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Medication Safety Issues
Sound-alike/look-alike issues:
Meridia® may be confused with Aredia®
Pronunciation
(si BYOO tra meen)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of obesity
Restrictions
C-IV
Pharmacotherapy for weight loss is recommended only for obese patients with a body mass index ?30 kg/m2, or ?27 kg/m2 in the presence of other risk factors such as hypertension, diabetes, and/or dyslipidemia or a high waist circumference; therapy should be used in conjunction with a comprehensive weight management program. Rule out organic causes of obesity (eg, untreated hypothyroidism) prior to use.
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were not observed in animal studies except at doses also causing maternal toxicity. There are no adequate and well-controlled studies in pregnant women. Use in pregnancy is not recommended.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to sibutramine or any component of the formulation; during or within 2 weeks of MAO inhibitors or concomitant centrally-acting appetite suppressants; anorexia nervosa, bulimia nervosa; poorly-controlled or uncontrolled hypertension, coronary artery disease, CHF arrhythmia; stroke
Warnings/Precautions
Concerns related to adverse effects:
• CNS effects: May impair the ability to engage in potentially hazardous activities.
•Hypertension: May cause increase in blood pressure; monitor baseline and on-therapy blood pressure. For patients experiencing a sustained increase in blood pressure dose reduction or discontinuation should be considered. Caution should be used in patients with hypertension and other cardiovascular conditions that might be exacerbated by increases in blood pressure. Should not be used in patients with coronary artery disease, HF, arrhythmia, or stroke.
• Primary pulmonary hypertension (PPH): A rare and frequently fatal pulmonary disease (PPH), has been reported to occur in patients receiving other agents with serotonergic activity which have been used as anorexiants. Although not reported in clinical trials, it is possible that sibutramine may share this potential; patients should be monitored closely.
• Serotonin syndrome (SS)/neuroleptic malignant syndrome (NMS)-like reactions: SS and NMS-like reactions have occurred with serotonin/norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs), including sibutramine, when used alone and particularly when used in combination with serotonergic agents (eg, triptans) or antidopaminergic agents (eg, antipsychotics). The diagnosis of SS can be made using the Hunter Serotonin Toxicity Criteria (Dunkley, 2003). Identification and differentiation of SS (eg, tremor, myoclonus, agitation) and more severe NMS-like reactions (eg, hyperthermia, muscle rigidity, autonomic instability, mental status changes) can be complex; monitor patients closely for either syndrome. Discontinue treatment (and any concomitant serotonergic and/or antidopaminergic agents) immediately if signs/symptoms arise.
• Tachycardia: May cause increased heart rate; monitor baseline and on-therapy pulse. For patients experiencing a sustained increase in pulse, dose reduction or discontinuation should be considered. Caution should be used in patients with hypertension and other cardiovascular conditions that might be exacerbated by increases heart rate. Should not be used in patients with coronary artery disease, CHF, arrhythmia. or stroke.
• Valvular heart disease: The use of some anorexigens has been associated with the development of valvular heart disease. Avoid stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that could increase the risk of sudden death that these conditions alone carry.
Disease-related concerns:
• Bleeding disorders: Use with caution in patients with bleeding disorders; rare cases of bleeding have occurred.
•Diabetes: Use with caution in patients with diabetes mellitus; antidiabetic agent requirements may be altered with anorexigens and concomitant dietary restrictions.
• Gallstones: Use with caution in patients with a history of gallstones; weight loss may precipitate or exacerbate gallstone formation.
• Glaucoma: Use with caution in patients with narrow-angle glaucoma; mydriasis has been reported.
• Hepatic impairment: Use with caution in patients with mild-moderate hepatic impairment; avoid use in severe impairment.
• Renal impairment: Use with caution in patients with mild-moderate renal impairment; avoid use in severe impairment.
• Psychiatric disorders: Use with caution and monitor closely in patients with a history of psychiatric symptoms; rare reports of depression, mania, psychosis, suicide, and suicidal ideation have been documented in patients on sibutramine.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; seizures have been reported with use.
• Tourette's syndrome: Use with caution in patients with Tourette's syndrome; stimulants may unmask tics.
Concurrent drug therapy issues:
• Serotonergic agents: As sibutramine blocks neuronal serotonin uptake, there is a potential for development of serotonin syndrome if used with other serotonergic agents; concurrent use of serotonergic agents (eg, SSRIs, sumatriptan, dihydroergotamine, dextromethorphan, meperidine, pentazocine, fentanyl, lithium) should be avoided.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <16 years of age.
