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Orlistat (Monograph)

Brand names: Alli, Xenical
Drug class: GI Drugs, Miscellaneous
- Lipase Inhibitors
ATC class: A08AB01
VA class: GA900
Chemical name: [2S-[2α(R*),3β]]-1-[(3-Hexyl-4-oxo-2-oxetanyl)methyl]dodecyl-N-formyl-l-leucine
Molecular formula: C29H53NO5
CAS number: 96829-58-2

Medically reviewed by Drugs.com on Feb 14, 2024. Written by ASHP.

Introduction

Reversible inhibitor of gastric and pancreatic lipases; exhibits antiobesity and antilipemic activity.

Uses for Orlistat

Obesity

Prescription orlistat (e.g., Xenical) is used as an adjunct to caloric restriction, increased physical activity, and behavioral modification in the treatment of exogenous obesity; also used to reduce the risk of weight regain after initial loss.

Use prescription orlistat in patients with initial body mass index (BMI) of ≥30 kg/m2; also use in those with BMI of ≥27 kg/m2 in the presence of risk factor or disease (e.g., hypertension, diabetes mellitus, hyperlipidemia). To calculate BMI, divide weight in kilograms (kg) by height in meters (m) squared.

Used as self-medication (e.g., Alli) to promote weight loss in overweight adults ≥18 years of age; use in conjunction with a reduced-calorie, low-fat diet.

Orlistat Dosage and Administration

Oral Administration

Administer orally 3 times daily, during (or up to 1 hour after) each main meal containing fat. However, efficacy apparently not affected by administering the drug up to 2 hours after midmeal.

Omit orlistat dose if a meal occasionally is missed or contains no fat.

Distribute daily intake of fat (30% of calories), carbohydrate, and protein over 3 main meals.

Manufacturers recommend use of multivitamin supplement containing fat-soluble vitamins (A, D, E, K) and beta carotene. Administer multivitamin ≥2 hours before or after orlistat; may administer vitamin supplement at bedtime for convenience. (See Concomitant Drug Therapy and Vitamin Use under Cautions.)

In patients receiving prescription orlistat and cyclosporine concomitantly, administer cyclosporine ≥3 hours before or after orlistat. Do not use orlistat for self-medication in organ transplant recipients, including those receiving cyclosporine. (See Concomitant Drug Therapy and Vitamin Use under Cautions and also see Specific Drugs under Interactions.)

In patients receiving prescription orlistat and levothyroxine concomitantly, administer levothyroxine ≥4 hours apart from orlistat. (See Specific Drugs under Interactions.)

Dosage

Pediatric Patients

Obesity
Oral

Adolescents ≥12 years of age: Recommended dosage of prescription orlistat (Xenical) is 120 mg 3 times daily with each main meal containing fat. No additional benefit with dosages >120 mg 3 times daily.

Reassess weight management and therapy periodically. Safety and efficacy beyond 4 years not established in clinical studies. However, if effective for weight loss or maintenance and no serious adverse effects occur, may continue orlistat as long as clinically indicated.

Not approved for self-medication for weight loss in pediatric patients.

Adults

Obesity
Oral

Recommended dosage of prescription orlistat (Xenical) is 120 mg 3 times daily with each main meal containing fat. No additional benefit with dosages >120 mg 3 times daily.

Reassess weight management and therapy periodically. Safety and efficacy beyond 4 years not established in clinical studies. However, if effective for weight loss or maintenance and no serious adverse effects occur, may continue orlistat as long as clinically indicated.

For self-medication for weight loss (e.g., Alli), usual dosage is 60 mg 3 times daily with each main meal containing fat.

Prescribing Limits

Pediatric Patients

Obesity
Oral

No additional benefit with dosages >120 mg 3 times daily.

Adults

Obesity
Oral

No additional benefit with dosages >120 mg 3 times daily.

For self-medication, do not exceed three 60-mg capsules daily.

Cautions for Orlistat

Contraindications

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions reported rarely during the postmarketing period; such reactions include pruritus, rash, urticaria, angioedema, bronchospasm, and anaphylaxis. Very rare cases of bullous eruption also reported.

Leukocytoclastic vasculitis reported rarely. Clinical signs have included palpable purpura, maculopapular lesions, arthralgia/myalgia, and bullous eruption. In one case, the condition rapidly improved following drug discontinuance, bed rest, and NSAIA therapy.

