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Xenical

Generic Name: Orlistat
Class: GI Drugs, Miscellaneous
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

Introduction

Reversible inhibitor of gastric and pancreatic lipases;1 2 4 5 6 8 9 10 11 12 13 14 18 19 21 22 47 51 exhibits antiobesity1 6 7 8 17 23 36 and antilipemic activity.1 3 4 5 6 7 8 20 36

Uses for Xenical

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.1 6 7 8 15 17 27 36

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).1 15 27 To calculate BMI, divide weight in kilograms (kg) by height in meters (m) squared.1

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.46

Xenical Dosage and Administration

Administration

Oral Administration

Administer orally 3 times daily, during (or up to 1 hour after) each main meal containing fat.1 8 19 20 23 27 46 47 However, efficacy apparently not affected by administering the drug up to 2 hours after midmeal.19 20

Omit orlistat dose if a meal occasionally is missed or contains no fat.1 27 47

Distribute daily intake of fat (30% of calories), carbohydrate, and protein over 3 main meals.1 27

Manufacturers recommend use of multivitamin supplement containing fat-soluble vitamins (A, D, E, K) and beta carotene.1 27 46 Administer multivitamin ≥2 hours before or after orlistat; may administer vitamin supplement at bedtime for convenience.1 8 27 37 46 (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.1 Do not use orlistat for self-medication in organ transplant recipients, including those receiving cyclosporine.46 (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.1 (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.1 6 7 8 17 23 27 36 No additional benefit with dosages >120 mg 3 times daily.1 23

Reassess weight management and therapy periodically.1 7 27 39 Safety and efficacy beyond 4 years not established in clinical studies.7 27 39 However, if effective for weight loss or maintenance and no serious adverse effects occur, may continue orlistat as long as clinically indicated.17

Not approved for self-medication for weight loss in pediatric patients.46

Adults

Obesity
Oral

Recommended dosage of prescription orlistat (Xenical) is 120 mg 3 times daily with each main meal containing fat.1 6 7 8 17 23 27 36 No additional benefit with dosages >120 mg 3 times daily.1 23

Reassess weight management and therapy periodically.1 7 27 39 Safety and efficacy beyond 4 years not established in clinical studies.7 27 39 However, if effective for weight loss or maintenance and no serious adverse effects occur, may continue orlistat as long as clinically indicated.17

For self-medication for weight loss (e.g., Alli), usual dosage is 60 mg 3 times daily with each main meal containing fat.46

Prescribing Limits

Pediatric Patients

Obesity
Oral

No additional benefit with dosages >120 mg 3 times daily.1 23

Adults

Obesity
Oral

No additional benefit with dosages >120 mg 3 times daily.1 23

For self-medication, do not exceed three 60-mg capsules daily.46

Cautions for Xenical

Contraindications

  • Pregnancy.1 (See Pregnancy under Cautions.)

  • Chronic malabsorption syndrome.1 27

  • Cholestasis.1 27

  • Known hypersensitivity to orlistat or any ingredient in the formulations.1 27 46 (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.1 Very rare cases of bullous eruption also reported.1

Leukocytoclastic vasculitis reported rarely.1 68 69 Clinical signs have included palpable purpura, maculopapular lesions, arthralgia/myalgia, and bullous eruption.1 68 69 In one case, the condition rapidly improved following drug discontinuance, bed rest, and NSAIA therapy.68

Concomitant Drug Therapy and Vitamin Use

Concomitant administration of orlistat and cyclosporine can result in decreased plasma concentrations of cyclosporine.1 40 41 42 43 44 Do not use orlistat for self-medication in organ transplant recipients because of possible interactions with the immunosuppressive agents used to prevent organ rejection.46 (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).1 7 8 17 25 26 27 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).1 27 37 46

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.1 17 27 (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.1 52 53 55 56 57 58 61 62 63 65 66 Elevations in serum aminotransferase (transaminase) and alkaline phosphatase concentrations and hepatitis also reported rarely.1 55

