CONTRAINDICATIONS
MERIDIA is contraindicated in patients receiving monoamine oxidase inhibitors (MAOIs) (see WARNINGS).

MERIDIA is contraindicated in patients with hypersensitivity to sibutramine or any of the inactive ingredients of MERIDIA.

MERIDIA is contraindicated in patients who have a major eating disorder (anorexia nervosa or bulimia nervosa).

MERIDIA is contraindicated in patients taking other centrally acting weight loss drugs.


WARNINGS

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.


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.


Concomitant Cardiovascular Disease
MERIDIA substantially increases blood pressure and/or pulse rate in some patients. Therefore, MERIDIA should not be used in patients with a history of coronary artery disease, congestive heart failure, arrhythmias, or stroke.


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.


PRECAUTIONS

Pulmonary Hypertension
Certain centrally-acting weight loss agents that cause release of serotonin from nerve terminals have been associated with pulmonary hypertension (PPH), a rare but lethal disease. In premarketing clinical studies, no cases of PPH have been reported with sibutramine capsules. Because of the low incidence of this disease in the underlying population, however, it is not known whether or not MERIDIA may cause this disease.


Seizures
During premarketing testing, seizures were reported in < 0.1% of sibutramine treated patients. MERIDIA should be used cautiously in patients with a history of seizures. It should be discontinued in any patient who develops seizures.


Bleeding
There have been reports of bleeding in patients taking sibutramine. While a causal relationship is unclear, caution is advised in patients predisposed to bleeding events and those taking concomitant medications known to affect hemostasis or platelet function.


Gallstones
Weight loss can precipitate or exacerbate gallstone formation.


Renal Impairment
MERIDIA should be used with caution in patients with mild to moderate renal impairment. MERIDIA should not be used in patients with severe renal impairment, including those with end stage renal disease on dialysis (see Pharmacokinetics-Special Populations-Renal Insufficiency).


Hepatic Dysfunction
Patients with severe hepatic dysfunction have not been systematically studied; MERIDIA should therefore not be used in such patients.


Interference With Cognitive and Motor Performance
Although sibutramine did not affect psychomotor or cognitive performance in healthy volunteers, any CNS active drug has the potential to impair judgment, thinking or motor skills.


Information For Patients
Physicians should instruct their patients to read the patient package insert before starting therapy with MERIDIA and to reread it each time the prescription is renewed.

Physicians should also discuss with their patients any part of the package insert that is relevant to them. In particular, the importance of keeping appointments for follow-up visits should be emphasized.

Patients should be advised to notify their physician if they develop a rash, hives, or other allergic reactions.

Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, especially weight-reducing agents, decongestants, antidepressants, cough suppressants, lithium, dihydroergotamine, sumatriptan (Imitrex®), or tryptophan, since there is a potential for interactions.

Patients should be reminded of the importance of having their blood pressure and pulse monitoredat regular intervals.