XENICAL SIDE EFFECTS
- Generic Name: orlistat 120 mg
- Brand Name: Xenical
- Drug Class: Gastrointestinal Agents, Other
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 1 : Commonly Observed Adverse Events
| Adverse Event | Year 1 | Year 2 | ||
| 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 †Oily discharge may be clear or have a coloration such as orange or brown. |
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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 2 : Other Treatment-Emergent Adverse Events From Seven Placebo-Controlled Clinical Trials
| Body System/ Adverse Event |
Year 1 | Year 2 | ||
| 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 T ract 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 |
| – None reported at a frequency ≥ 2% and greater than placebo * Treatment designates XENICAL 120 mg three times a day plus diet or placebo plus diet |
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Table 3 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 3 : Incidence of Low Vitamin Values on Two or More Consecutive Visits (Nonsupplemented Adult Patients With Normal Baseline Values – Firs t and Second Year)
| Placebo* | XENICAL* | |
| Vitamin A | 1.0% | 2.2% |
| Vitamin D | 6.6% | 12.0% |
| Vitamin E | 1.0% | 5.8% |
| Beta-carotene | 1.7% | 6.1% |
| * Treatment designates placebo plus diet or XENICAL plus diet | ||
Table 4 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 4 : Incidence of Low Vitamin Values on Two or More Consecutive Vis its (Pediatric Patients With Normal Baseline Values*)
| Placebo† | XENICAL† | |
| Vitamin A | 0.0% | 0.0% |
| Vitamin D | 0.7% | 1.4% |
| Vitamin E | 0.0% | 0.0% |
| Beta-carotene | 0.8% | 1.5% |
| *All patients were treated with vitamin supplementation throughout the course of the study †Treatment designates placebo plus diet or XENICAL plus diet |
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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.
- 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 after treatment with XENICAL has 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.
SRC: NLM .