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Orlistat
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NOTE: Orlistat is indicated in individuals with an initial body mass index (BMI) of 30 kg/m2 or more or 27 kg/m2 or more in the presence of other risk factors (e.g., hypertension, diabetes mellitus, or dyslipidemia).[27971]
120 mg PO 3 times daily with each main meal containing fat.[27971] When used under optimal conditions, orlistat can reduce BMI and weight, and reduces the risk for weight regain in chronic use.[27971] [62880] [62881] Pharmacotherapy should be offered as chronic treatment along with lifestyle modifications to individuals affected by obesity when the potential benefits outweigh the risks. Short-term pharmacotherapy has not been shown to produce longer-term health benefits and cannot be generally recommended.[62881]
120 mg PO 3 times daily with each main meal containing fat.[27971] When used under optimal conditions, orlistat can reduce BMI and weight, and reduces the risk for weight regain in chronic use; however, in pediatric individuals, adherence at meal (e.g., school days) may be problematic.[27971] [58571] [62880] [62881] [63035] Pharmacotherapy is usually reserved for pediatric individuals with a BMI at the 95th percentile or more or meeting the adult BMI recommendations for use. Reserve pharmacotherapy for overweight children (BMI 85th to 94th percentile) for those with significant, severe comorbidities who have not responded to lifestyle modification.[58571] [63035] [71238]
60 mg PO 3 times daily with each main meal containing fat. Max: 180 mg/day.[60877] When used under optimal conditions, orlistat can reduce BMI and weight, and reduces the risk for weight regain in chronic use.[62880] [62881] Pharmacotherapy should be offered as chronic treatment along with lifestyle modifications to individuals affected by obesity when the potential benefits outweigh the risks. Short-term pharmacotherapy has not been shown to produce longer-term health benefits and cannot be generally recommended.[62881]
360 mg/day PO (Xenical, Rx-only), 180 mg/day PO (Alli, OTC use).
360 mg/day PO (Xenical, Rx-only), 180 mg/day PO (Alli, OTC use).
360 mg/day PO (e.g., Xenical, Rx-only); OTC use (e.g., Alli) not recommended.
12 years: 360 mg/day PO (Xenical, Rx-only); OTC use (i.e., Alli) not recommended.
1 to 11 years: Safety and efficacy have not been established.
Not indicated.
No dosage adjustments are needed. During treatment, if signs or symptoms of liver injury occur, discontinue treatment.[27971] Some guidelines suggest avoidance of orlistat and other weight-loss medications in patients with severe hepatic disease.[62881]
No dosage adjustments are needed.[27971]
† Off-label indicationOrlistat is a gastrointestinal lipase inhibitor. It is used by prescription (Xenical) as an adjunct to lifestyle modifications for weight loss and chronic weight management in adults and pediatric patients 12 years and older.[27971] A low-dose non-prescription product (Alli) is available for overweight adults.[60877] Orlistat can produce a mean weight loss of approximately 4% and can reduce the risk for weight regain in chronic use.[25614] Modification of some cardiovascular risk factors in obese patients after 1 year of treatment have been noted.[25615] Unlike other weight loss medications, orlistat works non-systemically, blocking the absorption of dietary fat. The non-systemic action of orlistat can be beneficial in obese patients with conditions such as cardiovascular disease, renal disease, or substance abuse; however, treatment is associated with significant gastrointestinal side effects (loose/oily stools, flatulence, fecal urgency) that can affect treatment adherence, limiting the utility of the drug for chronic weight management. Because orlistat reduces the absorption of fat-soluble vitamins, a daily multivitamin containing fat-soluble vitamins (i.e., vitamins A,D,E,K) is recommended during therapy. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications should be offered as chronic treatment along with lifestyle modifications to patients with obesity when the potential benefits outweigh the risks. Short-term pharmacotherapy has not been shown to produce longer-term health benefits and cannot be generally recommended. A generalized heirarchy for medication preferences that would be applicable to all obese patients cannot currently be scientifically justified. Individualized weight loss pharmacotherapy is recommended, based upon factors such as the specific characteristics of each weight loss medication, the presence of weight-related complications, and the medical history of the patient.[62881] In pediatric patients, orlistat remains the only FDA-approved medication for weight loss; pharmacotherapy is usually reserved for pediatric patients with a BMI at the 95th percentile or more. Pharmacotherapy for overweight children (BMI 85th to 94th percentile) should be reserved for those with significant, severe comorbidities who have not responded to lifestyle modification.[58571][63035] Orlistat was initially approved by the FDA in 1999 as a prescription product; the reduced-dose non-prescription status was attained in 2007.
