Orlistat — BrandWiki

Orlistat

verifiedfields	changed
watchedfields	changed
verifiedrevid	408353644
width	300
image2	Orlistat ball-and-stick model.png
width2	300
tradename	Xenical, Alli
medlineplus	a601244
licence eu	yes
dailymedid	Orlistat
licence us	Orlistat
pregnancy au	B1
routes of administration	By mouth
atc prefix	A08
atc suffix	AB01
legal au	S3
legal ca	Rx-only
legal uk	P
legal uk comment	/ POM‡R1R‡‡R2R‡‡R3R‡
legal us	OTC
legal us comment	/ Rx-only‡R4R‡‡R5R‡
legal eu	OTC
legal eu comment	/ Rx-only‡R6R‡‡R7R‡
bioavailability	Negligible‡R8R‡
protein bound	>99%
metabolism	In the GI tract
elimination half-life	1 to 2 hours
excretion	Fecal
cas number	96829-58-2
pubchem	3034010
iuphar ligand	5277
drugbank	DB01083
chemspiderid	2298564
unii	95M8R751W8
kegg	D04028
chebi	94686
chembl	175247
synonyms	tetrahydrolipstatin
iupac name	(S)-((S)-1-((2S,3S)-3-Hexyl-4-oxooxetan-2-yl)tridecan-2-yl) 2-formamido-4-methylpentanoate
c	29
h	53
n	1
o	5
smiles	O=C(O[C@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)CCCCCCCCCCC)[C@@H](NC=O)CC(C)C
stdinchi	1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1
stdinchikey	AHLBNYSZXLDEJQ-FWEHEUNISA-N

Orlistat, sold under the brand name Xenical among others, is a medication used to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake. It is intended for use in conjunction with a healthcare provider-supervised reduced-calorie diet.[4]

Orlistat is the saturated derivative of lipstatin, a potent natural inhibitor of pancreatic lipases isolated from the bacterium Streptomyces toxytricini.[9] However, due to its relative simplicity and stability, orlistat was chosen over lipstatin for development as an anti-obesity drug.[10]

The effectiveness of orlistat in promoting weight loss is definite but modest. Pooled data from clinical trials suggest that people given orlistat in addition to lifestyle modifications, such as diet and exercise, lose about 2 - 3 kg more than those not taking the drug over the course of a year.[11]

Side effects

The primary side effects of the drug are gastrointestinal-related, and include steatorrhea (oily, loose stools with excessive flatus due to unabsorbed fats reaching the large intestine), fecal incontinence and frequent or urgent bowel movements.[15] To minimize these effects, foods with high fat content should be avoided; the manufacturer advises consumers to follow a low-fat, reduced-calorie diet. Oily stools and flatulence can be controlled by reducing the dietary fat content to somewhere in the region of 15 grams per meal.[16] The manual for Alli makes it clear that orlistat treatment involves aversion therapy, encouraging the user to associate eating fat with unpleasant treatment effects.[17]

Side effects are most severe when beginning therapy and may decrease in frequency with time;[4] it has also been suggested that the decrease in side effects over time may be associated with long-term compliance with a low-fat diet.[18]

On 26 May 2010, the U.S. Food and Drug Administration (FDA) approved a revised label for Xenical to include new safety information about cases of severe liver injury that have been reported rarely with the use of this medication.[19]

An analysis of over 900 orlistat users in Ontario showed that their rate of acute kidney injury was more than triple that of non-users.[20]

A study from 2013 looked at 94,695 participants receiving orlistat in the UK between 1999 and 2011.[21] The study showed no evidence of an increased risk of liver injury during treatment.[21] They concluded:[21]

"The incidence of acute liver injury was higher in the periods both immediately before and immediately after the start of orlistat treatment. This suggests that the observed increased risks of liver injury linked to the start of treatment may reflect changes in health status associated with the decision to begin treatment rather than any causal effect of the drug."

Long-term

Despite a higher incidence of breast cancer amongst those taking orlistat in early, pooled clinical trial data—the analysis of which delayed FDA review of orlistat[22]—a two-year study published in 1999 found similar rates between orlistat and placebo (0.54% versus 0.51%), and evidence that tumors predated treatment in 3 of the 4 participants who had them.[23] There is evidence from an in vitro study to suggest that the introduction of specific varied preparations containing orlistat, namely the concurrent administration of orlistat and the monoclonal antibody trastuzumab, can induce cell death in breast cancer cells and block their growth.[24]

Fecal fat excretion promotes colon carcinogenesis. In 2006 the results of 30-day study were published indicating that orlistat at a dosage of 200 mg/kg chow administered to rats consuming a high-fat chow and receiving two 25 mg/kg doses of the potent carcinogen 1,2-dimethylhydrazine produced significantly higher numbers of aberrant crypt foci (ACF) colon lesions than did the carcinogen plus high-fat chow without orlistat.[25]

Legal status

Orlistat is available both with and without a prescription.[4][5][36]

Australia and New Zealand

In Australia and New Zealand, orlistat is available as a "Pharmacist Only Medicine".[37] In 2007, the Committee decided to keep orlistat as a Schedule 3 drug, but withdrew its authorization of direct-to-consumer Xenical advertising, stating this "increased pressure on pharmacists to provide orlistat to consumers...this in turn had the potential to result in inappropriate patterns of use".[38]

United States

Orlistat was initially approved by the U.S. Food and Drug Administration in April 1999 as a prescription-only medication.[39] On 23 January 2006, an FDA advisory panel voted 11 to 3 to recommend the approval of an OTC formulation of orlistat, to be sold under the brand name Alli by GlaxoSmithKline.[40] Approval was granted on 7 February 2007,[41] and Alli became the first weight loss drug officially sanctioned by the U.S. government for over-the-counter use.[42] Consumer advocacy organization Public Citizen opposed over-the-counter approval for orlistat.[43]

Alli became available in the U.S. in June 2007. It is sold as 60 mg capsules—half the dosage of prescription orlistat.[43][42]

European Union and Switzerland

On 21 January 2009, the European Medicines Agency granted approval for the sale of orlistat without a prescription.[44][45]

At least since September 2017, tablets with 60 mg orlistat can be freely sold in Swiss drugstores. Formulations with 120 mg per tablet require a prescription, but can be sold without one in pharmacies under an exemption rule, which is based on a list of easily diagnosable diseases.[46]

Generic formulations

U.S. patent protection for Xenical, originally to end on 18 June 2004, was extended by five years (until 2009) by the U.S. Patent and Trademark Office. The extension was granted on 20 July 2002,[47] and expired on 18 June 2009.[48]

Generic orlistat is available in Iran under the brand Venustat manufactured by Aburaihan Pharmaceutical co., in India, under the brands Orlean (Eris), Vyfat, Olistat, Obelit, Orlica and Reeshape.[49] In Russia, orlistat is available under the brand names Xenical (Hoffmann–La Roche), Orsoten/Orsoten Slim (KRKA d. d.) and Xenalten (OBL-Pharm). In Austria, orlistat is available under the brand name Slimox. In Malaysia, orlistat is available under the brand name Cuvarlix and is marketed by Pharmaniaga. In the Philippines orlistat is available under the brand name RedoXfat Plus manufactured by ATC Healthcare