DrugindexOnline^{2nd edition}

Pronouncation: (OR-li-stat)
Class: Lipase inhibitor

Trade Names:
Alli
- Capsules 60 mg

Trade Names:
Xenical
- Capsules 120 mg

Mechanism of Action

Pharmacology

Reversible lipase inhibitor for obesity management that acts by inhibiting absorption of dietary fats.

Pharmacokinetics

Absorption

Systemic absorption is minimal. T _max is approximately 8 h.

Distribution

More than 99% protein bound to plasma, mainly albumin and lipoprotein.

Metabolism

Occurs mainly in the GI wall. Two metabolites are M1 (4-member lactone ring hydrolyzed) and M3 (M1 with N-formyl leucine moiety cleaved); considered pharmacologically inconsequential.

Elimination

Eliminated by fecal excretion (major route); biliary excretion for metabolites. 97% eliminated through feces, 83% as unchanged drug, and less than 2% through urine.

The t _½ for M1 metabolite is approximately 3 h; t _½ for M3 metabolite is approximately 13.5 h; t _½ of absorbed orlistat is 1 to 2 h.

Indications and Usage

Rx

Obesity management, including weight loss and weight maintenance, when used in combination with a reduced-calorie diet; reduction of the risk for weight regain after prior weight loss.

OTC

Weight loss in overweight adults 18 yr of age and older along with a reduced-calorie and low-fat diet.

Contraindications

Chronic malabsorption syndrome; reduction of cholestasis; standard considerations.

Dosage and Administration

Rx
Adults and Children 12 yr of age and older

PO 120 mg 3 times daily with each main meal containing fat, during or up to 1 h after the meal.

OTC
Adults

PO 60 mg with each fat-containing meal (max, 3 doses daily).

General Advice

• Patient should be on nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat.
• Daily fat, carbohydrate, and protein intake should be distributed over 3 main meals.
• If a meal is missed or contains no fat, the orlistat dose may be omitted.
• Because orlistat reduces absorption of some fat-soluble vitamins and beta-carotene, multivitamins should be taken to ensure adequate nutrition.
• Multivitamin supplements should be taken at least 2 h before or after taking orlistat.

Storage/Stability

Store Rx at 59° to 86°F. Store OTC at 68° to 77°F. Protect from light and humidity.

Drug Interactions

Amiodarone, beta-carotene

Plasma concentrations may be reduced slightly by orlistat.

Cyclosporine

Plasma concentrations may be reduced by orlistat. Take cyclosporine at least 2 h before or after orlistat.

Fat-soluble vitamins

30% reduction in beta-carotene supplement absorption was shown when administered with orlistat. Orlistat inhibited absorption of a vitamin E acetate supplement approximately 60%. The effect on the absorption of supplemental vitamin D, vitamin A, and nutritionally derived vitamin K is unknown.

Pravastatin

In 24 healthy-weight, mildly hypercholesterolemic subjects receiving orlistat 120 mg 3 times a day for 10 days, the effect was additive to the lipid-lowering effect of pravastatin. Modest increases (approximately 30%) in pravastatin plasma concentrations were observed during coadministration with orlistat.

Warfarin

Vitamin K levels tended to decline in patients taking orlistat. Because vitamin K absorption may be decreased with orlistat, closely monitor patients on chronic stable doses of warfarin who are prescribed orlistat for changes in coagulation parameters.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (31%); fatigue (7%); dizziness, psychiatric anxiety (5%); sleep disorder (4%); depression, pedal edema (3%).

Dermatologic

Rash (4%); dry skin (2%); bullous eruption, pruritus, urticaria (postmarketing).

EENT

Otitis (4%); ear, nose, and throat symptoms (2%).

GI

Oily spotting (27%); abdominal pain/discomfort (26%); flatus with discharge (24%); fecal urgency (22%); fatty/oily stool (20%); oily evacuation (12%); increased defecation (11%); fecal incontinence, nausea (8%); infectious diarrhea, rectal pain/discomfort (5%); gingival disorder, tooth disorder, vomiting (4%); abdominal distention, pancreatitis (postmarketing).

Genitourinary

Menstrual irregularity (10%); vaginitis (4%).

Hepatic

Hepatitis (postmarketing).

Lab Tests

Decreased prothrombin, increased alkaline phosphatase, INR, and transaminases (postmarketing).

Metabolic-Nutritional

Hypoglycemia (postmarketing).

Musculoskeletal

Back pain (14%); lower extremity pain (11%); arthritis (5%); myalgia (4%); joint disorder, tendonitis (2%).

Respiratory

Influenza (40%); upper respiratory tract infection (38%); lower respiratory tract infection (8%); bronchospasm (postmarketing).

Miscellaneous

Anaphylaxis, angioedema (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Not known if orlistat is excreted in human milk.

Children

Rx

Safety and efficacy not established in children younger than 12 yr of age.

OTC

Safety and efficacy not established.

Special Risk Patients

Patients with anorexia nervosa or bulimia should not take orlistat because of the potential for misuse. Exercise caution when prescribing orlistat to patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis because of the risk of development of increased levels of urinary oxalate following treatment with orlistat.

Diabetic patients

Weight-loss induction by orlistat may be accompanied by improved metabolic control in diabetic patients, which might require a reduction in dose of oral hypoglycemic medication or insulin.

GI reactions

GI adverse reactions may increase if orlistat is taken with a diet high in fat (more than 30% total daily calories from fat).

Patient Information

• Rx and OTC
• Remind patient to read the patient information leaflet before starting treatment and with each refill.
• Advise patient to take prescribed dose 3 times daily with each main meal containing fat.
• Dose should be taken during or up to 1 h after meal.
• Advise patient that drug may be omitted if a meal is missed or contains no fat.
• Warn patient that drug must be used in conjunction with nutritionally balanced, reduced-calorie diet.
• Advise patient that taking more drug than prescribed does not increase weight loss.
• Instruct patient to take a multivitamin supplement containing fat-soluble vitamins every day at least 2 h before or after taking drug (eg, bedtime).
• Warn patient that daily intake of fat must be less than 30% and that ingesting larger quantities of fat in the diet will result in GI adverse reactions.
• Advise patient to report bothersome adverse reactions to health care provider.

• OTC
• Instruct patients not to take orlistat if they are organ transplant patients or are taking cyclosporine, have been diagnosed with problems absorbing food, or are not overweight.