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GI symptoms that occurred at least twice that of placebo in >= 5% of patients taking orlistat during double-blind, placebo-controlled clinical trials include flatulence with discharge (23.9% year 1; 4.4% year 2; placebo roughly 1%), fecal urgency (22.1% year 1; 2.8% year 2; placebo 6.7% year 1), fecal incontinence (7.7% year 1; 1.8% year 2; placebo < 1%), steatorrhea (20% year 1; 6% year 2; placebo 2.9% year 1), oily spotting (26.6% year 1; 4.4% year 2; placebo roughly 1%), oily evacuation (12% year 1; 2.3% year 2; placebo < 1%) and increased defecation (10.8% year 1; 2.6% year 2; placebo 4.1% year 1). These and other commonly observed adverse effects were usually mild to moderate with approximately 50% lasting for less than one week. At least 1 GI event occurred in 79% of patients in the orlistat group compared to 59% in the placebo group. During the first year of trials, the dropout rate due to adverse effects, primarily steatorrhea, was significantly higher for orlistat (9.1%) compared to placebo (4%) groups. Adverse effects decreased during the second year of study. Overall dropout rates due to adverse effects were similar for both groups over the 2 year period.[25613] Adverse gastrointestinal events associated with orlistat may increase with a diet containing greater than 30% of calories from fat. To prevent exacerbation of GI reactions, patients should adhere to the recommended diet plan while taking orlistat. Psyllium has been reported to be an effective fiber adjunct to reduce some of the GI side effects associated with orlistat.[25613] [27971]
The following adverse events occurred in >= 2% of patients taking orlistat during the first or second year of double-blind, placebo-controlled clinical trials (and at a percentage rate greater than placebo): abdominal pain (25.5 vs. 21.4% placebo); nausea/vomiting (8.1/3.1% vs. 7.3/3.5% placebo); dizziness (5.2 vs. 5% placebo); infectious diarrhea (5.3 vs. 4.4% placebo); rectal pain (5.2 vs. 4% placebo); gingival disorder (4.1 vs. 2.9% placebo); headache (31 vs. 28% placebo); influenza (39.7 vs. 36.2% placebo); general musculoskeletal pain, such as back pain (13.9 vs. 12.1% placebo), arthritis (5.4 vs. 4.8% placebo), and myalgia (4.2 vs. 3.3% placebo); menstrual irregularity (9.8 vs. 7.5% placebo); fatigue (7.2 vs. 6.4% placebo); pedal edema (2.8 vs. 1.9% placebo); anxiety/depression (2.8/3.4% vs. 2.1/2.5% placebo); rash (unspecified) (4.3 vs. 4% placebo); respiratory tract infection (46 vs. 40% placebo); otitis (4.3 vs. 3.4% placebo); urinary tract infection (5.9 vs. 4.8% placebo); vaginitis (2.6 vs. 1.9% placebo). In the 4-year XENDOS study, the general pattern of adverse events was similar to that reported for the 1- and 2-year studies with the total incidence of gastrointestinal-related adverse events occurring in year 1 decreasing each year over the 4-year period.[27971]
Low serum levels of beta-carotene and vitamins A, D, and E were observed in a greater percentage of patients receiving orlistat compared to those taking placebo. Actual deficiencies due to hypovitaminosis may be prevented through the use of a daily multivitamin supplement that contains fat-soluble vitamins.[27971]
An increased risk of cholelithiasis has been associated with rapid and substantial weight loss. In a study investigating the use of orlistat in preventing type 2 diabetes, the rates of cholelithiasis were 2.9% (47/1649) for patients randomized to orlistat and 1.8% (30/1655) for patients randomized to placebo. The increased risk of cholelithiasis was not seen in orlistat trials not evaluating the prevention of type 2 diabetes.[27971] Nevertheless, clinicians should inform patients who take orlistat about this potential risk and instruct them to seek medical attention if they experience severe or prolonged abdominal pain and/or nausea and vomiting.
