Orlistat-Associated Adverse Effects and Drug Interactions

Abstract

Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

“…Orlistat accelerates gastric emptying, this could lead to exaggerated postprandial hyperglycemia, 127 and the presence of undigested fat in the bowels causes side effects (such as diarrhea, abdominal pain, oily stools and fecal spotting) that limit use of orlistat. 128 …”

“…Nonetheless, a half dose of orlistat (Alli ® , 60 mg rather than 120 mg 3 times daily) has been approved in Australasia, USA and the EU for over-the-counter use. 128 Data from very recent studies report that the administration of half dose of orlistat in conjunction with a reduced calorie, lower-fat diet to overweight and obese participants significantly reduced their body weight (5.96 kg vs 3.91 kg) waist circumference and visceral fat (15.7% vs 9.4%). 129,130 It is important to note that both studies this dose was well tolerated by participants.…”

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“…In addition to losing weight, Orlistat within a prescribed diet has been shown to be safe and more effective than diet alone in modifying some of the risk of coronary artery disease and other obesity-related comorbidities. The most commonly reported adverse effects of Orlistat are a range of gastrointestinal side effects, including steathorrhea, bloating, oily spotting, fecal urgency, and fecal incontinence, as well as hepatic adverse effects [19,38]. These adverse effects are similar to those observed for other lipase inhibitors tested in phase II studies, such as Cetilistat (ATL-962) [39].…”

Multifactorial treatment for improvement of renal function and cardiovascular risk: an ATTEMPT for patients with metabolic syndrome and chronic kidney disease

“…Lifestyle measures such as diet and physical exercise are first-line options, followed by orlistat treatment and bariatric surgery in selected cases. The use of orlistat is generally safe, although rare cases of acute kidney injury have been reported 46 . New combination drug treatments for weight loss, such as naltrexone sustained-release (SR) þ bupropion SR, are being assessed in clinical trials 47 .…”