Weight management, chronic (alternative agent):
Note: For use as an adjunct to diet and exercise in patients who cannot take preferred agents and who have a BMI ≥30 kg/m2 or patients with a BMI ≥27 kg/m2 and ≥1 weight-associated comorbidity (eg, hypertension, dyslipidemia) (AACE/ACE [Garvey 2016]; ES [Apovian 2015]). Administer a multivitamin at bedtime due to impaired absorption of fat-soluble vitamins.
Xenical: Oral: 120 mg 3 times daily with each main meal containing fat (during or up to 1 hour after the meal); omit dose if meal is occasionally missed or contains no fat (manufacturer’s labeling). Note: Some experts initiate with the 60 mg dose (Alli) to improve GI tolerability, or switch to the 60 mg dose if 120 mg is poorly tolerated (Anderson 2007; Perreault 2022). Consider discontinuation if weight loss is <4% to 5% of baseline after 3 months (AACE/ACE [Garvey 2016]; ES [Apovian 2015]; Perreault 2022).
Alli: OTC labeling: Oral: 60 mg 3 times daily with each main meal containing fat; maximum OTC dose: 180 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment unlikely due to low systemic absorption. Discontinue use if oxalate nephropathy develops.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment unlikely due to low systemic absorption.
(For additional information see "Orlistat: Pediatric drug information")
Obesity management:
Children ≥8 years to <12 years: Very limited data available: Oral: 120 mg 3 to 4 times daily with each meal. Dosing based on a prospective, open-label study (n=11, age: 8.3 to 12.3 years) evaluating the efficacy of orlistat in obese prepubertal children defined as a BMI standard deviation score ≥4 standard deviations above normal and Tanner stage 1 to 2; median weight loss was 4 kg (range of weight change: –12.7 to +2.5 kg) and decreased fat intake was described (Norgren 2003).
Children ≥12 years and Adolescents: Xenical: Oral: 120 mg 3 times daily administered with each main meal containing fat (during or up to 1 hour after eating); omit dose if meal is occasionally missed or contains no fat.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, dosage adjustment unlikely due to low systemic absorption.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, dosage adjustment unlikely due to low systemic absorption.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Alli: 60 mg [contains fd&c blue #2 (indigotine)]
Xenical: 120 mg [contains fd&c blue #2 (indigotine)]
Generic: 120 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Xenical: 120 mg [contains fd&c blue #2 (indigotine)]
Oral: Administer during or up to 1 hour after each main meal containing fat; separate dose by at least 2 hours from multivitamin containing fat-soluble vitamins. Omit dose if a meal is missed or contains no fat.
Oral: Administer during or up to 1 hour after each main meal containing fat; separate dose by at least 2 hours from multivitamin daily supplement. Omit dose if a meal is missed or contains no fat.
Weight management, chronic:
OTC: Weight loss in overweight adults when used along with a reduced-calorie and low-fat diet.
Rx: Weight management, including weight loss and weight maintenance, when used in conjunction with a reduced-calorie diet; to reduce the risk for weight regain after prior weight loss.
Limitations of use: Orlistat is indicated for patients with an initial body mass index of ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia).
