orlistat (Rx, OTC)

1-10%

Oily spotting (5%)

Frequency Not Defined

Flatulence

Fatty/oily stool

Increased defecation

Fecal incontinence

Nausea

Vomiting

Reduced absorption of fat soluble vitamins and beta-carotene

Liver failure

Oxalate nephropathy

Leukocytoclastic vasculitis

Contraindications

Pregnancy

Chronic malabsorption syndrome

Cholestasis

Hypersensitivity

Cautions

If a meal is missed or contains no fat, dose should be omitted

Daily fat intake (30% of calories), carbohydrate, and protein should be evenly distributed over 3 main meals

Multivitamin supplement (including vitamin A, D, E, K) is recommended; supplement should be taken once a day at least 2 hours before or after the administration of orlistat, such as at bedtime

Postmarketing reports of severe liver injury with hepatocellular necrosis or acute hepatic failure with some cases resulting in liver transplant or death; patients should be instructed to report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, dark urine, light-colored stools, or right upper quadrant pain) while receiving therapy; when these symptoms occur, this and other suspect medications should be discontinued immediately and liver function tests and ALT and AST levels obtained

Some patients may develop increased levels of urinary oxalate following treatment; cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure reported; monitor renal function when prescribing therapy to patients at risk for renal impairment and use with caution in those with a history of hyperoxaluria or calcium oxalate nephrolithiasis

Substantial weight loss can increase risk of cholelithiasis

Exclude organic causes of obesity (eg, hypothyroidism), before prescribing therapy

May increase gastrointestinal events when taking a diet high on fat (>30% total daily calories from fat)

Weight-loss may affect glycemic control in patients with diabetes mellitus; a reduction in dose of oral hypoglycemic medication (eg, sulfonylureas) or insulin may be required in some patients

Avoid with anorexia nervosa or bulimia

Drug interaction overview

• Cyclosporine: Should not be simultaneously coadministered with cyclosporine; can decrease cyclosporine exposure; to reduce chance of a drug-drug interaction, cyclosporine should be taken at least 3 hours before or after orlistat
• Levothyroxine: Administer 4 hr apart; monitored for changes in thyroid function
• Amiodarone PO: A pharmacokinetic study showed reduced amiodarone and desethylamiodarone systemic exposure when coadministered with orlistat
• Antiepileptic drugs (AEDs): Convulsions reported with coadministration of AEDs and orlistat; monitor serum AED levels
• Antiretroviral drugs: Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs; HIV RNA levels should be frequently monitored in patients taking orlistat and antiretrovirals drugs; if HIV viral load increases, discontinue orlistat

• Warfarin

  • Vitamin K absorption may be decreased with orlistat
  • Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been with coadministration of orlistat and anticoagulants
  • Patients on chronic stable doses of warfarin or other anticoagulants who are prescribed orlistat should be monitored closely for coagulation parameters changes

• Vitamin supplements

  • Orlistat may reduce absorption of some fat-soluble vitamins and beta-carotene
  • Instruct patient to take a multivitamin containing fat-soluble vitamins to ensure adequate nutrition
  • Take vitamin supplement at least 2 hr before or after taking orlistat, such as at bedtime

Pregnancy Category: X; weight loss offers no potential benefit to a pregnant woman and may result in fetal harm; a minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese

Lactation: Not recommended; not known if orlistat is distributed in breast milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits gastric and pancreatic lipases, prevents triglyceride hydrolysis resulting in decreased absorption of dietary fats

Absorption

Bioavailability: 5%; absorption is very low and systemic absorption of orlistat is not required for clinical efficacy

Onset: 24-48 hr

Duration: 48-72 hr

Peak Plasma Time: 6-8 hr

Distribution

Protein Bound: 99%

Metabolism

Metabolized in intestinal wall

Metabolites: M1 & M3 (both probably inactive)

Elimination

Half-Life: 1-2 hr

Renal Clearance: 0.1% of dose/hr

Excretion: Feces 95-97% (including biliary); urine < 3%

Oral Administration

Take with each fat-containing meal (during or up to 1 hr after the meal)

The patient should be on a nutritionally balanced, reduced-calorie diet that contains ~30% of calories from fat

Daily intake of fat, carbohydrate, and protein should be distributed over 3 main meals

If a meal is occasionally missed or contains no fat, omit the orlistat dose