Concomitant Drug Therapy and Vitamin Use

Concomitant administration of orlistat and cyclosporine can result in decreased plasma concentrations of cyclosporine. Do not use orlistat for self-medication in organ transplant recipients because of possible interactions with the immunosuppressive agents used to prevent organ rejection. (See Oral Administration under Dosage and Administration and also see Specific Drugs under Interactions.)

Fat-soluble vitamin deficiency is unlikely but possible (see Specific Drugs under Interactions). Manufacturers consider routine (once-daily) supplementation with a multivitamin containing fat-soluble vitamins (A, D, E, K) and beta carotene a prudent precaution (see Oral Administration under Dosage and Administration).

In patients with diabetes mellitus, weight loss may improve glycemic control; dosage reductions or discontinuance of concomitant antidiabetic therapy (e.g., insulin, metformin, sulfonylureas) may be necessary. (See Specific Drugs under Interactions.)

Hepatic Effects

Severe hepatotoxicity (e.g., hepatocellular necrosis, acute hepatic failure), sometimes resulting in liver transplantation or death, reported rarely during postmarketing experience. Elevations in serum aminotransferase (transaminase) and alkaline phosphatase concentrations and hepatitis also reported rarely.

In August 2009, FDA reported that it was conducting an ongoing safety review of orlistat prompted by reports of adverse hepatic-related effects (e.g., serious hepatic injury requiring hospitalization, liver failure) in patients receiving the drug. The most commonly reported adverse effects included jaundice, weakness, and abdominal pain. In May 2010, FDA's completed safety review of the available data identified 13 cases of severe liver injury reported in orlistat-treated patients; 2 resulted in death and 3 resulted in liver transplantation. FDA states that a causal relationship to orlistat cannot be established at this time.

Weigh the benefits of weight loss with orlistat against the potential risks of therapy when considering whether the drug is appropriate for patients. Instruct patients to report any signs or symptoms possibly associated with the development of hepatic injury (see Advice to Patients). If such manifestations occur or liver injury is suspected, immediately discontinue orlistat and any other suspect drugs and perform liver function tests (including serum ALT and AST concentrations).

Hyperoxaluria

Possible increased concentrations of urinary oxalate. Cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure reported in orlistat-treated patients.

If prescription orlistat is used in patients at risk for renal impairment, monitor renal function. Also use with caution in patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis. (See Advice to Patients.)

Cholelithiasis

Substantial weight loss may increase risk of cholelithiasis.

Cholelithiasis reported in patients receiving orlistat and placebo recipients in the clinical trial that evaluated the effect of orlistat on the time to onset of type 2 diabetes mellitus. In this trial, the incidence of cholelithiasis was similar for patients receiving orlistat or placebo at similar amounts of weight loss. An increased risk of cholelithiasis was not observed in orlistat clinical trials that were not evaluating the prevention of type 2 diabetes. (See Advice to Patients.)

Obesity Evaluation

Rule out organic causes of obesity (e.g., hypothyroidism) before initiating orlistat therapy.

Dietary Guidelines

Adherence to dietary recommendations minimizes adverse GI effects related to fat intake, as well as contributes to weight loss. (See Administration under Dosage and Administration.)

Abuse Potential

Potential for abuse in inappropriate patient populations (e.g., anorexia nervosa, bulimia).

Specific Populations

Pregnancy

Category X. (See Contraindications under Cautions.)

Weight loss offers no potential benefit to pregnant women and may result in fetal harm.

Embryotoxicity and teratogenicity not observed in animal studies.

If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard of maternal weight loss.

Lactation

Not known whether orlistat is distributed into milk; use with caution.

Pediatric Use

Safety and efficacy of prescription orlistat (Xenical) not established in children <12 years of age. Adverse effects in adolescent patients were similar to those observed in adults.

Do not use for self-medication (Alli) in children <18 years of age.

Geriatric Use

Insufficient experience with geriatric patients ≥65 years of age to determine whether response differs from younger adults.

Renal Impairment

Cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure reported; manufacturer of prescription orlistat recommends monitoring renal function in patients at risk for renal impairment. (See Hyperoxaluria under Cautions and also see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation, fecal incontinence.

In clinical studies, adverse effects reported in individuals receiving orlistat 60 mg 3 times daily were similar to those reported in patients receiving 120 mg 3 times daily, and were primarily GI related.

