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Orlistat and possible drug interactions that can affect over-the-counter sales

by Karen Baxter and Jennifer Sharp

OrlistatA recent Drug Safety Update from the Medicines and Healthcare products Regulatory Agency and the Commission on Human Medicines highlighted the updated information regarding the drug interactions of orlistat with levothyroxine and antiepileptic drugs (February 2010).

The bulletin gives the full details of the advice, and patients taking these drugs are advised to consult their doctor before taking orlistat.

In addition to the interactions mentioned in this bulletin, there are a number of other drugs that can interact with orlistat, and which pharmacists should be aware of when considering selling the over-the-counter product (Alli).

What mechanisms are involved in orlistat interactions?

Orlistat works by preventing dietary fat absorption (through inhibiting gastrointestinal lipases) and all the known pharmacokinetic interactions of this drug appear usually to occur as a result of altered absorption of the affected drug.

Orlistat can also interact by improving conditions, such as hypertension, hyperlipidaemia and diabetes (due to the resulting weight loss), which are associated with obesity, although strictly speaking, these are drug-disease interactions.

Which interactions are clinically significant?

Drug interactions with orlistat

  • Ciclosporin
  • Vitamin K antagonist anticoagulants
  • Hormonal contraceptives
  • Levothyroxine
  • Antiepileptic drugs
  • Fat soluble vitamins
  • Amiodarone
  • Tacrolimus
  • Acarbose

As with the interactions of any drug, the interactions of orlistat are most likely to be important when the affected drug has a narrow therapeutic index.

Orlistat has been shown to reduce the absorption of ciclosporin, particularly from Sandimmun, which was formulated in oil, but an effect has also been seen with Neoral, and at least one transplant rejection episode is thought to have occurred as a result of this interaction.

The use of ciclosporin is, therefore, a contraindication to the over-the-counter sale of orlistat, but the drug may be prescribed to a patient taking ciclosporin if monitoring of ciclosporin levels is increased. There appears to be little information about interactions with other immunosuppressant drugs, but one study suggests that tacrolimus will interact similarly and so it may be advisable to follow similar precautions to those for ciclosporin.

Another narrow therapeutic index drug that has been shown to interact with orlistat is amiodarone. Orlistat modestly reduces its absorption. (Note that amiodarone is a lipo-philic drug.)

The extent of this interaction seems unlikely to be clinically relevant in most patients, but the UK manufacturer of Alli, GlaxoSmithKline, recommends that patients taking amiodarone should consult a doctor before taking orlistat, and suggests that increased clinical and electrocardiogram monitoring may be necessary, with doses of amiodarone adjusted if its efficacy is reduced. Similar monitoring advice is given by the UK manufacturers of prescription-only orlistat.

The decrease in fat absorption that occurs with orlistat will result in a decrease in the absorption of the fat soluble vitamins (ie, vitamins A, D, E and K), and those taking orlistat are advised to take supplements. These should be taken at least two hours before or after orlistat or at bedtime. However, one study suggested that some patients may still have low levels of vitamin D despite vitamin supplementation, although this requires further confirmation.

A reduction in the absorption of vitamin K by orlistat can also affect the anticoagulant efficacy of oral anticoagulants that are vitamin K antagonists, such as warfarin, other coumarins and the indanediones.

Cases of altered international normalised ratios have been reported with concurrent use. The over-the-counter orlistat is, therefore, contra-indicated with the use of warfarin. However, orlistat may be prescribed to a patient taking warfarin if his or her coagulation parameters are closely monitored.

Dietary modifications are required when orlistat is taken. In particular, a reduction in dietary fat intake is advised. Those who do not follow this advice can develop diarrhoea or steatorrhoea.

Diarrhoea can alter gastrointestinal transit time and, as a result, can affect the absorption of a number of drugs. The manufacturers of orlistat point out an interaction with the hormonal contraceptives and highlight the need for additional contraceptive precautions should diarrhoea develop.

Patients with diabetes and taking acarbose, are advised against using orlistat by the manufacturers because of a lack of studies on the safety of concurrent use.

There are currently few known clinically important drug interactions with orlistat, and those that do occur can usually be handled by increased monitoring. However, because of the need for further monitoring, sometimes these interactions present a contraindication to the over-the-counter sale of orlistat and pharmacists should be aware of them.

StockleyThis article has been produced by Karen Baxter and Jennifer Sharp on behalf of the Stockley editorial team.

Citation: The Pharmaceutical Journal URI: 11009379

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