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.52 53 55 56 57 58 61 The most commonly reported adverse effects included jaundice, weakness, and abdominal pain.52 53 55 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.65 66 FDA states that a causal relationship to orlistat cannot be established at this time.65 66

Weigh the benefits of weight loss with orlistat against the potential risks of therapy when considering whether the drug is appropriate for patients.65 66 Instruct patients to report any signs or symptoms possibly associated with the development of hepatic injury (see Advice to Patients).1 27 52 53 65 66 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).1 65 66

Hyperoxaluria

Possible increased concentrations of urinary oxalate.1 67 Cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure reported in orlistat-treated patients.1 67

If prescription orlistat is used in patients at risk for renal impairment, monitor renal function.1 Also use with caution in patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis.1 (See Advice to Patients.)

Cholelithiasis

Substantial weight loss may increase risk of cholelithiasis.1

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.1 In this trial, the incidence of cholelithiasis was similar for patients receiving orlistat or placebo at similar amounts of weight loss.1 An increased risk of cholelithiasis was not observed in orlistat clinical trials that were not evaluating the prevention of type 2 diabetes.1 (See Advice to Patients.)

Obesity Evaluation

Rule out organic causes of obesity (e.g., hypothyroidism) before initiating orlistat therapy.1

Dietary Guidelines

Adherence to dietary recommendations minimizes adverse GI effects related to fat intake, as well as contributes to weight loss.1 27 46 (See Administration under Dosage and Administration.)

Abuse Potential

Potential for abuse in inappropriate patient populations (e.g., anorexia nervosa, bulimia).1

Specific Populations

Pregnancy

Category X.1 (See Contraindications under Cautions.)

Weight loss offers no potential benefit to pregnant women and may result in fetal harm.1

Embryotoxicity and teratogenicity not observed in animal studies.1

If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard of maternal weight loss.1

Lactation

Not known whether orlistat is distributed into milk; use with caution.1 27 46 47

Pediatric Use

Safety and efficacy of prescription orlistat (Xenical) not established in children <12 years of age.1 Adverse effects in adolescent patients were similar to those observed in adults.1

Do not use for self-medication (Alli) in children <18 years of age.46

Geriatric Use

Insufficient experience with geriatric patients ≥65 years of age to determine whether response differs from younger adults.1

Renal Impairment

Cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure reported;1 67 manufacturer of prescription orlistat recommends monitoring renal function in patients at risk for renal impairment.1 (See Hyperoxaluria under Cautions and also see Special Populations under Pharmacokinetics.)1

Common Adverse Effects

Oily spotting,1 7 8 48 49 flatus with discharge,1 7 8 46 48 fecal urgency,1 7 8 48 49 fatty/oily stool,1 7 8 48 49 oily evacuation,1 8 49 increased defecation,1 7 8 46 48 49 fecal incontinence.1 7 8 46 49

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.49 50

Interactions for Xenical

Specific Drugs

Drug

Interaction

Comments

Alcohol

Pharmacokinetics of ethanol and systemic exposure and pharmacodynamics of orlistat not substantially affected1 35

Amiodarone

Decreased systemic exposure of amiodarone and its metabolite desethylamiodarone by 23–27%1 64

Effect of initiating orlistat in patients receiving a stable dosage of amiodarone not studied1

Anticonvulsants

Possible decreased absorption and reduced efficacy of anticonvulsants may result in seizures;1 70 seizures observed in some patients during concurrent use of some anticonvulsants (e.g., lamotrigine, valproic acid)1 70

Pharmacokinetics of phenytoin not substantially affected1 34

Monitor for possible changes in frequency and/or severity of seizures1

Patients should consult a clinician or pharmacist before initiating orlistat for self-medication46

