Orlistat safety update
- Medicines and Healthcare products Regulatory Agency
- 1 February 2010
- Therapeutic area:
- Nutrition and dietetics
A recent Europe-wide review of the safety information for alli has led to a number of updates, which bring the product information in line with that for Xenical.
Article date: February 2010
Orlistat is a potent, specific, and long-acting inhibitor of gastrointestinal lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by preventing the gastric and pancreatic lipases from hydrolysing dietary fat, in the form of triglycerides, into absorbable free fatty acids and monoglycerides.
Orlistat is available in Europe as 120 mg capsules under the brand name Xenical, and as 60 mg capsules under the brand name alli, for weight loss in combination with a reduced-calorie, lower-fat diet. Xenical has been licensed since 1998 and is available as a prescription-only medicine; alli was licensed in January 2009 and is available without a prescription under the supervision of a pharmacist.
alli: updated safety information
A recent Europe-wide review of the safety information for alli has led to a number of updates, which bring the product information in line with that for Xenical. Pharmacists should be aware of this information so that they can appropriately advise consumers who wish to buy alli or discuss its use.
Patients with kidney disease should consult a doctor before starting alli because use of orlistat could rarely (≥1/10 000 to <1/1000) lead to hyperoxaluria and oxalate nephropathy.
Interaction with levothyroxine
Patients who are taking levothyroxine should consult a doctor before starting alli because reduced control of hypothyroidism may occur when alli and levothyroxine are taken at the same time. This could be due to decreased absorption of iodine salts or levothyroxine (or both). These medicines may need to be taken at different times to reduce the risk of interaction, and the dose of levothyroxine may need to be adjusted.
Interaction with antiepileptic drugs
Patients who are taking an antiepileptic drug should consult a doctor before starting alli because loss or seizure control have been reported during concomitant treatment with orlistat and antiepileptic drugs such as sodium valproate and lamotrigine. Orlistat may decrease the absorption of antiepileptic drugs, leading to loss of seizure control. During concomitant treatment, patients should be monitored for possible changes in the frequency and severity of convulsions. If this occurs, consideration could be given to administering orlistat and antiepileptic drugs at different times.
Pancreatitis has also been added as an undesirable effect of alli treatment after reports in a number of patients (frequency unknown).
alli: reports of counterfeit capsules in the USA
We are aware that consumers may be at risk after reports in the USA of counterfeit alli that contained sibutramine rather than orlistat. Although the counterfeit product has not been found in the UK, it is still potentially available to UK customers via the internet. Consumers should not buy medicines from unregulated websites.
Review of hepatotoxicity with orlistat
In July 2009, there was a Europe-wide review of a possible association between orlistat and serious hepatic reactions. The review included non-clinical, clinical trial, and post-marketing safety data provided by the licence holders and a review of suspected adverse reaction reports submitted to the MHRA. Data from the licence holders have also been submitted to the US Food and Drug Administration, which is also conducting a review.
The European review concluded that there is insufficient evidence to show that Xenical or alli are associated with more serious liver disorders than those already listed in the product information, and that no further action was recommended at this time.
The current product information for Xenical and alli contains a warning that hepatitis, cholelithiasis, and increased transaminases and alkaline phosphatase are possible side effects, and that patients who experience symptoms such as yellowing of the skin and eyes, itching, stomach pain, and liver tenderness should stop taking the capsules and tell their doctor.
The MHRA, together with European regulatory authorities, will continue to monitor all adverse reactions associated with orlistat. Suspected adverse reactions can be reported to us via the Yellow Card Scheme (see www.yellowcard.gov.uk) and we welcome reports direct from patients.
Further information about alli is provided in the May 2009 issue of Drug Safety Update.
Article citation: Drug Safety Update Feb 2010, vol 3 issue 7: 4.
Published: 1 February 2010
Therapeutic area: Nutrition and dietetics