Adverse Reactions
>10%:
Central nervous system: Headache (30%), insomnia (11%)
Gastrointestinal: Xerostomia (17%), anorexia (13%), constipation (12%)
1% to 10%:
Cardiovascular: Tachycardia (3%), vasodilation (2%), hypertension (2%), palpitation (2%), chest pain (2%)
Central nervous system: Dizziness (7%), nervousness (5%), anxiety (5%), depression (4%), somnolence (2%), CNS stimulation (2%), emotional lability (1%)
Dermatologic: Rash (4%)
Endocrine & metabolic: Dysmenorrhea (4%)
Gastrointestinal: Appetite increased (9%), nausea (6%), abdominal pain (5%), dyspepsia (5%), gastritis (2%), taste perversion (2%)
Genitourinary: Vaginal Monilia (1%)
Hepatic: Abnormal LFTs (2%)
Neuromuscular & skeletal: Back pain (8%), weakness (6%), arthralgia (6%), neck pain (2%), myalgia (2%), paresthesia (2%), tenosynovitis (1%), joint disorder (1%)
Otic: Ear disorder (2%)
Respiratory: Pharyngitis (10%), rhinitis (10%), sinusitis (5%), cough (4%)
Miscellaneous: Flu-like syndrome (8%), diaphoresis (3%), allergic reactions (2), thirst (2%)
<1%: Bruising
Frequency not defined:
Cardiovascular: Peripheral edema
Central nervous system: Thinking abnormal, agitation, fever
Dermatologic: Pruritus
Endocrine & metabolic: Menstrual disorders/irregularities
Gastrointestinal: Diarrhea, flatulence, gastroenteritis, tooth disorder
Neuromuscular & skeletal: Arthritis, hypertonia, leg cramps
Ocular: Amblyopia
Respiratory: Bronchitis, dyspnea
Postmarketing and/or case reports (frequency not defined; limited to important or life-threatening): Amnesia, anaphylactic shock, anaphylactoid reaction, anemia, angina, angioedema, arrhythmia, arthrosis, atrial fibrillation, blurred vision, cardiac arrest, cerebrovascular accident, CHF, cholecystitis, cholelithiasis, GI hemorrhage, goiter, hematuria, hyper-/hypoglycemia, hyper-/hypothyroidism, hypersensitivity reaction, impotence, interstitial nephritis, intestinal obstruction, intraocular pressure increased, leukopenia, lymphadenopathy, mania, mouth/stomach ulcer, mydriasis, photosensitivity, psychosis, seizure, serotonin syndrome, stroke, suicidal ideation, syncope, thrombocytopenia, tongue edema, torsade de pointes, Tourette's syndrome, urinary retention, urticaria, transient ischemic attack, vascular headache, ventricular arrhythmia, vertigo
Metabolism/Transport Effects
Substrate of CYP3A4 (major)
Drug Interactions
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ergot Derivatives: Sibutramine may enhance the serotonergic effect of Ergot Derivatives. This may cause serotonin syndrome. Risk X: Avoid combination
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Serotonin Modulators: Sibutramine may enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid excess ethanol ingestion.
Herb/Nutraceutical: St John's wort and SAMe may decrease sibutramine levels.
Storage
Store at room temperature of 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Sibutramine and its two primary metabolites block the neuronal uptake of norepinephrine, serotonin, and (to a lesser extent) dopamine. There is no monoamine-releasing (or depleting) activity.
Pharmacodynamics/Kinetics
Absorption: 77%; rapid
Protein binding, plasma: Parent drug and metabolites: >94%
Metabolism: Hepatic; undergoes first-pass metabolism via CYP3A4; forms two primary metabolites (M1 and M2; active)
Half-life elimination: Sibutramine: 1 hour; Metabolites: M1: 14 hours; M2: 16 hours
Time to peak: Sibutramine: 1.2 hours; Metabolites (M1 and M2): 3-4 hours
Excretion: Primarily urine (77% as inactive metabolites); feces
Dosage
Children ?16 years and Adults:
Initial: 10 mg once daily; after 4 weeks may titrate up to 15 mg once daily as needed and tolerated (may be used for up to 2 years, per manufacturer labeling)
Maintenance: 5-15 mg once daily
Dosage adjustment in renal/hepatic impairment: Should not be used in patients with severe renal or hepatic impairment
Administration: Oral
May administer with or without food.
Monitoring Parameters
Weight, waist circumference, blood pressure, heart rate. Do initial blood pressure and heart rate evaluation and then monitor regularly during therapy. If patient has sustained increases in either blood pressure or pulse rate, consider discontinuing or reducing the dose of the drug.