Antidiabetic agents

Potential for improved glycemic control with weight loss1 17 29

Pharmacokinetics and pharmacodynamics of glyburide not substantially affected1

Antidiabetic dosage reduction or discontinuance may be necessary1 17 29

Patients should consult a clinician or pharmacist before initiating orlistat for self-medication; antidiabetic dosage adjustment may be necessary46

Antilipemic agents

Possible additive antilipemic effects1

Pravastatin pharmacokinetics unaffected1

Pharmacokinetics of simvastatin and its active metabolite not substantially affected64

Contraceptives, oral

Pharmacodynamics of oral contraceptives not substantially affected1 33

Cyclosporine and other immunosuppressive agents

Decreased systemic exposure and peak concentrations of cyclosporine by 31 and 25%, respectively1 40 41 42 43 44

Cyclosporine: Avoid simultaneous administration; administer cyclosporine ≥3 hours before or after prescription orlistat; consider more frequent monitoring of cyclosporine concentrations1 41 43

Do not use orlistat for self-medication in organ transplant recipients because of possible interactions with immunosuppressive agents (e.g., cyclosporine)46

Digoxin

Pharmacokinetics of single-dose digoxin not substantially affected by multiple-dose orlistat1 30

Fluoxetine

Pharmacokinetics of fluoxetine and its metabolite norfluoxetine not substantially affected64

Nifedipine

Bioavailability of extended-release nifedipine tablets not substantially affected1 31 32

Thyroid agents

Hypothyroidism reported during concurrent orlistat and levothyroxine administration1 60 61

Monitor patients receiving orlistat and levothyroxine concomitantly for changes in thyroid function; administer drugs at least 4 hours apart1

Before initiating orlistat for self-medication, consult a clinician or pharmacist if receiving thyroid agents; thyroid agent dosage adjustment may be needed46

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 individuals1 7 8 17 25 26 27 36 46

Supplementation needed only occasionally in clinical studies;7 8 17 25 26 36 however, manufacturers recommend routine supplementation with multivitamin containing fat-soluble vitamins and beta carotene1 27 37 46

Warfarin

Potential for decreased vitamin K concentrations1 28

Pharmacokinetics and pharmacodynamics of R-warfarin and S-warfarin not substantially affected1 28

Decreased prothrombin, increased INR, and unbalanced anticoagulant therapy resulting in changes in hemostatic parameters reported in patients concurrently receiving anticoagulants1

Closely monitor coagulation parameters; adjust warfarin dosage if necessary1 46

Before initiating orlistat for self-medication, consult a clinician or pharmacist if receiving warfarin; warfarin dosage adjustment may be needed46

Xenical Pharmacokinetics

Absorption

Bioavailability

Minimally absorbed; systemic exposure to orlistat is minimal.1 6 21 22

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.1

Geriatric patients: Pharmacokinetics not evaluated.1

Renal or hepatic impairment: Pharmacokinetics not specifically studied.1

Distribution

Plasma Protein Binding

>99% in vitro (mainly to lipoproteins and albumin).1

Elimination

Metabolism

Metabolized to clinically unimportant metabolites, mainly M1 and M3.1

Elimination Route

Excreted principally in feces (approximately 97%), mainly as unchanged drug (83%).1 6 21 22

Half-life

Absorbed orlistat: 1–2 hours.1

Stability

Storage

Oral

Capsules

Prescription orlistat (Xenical): Tight containers at 25°C (may be exposed to 15–30°C).1

Orlistat for self-medication (Alli): 20-25°C; protect from excessive light, humidity, and temperatures >30°C.46

Actions

  • Decreases GI lumen absorption of dietary fat (triacylglycerol) by reversibly inhibiting gastric and pancreatic lipase-mediated triglyceride hydrolysis,1 2 4 6 12 18 19 20 21 22 51 thereby decreasing intestinal concentrations of absorbable free fatty acids and monoglycerides.1 4 6 12

  • About one-fourth to one-third of dietary fat will not be absorbed at recommended dosages.1 6 12 18 19 20 47

