Meridia (Sibutramine Hydrochloride) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

In placebo-controlled studies, 9% of patients treated with MERIDIA (n=2068) and 7% of patients treated with placebo (n=884) withdrew for adverse events.

In placebo-controlled studies, the most common events were dry mouth, anorexia, insomnia, constipation and headache. Adverse events in these studies occurring in >/=1% of MERIDIA treated patients and more frequently than in the placebo group are shown in the following table.

The following additional adverse events were reported in >/= 1% of all patients who received MERIDIA in controlled and uncontrolled pre-marketing studies.

Body as a Whole: fever.

Digestive System: diarrhea, flatulence, gastroenteritis, tooth disorder.

Metabolic and Nutritional: peripheral edema.

Musculoskeletal System: arthritis.

Nervous System: agitation, leg cramps, hypertonia, thinking abnormal.

Respiratory System: bronchitis, dyspnea.

Skin and Appendages: pruritus.

Special Senses: amblyopia.

Urogenital System: menstrual disorders.

OTHER ADVERSE EVENTS

CLINICAL STUDIES

Seizures: Convulsions were reported as an adverse event in three of 2068 (0.1%) MERIDIA treated patients and in none of 884 placebo-treated patients in placebo-controlled premarketing obesity studies. Two of the three patients with seizures had potentially predisposing factors (one had a prior history of epilepsy; one had a subsequent diagnosis of brain tumor). The incidence in all subjects who received MERIDIA (three of 4,588 subjects) was less than 0.1%.

Ecchymosis/Bleeding Disorders: Ecchymosis (bruising) was observed in 0.7% of MERIDIA treated patients and in 0.2% of placebo-treated patients in pre-marketing placebo-controlled obesity studies. One patient had prolonged bleeding of a small amount which occurred during minor facial surgery. MERIDIA may have an effect on platelet function due to its effect on serotonin uptake.

Interstitial Nephritis: Acute interstitial nephritis (confirmed by biopsy) was reported in one obese patient receiving MERIDIA during pre-marketing studies. After discontinuation of the medication, dialysis and oral corticosteroids were administered; renal function normalized. The patient made a full recovery.

Altered Laboratory Findings: Abnormal liver function tests, including increases in AST, ALT, GGT, LDH, alkaline phosphatase and bilirubin, were reported as adverse events in 1.6% of MERIDIA-treated obese patients in placebo-controlled trials compared with 0.8% of placebo patients. In these studies, potentially clinically significant values (total bilirubin >/=2 mg/dL; ALT, AST, GGT, LDH, or alkaline phosphatase >/=3x upper limit of normal) occurred in 0% (alkaline phosphatase) to 0.6% (ALT) of the MERIDIA treated patients and in none of the placebo-treated patients. Abnormal values tended to be sporadic, often diminished with continued treatment, and did not show a clear dose-response relationship.

POSTMARKETING REPORTS

Voluntary reports of adverse events temporally associated with the use of MERIDIA are listed below. It is important to emphasize that although these events occurred during treatment with MERIDIA, they may have no causal relationship with the drug. Obesity itself, concurrent disease states/risk factors, or weight reduction may be associated with an increased risk for some of these events.

Psychiatric: Cases of depression, suicidal ideation and suicide have been reported rarely in patients on sibutramine treatment. However, a relationship has not been established between the occurrence of depression and/or suicidal ideation and the use of sibutramine. If depression occurs during treatment with sibutramine, further evaluation may be necessary.

Hypersensitivity: Allergic hypersensitivity reactions ranging from mild skin eruptions and urticaria to angioedema and anaphylaxis have been reported (see " CONTRAINDICATIONS " and " PRECAUTIONS - Information For Patients ", and other reports of allergic reactions listed below).

Other: Abnormal dreams, abnormal ejaculation, abnormal gait, abnormal vision, alopecia, amnesia, anaphylactic shock, anaphylactoid reaction, anemia, anger, angina pectoris, arthrosis, atrial fibrillation, blurred vision, bursitis, cerebrovascular accident, chest pressure, chest tightness, cholecystitis, cholelithiasis, concentration impaired, confusion, congestive heart failure, depression aggravated, dermatitis, dry eye, duodenal ulcer, epistaxis, eructation, eye pain, facial edema, gastrointestinal hemorrhage, Gilles de la Tourette's syndrome, goiter, heart arrest, heart rate decreased, hematuria, hyperglycemia, hyperthyroidism, hypesthesia, hypoglycemia, hypothyroidism, impotence, increased intraocular pressure, increased salivation, increased urinary frequency, intestinal obstruction, leukopenia, libido decreased, libido increased, limb pain, lymphadenopathy, manic reaction, micturition difficulty, mood changes, mouth ulcer, myocardial infarction, nasal congestion, nightmares, otitis externa, otitis media, petechiae, photosensitivity (eyes), photosensitivity (skin), respiratory disorder, serotonin syndrome, short term memory loss, speech disorder, stomach ulcer, sudden unexplained death, supraventricular tachycardia, syncope, thrombocytopenia, tinnitus, tongue edema, torsade de pointes, transient ischemic attack, tremor, twitch, urinary retention, urticaria, vascular headache, ventricular tachycardia, ventricular extrasystoles, ventricular fibrillation, vertigo, yawn.

DRUG ABUSE AND DEPENDENCE

CONTROLLED SUBSTANCE

MERIDIA is controlled in Schedule IV of the Controlled Substances Act (CSA).

ABUSE AND PHYSICAL AND PSYCHOLOGICAL DEPENDENCE

Physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., drug development of tolerance, incrementation of doses, drug seeking behavior).