo-controlled clinical trials and are primarily a manifestation of the mechanism of action. (Commonly observed is defined as an incidence of >/=5% and an incidence in the Xenical 120 mg group that is at least twice that of placebo.)

Table 7. Commonly Observed Adverse Events
  Year 1 Year 2
Adverse Event Xenical
% Patients
(N=1913)
Placebo
% Patients
(N=1466)
Xenical
% Patients
(N=613)
Placebo
% Patients
(N=524)
Oily Spotting 26.6 1.3 4.4 0.2
Flatus with Discharge 23.9 1.4 2.1 0.2
Fecal Urgency 22.1 6.7 2.8 1.7
Fatty/Oily Stool 20.0 2.9 5.5 0.6
Oily Evacuation 11.9 0.8 2.3 0.2
Increased Defecation 10.8 4.1 2.6 0.8
Fecal Incontinence  7.7 0.9 1.8 0.2
*Treatment designates Xenical three times a day plus diet or placebo plus diet

These and other commonly observed adverse reactions were generally mild and transient, and they decreased during the second year of treatment. In general, the first occurrence of these events was within 3 months of starting therapy. Overall, approximately 50% of all episodes of GI adverse events associated with orlistat treatment lasted for less than 1 week, and a majority lasted for no more than 4 weeks. However, GI adverse events may occur in some individuals over a period of 6 months or longer.

Discontinuation of Treatment:   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.

Incidence in Controlled Clinical Trials:   The following table lists other treatment-emergent adverse events from seven multicenter, double-blind, placebo-controlled clinical trials that occurred at a frequency of >/=2% among patients treated with Xenical 120 mg three times a day and with an incidence that was greater than placebo during year 1 and year 2, regardless of relationship to study medication.

Table 8. Other Treatment-Emergent Adverse Events From
Seven Placebo-Controlled Clinical Trials
  Year 1 Year 2
Body System/
Adverse Events
Xenical
% Patients
(N=1913)
Placebo
% Patients
(N=1466)
Xenical
% Patients
(N=613)
Placebo
% Patients
(N=524)
Gastrointestinal System
 Abdominal Pain/Discomfort 25.5 21.4 -- --
 Nausea 8.1 7.3 3.6 2.7
 Infectious Diarrhea 5.3 4.4 -- --
 Rectal Pain/Discomfort 5.2 4.0 3.3 1.9
 Tooth Disorder 4.3 3.1 2.9 2.3
 Gingival Disorder 4.1 2.9 2.0 1.5
 Vomiting 3.8 3.5 -- --
Respiratory System
 Influenza 39.7 36.2 -- --
 Upper Respiratory Infection 38.1 32.8 26.1 25.8
 Lower Respiratory Infection 7.8 6.6 -- --
 Ear, Nose & Throat Symptoms 2.0 1.6 -- --
Musculoskeletal System
 Back Pain 13.9 12.1 -- --
 Pain Lower Extremities -- -- 10.8 10.3
 Arthritis 5.4 4.8 -- --
 Myalgia 4.2 3.3 -- --
 Joint Disorder 2.3 2.2 -- --
 Tendonitis -- -- 2.0 1.9
Central Nervous System
 Headache 30.6 27.6 -- --
 Dizziness 5.2 5.0 -- --
Body as a Whole
 Fatigue 7.2 6.4 3.1 1.7
 Sleep Disorder 3.9 3.3 -- --
Skin & Appendages
 Rash 4.3 4.0 -- --
 Dry Skin 2.1 1.4 -- --
Reproductive, Female
 Menstrual Irregularity 9.8 7.5 -- --
 Vaginitis 3.8 3.6 2.6 1.9
Urinary System
 Urinary Tract Infection 7.5 7.3 5.9 4.8
Psychiatric Disorder
 Psychiatric Anxiety 4.7 2.9 2.8 2.1
 Depression -- -- 3.4 2.5
Hearing & Vestibular Disorders
 Otitis 4.3 3.4 2.9 2.5
Cardiovascular Disorders        
 Pedal Edema -- -- 2.8 1.9
*Treatment designates Xenical 120 mg three times a day plus diet or placebo plus diet
--None reported at a frequency >/=2% and greater than placebo

Other Clinical Studies or Postmarketing Surveillance: Rare cases of hypersensitivity have been reported with the use of Xenical. Signs and symptoms have included pruritus, rash, urticaria, angioedema, and anaphylaxis.

Preliminary data from Xenical and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when Xenical was coadministered with cyclosporine.

Xenical Overdosage

Single doses of 800 mg Xenical 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.

Should a significant overdose of Xenical occur, it is recommended that the patient be observed for 24 hours. Based on human and animal studies, systemic effects attributable to the lipase-inhibiting properties of orlistat should be rapidly reversible.

Xenical Dosage and Administration

The recommended dose of Xenical is one 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 Xenical can be omitted.

Because Xenical 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 vitamins to ensure adequate nutrition. The supplement should be taken at least 2 hours before or after the administration of Xenical, such as at bedtime.

Doses above 120 mg three times a day have not been shown to provide additional benefit.

Based on fecal fat measurements, the effect of Xenical is 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.

The safety and effectiveness of Xenical beyond 2 years have not been determined at this time.

How is Xenical Supplied

Xenical is a dark-blue, hard-gelatin capsule containing pellets of powder.

Xenical 120 mg Capsules: Dark-blue, two-piece, No. 1 opaque hard-gelatin capsule imprinted with Roche and Xenical 120 in light-blue ink -- bottle of 90 (NDC 0004-0256-52).

Storage Conditions:    Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) Keep bottle tightly closed.

Xenical should not be used after the given expiration date. inserted by FC2 system