In rare cases, leukocytoclastic vasculitis has been reported during post-marketing use of orlistat, with clinical signs including palpable purpura, maculopapular rash, or bullous rash or eruption. Rare post-marketing cases of hypersensitivity reactions have been reported with the use of orlistat. Signs and symptoms have included pruritus, rash (unspecified), urticaria, angioedema, bronchospasm, and anaphylactoid reactions.[27971]
Cases of elevated hepatic enzymes, increased alkaline phosphatase, exceptional cases of hepatitis, severe liver injury with hepatic necrosis, and acute hepatic failure have been reported during post-marketing use of orlistat. In addition, in August, 2009, the FDA announced that it was reviewing reports of liver-related adverse events associated with the use of prescription and over-the-counter orlistat; after a comprehensive review, the FDA identified 13 total reports of severe liver injury with orlistat. Of the 13 cases, 2 patients died from hepatic failure and 3 patients required liver transplantation. No definite association between liver injury and orlistat has been established. At this time, the FDA advises that healthcare professionals weigh the benefits of weight loss with orlistat against the potential risks when determining if orlistat is appropriate for patients. Patients should report signs and symptoms of liver injury to their health care provider immediately.[40642] [27971]
Post-marketing cases of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants. In clinical trials in obese diabetic patients, hypoglycemia and abdominal distension were also observed.[27971]
During post-marketing surveillance, cases of pancreatitis have been reported with the use of orlistat. No causal relationships or plausible mechanisms have been identified to account for this effect in weight-loss therapy.[27971]
During post-marketing surveillance, hypothyroidism has been reported in patients treated concomitantly with orlistat and levothyroxine. Patients treated with orlistat and levothyroxine should be monitored for changes in thyroid function; orlistat may interfere with the absorption of levothyroxine from the gastrointestinal tract. Administer levothyroxine and orlistat at least 4 hours apart.[27971]
During post marketing surveillance of orlistat therapy, seizures have been reported in patients treated concomitantly with orlistat and anticonvulsant drugs. Patients should be monitored for changes in the frequency or severity of seizures.[27971]
Orlistat reduces the absorption of vitamin D and may lead to vitamin D deficiency. Patients should be monitored and supplemented with vitamin D when necessary.[63388]
Postmarketing reports of acute oxalate nephropathy and hyperoxaluria have occurred in patients with or at risk for renal disease following treatment with orlistat. As these reports are made voluntarily, the frequency and causal relationship to orlistat exposure is not established.[27971]
The coadministration of certain medications may lead to harm and require avoidance or therapy modification; review all drug interactions prior to concomitant use of other medications.
This medication is contraindicated in patients with a history of hypersensitivity to it or any of its components.