Drug Interactions

Specific Drugs

Drug

Interaction

Comments

Alcohol

Pharmacokinetics of ethanol and systemic exposure and pharmacodynamics of orlistat not substantially affected

Amiodarone

Decreased systemic exposure of amiodarone and its metabolite desethylamiodarone by 23–27%

Effect of initiating orlistat in patients receiving a stable dosage of amiodarone not studied

Anticonvulsants

Possible decreased absorption and reduced efficacy of anticonvulsants may result in seizures; seizures observed in some patients during concurrent use of some anticonvulsants (e.g., lamotrigine, valproic acid)

Pharmacokinetics of phenytoin not substantially affected

Monitor for possible changes in frequency and/or severity of seizures

Patients should consult a clinician or pharmacist before initiating orlistat for self-medication

Antidiabetic agents

Potential for improved glycemic control with weight loss

Pharmacokinetics and pharmacodynamics of glyburide not substantially affected

Antidiabetic dosage reduction or discontinuance may be necessary

Patients should consult a clinician or pharmacist before initiating orlistat for self-medication; antidiabetic dosage adjustment may be necessary

Antilipemic agents

Possible additive antilipemic effects

Pravastatin pharmacokinetics unaffected

Pharmacokinetics of simvastatin and its active metabolite not substantially affected

Contraceptives, oral

Pharmacodynamics of oral contraceptives not substantially affected

Cyclosporine and other immunosuppressive agents

Decreased systemic exposure and peak concentrations of cyclosporine by 31 and 25%, respectively

Cyclosporine: Avoid simultaneous administration; administer cyclosporine ≥3 hours before or after prescription orlistat; consider more frequent monitoring of cyclosporine concentrations

Do not use orlistat for self-medication in organ transplant recipients because of possible interactions with immunosuppressive agents (e.g., cyclosporine)

Digoxin

Pharmacokinetics of single-dose digoxin not substantially affected by multiple-dose orlistat

Fluoxetine

Pharmacokinetics of fluoxetine and its metabolite norfluoxetine not substantially affected

Nifedipine

Bioavailability of extended-release nifedipine tablets not substantially affected

Thyroid agents

Hypothyroidism reported during concurrent orlistat and levothyroxine administration

Monitor patients receiving orlistat and levothyroxine concomitantly for changes in thyroid function; administer drugs at least 4 hours apart

Before initiating orlistat for self-medication, consult a clinician or pharmacist if receiving thyroid agents; thyroid agent dosage adjustment may be needed

Vitamins, fat-soluble (A, D, E, K) and beta carotene

Concentrations of some fat-soluble vitamins and beta carotene decreased but remained within normal range in most individuals

Supplementation needed only occasionally in clinical studies; however, manufacturers recommend routine supplementation with multivitamin containing fat-soluble vitamins and beta carotene

Warfarin

Potential for decreased vitamin K concentrations

Pharmacokinetics and pharmacodynamics of R-warfarin and S-warfarin not substantially affected

Decreased prothrombin, increased INR, and unbalanced anticoagulant therapy resulting in changes in hemostatic parameters reported in patients concurrently receiving anticoagulants

Closely monitor coagulation parameters; adjust warfarin dosage if necessary

Before initiating orlistat for self-medication, consult a clinician or pharmacist if receiving warfarin; warfarin dosage adjustment may be needed

Orlistat Pharmacokinetics

Absorption

Bioavailability

Minimally absorbed; systemic exposure to orlistat is minimal.

Special Populations

In adolescents, plasma concentrations of orlistat and its 2 metabolites, M1 and M3, were similar to those observed in adults receiving an equivalent dosage.

Geriatric patients: Pharmacokinetics not evaluated.

Renal or hepatic impairment: Pharmacokinetics not specifically studied.

Distribution

Plasma Protein Binding

>99% in vitro (mainly to lipoproteins and albumin).

Elimination

Metabolism

Metabolized to clinically unimportant metabolites, mainly M1 and M3.

Elimination Route

Excreted principally in feces (approximately 97%), mainly as unchanged drug (83%).

Half-life

Absorbed orlistat: 1–2 hours.

Stability

Storage

Oral

Capsules

Prescription orlistat (Xenical): Tight containers at 25°C (may be exposed to 15–30°C).

Orlistat for self-medication (Alli): 20-25°C; protect from excessive light, humidity, and temperatures >30°C.

Actions

Advice to Patients

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Orlistat

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

60 mg

Alli

GlaxoSmithKline

120 mg

Xenical

Genentech

AHFS DI Essentials™. © Copyright 2024, Selected Revisions February 24, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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