  • Decreases concentrations of LDL1 3 4 5 6 7 8 20 36 51 and total1 4 5 6 7 8 20 36 cholesterol; variable effects on serum triglycerides1 3 4 5 6 7 20 and HDL cholesterol.3 4 6 7

Advice to Patients

  • Provide copy of manufacturer’s patient information for prescription orlistat (Xenical).1 Advise patient to read patient information before beginning treatment and each time prescription is refilled.1

  • When using orlistat for self-medication (Alli), importance of reading the product labeling.46 Information for individuals considering therapy with orlistat or starting orlistat is available at .46

  • In patients taking prescription orlistat, importance of adherence to clinician’s dietary and, if applicable, exercise recommendations.1 15 17 Importance of patients using a nutritionally balanced, mildly reduced-calorie diet that contains no more than 30% of total daily calories from fat.27 Evenly distribute daily intake of fat, carbohydrates, and protein over 3 main meals.1 Omit orlistat dose if meal contains no fat or is skipped.1 47

  • Because orlistat works by blocking the absorption of dietary fat, importance of advising patients that they will likely experience some changes in bowel habits.27 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.27 The changes may include oily spotting, gas with discharge, increased number of bowel movements, and inability to control bowel movements.27 Due to the presence of undigested fat, the oil seen in the bowel movement may be clear or orange or brown in color.27

  • 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.1 27 46

  • 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.46 47

  • Risk of oxalate nephrolithiasis/nephropathy.1 27 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).27

  • Possible increased risk for the formation of gall stones in some patients.1 27 Weight loss with orlistat can increase the risk of gall stones.1 27 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.27

  • Importance of informing patients that there have been rare reports of severe liver injury in orlistat-treated patients.1 27 52 53 65 66 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.1 52 53 65 66 Other symptoms may include abdominal or right upper quadrant pain, nausea, vomiting, light-colored stools, itching, or loss of appetite.1 27 52 53 65 66 (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.1 27 46 47

  • 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.1 27 46

  • Risk of fetal harm because of maternal weight loss if used during pregnancy.1 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.1 Importance of advising women of childbearing potential to avoid pregnancy.1 Importance of women informing clinicians if they are or plan to become pregnant or are breast-feeding.1 27 46 (See Pregnancy under Cautions.)

  • Importance of informing patients of other precautionary information.1 46 (See Cautions.)

Preparations

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 2017, Selected Revisions February 24, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Genentech USA, Inc,. Xenical (orlistat) capsules prescribing information. South San Francisco, CA; 2015 Aug.

2. Hauptman JB, Jeunet FS, Hartmann D. Initial studies in humans with the novel gastrointestinal lipase inhibitor Ro 18-0647 (tetrahydrolipstatin). Am J Clin Nutr. 1992; 55(Suppl):309S-13. [PubMed 1728845]

3. Reitsma JB, Castro Cabezas M, de Bruin TW et al. Relationship between improved postprandial lipemia and low-density lipoprotein metabolism during treatment with tetrahydrolipstatin, a pancreatic lipase inhibitor. Metabolism. 1994; 43:293-8. [PubMed 8139476]

4. Tonstad S, Pometta D. Erkelens DW et al. The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. Eur J Clin Pharmacol. 1994; 46:405-10. [PubMed 7957533]

5. Zavoral JH. Treatment with orlistat reduces cardiovascular risk in obese patients. J Hypertens. 1998; 16(12 Part 2):2013-7. [PubMed 9886891]

6. McNeely W, Benfield P. Orlistat. Drugs. 1998; 56:241-9. [PubMed 9711448]

7. Sjöström L, Rissanen A, Andersen T et al. Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998; 352:167-72. [PubMed 9683204]

8. Davidson MH, Hauptman J, DiGirolamo M et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA. 1999; 281:235-42. [PubMed 9918478]

9. Borgstrom B. Mode of action of tetrahydrolipstatin: a derivative of the naturally occurring lipase inhibitor lipstatin. Biochim Biophys Acta. 1988; 962:308-16. [PubMed 3167082]

