XENICAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XENICAL (XENICAL).
Reversible inhibitor of gastric and pancreatic lipases, preventing hydrolysis of dietary triglycerides into absorbable free fatty acids and monoglycerides.
| Metabolism | Minimally absorbed; metabolism occurs mainly in the gastrointestinal wall via hydrolysis to inactive metabolites; <1% absorbed drug is metabolized via glucuronidation and oxidation. |
| Excretion | Primarily fecal (approximately 97% of absorbed dose), with less than 2% renal elimination as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is approximately 1-2 hours for the parent drug; clinically relevant as rapid clearance limits systemic exposure. |
| Protein binding | Orlistat is highly protein-bound (>99%), primarily to albumin and lipoproteins. |
| Volume of Distribution | Volume of distribution is about 70 L (approx 1 L/kg), indicating extensive distribution into tissues. |
| Bioavailability | Oral bioavailability is extremely low (<1%) due to minimal absorption and extensive first-pass metabolism. |
| Onset of Action | Oral: onset of weight loss effect typically observed within 2 weeks of therapy initiation. |
| Duration of Action | Duration of action is approximately 7 hours after a single oral dose; clinical effect persists with continued dosing. |
| Molecular Weight | 495.74 |
| Action Class | Lipase inhibitor |
| Brand Substitutes | Zerofat 120mg Capsule, Reesize 120 Capsule, O-Stat 120 Capsule, Orlifit-N-Slim 120 Capsule, Obeset 120 Capsule |
120 mg orally three times daily with each main meal containing fat (during or up to 1 hour after the meal). Omit dose if meal is skipped or contains no fat.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for renal impairment. Not studied in ESRD. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment. Not studied in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Not recommended for use in children <12 years. Adolescents ≥12 years: same adult dose of 120 mg three times daily. |
| Geriatric use | No specific dose adjustment; same as adult dosing. Monitor for potential drug interactions and nutritional deficiencies due to fat malabsorption. |
| 1st trimester | Avoid. Weight loss offers no potential benefit to the pregnant woman and may cause fetal harm. Orlistat is a lipase inhibitor that reduces absorption of dietary fats, potentially leading to inadequate maternal weight gain and nutritional deficiencies. |
| 2nd trimester | Avoid. Same risks as first trimester. Insufficient data to assess fetal risk. |
| 3rd trimester | Avoid. Same risks as first trimester. Potential for maternal malnutrition affecting fetal growth. |
Clinical note
Comprehensive clinical and safety monograph for XENICAL (XENICAL).
| Placental transfer | Orlistat is minimally absorbed (plasma concentrations are negligible), and systemic bioavailability is very low. Therefore, placental transfer is expected to be minimal or absent. |
| Breastfeeding | Orlistat is minimally absorbed systemically; however, due to the potential for adverse effects on the nursing infant from maternal nutritional deficiency, caution is advised. An alternate drug may be preferred, especially while nursing an infant with poor nutritional status. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to orlistat or any component of the formulationChronic malabsorption syndromeCholestasis
| Precautions | Risk of cholelithiasis and cholecystitis due to rapid weight loss, Fat-soluble vitamin deficiencies (A, D, E, K) requiring supplementation, Gastrointestinal adverse effects (steatorrhea, fecal urgency, oily spotting) may worsen with high-fat meals, Interference with thyroid hormone absorption if taken concurrently |
| Food/Dietary | Avoid high-fat meals (>30% calories from fat) to reduce GI side effects. Do not take with meals containing no fat. May reduce absorption of fat-soluble vitamins (A, D, E, K). Administer multivitamin supplement at bedtime, at least 2 hours apart from orlistat. |
Loading safety data…
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Xenical (orlistat) is minimally absorbed systemically. In animal studies, no evidence of teratogenicity was observed at doses up to 10 times the human dose. There are no adequate and well-controlled studies in pregnant women. Based on negligible systemic absorption, the risk for fetal harm is low. However, due to potential for fat-soluble vitamin deficiency (A, D, E, K) from drug mechanism, maternal supplementation should be considered. No trimester-specific risks identified; avoid use in pregnancy as a precaution. |
| Fetal Monitoring | Monitor maternal weight and dietary compliance. Assess for fat-soluble vitamin (A, D, E, K) levels especially if prolonged use. Fetal monitoring: routine prenatal care; no specific fetal monitoring required due to low systemic exposure. |
| Fertility Effects | No known adverse effects on fertility. Orlistat does not affect reproductive hormones or fertility parameters in animal studies. Limited human data; no negative impact expected. |
| Clinical Pearls | Administer with or within 1 hour of a meal containing fat. Avoid if chronic malabsorption syndrome or cholestasis. Monitor for signs of fat-soluble vitamin deficiency; consider supplementation with ADEK vitamins. May reduce absorption of amiodarone, cyclosporine, and thyroid hormones. Use with caution in patients with history of oxalate nephrolithiasis. |
| Patient Advice | Take with each main meal containing fat, usually up to 3 times daily. · Skip dose if meal is skipped or contains no fat. · Common side effects: oily spotting, gas with discharge, urgent bowel movements, fatty/oily stools. These indicate drug is working. · Adhere to a low-fat diet (≤30% calories from fat) to minimize gastrointestinal side effects. · Take a multivitamin containing fat-soluble vitamins A, D, E, K at bedtime, at least 2 hours after last dose. · Weight loss is gradual; expect 1-2 lbs per week. Maximum effect at 6 months. · Consult doctor if severe abdominal pain, bloody stools, or signs of kidney stones. |