Xenical may be confused with Xeloda
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Vitamin deficiency (including decreased carotene levels [beta-carotene: 2% to 6%], vitamin A deficiency [2%], vitamin D deficiency [1% to 12%], vitamin E deficiency [6%])
Gastrointestinal: Abdominal distress (≤26%), abdominal pain (≤26%), bowel urgency (3% to 22%), flatulence with discharge (2% to 24%), frequent bowel movements (3% to 11%), oily evacuation (2% to 12%), oily rectal leakage (4% to 27%), steatorrhea (6% to 20%)
Infection: Influenza (40%)
Nervous system: Headache (31%)
Neuromuscular & skeletal: Back pain (14%), lower extremity pain (11%)
Respiratory: Upper respiratory tract infection (38%)
1% to 10%:
Cardiovascular: Pedal edema (3%)
Dermatologic: Xeroderma (2%)
Endocrine & metabolic: Menstrual disease (10%)
Gastrointestinal: Cholelithiasis (3%), fecal incontinence (2% to 8%), gingival disease (4%), infectious diarrhea (5%), nausea (4% to 8%), rectal pain (3% to 5%)
Genitourinary: Urinary tract infection (6% to 8%), vaginitis (3%)
Nervous system: Anxiety (3% to 5%), fatigue (3% to 7%), sleep disorder (4%)
Neuromuscular & skeletal: Myalgia (4%)
Respiratory: Lower respiratory tract infection (8%)
Postmarketing:
Cardiovascular: Hypertension (Persson 2000)
Dermatologic: Bullous skin disease
Endocrine & metabolic: Hyperoxaluria (Solomon 2017)
Gastrointestinal: Gastrointestinal hemorrhage (lower), pancreatitis (including acute pancreatitis) (Kose 2015)
Genitourinary: Crystalluria (calcium oxalate) (Handing 2022)
Hematologic & oncologic: Macrocytic anemia (Palacios-Martinez 2013), thrombocytopenia (Palacios-Martinez 2013)
Hepatic: Hepatic failure (Livertox 2020), hepatic necrosis, hepatitis (Livertox 2020), increased serum alkaline phosphatase (Livertox 2020), increased serum transaminases (Livertox 2020)
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity angiitis (Gonzalez-Gay 2002), hypersensitivity reaction
Neuromuscular & skeletal: Myopathy (Palacios-Martinez 2013)
Renal: Acute kidney injury (oxalate nephropathy) (Cui 2022), calcium oxalate nephrolithiasis, renal tubular necrosis (Humayun 2016)
Hypersensitivity to orlistat or to any component of the formulation; pregnancy; chronic malabsorption syndrome; cholestasis
Concerns related to adverse effects:
• Cholelithiasis: Substantial weight loss may increase the risk of cholelithiasis.
• Hepatotoxicity: Cases of severe liver injury (some fatal) with hepatocellular necrosis or acute hepatic failure have been reported; liver transplantation has been required in some patients. Patients should be instructed to report any symptoms of hepatic impairment (eg, anorexia, pruritus, jaundice, dark urine, light colored stools, right upper quadrant pain); discontinue therapy immediately and obtain liver function tests if symptoms occur.
• Increased urinary oxalate: Increased levels of urinary oxalate following treatment may occur in some patients; cases of oxalate nephrolithiasis and oxalate nephropathy with renal failure have been reported.
Disease-related concerns:
• Diabetes: Monitor patients with diabetes closely; weight loss may affect glycemic control. Dosage adjustments of antidiabetic medications may be necessary.
Special populations:
• Pediatric: When used in adolescents, weight related to growth is accounted for in BMI, therefore, reduction in BMI is a better indicator of weight loss.
Other warnings/precautions:
• Appropriate use: Prior to use, other causes for obesity (eg, hypothyroidism) should be ruled out. According to Endocrine Society practice guidelines, weight loss medication should be discontinued and alternative treatment considered if weight loss is <5% of body weight at 3 months or if safety/tolerability issues arise (Apovian 2015).
• Dietary guidelines: Patients should be advised to adhere to dietary guidelines; if taken with a diet high in fat (>30% total daily calories from fat), gastrointestinal adverse events may increase. Distribute daily fat intake over 3 main meals. If taken with any 1 meal very high in fat, the possibility of gastrointestinal effects increases. Counsel patients to take a multivitamin supplement that contains fat-soluble vitamins ≥2 hours before or after orlistat administration to ensure adequate nutrition; orlistat has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene.
• Potential for misuse: The potential exists for misuse in inappropriate patient populations (eg, patients with anorexia nervosa or bulimia) similar to any weight loss agent.