10. Hadvary P, Lengsfeld H, Wolfer H. Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin. Biochem J. 1988; 256:357-61. [PubMed 3223916]

11. Hadvary P, Sidler W, Meister W et al. The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase. J Biol Chem. 1991; 266:2021-7. [PubMed 1899234]

12. Guerciolini R. Mode of action of orlistat. Int J Obes Relat Metab Disord. 1997; 21(Suppl 3):12S-3.

13. Lookene A, Skottova N, Olivercrona G. Interactions of lipoprotein lipase with the active-site inhibitor tetrahydrolipstatin (Orlistat). Eur J Biochem. 1994; 222:395-403. [PubMed 8020477]

14. Pottoff AP, Haalck L, Spener F. Inhibition of lipases from Chromobacterium viscosum and Rhizopus oryzae by tetrahydrolipstatin. J Mass Spectrom. 1997; 32:739-49. [PubMed 9241856]

15. National Institutes of Health, National Heart, Lung, and Blood Institute. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. 1998 Jun.

16. Froelich F, Hartmann D, Guezelhan C et al. Influence of orlistat on the regulation of gallbladder contraction in man: a randomized double-blind placebo-controlled crossover study. Dig Dis Sci. 1996; 41:2404-8. [PubMed 9011450]

17. Hollander PA, Elbein SC, Hirsch IB et al. Role of orlistat in the treatment of obese patients with type 2 diabetes: a 1-year randomized double-blind study. Diabetes Care. 1998; 21:1288-94. [PubMed 9702435]

18. Zhi J, Melia AT, Guerciolini MD et al. Retrospective population-based analysis of the dose-response (fecal fat excretion) relationship of orlistat in normal and obese volunteers. Clin Pharmacol Ther. 1994; 56:82-5. [PubMed 8033498]

19. Hussain Y, Güzelham C, Odink J et al. Comparison of the inhibition of dietary fat absorption by full versus divided doses of orlistat. J Clin Pharmacol. 1994; 34:1121-5. [PubMed 7876405]

20. Hartmann D, Hussain Y, Güzelhan C et al. Effect on dietary fat absorption of orlistat, administered at different times relative to meal intake. Br J Clin Pharmacol. 1993; 36:266-70. [PubMed 9114915]

21. Zhi J, Melia AT, Funk C et al. Metabolic profiles of minimally absorbed orlistat in obese/overweight volunteers. J Clin Pharmacol. 1996; 36:1006-11. [PubMed 8973989]

22. Zhi J, Melia AT, Eggers H et al. Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers. J Clin Pharmacol. 1995; 35:1103-8. [PubMed 8626884]

23. Van Gaal LF, Broom JI, Enzi G et al et al. Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Eur J Clin Pharmacol. 1998; 54:125-32. [PubMed 9626916]

24. Güzelhan C, Odink J, Niestijl Jansen-Zuidema JJ et al. Influence of dietary composition on the inhibition of fat absorption by orlistat. J Int Med Res. 1994; 22:255-65. [PubMed 7867870]

25. Melia AT, Koss-Twardy SG, Zhi J. The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers. J Clin Pharmacol. 1996; 36:647-53. [PubMed 8844448]

26. Zhi J, Melia AT, Koss-Twardy SG et al. The effect of orlistat, an inhibitor of dietary fat absorption, on the pharmacokinetics of β-carotene in healthy volunteers. J Clin Pharmacol. 1996; 36:152-9. [PubMed 8852391]

27. Genentech, Inc. Xenical (orlistat) capsules patient information. South San Francisco, CA; 2010 May.

28. Zhi J, Melia AT, Guerciolini R et al. The effect of orlistat on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. J Clin Pharmacol. 1996; 36:659-6. [PubMed 8844450]

