Alli - General Information

Alli is a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake. Alli works by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. Without this enzyme, triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested.


Pharmacology of Alli

Alli is a lipase inhibitor for obesity management that acts by
inhibiting the absorption of dietary fats. At the recommended
therapeutic dose of 120 mg three times a day, orlistat inhibits
dietary fat absorption by approximately 30%. It works by inhibiting
pancreatic lipase, an enzyme that breaks down fat in the
intestine. Without this enzyme, fat from the diet is excreted
undigested, and not absorbed by the body. Because some vitamins are
fat soluble, the effect of orlistat is to reduce their body
absorption. Therefore the drug should only be taken in conjuction with
fatty meals, and a multivitamin tablet containing these vitamins (D E
K and beta-carotene) should be taken once a day, at least 2 hours
before or after taking the drug. In the March 15, 2004 issue of Cancer
Research, [1] Steven J. Kridel et al. state that orlistat may also inhibit growth of prostate cancer, and in theory may be useful in treating other cancers, by interfering with the metabolism of fats.


Alli for patients

Patients should read the Patient Information before starting treatment with XENICAL and each time their prescription is renewed.


What is Xenical used for?

Xenical is used to help obese people who fit certain weight and height requirements lose weight and maintain weight loss. Xenical works in your intestines, where it blocks some of the fat you eat from being absorbed. This undigested fat is then eliminated in your bowel movements. Use Xenical together with a reduced-calorie diet. The weight management effects of Xenical continue only as long as you are taking it.

Who should not take Xenical?

You cannot take Xenical if you:

  • have problems absorbing food
  • have gallbladder problems
  • are pregnant, or breast-feeding a child

People with certain kidney problems may not be able to take Xenical.

General Precautions with Xenical:

  • Your daily intake of fat should be evenly divided over 3 main meals.
  • Xenical can decrease the absorption some fat-soluble vitamins and beta-carotene. Therefore when being treated with Xenical, take a multivitamin supplement that contains vitamins D, E, K, and beta-carotene. Take your multivitamin once a day at least 2 hours before or after taking Xenical, such as bedtime.
  • Review all medications that you are taking with your health care provider, including those that you take without a prescription. If you are taking cyclosporine you may have to be monitored more closely.
  • If you are diabetic, Xenical may affect your blood sugar control. See your doctor regularly for monitoring and treatment adjustments.

What should I tell my doctor or health care provider?

Tell your health care provider if you are trying to become pregnant, are already pregnant, or are breast-feeding.

What are some possible side effects of Xenical? (This is NOT a complete list of side effects reported with Xenical. Your health care provider can discuss with you a more complete list of side effects.)

  • Oily spotting
  • Gas with discharge
  • Urgent need to have a bowel movement
  • Oily or fatty stools
  • Oily discharge
  • Increased number of bowel movements
  • Inability to control bowel movements

For more detailed information about Xenical, ask your health care provider.


Alli Interactions

Alcohol: In a multiple-dose study in 30 normal weight subjects, coadministration of XENICAL and 40 grams of alcohol (e.g., approximately 3 glasses of wine) did not result in alteration of alcohol pharmacokinetics, orlistat pharmacodynamics (fecal fat excretion), or systemic exposure to orlistat.

Cyclosporine: Preliminary data from a XENICAL and cyclosporine drug interaction study indicate a reduction in cyclosporine plasma levels when XENICAL was coadministered with cyclosporine.

Digoxin: In 12 normal-weight subjects receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not alter the pharmacokinetics of a single dose of digoxin.

Fat-soluble Vitamin Supplements and Analogues: A pharmacokinetic interaction study showed a 30% reduction in beta-carotene supplement absorption when concomitantly administered with XENICAL. XENICAL inhibited absorption of a vitamin E acetate supplement by approximately 60%. The effect of orlistat on the absorption of supplemental vitamin D, vitamin A, and nutritionally-derived vitamin K is not known at this time.

