Pharmacy & Therapeutics - December 2008 - (Page 727)

CONTINUING EDUCATION CREDIT or if it contains no fat, the dose of orlistat can be omitted. Because orlistat can block the absorption of approximately 30% of dietary fat, patients should be counseled to maintain a diet containing 30% or fewer calories from fat. Patients should also supplement their diets with a multivitamin containing fat-soluble vitamins A, D, E, and K as well as beta-carotene, because orlistat reduces the absorption of these components from dietary sources. Orlistat is now available as a nonprescription product and is marketed as Alli by GlaxoSmithKline. It is taken as a 60-mg dose orally three times daily. The drug itself is only minimally absorbed and excreted as unchanged drug in the feces. It is metabolized within the gut wall to form inactive metabolites. Side effects of orlistat primarily affect the GI tract and result from the inhibition of fat absorption. These effects may include abdominal pain, soft or liquid stools, increased defecation, and flatulence. Oily spotting, fecal incontinence, and hemorrhoids have also been reported (Table 5).10 The effects appear to be dose-related, and some effects may decrease over time. Patients should be counseled that increased adverse effects might be related to the amount of fat consumed in the diet.11 Orlistat has been shown to produce weight loss of 2.9 kg greater than placebo when taken for 12 months. When orlistat and sibutramine were compared in clinical trials, sibutramine produced significantly greater weight reduction than orlistat in terms of kilograms lost. Table 4 Contraindications and Adverse Effects Associated with Sibutramine (Meridia) Contraindications • Anorexia nervosa or bulimia nervosa • Concomitant monoamine oxidase (MAO) inhibitor use • Concomitant use of centrally acting appetite suppressants • Hypersensitivity to sibutramine Adverse effects • Increased systolic and diastolic blood pressure • Increased heart rate • Tachycardia and palpitations • Dry mouth • Constipation • Serotonin syndrome From Meridia package insert, Abbott, 2006.9 receptors. This risk is increased significantly if the patient is currently taking other medications that increase serotonin in the CNS, such as selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase (MAO) inhibitors. In clinical trials, sibutramine has resulted in weight loss of 4.45 kg or greater, with most patients losing at least 5% of their baseline body weight throughout the course of therapy. Significant weight reduction occurred after two to four weeks of therapy, and patients were able to maintain their original weight loss for up to 18 months by continuing to take the drug. Other possible benefits of weight loss with sibutramine include decreased levels of triglycerides and low-density lipoprotein (LDL) cholesterol and increased high-density lipoprotein (HDL) cholesterol levels.10 Orlistat. Orlistat (Xenical) is a nonsystemic inhibitor of gastrointestinal (GI) lipases that are necessary for the breakdown of fat in the GI tract. The unabsorbable fat is then excreted. Orlistat is a synthetic derivative of lipostatin isolated from a soil bacterium, Streptomyces toxytricini. The recommended dose is 120 mg orally three times daily during or within one hour of each fat-containing meal. If a meal is skipped Investigational Therapies Rimonabant (Acomplia). As a result of the growing population of patients with obesity, there is a wide demand for researchers to examine new safe and effective treatment options. This exploration led to the development of a new medication, rimonabant (Sanofi-Aventis). This drug is distinct because of its novel mechanism of action as a selective cannabinoid-1 (CB-1) receptor antagonist. In the CNS, endocannabinoids are released and stimulate appetite, lipogenesis, and fat accumulation in the periphery. Rimonabant works to block these effects of endocannabinoids. Studies had shown that rimonabant’s blockade of the CB-1 receptor could induce a state similar to melancholic depression as well as increase the risk of suicidal behavior.12 Patients with a history of psychiatric illness or psychiatric disorders should consider other treatment options before deciding to initiate therapy with rimonabant. Other side effects include nausea, mood alteration, anxiety, and dizziness. Hepatic CYP 3A and amidohydrolase pathways are involved in the drug’s metabolism. The use of tobacco, alcohol consumption, or coadminstration of CYP 3A4 inducers, such as phenytoin (Dilantin, Pfizer), phenobarbital, carbamazepine (Carbitrol, Shire; Tegretol, Novartis), and rifampin, may reduce the plasma concentration of rimonabant, just as CYP 3A4 inhibitors like clarithromycin (Biaxin, Abbott), ritonavir (Norvir, Abbott), itraconazole (Sporanox, Janssen), and ketoconazole (Nizoral, Janssen) can cause an increase in serum concentrations of rimonabant. Rimonabant is absorbed quickly following oral administration and exhibits linear pharmacokinetics. A maximum serum concentration is attained in approximately two hours after oral administration of 20 mg. In a nonobese individual, the termi- Table 5 Contraindications and Adverse Effects Associated with Orlistat (Xenical) Contraindications • Cholestasis • Chronic malabsorption syndrome • Hypersensitivity to orlistat products Adverse effects • Abdominal pain • Soft or liquid stools • Increased defecation and flatulence • Oily spotting • Fecal incontinence • Hemorrhoids From Xenical package insert, Roche, 2007.10 Vol. 33 No. 12 • December 2008 • P&T® 727

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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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