• Self-medication (OTC use): Prior to use, patients should contact their healthcare provider if they have ever had kidney stones, gall bladder disease, or pancreatitis. Patients taking medications for diabetes or thyroid disease, seizures, anticoagulants, or other weight-loss products should consult their healthcare provider or pharmacist before use. Patients who have had an organ transplant should not use orlistat. If severe and/or continuous abdominal pain, itching, yellowing of the eyes or skin, dark urine, loss of appetite occurs, or seizures worsen, use should be discontinued and healthcare provider consulted.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amiodarone: Orlistat may decrease the serum concentration of Amiodarone. Risk C: Monitor therapy
Antiretroviral Agents: Orlistat may decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Antiseizure Agents: Orlistat may decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
CycloSPORINE (Systemic): Orlistat may decrease the serum concentration of CycloSPORINE (Systemic). Management: Administer oral cyclosporine 3 hours after orlistat. Monitor for decreased serum concentrations of oral cyclosporine, even with the recommended dose separation. Risk D: Consider therapy modification
Levothyroxine: Orlistat may decrease the serum concentration of Levothyroxine. Management: Separate administration of oral levothyroxine and orlistat by a least 4 hours. Monitor patients closely for signs and symptoms of hypothyroidism. Risk D: Consider therapy modification
Propafenone: Orlistat may decrease the serum concentration of Propafenone. Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Triheptanoin: Orlistat may decrease serum concentrations of the active metabolite(s) of Triheptanoin. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Orlistat may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Vitamins (Fat Soluble): Orlistat may decrease the absorption of Vitamins (Fat Soluble). Management: Administer oral fat soluble vitamins at least 2 hours before or 2 hours after the administration of orlistat. Avoid concomitant administration due to the risk of impaired vitamin absorption. Risk D: Consider therapy modification
Use of orlistat in combination with lifestyle modification (caloric restriction and increased physical activity) was evaluated in patients with overweight/obesity and patients with polycystic ovary syndrome (PCOS). Patients were treated for 16 weeks prior to receiving 4 cycles of ovulation induction. Patients were required to use contraception during treatment with orlistat. Weight loss was significant and ovulation rates were increased in all patients who received lifestyle modification (with or without orlistat), however there was no difference in pregnancy rates, pregnancy loss, or live births (Legro 2015). Orlistat has also been evaluated in patients with overweight/obesity and infertility 4 to 12 weeks prior to in vitro fertilization and embryo transfer (IVF-ET). Although patients treated with orlistat had a significant weight loss, the live birth weight was not increased (Wang 2021).
Obesity increases the risk of infertility. Optimal weight control prior to conception improves pregnancy outcomes. However, medications for weight loss are not recommended prior to pregnancy due to safety issues and adverse events. Weight loss medications should be discontinued prior to conception (ACOG 2021; Wharton 2020).
Outcome information following maternal use of orlistat during pregnancy is limited (Källén 2014; Perrio 2007).
An increased risk of adverse maternal and fetal events is associated with obesity. However, moderate gestational weight gain based on pre-pregnancy BMI is required for positive fetal outcomes in all pregnancies, including patients with overweight or obesity. Therefore, medications for weight loss therapy are not recommended during pregnancy (ACOG 2021; Wharton 2020). Due to the lack of clinical benefit and potential for fetal harm, use of orlistat is contraindicated in pregnant patients.
It is not known if orlistat is present in breast milk.
Orlistat has minimal systemic absorption. The manufacturer recommends caution be used if administered to a breastfeeding patient. Due to safety concerns, medications for weight loss therapy are not recommended for patients who are breastfeeding (Wharton 2020).
Multivitamin supplements that contain fat-soluble vitamins should be taken once daily at least 2 hours before or after the administration of orlistat (ie, bedtime). Gastrointestinal effects of orlistat may increase if taken with any one meal very high in fat. Distribute daily intake of carbohydrates, fat (~30% of daily calories), and protein over three main meals.
BMI; weight; diet (calorie and fat intake); serum glucose in patients with diabetes; LFTs in patients exhibiting symptoms of hepatic impairment; renal function in patients at risk for renal impairment or with a history of calcium oxalate nephrolithiasis or hyperoxaluria.
Adult classification of weight by BMI (kg/m2):
Underweight: <18.5
Normal: 18.5 to 24.9
Overweight: 25 to 29.9
Obesity, class I: 30 to 34.9
Obesity, class II: 35 to 39.9
Obesity, class III: ≥40
Waist circumference: In adults with a BMI of 25 to 34.9 kg/m2, high-risk waist circumference for adiposity-related disease is defined as (AACE/ACE [Garvey 2016]):
Males >102 cm (>40 in).
Females >88 cm (>35 in).
A reversible inhibitor of gastric and pancreatic lipases, thus inhibiting absorption of dietary fats by 30%.
Onset of action: 24-48 hours
Duration: 48-72 hours
Absorption: Minimal
Protein binding: >99% (lipoproteins and albumin)
Metabolism: Metabolized within the gastrointestinal wall; forms inactive metabolites
Half-life elimination: 1-2 hours
Time to peak, serum: ~8 hours
Excretion: Feces (~97%, 83% as unchanged drug); urine (<2%)
Capsules (Alli Oral)
60 mg (per each): $0.59
Capsules (Orlistat Oral)
120 mg (per each): $8.67
Capsules (Xenical Oral)
120 mg (per each): $10.05
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