Medications> Obesity>

INDICATIONS

• Obesity management including weight loss and weight maintenance in patients with a body mass index (BMI) > 30 kg/m² OR > 27 kg/m² in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia).

MECHANISM

• Orlistat blocks the absorption of dietary fat by inhibiting gastrointestinal lipase.

USUAL ADULT DOSING

• 120 mg (one capsule) orally three times a day with each main fat-containing meal, taken during the meal or up to one hour after the meal.
• Doses above 120 mg three times a day have not been shown to provide additional benefit.

FORMS

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

DOSING IN SPECIAL POPULATIONS

• Usual dose

• Usual dose likely.

• Category B

• No data. Generally not recommended.

ADVERSE DRUG REACTIONS

• Gastrointestinal side effects are most common, especially with diets high in fat (>30% total daily calories from fat).

• Flatulence with discharge
• Fecal urgency and incontinence
• Steatorrhea
• Oily spotting and oily evacuation
• Increased defecation

• Abdominal Pain
• Nausea/vomiting
• Dizziness
• Infectious diarrhea
• Rectal pain

• Hypersensitivity reaction: pruritus, rash (unspecified), urticaria, angioedema, bronchospasm, and anaphylactoid reactions
• Bullous rash or eruption
• Elevated hepatic enzymes
• Increased alkaline phosphatase

DRUG INTERACTIONS

• Due to orlistat's mechanism of action, the potential exists for the malabsorption of fat soluble drugs and dietary supplements
• Vitamin A, D, E, and K, beta-carotene: fat-soluble vitamin supplements (and analogues) should be administered at least 2 hrs before or after the administration of orlistat
• Warfarin: INR may be increased secondary to lower absorption of vitamin K. Warfarin dose may need to be decreased.
• Cyclosporine: reduces the absorption of Cyclosporine. Cyclosporine should be administered at least 2 hrs before or after orlistat
• Amiodarone and propafenone: absorption may be decreased. Administer these drugs 2 hrs before or after orlistat.
• Levothyroxine: absorption may be significantly decreased. Administer levothyroxine 4 hrs before or after orlistat.
• Pravastatin, digoxin, phenytoin, oral contraceptives, nifedipine, and glyburide: pharmacokinetics were not affected by orlistat co-administration.

PHARMACOKINETIC

COMMENTS

• Compared to placebo, orlistat produces a modest weight reduction of 2.9 kg over two years.
• Patients should be strongly encouraged to take a multivitamin supplement that contains fat-soluble vitamins (A, D, E, and K)
• For obese patients with elevated blood pressure, cardiovascular disease, or dyslipidemia, orlistat is suggested as first line pharmacologic therapy given its excellent cardiovascular safety profile and beneficial effects on lipids as compared to sibutramine which was recently taken off the market in October 2010 due to adverse cardiovascular effects.
• Orlistat is not recommended in patients with chronic malabsorption syndromes or cholestasis.

REFERENCES