Organic causes of obesity, such as hypothyroidism, should be ruled out prior to prescribing orlistat, and should be treated as per clinical standards of care.[27971][60877]
Orlistat is contraindicated for use in patients with chronic malabsorption syndrome.[27971] [60877]
Orlistat is contraindicated for use in individuals with cholestasis; individuals with a history of gallbladder disease should consult a healthcare provider before use.[27971] [60877] Substantial weight loss can increase the risk of cholelithiasis or gallbladder disease. In a clinical trial of orlistat, the rates of cholelithiasis as an adverse event were 2.9% (47/1649) for individuals randomized to orlistat and 1.8% (30/1655) for individuals randomized to placebo. The long-term effects on gallstone formation have not been determined; orlistat use does not appear to influence gallbladder motility.[27971] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, close monitoring for cholelithiasis is recommended in individuals undergoing weight loss therapy, regardless of modality. Effective preventative measures for obese individuals at risk for cholelithiasis include a slower rate of weight loss, increasing/including some dietary fat in the diet (assuming the individual has been on a very low-calorie diet containing little or no fat), or administration of ursodeoxycholic acid. The AACE/ACE Obesity Guidelines also recommend monitoring for pancreatitis due to a proven association between pancreatitis and obesity and reports of pancreatitis occurring in individuals receiving orlistat. The drug should be withheld if pancreatitis occurs or the individual has a previous history of pancreatitis.[62881]
Carefully consider the risk: benefit ratio of using orlistat in individuals with hepatic disease.[27971] [40642] [60877] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, all weight loss medications should be used cautiously in individuals with hepatic failure. AACE/ACE Obesity Guidelines recommends to use orlistat with caution in individuals with mild hepatic impairment (Child-Pugh class A) or moderate hepatic impairment (Child-Pugh class B), and to avoid using orlistat in individuals with in severe hepatic impairment (i.e., Child-Pugh class C).[62881]
Monitor renal function when prescribing orlistat to individuals at risk for renal impairment or renal failure. Use with caution in individuals with a history of hyperoxaluria or calcium oxalate nephrolithiasis. Some individuals may develop increased levels of urinary oxalate following treatment with orlistat, and cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure have been reported.[27971] [60877] The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines do not recommend use in individuals with a history or risk factors for oxalate nephropathy. AACE/ACE Obesity Guidelines consider orlistat a weight reduction option for obese individuals with mild to moderate renal impairment (i.e., CrCl 30 to 79 mL/minute). Individuals with severe renal disease or impairment (CrCl less than 30 mL/minute) should be monitored closely for oxalate nephropathy if orlistat is used.[62881]
Weight loss may affect glycemic control in individuals with diabetes mellitus. A reduction in dose of oral hypoglycemic medication (e.g., sulfonylureas) or insulin may be required in some individuals. Individuals with diabetes should be advised to continue to routinely monitor blood glucose and report any changes in blood glucose control to their healthcare provider.[27971] [60877]
Use orlistat with caution in individuals with an eating disorder, such as anorexia nervosa or bulimia nervosa.[27971] [60877] [62881]
Orlistat is contraindicated for use during pregnancy because weight loss offers no potential benefit to a pregnant woman and weight loss, coupled with reduced absorption of fat-soluble vitamins (A, D, E, K) 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, due to the obligatory weight gain that occurs in maternal tissues during pregnancy and the need to provide appropriate nutrition to the developing fetus. No embryotoxicity or teratogenicity was seen in animals that received orlistat at doses much higher than the recommended human dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus.[27971] Pregnant women must also avoid nonprescription use of the drug.[60877] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications must not be used during pregnancy. The AACE/ACE Obesity Guidelines recommend that women of childbearing potential receiving orlistat use adequate contraception and discontinue orlistat if pregnancy occurs.[62881]
The manufacturer recommends caution when administering orlistat to a breast-feeding woman; nonprescription use should be avoided. The minimal systemic bioavailability of orlistat suggests that the drug is not expressed in breast milk; however, it is not known with certainty if orlistat is present in human milk.[27971] [60877] It is not known if the effects of orlistat on maternal availability of fat-soluble vitamins would affect breast milk quality or quantity. Women who are breast-feeding should be encouraged to take proper vitamin supplementation as suggested by orlistat product labeling to avoid deficiencies of fat-soluble vitamins. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, the use of orlistat in breast-feeding women is generally not recommended.[62881]
