"Nov. 9, 2011 -- The FDA is again considering approval of an experimental weight loss drug it rejected a year ago over concerns about potential heart problems and birth defects in babies born to women who take the drug.
(Generic versions may still be available.)
In placebo-controlled studies, 9% of patients treated with sibutramine (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 sibutramine treated patients and more frequently than in the placebo group are shown in the following table.
Obese Patients in Placebo-Controlled Studies
(n = 2068)
(n = 884)
|BODY AS A WHOLE|
|Hypertension/increased blood pressure||2.1||0.9|
|METABOLIC & NUTRITIONAL|
|Cough incr ease||3.8||3.3|
|SKIN & APPENDAGES|
|Urinary tract infection||2.3||2.0|
The following additional adverse events were reported in ≥ 1% of all patients who received sibutramine in controlled and uncontrolled premarketing studies.
Body as a Whole: fever.
Metabolic and Nutritional: peripheral edema.
Musculoskeletal System: arthritis.
Nervous System: agitation, leg cramps, hypertonia, thinking abnormal.
Skin and Appendages: pruritus.
Special Senses: amblyopia.
Urogenital System: menstrual disorders.
Other Adverse Events
Convulsions were reported as an adverse event in three of 2068 (0.1%) sibutramine treated patients and in none of 884 placebo-treated patients in placebo-cont rolled 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 sibutramine (three of 4,588 subjects) was less than 0.1%.
Ecchymosis (bruising) was observed in 0.7% of sibutramine trea ted patients and in 0.2% of placebo-treated patients in premarketing placebo-controlled obesity studies. One patient had prolonged bleeding of a small amount which occurred during minor facial surgery. Sibutramine may have an effect on platelet function due to its effect on serotonin uptake.
Acute interstitial nephritis (confirmed by biopsy) was reported in one obese patient receiving sibutramine during premarketing 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 sibutramine-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 ≥ 3 × upper limit of normal) occurred in 0% (alkaline phosphatase) to 0.6% (ALT) of the sibutramine 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.
Voluntary reports of adverse events temporally associated with the use of sibutramine are listed below. It is important to emphasize that although these events occurred during treatment with sibutramine, 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.
Cases of depression, psychosis, mania, suicidal ideation and suicide have been reported rarely in patients on sibutramine treatment. However, a relationship has not been established between these events and the use of sibutramine. If any of these events should occur during treatment with sibutramine, discontinuation should be considered.
Allergic hypersensitivity reactions ranging from mild skin eruptions and urticaria to angioedema and anaphylaxis have been reported (see CONTRAINDICATIONS and PATIENT INFORMATION, and other reports of allergic reactions listed below).
Other Postmarketing Reported Events
Body as a Whole: anaphylactic shock, anaphylactoid reaction, chest pressure, chest tightness, facial edema, limb pain, sudden unexplained death.
Cardiovascular System: angina pectoris, atrial fibrillation, congestive heart failure, heart arrest, heart rate decreased, myocardial infarction, supraventricular tachycardia, syncope, torsade de pointes, vascular headache, ventricular tachycardia, ventricular extrasystoles, ventricular fibrillation.
Nervous System: abnormal dreams, abnormal gait, amnesia, anger, cerebrovascular accident, concentration impaired, confusion, depression aggravated, Gilles de la Tourette's syndrome, hypesthesia, libido decreased, libido increased, mood changes, nightmares, short term memory loss, speech disorder, transient ischemic attack, tremor, twitch, vertigo.
Drug Abuse And Dependence
MERIDIA (sibutramine hydrochloride monohydrate) 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).
Read the Meridia (sibutramine hydrochloride monohydrate) Side Effects Center for a complete guide to possible side effects
CNS Active Drugs
The use of MERIDIA (sibutramine hydrochloride monohydrate) in combination with other CNS-active drugs, particularly serotonergic agents, has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of MERIDIA (sibutramine hydrochloride monohydrate) with other centrally-acting drugs is indicated (see CONTRAINDICATIONS and WARNINGS).
In patients receiving monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, selegiline) in combination with serotonergic agents (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine), there have been reports of serious, sometimes fatal, reactions (“serotonin syndrome;” see below). Because sibutramine inhibits serotonin reuptake, MERIDIA should not be used concomitantly with a MAOI (see CONTRAINDICATIONS ). At least 2 weeks should elapse between discontinuation of a MAOI and initiation of treatment with MERIDIA (sibutramine hydrochloride monohydrate) . Similarly, at least 2 weeks should elapse between discontinuation of MERIDIA (sibutramine hydrochloride monohydrate) and initiation of treatment with a MAOI.
The rare, but serious, constellation of symptoms term ed “serotonin syndrome” has also been reported with the concomitant use of selective serotonin reuptake inhibitors and agents for migraine therapy, such as Imitrex® (sumatriptan succinate) and dihydroergotamine, certain opioids, such as dextromethorphan, meperidine, pentazocine and fentanyl, lithium, or tryptophan. Serotonin syndrome has also been reported with the concomitant use of two serotonin reuptake inhibitors. The syndrome requires immediate medical attention and may inclu de one or more of the following symptoms: excitement, hypomania, restlessness, loss of consciousness, confusion, disorientation, anxiety, agitation, motor weakness, myoclonus, tremor, hemiballismus, hyperreflexia, ataxia, dysarthria, incoordination, hyperthermia, shivering, pupillary dilation, diaphoresis, emesis, and tachycardia.
Because sibutramine inhibits serotonin reuptake, in general, it should not be administered with other serotonergic agents such as those listed above. However, if such a combination is clinically indicated , appropriate observation of the patient is warranted.
Drugs That May Raise Blood Pressure and/or Heart Rate
Concomitant use of MERIDIA (sibutramine hydrochloride monohydrate) and other agents that may raise blood pressure or heart rate have not been evaluated. These include certain decongestants, cough, cold, and allergy medications that contain agents such as ephedrine, or pseudoephedrine. Caution should be used when prescribing MERIDIA (sibutramine hydrochloride monohydrate) to patients who use these medications.
In a double-blind, placebo-controlled, crossover study in 19 volunteers, administration of a single dose of ethanol (0.5 mL/kg) together with 20 mg of sibutramine resulted in no psychomotor interactions of clinical significance between alcohol and sibutramine. However, the concomitant use of MERIDIA (sibutramine hydrochloride monohydrate) and excess alcohol is not recommended.
The suppression of ovulation by oral contraceptives was not inhibited by sibutramine. In a crossover study, 12 healthy female volunteers on oral steroid contraceptives received placebo in one period and 15 mg sibutramine in another period over the course of 8 weeks. No clinically significant systemic interaction was observed; therefore, no requirement for alternative contraceptive precautions are needed when patients taking oral contraceptives are concurrently prescribed sibutramine.
Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.
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