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

• Pregnancy. (See Pregnancy under Cautions.)

• Chronic malabsorption syndrome.

• Cholestasis.

• Known hypersensitivity to orlistat or any ingredient in the formulations. (See Sensitivity Reactions under Cautions.)

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

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

• Decreases GI lumen absorption of dietary fat (triacylglycerol) by reversibly inhibiting gastric and pancreatic lipase-mediated triglyceride hydrolysis, thereby decreasing intestinal concentrations of absorbable free fatty acids and monoglycerides.

• About one-fourth to one-third of dietary fat will not be absorbed at recommended dosages.

• Decreases concentrations of LDL and total cholesterol; variable effects on serum triglycerides and HDL cholesterol.

Advice to Patients

• Provide copy of manufacturer’s patient information for prescription orlistat (Xenical). Advise patient to read patient information before beginning treatment and each time prescription is refilled.

• When using orlistat for self-medication (Alli), importance of reading the product labeling. Information for individuals considering therapy with orlistat or starting orlistat is available at [Web].

• In patients taking prescription orlistat, importance of adherence to clinician’s dietary and, if applicable, exercise recommendations. Importance of patients using a nutritionally balanced, mildly reduced-calorie diet that contains no more than 30% of total daily calories from fat. Evenly distribute daily intake of fat, carbohydrates, and protein over 3 main meals. Omit orlistat dose if meal contains no fat or is skipped.

• Because orlistat works by blocking the absorption of dietary fat, importance of advising patients that they will likely experience some changes in bowel habits. These changes usually occur during the first weeks of treatment, particularly after meals containing higher amounts of fat than recommended, but may continue throughout therapy. The changes may include oily spotting, gas with discharge, increased number of bowel movements, and inability to control bowel movements. Due to the presence of undigested fat, the oil seen in the bowel movement may be clear or orange or brown in color.

• In patients taking prescription orlistat, importance of informing clinicians of any consistent problems absorbing food (chronic malabsorption), gallbladder problems (e.g., cholestasis), hepatic or renal disease (including nephrolithiasis), pancreatitis, eating disorders such as anorexia or bulimia, diabetes mellitus, thyroid disease, a seizure disorder, cardiac arrhythmias, or hypersensitivity to orlistat or any other components of the formulation.

• When used as self-medication, importance of patients advising clinicians if they have problems absorbing food (chronic malabsorption), gallbladder problems, kidney stones, pancreatitis, or severe or continuous abdominal pain.

• Risk of oxalate nephrolithiasis/nephropathy. Advise patients to promptly contact their clinician if they experience any symptoms of kidney stones or other renal problems (e.g., swelling [particularly of legs and feet], reduced or no urine output, frequent or painful urination, blood in the urine, loss of appetite, nausea and vomiting, or severe pain in the back, abdomen, or groin).

• Possible increased risk for the formation of gall stones in some patients. Weight loss with orlistat can increase the risk of gall stones. Importance of advising patients to promptly report any symptoms of pain in the upper right portion of the abdomen; the pain may be accompanied by nausea and vomiting.

• Importance of informing patients that there have been rare reports of severe liver injury in orlistat-treated patients. Importance of advising patients to contact their clinician if they experience any symptoms possibly associated with liver injury, such as weakness or fatigue, fever, jaundice (yellowing of the eyes or skin), or dark urine. Other symptoms may include abdominal or right upper quadrant pain, nausea, vomiting, light-colored stools, itching, or loss of appetite. (See Hepatic Effects under Cautions.)

• Importance of taking a multivitamin supplement containing vitamins A, D, E, and K and beta carotene once daily at least 2 hours before or after taking orlistat, such as at bedtime.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary supplements (including herbal preparations), particularly other antiobesity agents, anticonvulsants, antidiabetic agents, amiodarone, cyclosporine, warfarin, or thyroid agents.

• Risk of fetal harm because of maternal weight loss if used during pregnancy. Advise women that a minimum weight gain and no weight loss is recommended for all pregnant women, including those who are already overweight or obese. Importance of advising women of childbearing potential to avoid pregnancy. Importance of women informing clinicians if they are or plan to become pregnant or are breast-feeding. (See Pregnancy under Cautions.)

• Importance of informing patients of other precautionary information. (See Cautions.)

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.

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