29. Zhi J, Melia AT, Koss-Twardy SG et al. The influence of orlistat on the pharmacokinetics and pharmacodynamics of glyburide in healthy volunteers. J Clin Pharmacol. 1995; 35:521-5. [PubMed 7657854]

30. Melia AT, Zhi J, Koss-Twardy SG et al. The influence of reduced dietary fat absorption induced by orlistat on the pharmacokinetics of digoxin in healthy volunteers. J Clin Pharmacol. 1995; 35:840-3. [PubMed 8522642]

31. Melia AT, Mulligan TE, Zhi J. Lack of effect of orlistat on the bioavailability of a single dose of nifedipine extended-release tablets (Procardia XL) in healthy volunteers. J Clin Pharmacol. 1996; 36:352-5. [PubMed 8728349]

32. Weber C, Tam YK, Schmidtke-Schrezenmeier G et al. Effect of the lipase inhibitor orlistat on the pharmacokinetics of four different antihypertensive drugs in healthy volunteers. Eur J Clin Pharmacol. 1996; 51:87-90. [PubMed 8880057]

33. Hartmann D, Gzelhan C, Zuiderwijk PBM et al. Lack of interaction between orlistat and oral contraceptives. Eur J Clin Pharmacol. 1996; 50:421-4. [PubMed 8839667]

34. Melia AT, Mulligan TE, Zhi J. The effect of orlistat on the pharmacokinetics of phenytoin in healthy volunteers. J Clin Pharmacol. 1996; 36:654-8. [PubMed 8844449]

35. Melia AT, Zhi J, Zelasko R et al. The interaction of the lipase inhibitor orlistat with ethanol in healthy volunteers. Eur J Clin Pharmacol. 1998; 54:773-7. [PubMed 9923583]

36. James WP, Avenell A, Broom J et al. A one-year trial to assess the value of orlistat in the management of obesity. Int J Obes Relat Metab Disord. 1997; 21(Suppl 3):S24-30. [PubMed 9225173]

37. Roche Laboratories Inc, Nutley, NJ: Personal communication.

38. Roche Laboratories Inc. Xenical (orlistat) capsules prescribing information. Nutley, NJ; 1999 May.

39. Torgerson JS, Hauptman J, Boldrin MN et al. Xenical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as ann adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004; 27:155-61. [PubMed 14693982]

40. Zhi J, Moore R, Kanitra L et al. Pharmacokinetic evaluation of the possible interaction between selected concomitant medication and orlistat at steady state in healthy subjects. J Clin Pharmacol. 2002; 42:1011-9. [PubMed 12211217]

41. Barbaro D, Orsini P, Pallini S et al. Obesity in transplant patients: case report showing interference of orlistat with absorption of cyclosporine and review of literature. Endocr Pract. 2002; 8:124-6. [PubMed 11942778]

42. Nägele H, Petersen B, Bonacker U et al. Effect of orlistat on blood cyclosporin concentration in an obese heart transplant patient. Eur J Clin Pharmacol. 1999; 55:667-9. [PubMed 10638396]

43. Colman E, Fossler M. Reduction in blood cyclosporine concentrations by orlistat. New Engl J Med. 2000; 342:1141-2. (letter) [PubMed 10766596]

44. Asberg A. Interactions between cyclosporin and lipid-lowering drugs: implications for organ transplant recipients. Drugs. 2003; 63:367-78. [PubMed 12558459]

45. Roche Laboratories Inc, Nutley, NJ: Personal communication.

46. GlaxoSmithKline Consumer Healthcare Holdings (US) LLC. Alli (orlistat) capsules label. Moon Township, PA; 2016 Jun.

47. Alli Key Facts. From Alli Healthcare Professionals web site.

48. Anderson JW, Schwartz SM, Hauptman J et al. Low-dose orlistat effects on body weight of mildly to moderately overweight individuals: a 16 week, double-blind, placebo-controlled trial. Ann Pharmacother. 2006; 40:1717-23. [PubMed 16940406]

