warnings
WARNINGS Concomitant Cardiovascular Disease Due to an increased risk of heart attack and stroke in patients with cardiovascular disease, MERIDIA should not be used in patients with a history of coronary artery disease, congestive heart failure, arrhythmias, or stroke. Blood Pressure and Pulse MERIDIA SUBSTANTIALLY INCREASES BLOOD PRESSURE AND/OR PULSE RATE IN SOME PATIENTS. REGULAR MONITORING OF BLOOD PRESSURE AND PULSE RATE IS REQUIRED WHEN PRESCRIBING MERIDIA. In placebo-controlled obesity studies, sibutramine 5 to 20 mg once daily was associated with mean increases in systolic and diastolic blood pressure of approximately 1 to 3 mm Hg relative to placebo, and with mean increases in pulse rate relative to placebo of approximately 4 to 5 beats per minute. Larger increases were seen in some patients, particularly when therapy with sibutramine was initiated at the higher doses (see table below). In premarketing placebo-controlled obesity studies, 0.4% of patients treated with sibutramine were discontinued for hypertension (SBP ≥160 mm Hg or DBP ≥ 95 mm Hg), compared with 0.4% in the placebo group, and 0.4% of patients treated with sibutramine were discontinued for tachycardia (pulse rate ≥ 100 bpm), compared with 0.1% in the placebo group. Blood pressure and pulse should be measured prior to starting therapy with MERIDIA and should be monitored at regular intervals thereafter. For patients who experience a sustained increase in blood pressure or pulse rate while receiving MERIDIA, either dose reduction or discontinuation should be considered. MERIDIA should be given with caution to those patients with a history of hypertension (see DOSAGE AND ADMINISTRATION ), and should not be given to patients with uncontrolled or poorly controlled hypertension. Percent Outliers in Studies 1 and 2 Dose (mg) % Outliers* * Outlier defined as increase from baseline of ≥ 15 mm Hg for three consecutive visits (SBP), ≥ 10 mm Hg for three consecutive visits (DBP), or pulse ≥ 10 bpm for three consecutive visits. SBP DBP Pulse Placebo 9 7 12 5 6 20 16 10 12 15 28 15 13 17 24 20 14 22 37 Potential Interaction With Monoamine Oxidase Inhibitors MERIDIA is a norepinephrine, serotonin and dopamine reuptake inhibitor and should not be used concomitantly with MAOIs (see PRECAUTIONS, Drug Interactions subsection). There should be at least a 2-week interval after stopping MAOIs before commencing treatment with MERIDIA. Similarly, there should be at least a 2-week interval after stopping MERIDIA before starting treatment with MAOIs. Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-Like Reactions The development of a potentially life-threatening serotonin syndrome, or Neuroleptic Malignant Syndrome (NMS)-like reactions, has been reported with SNRIs and SSRIs alone, including MERIDIA treatment, but particularly with concomitant use of serotonergic drugs (including triptans), with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms [e.g., nausea, vomiting, diarrhea] (see PRECAUTIONS, Drug Interactions ). Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms. Glaucoma Because MERIDIA can cause mydriasis, it should be used with caution in patients with narrow angle glaucoma. Miscellaneous Organic causes of obesity (e.g., untreated hypothyroidism) should be excluded before prescribing MERIDIA.