ALLI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALLI (ALLI).
Orlistat is a reversible inhibitor of gastric and pancreatic lipases, preventing hydrolysis of dietary triglycerides into absorbable free fatty acids and monoglycerides. This reduces fat absorption by approximately 30%.
| Metabolism | Metabolized primarily in the gastrointestinal tract; minimal systemic absorption. <1% is absorbed and metabolized via hydrolysis to inactive metabolites. Excreted mainly in feces. |
| Excretion | Fecal: approximately 97% (83% as unchanged drug, 4% as metabolites); Renal: less than 1%. |
| Half-life | Terminal elimination half-life is approximately 1-2 hours for orlistat; however, the pharmacodynamic effect (fecal fat excretion) persists due to the drug's local action in the GI tract. |
| Protein binding | Orlistat is 99% bound to plasma proteins (mainly albumin and lipoproteins). |
| Volume of Distribution | Volume of distribution is not clinically meaningful due to minimal systemic absorption; estimated to be low (<1 L/kg). |
| Bioavailability | Oral bioavailability is extremely low (<1%) due to local action in the GI tract and minimal systemic absorption. |
| Onset of Action | Oral: 24-48 hours for inhibition of dietary fat absorption. |
| Duration of Action | Duration of action is approximately 24-48 hours after a single dose; clinical effect persists as long as the drug is taken with meals containing fat. |
60 mg orally three times daily with each main meal containing fat.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | Not recommended in patients with cholestasis or chronic malabsorption syndrome. No Child-Pugh based data. |
| Pediatric use | Not recommended for use in children under 12 years of age. |
| Geriatric use | No specific dose adjustment; same as adult dosing. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALLI (ALLI).
| Breastfeeding | Not known if excreted in human milk. Due to minimal systemic absorption, risk to breastfed infant is considered low. M/P ratio not established. Caution advised for preterm or low-birth-weight infants. |
| Teratogenic Risk | No trimester-specific human studies. Minimal systemic absorption (approx. 0.3% of 60 mg dose). Fat-soluble vitamin absorption (A, D, E, K) may be reduced. Theoretical risk of maternal vitamin deficiency affecting fetal development. FDA Pregnancy Category B; no evidence of teratogenicity in animal studies. |
■ FDA Black Box Warning
None.
| Common Effects | Bloating Stomach cramp Flatulence |
| Serious Effects |
["Chronic malabsorption syndrome","Cholestasis","Pregnancy and breastfeeding (relative)","Hypersensitivity to orlistat or any component"]
| Precautions | ["May cause liver injury (rare cases of hepatitis, cholestasis); discontinue if symptoms occur","Risk of cholelithiasis due to rapid weight loss","Fat-soluble vitamin deficiencies (A, D, E, K) - supplement if necessary","May increase urinary oxalate leading to nephrolithiasis","Avoid use in patients with chronic malabsorption syndrome or cholestasis"] |
| Food/Dietary | High-fat meals (>30% of calories from fat) exacerbate gastrointestinal side effects (oily spotting, steatorrhea, flatus with discharge, fecal urgency). Should be taken with a low-fat diet. Avoid concurrent intake of psyllium or other fiber supplements, as they may cause bloating. Orlistat reduces absorption of fat-soluble vitamins; dietary sources of vitamins A, D, E, and K may be less effective, necessitating supplementation. |
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| Fetal Monitoring |
| Monitor maternal weight gain, nutritional status, and vitamin levels (A, D, E, K) during prolonged use. Assess fetal growth via ultrasound if maternal nutritional deficiency suspected. |
| Fertility Effects | No known adverse effects on fertility in humans. Theoretical potential due to vitamin malabsorption, but unlikely given low systemic exposure. |
| Clinical Pearls | Orlistat (Alli) is a reversible inhibitor of gastric and pancreatic lipases, reducing dietary fat absorption by about 30%. Counsel patients on the necessity of a low-fat diet (<30% calories from fat) to minimize gastrointestinal adverse effects (e.g., oily spotting, flatus with discharge, fecal urgency). Monitor for potential interactions with warfarin (increased INR) and cyclosporine. Advise taking a multivitamin containing fat-soluble vitamins (A, D, E, K) at bedtime, at least 2 hours after orlistat dose, due to impaired absorption. Not effective for weight maintenance; use as adjunct to lifestyle modification. |
| Patient Advice | Take Alli with or up to 1 hour after a meal containing fat, but skip dose if meal contains no fat. · Limit dietary fat to less than 30% of total calories to reduce side effects like oily stools or gas. · Take a daily multivitamin with fat-soluble vitamins (A, D, E, K) at bedtime, at least 2 hours after your last Alli dose. · Avoid high-fat meals (e.g., fast food, fried items) to prevent gastrointestinal discomfort and urgency. · Do not use Alli if you have chronic malabsorption syndrome, cholestasis, or are pregnant/breastfeeding. · Report any unexplained weight loss or changes in bowel habits to your healthcare provider. · Alli is intended for adults with a BMI ≥25 kg/m² and should be used with a reduced-calorie diet and exercise. |