FDA Approves Labeling Changes for Over-the-Counter (OTC) Weight Loss Drug alli (Orlistat) to Warn of Risk of Kidney Stones and Kidney Injury

What Is FDA Doing? The Food and Drug Administration (FDA) has approved changes to the Drugs Facts Label of the over-the-counter (OTC) weight loss drug, alli (orlistat) 60 mg capsules, to warn of risks of acute kidney injury, which is a rare side effect of the medication. The labeling now advises consumers to ask a health care provider before using alli if they have ever had kidney disease or kidney stones. The labeling changes also tell consumers to stop using alli and ask a doctor if they develop symptoms of kidney injury or kidney stones, such as back or groin pain, painful urination, blood in the urine, feet and leg swelling, or less frequent urination. The risk of renal (kidney) injury is now described consistently across the labeling for all FDA-approved orlistat products, including those available OTC and those available in a higher strength by prescription. What Is alli? alli (orlistat) 60 mg capsules are approved for nonprescription use for weight loss in overweight adults 18 years and older, when used along with a reduced-calorie and low-fat diet. alli is the only FDA-approved OTC (nonprescription) weight loss aid. A higher-strength orlistat product, Xenical (orlistat) 120 mg capsules, is available by prescription. Xenical is indicated for obesity management, including weight loss and weight maintenance, when used in conjunction with a reduced-calorie diet and to reduce the risk for weight regain after prior weight loss. Orlistat is a lipase inhibitor that works by binding to enzymes that break down fats. As a result, people absorb less dietary fat from the digestive tract. What Should Consumers Do? Consumers should read the Drugs Facts Label carefully before starting alli. It is important for consumers to read the labeling of all OTC medications because they may not have seen a health care provider before deciding to take the medication. Consumers should be aware there have been rare reports of the following side effects in people taking alli: acute kidney injury (kidneys suddenly cannot filter waste products from the blood and harmful levels of waste may build up). Mild cases may be reversible, but untreated severe cases can be fatal. hyperoxaluria (high urinary levels of the waste product oxalate, a compound made by the liver and ingested through the diet) calcium oxalate nephrolithiasis (kidney stones that form when oxalate combines with calcium in the urinary tract) oxalate nephropathy (calcium oxalate crystals form inside the kidneys and interfere with normal kidney function) If consumers ever had kidney disease or kidney stones, they should ask a health care provider before taking alli. If consumers experience symptoms of acute kidney injury or kidney stones, they should stop taking alli and consult a health care provider for further guidance. Symptoms may include: back or groin pain painful urination blood in the urine feet and leg swelling less frequent urination If consumers experience side effects or do not respond well to alli, they should talk to a health care provider to consider next steps, including whether other treatment options might be right for them. What Should Health Care Providers Do? Health care providers who counsel patients about weight loss should inform them about the rare reports of acute kidney injury, hyperoxaluria, calcium oxalate nephrolithiasis, or oxalate nephropathy associated with orlistat products. If a patient taking alli presents with signs of acute kidney injury or nephrolithiasis, providers should advise them to stop the drug and proceed with appropriate evaluation and management. What Did FDA Find? FDA received periodic safety reports of acute kidney injury associated with alli, which prompted a revaluation of this safety signal in the nonprescription product. Specifically, FDA searched the FDA Adverse Event Monitoring System (AEMS) and the medical literature to identify cases of acute kidney injury, oxalate nephropathy, hyperoxaluria, and/or calcium oxalate kidney stones that occurred following use of alli. Search dates were from alli’s approval date on February 9, 2007, through December 31, 2023. We identified 12 cases of kidney complications associated with alli use, including nine from AEMS and three from the literature. The median patient age was 61 years (range 36-76 years), and there were slightly more females (7) than males (5). Among the eight patients who reported alli use prior to kidney injury, the median exposure time was 2.5 months (range 0.7-17 months). The types of kidney complications varied among the 12 cases: eight reported acute kidney injury, two reported acute kidney injury with oxalate nephropathy, and two had hyperoxaluria with calcium oxalate kidney stones. The severity of these cases was substantial, with eight patients requiring hospitalization and five requiring dialysis. Seven patients experienced improvement in their conditions, one had not improved at the time the report was made, and four reports did not describe the outcomes. Dosing information was available for four patients, all of whom reported taking either 60 mg or 120 mg of orlistat three times daily. Our data analysis also suggests that orlistat-associated oxalate nephropathy and kidney injury may not be dose-dependent, as the difference in dietary fat absorption inhibition between the 120 mg (Xenical) and 60 mg (alli) doses is 5%, indicating the risk exists at both prescription and nonprescription doses. Based on these postmarketing cases demonstrating evidence of kidney injury associated with oxalate crystals in individuals using alli and biological plausibility — as well as findings that the risks may not be dose-dependent — the risk of kidney injury was added to Drug Facts Label for alli, aligning labeling for all FDA-approved orlistat products. There are limitations to the information available to FDA. The actual number of cases involving kidney problems after alli use may be higher, as consumers and health care professionals do not always report side effects to FDA. Many reports were missing information, including clinical details such as kidney stone composition and past medical history. Several people had other possible reasons for their kidney diagnoses besides taking alli, including obesity, diabetes, high blood pressure, and history of kidney disease or kidney stones. These conditions could also have increased the risk of kidney problems associated with the use of alli. How Do I Report Side Effects from alli? To help FDA track safety issues with medicines, we urge consumers and health care professionals to report side effects involving alli or other medicines to the FDA MedWatch program using the information in the “Contact FDA” box at the bottom of this page. How Can I Get New Safety Information About Medicines I’m Taking? You can sign up for email alerts about Drug Safety Communications on medicines or medical specialties of interest to you.