Xenical Side Effects Center

SIDE EFFECTS

Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in patients.

Commonly Observed (Based On First Year And Second Year Data)

Gastrointestinal (GI) symptoms were the most commonly observed treatment-emergent adverse events associated with the use of XENICAL in the seven 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 2 Commonly Observed Adverse Events

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 XENICAL 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.

Other Adverse Clinical Events

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 3 Other Treatment-Emergent Adverse Events From Seven Placebo-Controlled Clinical Trials

Table 4 illustrates the percentage of adult patients on XENICAL and placebo who developed a low vitamin level on two or more consecutive visits during 1 and 2 years of therapy in studies in which patients were not previously receiving vitamin supplementation.

Table 4 Incidence of Low Vitamin Values on Two or More Consecutive Visits (Nonsupplemented Adult Patients With Normal Baseline Values -First and Second Year)

Table 5 illustrates the percentage of adolescent patients on XENICAL and placebo who developed a low vitamin level on two or more consecutive visits during the 1-year study.

Table 5 Incidence of Low Vitamin Values on Two or More Consecutive Visits (Pediatric Patients With Normal Baseline Values*)

In the 4-year XENDOS study, the general pattern of adverse events 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 each year over the 4-year period.

In clinical trials in obese diabetic patients, hypoglycemia and abdominal distension were also observed.

Pediatric Patients

In clinical trials with XENICAL in adolescent patients ages 12 to 16 years, the profile of adverse reactions was generally similar to that observed in adults.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of XENICAL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to XENICAL exposure.

• Rare cases of increase in transaminases and in alkaline phosphatase and hepatitis that may be serious have been reported. There have been reports of hepatic failure observed with the use of XENICAL in postmarketing surveillance, with some of these cases resulting in liver transplant or death [see WARNINGS AND PRECAUTIONS].
• Rare cases of hypersensitivity have been reported with the use of XENICAL. Signs and symptoms have included pruritus, rash, urticaria, angioedema, bronchospasm and anaphylaxis. Very rare cases of bullous eruption have been reported.
• Rare cases of leukocytoclastic vasculitis have been reported. Clinical signs include palpable purpura, maculopapular lesions, or bullous eruption.
• Acute oxalate nephropathy and hyperoxaluria after treatment with XENICAL have been reported in patients with or at risk for renal disease.
• Pancreatitis has been reported with the use of XENICAL in postmarketing surveillance. No causal relationship or physiopathological mechanism between pancreatitis and obesity therapy has been definitively established.
• Lower gastrointestinal bleeding has been reported in patients treated with XENICAL. Most reports are nonserious; severe or persistent cases should be investigated further.

DRUG INTERACTIONS

Cyclosporine

Data from a XENICAL and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when XENICAL was coadministered with cyclosporine. XENICAL and cyclosporine should not be simultaneously coadministered. Cyclosporine should be administered 3 hours after the administration of XENICAL [see DOSAGE AND ADMINISTRATION, and WARNINGS AND PRECAUTIONS].

Fat-Soluble Vitamin Supplements And Analogues

Data from a pharmacokinetic interaction study showed that the absorption of beta-carotene supplement is reduced when concomitantly administered with XENICAL. XENICAL inhibited absorption of a vitamin E acetate supplement. The effect of XENICAL on the absorption of supplemental vitamin D, vitamin A, and nutritionally-derived vitamin K is not known at this time [see CLINICAL PHARMACOLOGY, and WARNINGS AND PRECAUTIONS].

Levothyroxine

Hypothyroidism has been reported in patients treated concomitantly with XENICAL and levothyroxine postmarketing. Patients treated concomitantly with XENICAL and levothyroxine should be monitored for changes in thyroid function. Administer levothyroxine and XENICAL at least 4 hours apart [see DOSAGE AND ADMINISTRATION].

Anticoagulants Including Warfarin

Vitamin K absorption may be decreased with XENICAL. Reports of decreased prothrombin, increased INR and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with XENICAL and anticoagulants. Patients on chronic stable doses of warfarin or other anticoagulants who are prescribed XENICAL should be monitored closely for changes in coagulation parameters [see CLINICAL PHARMACOLOGY].

Amiodarone

A pharmacokinetic study, where amiodarone was orally administered during orlistat treatment, demonstrated a reduction in exposure to amiodarone and its metabolite, desethylamiodarone [see CLINICAL PHARMOCOLOGY]. A reduced therapeutic effect of amiodarone is possible. The effect of commencing orlistat treatment in patients on stable amiodarone therapy has not been studied.

Antiepileptic Drugs

Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic drugs. Patients should be monitored for possible changes in the frequency and/or severity of convulsions.

Antiretroviral Drugs

Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs such as atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, and with the combinations lopinavir/ritonavir and emtricitabine/efavirenz/tenofovir disoproxil fumarate. The exact mechanism for this is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. HIV RNA levels should be frequently monitored in patients who take XENICAL while being treated for HIV infection. If there is a confirmed increase in HIV viral load, XENICAL should be discontinued.

Read the entire FDA prescribing information for Xenical (Orlistat 120 mg)