The safety and efficacy of orlistat have not been evaluated in children less than 12 years of age; do not give to infants. Because orlistat may reduce the absorption of certain nutrients essential for proper growth and development, use in children under 12 years of age has not been advised. Use of orlistat in adolescents 12 years and older should be in conjunction with a healthcare professional's approval and prescription. Monitor weight and growth, and, ensure the use of a properly selected multivitamin supplement daily.[27971] Nonprescription use is not advised in pediatric patients as the nonprescription product has been approved only for use in overweight adults.[60877] In pediatric patients 12 years and older, pharmacotherapy is usually reserved for pediatric patients with a BMI at the 95th percentile or more or meeting the adult BMI recommendations for use. Reserve medication therapy for overweight children (BMI 85th to 94th percentile) in those with significant, severe comorbidities who have not responded to lifestyle modification.[58571] [63035] Orlistat can reduce BMI and weight and reduces the risk for weight regain in chronic use; however, in pediatric patients, adherence at meals (e.g., school days, etc.) and side effects may be problematic.[27971] [62880] [62881] [58571] [63035]
Orlistat produces weight loss through inhibition of nutrient absorption. A covalent bond is formed with the active serine residue site of gastric and pancreatic lipases within the lumen of the stomach and the small intestine. As these enzymes become unavailable to hydrolyze dietary triglycerides into free fatty acids and monoglycerides, less fat is absorbed by the body. This results in decreased caloric intake that may result in negative energy balance and weight loss. Therefore, systemic absorption of the drug is not needed to produce a weight-lowering effect. At the recommended therapeutic dose of 120 mg orlistat PO three times per day, dietary fat absorption is inhibited by approximately 30%. Because orlistat may reduce the absorption of fat-soluble vitamins A, D, E, K, and beta-carotene, it is recommended patients take a daily multivitamin containing these vitamins during therapy, with the multivitamin supplement taken at least 2 hours before or after the administration orlistat.[27971]
Revision Date: 10/13/2025, 02:46:12 PMOrlistat is administered orally and has minimal systemic absorption. Sporadic intact amounts of orlistat, low plasma concentration levels (<10 ng/ml), and no evidence of accumulation were observed during therapeutic studies. In vitro, orlistat was > 99% bound to plasma proteins (primarily lipoproteins and albumin) with minimal partitioning into erythrocytes. Metabolism of orlistat to weakly active and inactive metabolites is believed to occur mainly within the gastrointestinal wall. Approximately 83% of a single oral dose of orlistat was excreted unchanged in the feces. Renal excretion was < 2% of the dose. Complete excretion of both urinary and fecal orlistat was reached in 3 to 5 days. The estimated half-life of the absorbed portion of orlistat was approximately 1 to 2 hours.
Peak plasma concentrations of orlistat (<5 ng/ml) occurred approximately 8 hours after a 360 mg dose. Based on fecal fat measurements, the effect of orlistat may be seen within 24 to 48 hours.
Orlistat is contraindicated for use during pregnancy because weight loss offers no potential benefit to a pregnant woman and weight loss, coupled with reduced absorption of fat-soluble vitamins (A, D, E, K) 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, due to the obligatory weight gain that occurs in maternal tissues during pregnancy and the need to provide appropriate nutrition to the developing fetus. No embryotoxicity or teratogenicity was seen in animals that received orlistat at doses much higher than the recommended human dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus.[27971] Pregnant women must also avoid nonprescription use of the drug.[60877] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications must not be used during pregnancy. The AACE/ACE Obesity Guidelines recommend that women of childbearing potential receiving orlistat use adequate contraception and discontinue orlistat if pregnancy occurs.[62881]
The manufacturer recommends caution when administering orlistat to a breast-feeding woman; nonprescription use should be avoided. The minimal systemic bioavailability of orlistat suggests that the drug is not expressed in breast milk; however, it is not known with certainty if orlistat is present in human milk.[27971] [60877] It is not known if the effects of orlistat on maternal availability of fat-soluble vitamins would affect breast milk quality or quantity. Women who are breast-feeding should be encouraged to take proper vitamin supplementation as suggested by orlistat product labeling to avoid deficiencies of fat-soluble vitamins. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, the use of orlistat in breast-feeding women is generally not recommended.[62881]
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