Reference Range
Adult classification of weight by BMI (kg/m2):
Underweight: <18.5
Normal: 18.5-24.9
Overweight: 25-29.9
Obese, class I: 30-34.9
Obese, class II: 35-39.9
Extreme obesity (class III): ?40
Waist circumference: In adults with a BMI of 25-34.9 kg/m2, high-risk waist circumference is defined as:
Men >102 cm (>40 in)
Women >88 cm (>35 in)
Dietary Considerations
Sibutramine, as an appetite suppressant, is the most effective when combined with a low calorie diet and behavior modification counseling.
Patient Education
Take exactly as directed; do not increase dose or frequency without consulting prescriber. May be taken with meals (do not take at bedtime). Avoid alcohol, caffeine, or OTC medications that act as stimulants. You may experience restlessness, dizziness, sleepiness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); insomnia (taking medication early in morning may help, warm milk, and quiet environment at bedtime may help); increased appetite, nausea or vomiting (small frequent meals, frequent mouth care may help); constipation (increased exercise, fluids, fruit, or fiber may help); diarrhea; or altered menstrual periods (reversible when drug is discontinued). Report chest pain, palpitations, or irregular heartbeat; excessive nervousness, excitation, or sleepiness; back pain, muscle weakness, or tremors; CNS changes (acute headache, aggressiveness, restlessness, excitation, sleep disturbances); menstrual pattern changes; rash; blurred vision; runny nose, sinusitis, cough, or respiratory difficulty. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
Additional Information
Physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (eg, development of tolerance, excessive increases of doses, drug seeking behavior).
Cardiovascular Considerations
Sibutramine may induce a significant blood pressure increase and should be avoided in patients with cardiovascular disease. The hypertensive effect of sibutramine may theoretically potentiate the nocturnal hypertension in patients with sleep apnea. Because this drug is used in the management of obesity, it is likely that many of the patients receiving it will have coexisting obstructive sleep apnea.
Unlike dexfenfluramine and fenfluramine, the medication does not cause the release of serotonin from neurons. Tests done on humans show no evidence of valvular heart disease and experiments done on animals show no evidence of the neurotoxicity which was found in similar testing using animals treated with fenfluramine and dexfenfluramine; has minimal potential for abuse.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and taste perversion (see Dental Health Professional Considerations).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
The mechanism of action is thought to be different from the “fen” drugs. Sibutramine works to suppress the appetite by inhibiting the reuptake of norepinephrine and serotonin. Unlike dexfenfluramine and fenfluramine, it is not a serotonin releaser. Sibutramine is closer chemically to the widely used antidepressants such as fluoxetine (Prozac®). The FDA approved sibutramine over the objections of its own advisory panel, who called the drug too risky. FDA reported that the drug causes blood pressure to increase, generally by a small amount, though in some patients the increases were higher. It is now recommended that patients taking sibutramine have their blood pressure evaluated regularly.
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Monitor therapeutic response and periodically evaluate the need for continued use. Monitor vital signs, weight, and adverse reactions at start of therapy, when changing dosage, and at regular intervals during therapy. Assess knowledge/teach patient appropriate use, possible side effects, and symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride:
Meridia®: 5 mg, 10 mg, 15 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Meridia)
5 mg (30): $109.99
10 mg (30): $109.99
15 mg (30): $139.99
References
Abenhaim L, Moride Y, Brenot F, et al, “Appetite-Suppressant Drugs and the Risk of Primary Pulmonary Hypertension. International Primary Pulmonary Hypertension Study Group,” N Engl J Med, 1996, 335(9):609-16.
“Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: Executive Summary. Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults,” Am J Clin Nutr, 1998, 68(4):899-917.
Dunkley EJ, Isbister GK, Sibbritt D, et al, “The Hunter Serotonin Toxicity Criteria: Simple and Accurate Diagnostic Decision Rules for Serotonin Toxicity,” QJM, 2003, 96(9):635-42.
King DJ and Devaney N, “Clinical Pharmacology of Sibutramine Hydrochloride (BTS 54524), A New Antidepressant, in Healthy Volunteers,” Br J Clin Pharmacol, 1988, 26(5):607-11.
Snow V, Barry P, Fitterman N, et al, “Pharmacologic and Surgical Management of Obesity in Primary Care: A Clinical Practice Guideline from the American College of Physicians,” Ann Intern Med, 2005, 142(7):525-31.
“U.S. Preventative Services Task Force. Screening for Obesity in Adults: Recommendations and Rationale,” Ann Intern Med, 2003, 139(11):933-49
International Brand Names
Lexi-Comp.com
Last full review/revision June 2009
Content last modified June 2009
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