49. Hauptman J, Lucas C, Boldrin MN et al. Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med. 2000; 9:160-7. [PubMed 10693734]

50. Rössner S, Sjöström L, Noack R et al. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Obes Res. 2000; 8:49-61.

51. Curran MP, Scott LJ. Orlistat: a review of its use in the management of patients with obesity. Drugs. 2004; 64:2845-64. [PubMed 15563254]

52. Food and Drug Administration, Centers for Drug Evaluation and Research. Early communication about an ongoing safety review of orlistat (marketed as Alli and Xenical). Rockville, MD; 2009 Aug 24. From the FDA web site. Accessed 2009 Sep 9.

53. Food and Drug Administration. FDA News Release: FDA issues early communication about ongoing safety review of weight loss drug orlistat: review includes both prescription drug Xenical and OTC drug Alli. Rockville, MD; 2009 Aug 24. From the FDA web site. Accessed 2009 Oct 28.

55. Umemura T, Ichijo T, Matsumoto A et al. Severe hepatic injury caused by orlistat. Am J Med. 2006; 119:e7. [PubMed 16887401]

56. Lau G, Chan CL. Massive hepatocellular [correction of hepatocullular] necrosis: was it caused by Orlistat?. Med Sci Law. 2002; 42:309-12. [PubMed 12487515]

57. Kim DH, Lee EH, Hwang JC et al. [A case of acute cholestatic hepatitis associated with Orlistat]. Taehan Kan Hakhoe Chi. 2002; 8:317-20. [PubMed 12499790]

58. Montero JL, Muntané J, Fraga E et al. Orlistat associated subacute hepatic failure. J Hepatol. 2001; 34:173. [PubMed 11211898]

59. Roche Laboratories Inc. Xenical (orlistat) capsules patient information. Nutley, NJ; 2009 Jan.

60. Madhava K, Hartley A. Hypothyroidism in thyroid carcinoma follow-up: orlistat may inhibit the absorption of thyroxine. Clin Oncol Coll Radiol). 2005; 17:492. [PubMed 16149295]

61. Filippatos TD, Derdemezis CS, Gazi IF et al. Orlistat-associated adverse effects and drug interactions: a critical review. Drug Saf. 2008; 31:53-65. [PubMed 18095746]

62. Thurairajah PH, Syn WK, Neil DA et al. Orlistat (Xenical)-induced subacute liver failure. Eur J Gastroenterol Hepatol. 2005; 17:1437-8. [PubMed 16292105]

63. Alli Educational Resources. From Alli Healthcare Professionals web site. Accessed 2009 Sep 10.

64. Zhi J, Moore R, Kanitra L et al. Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers. J Clin Pharmacol. 2003; 43:428-35. [PubMed 12723464]

65. US Food and Drug Administration. FDA drug safety communication: completed safety review of Xenical/Alli (orlistat) and severe liver injury. Rockville, MD; 2010 May 26. From FDA website http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213038.htm. Accessed 2010 Nov 9.

66. US Food and Drug Administration. Questions and answers: orlistat and severe liver injury. Rockville, MD; 2010 May 26. From FDA website http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213040.htm. Accessed 2010 Nov 9.

67. Humayun Y, Ball KC, Lewin JR et al. Acute oxalate nephropathy associated with orlistat. J Nephropathol. 2016; 5:79-83. [PubMed 27152294]

68. Gonzalez-Gay MA, Garcia-Porrua C, Lueiro M et al. Orlistat-induced cutaneous leukocytoclastic vasculitis. Arthritis Rheum. 2002; 47:567. [PubMed 12382312]

69. Lazic T, Fonder M, Robinson-Bostom L et al. Orlistat-induced bullous leukocytoclastic vasculitis. Cutis. 2013; 91:148-9. [PubMed 23617088]

70. Roche Registration Limited,. Xenical (orlistat) 120-mg hard capsules summary of product characteristics. Welwyn Garden City, UK; 2008 Jul 29.

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