Glyburide: In 12 normal-weight subjects receiving orlistat 80 mg three times a day for 5 days, orlistat did not alter the pharmacokinetics or pharmacodynamics (blood glucose-lowering) of glyburide.

Nifedipine (extended-release tablets): In 17 normal-weight subjects receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not alter the bioavailability of nifedipine (extended-release tablets).

Oral Contraceptives: In 20 normal-weight female subjects, the treatment of XENICAL 120 mg three times a day for 23 days resulted in no changes in the ovulation-suppressing action of oral contraceptives.

Phenytoin: In 12 normal-weight subjects receiving XENICAL 120 mg three times a day for 7 days, XENICAL did not alter the pharmacokinetics of a single 300-mg dose of phenytoin.

Pravastatin: In a 2-way crossover study of 24 normal-weight, mildly hypercholesterolemic patients receiving XENICAL 120 mg three times a day for 6 days, XENICAL did not affect the pharmacokinetics of pravastatin.

Warfarin: In 12 normal-weight subjects, administration of XENICAL 120 mg three times a day for 16 days did not result in any change in either warfarin pharmacokinetics (both R- and S-enantiomers) or pharmacodynamics (prothrombin time and serum Factor VII). Although undercarboxylated osteocalcin, a marker of vitamin K nutritional status, was unaltered with XENICAL administration, vitamin K levels tended to decline in subjects taking XENICAL. Therefore, as vitamin K absorption may be decreased with XENICAL, patients on chronic stable doses of warfarin who are prescribed XENICAL should be monitored closely for changes in coagulation parameters.


Alli Contraindications

XENICAL is contraindicated in patients with chronic malabsorption syndrome or cholestasis, and in patients with known hypersensitivity to XENICAL or to any component of this product.


Additional information about Alli

Alli Indication: For obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet. Also used to reduce the risk for weight regain after prior weight loss.
Mechanism Of Action: Alli is a reversible inhibitor of lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine residue site of gastric and pancreatic lipases. The inactivated enzymes are thus unavailable to hydrolyze dietary fat in the form of triglycerides into absorbable free fatty acids and monoglycerides. As undigested triglycerides are not absorbed, the resulting caloric deficit may have a positive effect on weight control.
Drug Interactions: Anisindione Alli increases the anticoagulant effect
Dicumarol Alli increases the anticoagulant effect
Acenocoumarol Alli increases the anticoagulant effect
Warfarin Alli increases the anticoagulant effect
Cyclosporine Alli decreases the effect of cyclosporine
Food Interactions: Not Available
Generic Name: Orlistat
Synonyms: (-)-Tetrahydrolipstatin; Orlipastatum [INN-Latin]; Tetrahydrolipstatin; Orlipastat
Drug Category: Anti-Obesity Agents; Enzyme Inhibitors
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Orlistat: Xenical; Alli;
Absorption: Systemic absorption of orlistat is minimal, however systemic absorption of the drug is not needed for activity.
Toxicity (Overdose): The results of a massive overdose of Xenical are unknown, although the drug seems relatively harmless.
Protein Binding: >99% bound to plasma proteins (lipoproteins and albumin were major binding proteins).
Biotransformation: Metabolized primarily within the gastrointestinal wall forming relatively inactive metabolites. Metabolites M1 (4-member lactone ring hydrolyzed) and M3 (M1 with N-formyl leucine moiety cleaved) accounted for approximately 42% of total radioactivity in plasma. M1 and M3 have an open beta-lactone ring and extremely weak lipase inhibitory activity (1000- and 2500-fold less than orlistat, respectively).
Half Life: 1 to 2 hours.
Dosage Forms of Alli: Capsule Oral
Chemical IUPAC Name: [(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] (2S)-2-formamido-4-methylpentanoate
Chemical Formula: C29H53NO5
Orlistat on Wikipedia:
Organisms Affected: Humans and other mammals