Dosage Forms
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)]
Pharmacology
Mechanism of Action
A reversible inhibitor of gastric and pancreatic lipases, thus inhibiting absorption of dietary fats by 30%.
Pharmacokinetics/Pharmacodynamics
Absorption
Minimal
Metabolism
Metabolized within the gastrointestinal wall; forms inactive metabolites
Excretion
Feces (~97%, 83% as unchanged drug); urine (<2%)
Onset of Action
24-48 hours
Time to Peak
Serum: ~8 hours
Duration of Action
48-72 hours
Half-Life Elimination
1-2 hours
Protein Binding
>99% (lipoproteins and albumin)
Use: Labeled Indications
Obesity management:
OTC: Weight loss in overweight adults when used along with a reduced-calorie and low-fat diet.
Rx: Obesity 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 obese 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).
Contraindications
Hypersensitivity to orlistat or to any component of the formulation; pregnancy; chronic malabsorption syndrome; cholestasis
Dosage and Administration
Dosing: Adult
Obesity management: Oral:
Xenical: 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.
Alli: OTC labeling: 60 mg 3 times daily with each main meal containing fat (maximum dose: 180 mg/day).
Dosing adjustment with concomitant therapy:
Cyclosporine: Administer cyclosporine 3 hours after orlistat.
Levothyroxine: Administer levothyroxine and orlistat at least 4 hours apart and monitor for changes in thyroid function.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Obesity management (Xenical): Children ≥12 years and Adolescents: Refer to adult dosing.
Administration
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.
Dietary Considerations
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.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Drug Interactions
Amiodarone: Orlistat may decrease the serum concentration of Amiodarone. Monitor therapy
Anticonvulsants: Orlistat may decrease the serum concentration of Anticonvulsants. Exceptions: Fosphenytoin; PENTobarbital; Thiopental. Monitor therapy
Antiretroviral Agents: Orlistat may decrease the serum concentration of Antiretroviral Agents. Monitor therapy
CycloSPORINE (Systemic): Orlistat may decrease the serum concentration of CycloSPORINE (Systemic). Management: Administer orlistat at least 3 hours before or after oral cyclosporine. Monitor for decreased serum concentrations of oral cyclosporine, even with the recommended dose separation. 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. Consider therapy modification
Multivitamins/Fluoride (with ADE): Orlistat may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Specifically, orlistat may impair absorption of fat-solube vitamins. Management: Administer oral fat soluble vitamins (such as vitamins A, D, E, and/or K that are contained in many multivitamin products) at least 2 hours before or after the administration of orlistat. Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): Orlistat may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, orlistat may impair the absorption of fat-soluble vitamins. Management: Administer oral fat soluble vitamins (such as vitamins A, D, E, and/or K that are contained in many multivitamin products) at least 2 hours before or after the administration of orlistat. Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): Orlistat may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, orlistat may impair absorption of fat-solube vitamins. Management: Administer oral fat soluble vitamins (such as vitamins A, D, E, and/or K that are contained in many multivitamin products) at least 2 hours before or after the administration of orlistat. Consider therapy modification
Paricalcitol: Orlistat may decrease the serum concentration of Paricalcitol. Management: Monitor clinical response to paricalcitol closely when used with orlistat. When this combination must be used, consider administering paricalcitol at least 1 hour before or 4 to 6 hours after the administration of orlistat Consider therapy modification
Propafenone: Orlistat may decrease the serum concentration of Propafenone. 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. Consider therapy modification
Vitamin D Analogs: Orlistat may decrease the serum concentration of Vitamin D Analogs. More specifically, orlistat may impair absorption of Vitamin D Analogs. Management: Monitor clinical response (including serum calcium) to oral vitamin D analogs closely if used with orlistat. If this combination must be used, consider giving the vitamin D analog at least 2 hrs before or after orlistat. Exceptions: Calcipotriene; Calcitriol (Topical); Tacalcitol. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Orlistat may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Vitamins (Fat Soluble): Orlistat may decrease the serum concentration of Vitamins (Fat Soluble). Management: Administer oral fat soluble vitamins at least 2 hours before or after the administration of orlistat. Similar precautions do not apply to parenterally administered fat soluble vitamins. Exceptions: Calcipotriene. Consider therapy modification
Adverse Reactions
The frequency of most adverse reactions (especially gastrointestinal effects) decreases over time. Frequency not always defined.
Cardiovascular: Pedal edema (≤3%)
Central nervous system: Headache (≤31%), fatigue (3% to 7%), anxiety (3% to 5%), sleep disorder (≤4%)
Dermatologic: Xeroderma (≤2%)
Endocrine & metabolic: Menstrual disease (≤10%), hypoglycemia (in patients with diabetes)
Gastrointestinal: Oily rectal leakage (4% to 27%), abdominal distress (≤26%), abdominal pain (≤26%), flatulence with discharge (2% to 24%), bowel urgency (3% to 22%), steatorrhea (6% to 20%), oily evacuation (2% to 12%), frequent bowel movements (3% to 11%), nausea (4% to 8%), fecal incontinence (2% to 8%), infectious diarrhea (≤5%), rectal pain (3% to 5%), gingival disease (4%), cholelithiasis (3%), abdominal distension (in patients with diabetes)
Genitourinary: Urinary tract infection (6% to 8%), vaginitis (3%)
Infection: Influenza (≤40%)
Neuromuscular & skeletal: Back pain (≤14%), leg pain (≤11%), myalgia (≤4%)
Otic: Otitis (4%)
Respiratory: Upper respiratory tract infection (38%), lower respiratory tract infection (≤8%)
<1%, postmarketing, and/or case reports: Acute renal failure, anaphylaxis, angioedema, bronchospasm, bullous skin disease, calcium oxalate nephrolithiasis, gastrointestinal hemorrhage (lower), hepatic failure, hepatitis, hypersensitivity, hypersensitivity angiitis, increased serum alkaline phosphatase, increased serum transaminases, pancreatitis, pruritus, renal disease (secondary to increased urinary oxalate excretion), skin rash, urticaria
Warnings/Precautions
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. Monitor renal function in patients at risk for renal impairment; use with caution in patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis.
Disease-related concerns:
- Diabetes: Monitor patients with diabetes closely; weight loss may affect glycemic control. Dosage adjustments of antidiabetic medications may be necessary.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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.
Monitoring Parameters
BMI; weight; diet (calorie and fat intake); serum glucose in patients with diabetes; liver function tests in patients exhibiting symptoms of hepatic impairment; renal function in patients at risk for renal impairment.
Pregnancy
Pregnancy Risk Factor
X
Pregnancy Considerations
Outcome information following maternal use of orlistat during pregnancy is limited (Källén 2014; Perrio 2007).
An increased risk of adverse maternal and fetal outcomes is associated with obesity. However, moderate weight gain based on prepregnancy BMI is required for positive fetal outcomes. Therefore, medications for weight loss therapy are not recommended at conception or during pregnancy (ACOG 156 2015; Stang 2016). Due to the lack of clinical benefit and potential for fetal harm, use of orlistat is contraindicated in pregnant females.
Patient Education
What is this drug used for?
- It is used to help you lose weight.
Frequently reported side effects of this drug
- Loss of strength and energy
- Headache
- Diarrhea
- Menstrual changes
- Fatty or oily stools
- Nausea
- Leaking of stool
- Passing gas with discharge
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
- Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
- Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
- Gallstones like pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; yellow skin; or fever with chills.
- Black, tarry, or bloody stools
- Painful urination
- Passing a lot of urine
- Severe back pain
- Severe groin or thigh pain
- Swelling
- Severe abdominal pain
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
