Pharmacy & Therapeutics - December 2008 - (Page 726)

CONTINUING EDUCATION CREDIT in all bariatric surgery groups. The most weight loss occurred in the gastric bypass patients. Mortality rates were higher in controls at the 10-year follow-up. The study authors concluded that bariatric surgery not only achieves long-term weight loss but also decreases overall mortality. As with other weight-loss surgical procedures, gastric bypass is associated with risks, such as infection in the incision; leakage from the stomach into the abdominal cavity or where the intestine is connected, resulting in peritonitis; and nutritional deficiencies of vitamin B12 and iron, which can lead to anemia.6 Duodenal switch. Another surgical option that is becoming more popular in the U.S. is the duodenal switch, in which two-thirds of the stomach is removed and most of the small intestine is bypassed. It is the most invasive of the bariatric procedures. The initial weight loss with this procedure is similar to that with gastric bypass, but patients continue to lose weight in the second year after surgery and average weight loss is much higher. The risks associated with the duodenal switch are micronutrient deficiencies, malnutrition, and increased bowel movements. Patients opting for bariatric surgery must be highly motivated and compliant with changes in eating habits and lifestyle.1,7 Sibutramine (Meridia) and Orlistat (Xenical) Sibutramine (Meridia, Abbott) and orlistat (Xenical, Roche) are approved for the long-term management of obesity. Longterm therapy is indicated for obese patients with a BMI of 30 kg/m2 or greater and for patients with a BMI of 27 kg/m2 who also have diabetes, dyslipidemia, or hypertension. The safety and efficacy of these agents have not been established beyond two years. Sibutramine. Sibutramine is a non-amphetamine appetite suppressant that blocks the neuronal uptake of norepinephrine, serotonin, and dopamine. Sibutramine is labeled as a Schedule IV controlled substance despite its low potential for psychological addiction or drug dependence. The recommended initial dose is 10 mg orally once daily. This dose may be titrated after four weeks to a maximum of 15 mg once daily and may be decreased to 5 mg daily if intolerance develops. Sibutramine may be given with or without food. It is rapidly absorbed and is highly protein-bound (more than 94%). The parent drug undergoes first-pass metabolism via cytochrome P450 3A4 to form two active metabolites. The half-life of the metabolites is approximately 15 hours. Excretion occurs primarily in the urine. Side effects include increased systolic and diastolic blood pressure, increased heart rate, tachycardia, palpitations, dry mouth, and constipation (Table 4).9 An additional risk associated with sibutramine includes the possibility of the development of a life-threatening adverse drug reaction, known as serotonin syndrome, as a result of excess serotonergic activity at central nervous system (CNS) and peripheral serotonin Pharmacological Treatment Three drugs have been approved by the FDA for the treatment of obesity in the U.S. Only two of these are approved for long-term use. Phentermine (Adipex-P, Ionamin) Phentermine HCl, an appetite suppressant, is approved for short-term monotherapy in patients 16 years of age and older. Phentermine is structurally similar to dextroamphetamine and elicits its effect by stimulating the hypothalamus to result in decreased appetite. These effects are most likely mediated via norepinephrine and dopamine metabolism. Phentermine is available as tablets (Adipex-P, Gate) or as resin capsules (Ionamin, Celltech). The recommended dose for the tablet is 37.5 mg taken once daily or 18.75 mg taken twice daily. The tablet should be taken before breakfast or one to two hours after breakfast. The resin capsule, at a dose of 15 to 30 mg, is taken before breakfast or 10 to 14 hours before bedtime. Evening administration should be avoided because of the possibility of insomnia, although insomnia appears to be rare with the resin formulation. The drug is well absorbed and is excreted unchanged in the urine. The elimination half-life is 20 hours. Although phentermine is approved only for short-term therapy (12 weeks), physicians may continue to prescribe it for longer periods of time if it proves to be effective for the patient. Discontinuation of therapy should be considered if significant weight loss has not been achieved during the first four to six weeks. Anorectic agents should not be used in patients with cardiovascular disease, hyperthyroidism, or moderate-to-severe hypertension. Rare cases of valvular injury, as well as primary pulmonary hypertension (PPH), have been reported. Phentermine may exacerbate behavior and thought disturbances in psychotic patients (Table 3).8 Table 3 Contraindications and Adverse Effects Associated with Phentermine (Adipex-P) Contraindications • Advanced arteriosclerosis • Symptomatic cardiovascular disease • Moderate to severe hypertension (stage II or III) • Hyperthyroidism • Glaucoma • History of drug abuse • Concomitant monoamine oxidase (MAO) inhibitor use or within 14 days of phentermine use • Age younger than 16 years • Hypersensitivity to sympathomimetic amines or any component of the formulation Adverse effects • Exacerbation of symptoms of behavior and thought disorder in psychotic patients • Increased systolic and diastolic blood pressure • Tachycardia and palpitations • Euphoria • Insomnia and restlessness • Dry mouth • Diarrhea • Impotence or changes in libido • Tremor From Adipex-P package insert, Teva, 2005.8 726 P&T® • December 2008 • Vol. 33 No. 12

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Pharmacy & Therapeutics - December 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Interpreting Estimates of Treatment Effects Chemotherapy Foundation Symposium XXVI: Innovative Cancer Therapy for Tomorrow Third Annual Onmark National Payor/Provider Forum Fourth Annual Ophthalmic Drug Development and Delivery Summit Classification and Pharmacological Management Of Obesity CE Test and Forms Season’s Greetings: Thanks to Our Readers and Reviewers

Pharmacy & Therapeutics - December 2008

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