sibutramine hydrochloride monohydrate
Meridia

Available forms
Available by prescription only
Capsules: 5 mg, 10 mg, 15 mg

Indications and dosages
 Management of obesity, including weight loss and maintenance of weight loss; should be used in conjunction with a reduced-calorie diet. Adults: 10 mg P.O. once daily with or without food. May increase dose to 15 mg daily after 4 weeks if there is inadequate weight loss. Patients who don’t tolerate the 10-mg dose may receive 5 mg daily. Doses above 15 mg daily aren’t recommended.

Pharmacodynamics
Antiobesity action: Sibutramine produces its therapeutic effects by inhibiting the reuptake of norepinephrine, serotonin, and dopamine.

Pharmacokinetics
Absorption: Rapidly absorbed from the GI tract. On average, at least 77% is absorbed.
Distribution: Distributed extensively into tissues, especially the liver and kidney with relatively low transfer to the fetus. In vitro, sibutramine and the active desmethyl metabolites M₁ and M₂ are extensively bound (97%, 94%, and 94%, respectively) to human plasma proteins.
Metabolism: Undergoes extensive first-pass metabolism by the cytochrome P-450 3A4 isoenzyme to M₁ and M₂; elimination half-lives of M₁ and M₂ are 14 and 16 hours, respectively.
Excretion: About 77% of a single oral dose is excreted in the urine.

Contraindications and precautions
Contraindicated in patients taking MAO inhibitors or other centrally acting appetite-suppressant drugs. Also contraindicated in patients hypersensitive to drug or its inactive ingredients and in those with anorexia nervosa. Don’t use drug in patients with history of coronary artery disease, heart failure, arrhythmias, CVA, severe renal failure, hepatic dysfunction, or a history of seizures. Use cautiously in patients with angle-closure glaucoma.

Interactions
Drug-drug. CNS depressants: May enhance CNS depression. Use together cautiously.
Dextromethorphan, dihydroergotamine, fentanyl, fluoxetine, fluvoxamine, lithium, MAO inhibitors, meperidine, paroxetine, pentazocine, sertraline, sumatriptan, tryptophan, venlafaxine: May cause hyperthermia, tachycardia, and loss of consciousness. Don’t use together. At least 2 weeks should elapse between stopping an MAO inhibitor and starting sibutramine, and vice versa.
Drugs that inhibit cytochrome P-450 3A4 metabolism, such as erythromycin and ketoconazole: May inhibit sibutramine metabolism. Sibutramine dosage may need to be reduced.
Ephedrine, pseudoephedrine: May increase blood pressure or heart rate. Monitor patient carefully.
Drug-lifestyle. Alcohol use: May enhance CNS depression. Discourage alcohol use.

Adverse reactions
CNS: asthenia, headache, insomnia, dizziness, nervousness, anxiety, depression, paresthesia, somnolence, CNS stimulation, emotional lability, migraine.
CV: tachycardia, vasodilation, hypertension, palpitation, chest pain, generalized edema
EENT: laryngitis, thirst, dry mouth, rhinitis, pharyngitis, sinusitis, ear disorder, ear pain.
GI: taste perversion, anorexia, constipation, increased appetite, nausea, dyspepsia, gastritis, vomiting, abdominal pain, rectal disorder.
GU: dysmenorrhea, urinary tract infection, vaginal candidiasis, metrorrhagia.
Musculoskeletal: arthralgia, myalgia, tenosynovitis, joint disorder, neck or back pain.
Respiratory: increased cough.
Skin: rash, sweating, acne.
Other: herpes simplex, flulike syndrome, allergic reaction.

Effects on lab test results
• May increase ALT, AST, GGT, LDH, alkaline phosphatase, and bilirubin levels.

Overdose and treatment
There’s no specific antidote to sibutramine. Treatment should consist of general measures used in the management of overdose: Establish an airway, monitor cardiac and vital signs, and institute general symptomatic and supportive measures. Cautious use of beta blockers may be indicated to control elevated blood pressure or tachycardia. The benefits of forced diuresis and hemodialysis are unknown.

Special considerations
• Rule out organic causes of obesity before starting therapy.
• Drug is recommended for obese patients with an initial body mass index of 30 kg/m² or more or 27 kg/m² or more in the presence of other risk factors, such as hypertension, diabetes, or dyslipidemia.
• Measure blood pressure and heart rate before starting therapy, with dose changes, and at regular intervals during therapy because drug is known to increase both blood pressure and heart rate.
• If a patient hasn’t lost at least 4 lb (1.8 kg) in the first 4 weeks of treatment, reevaluate therapy to consider increasing dosage or stopping drug.
• Weight loss can precipitate or exacerbate gallstone formation.
• Although not reported with sibutramine, some centrally acting weight-loss agents have been linked to a rare but fatal condition known as primary pulmonary hypertension.
Breast-feeding patients
• It isn’t known whether drug or its metabolites appear in breast milk. Avoid use in breast-feeding women.
Pediatric patients
• Safety and efficacy in children younger than age 16 haven’t been established.
Geriatric patients
• Select dosage cautiously for elderly patients because they’re more likely to have decreased hepatic, renal, or cardiac function; concurrent disease; and other drug therapy.

Patient education
• Advise patient to read the package insert before starting therapy and to review again each time the prescription is renewed.
• Instruct patient to report rash, hives, or other allergic reactions immediately.
• Tell patient to obtain medical approval before taking other prescription or OTC drugs, especially other weight-reducing agents, decongestants, antidepressants, cough suppressants, lithium, dihydroergotamine, sumatriptan, or tryptophan, because there is a potential for drug interactions.
• Emphasize importance of regular follow-up visits.
• Advise patient to use drug with a reduced-calorie diet.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use