Orlistat

When warfarin or other anticoagulants are given in combination with orlistat, international normalised ratio (INR) values should be monitored.

There are some case reports of reduced efficacy of antiretroviral HIV medicines, antidepressants antipsychotics (including lithium) and benzodiazepines coincidental to the initiation of orlistat treatment in previously well-controlled patients. Therefore orlistat treatment should only be initiated after careful consideration of the possible impact in these patients.

Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic drugs e.g. valproate, lamotrigine, for which a causal relationship to an interaction cannot be excluded. Therefore, these patients should be monitored for possible changes in the frequency and/or severity of convulsions.

In the absence of pharmacokinetic interaction studies, the concomitant administration of orlistat with acarbose should be avoided.

A slight decrease in plasma levels of amiodarone, when given as a single dose, has been observed in a limited number of healthy volunteers who received orlistat concomitantly. In patients receiving amiodarone treatment, the clinical relevance of this effect remains unknown but may become clinically relevant in some cases. In patients receiving concomitant amiodarone treatment, reinforcement of clinical and ECG monitoring is warranted.

A decrease in ciclosporin plasma levels has been observed in a drug-drug-interaction study and also reported in several cases, when orlistat was administered concomitantly. This can lead to a decrease of immunosuppressive efficacy. Therefore the combination is not recommended. However, if such concomitant use is unavoidable, more frequent monitoring of ciclosporin blood levels should be performed both after addition of orlistat and upon discontinuation of orlistat in ciclosporin treated patients. Ciclosporin blood levels should be monitored until stabilised.

Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E and K). The vast majority of patients receiving up to four full years of treatment with orlistat in clinical studies had vitamin A, D, E and K and beta-carotene levels that stayed within normal range. In order to ensure adequate nutrition, patients on a weight control diet should be advised to have a diet rich in fruit and vegetables and use of a multivitamin supplement could be considered. If a multivitamin supplement is recommended, it should be taken at least two hours after the administration of orlistat or at bedtime.

Rare occurrence of hypothyroidism and/or reduced control of hypothyroidism may occur. The mechanism, although not proven, may involve a decreased absorption of iodine salts and/or levothyroxine.

The use of orlistat may be associated with hyperoxaluria and oxalate nephropathy leading sometimes to renal failure. This risk is increased in patients with underlying chronic kidney disease and/or volume depletion.

For orlistat no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women.

As it is not known whether orlistat is secreted into human milk, orlistat is contra-indicated during breast-feeding.

Orlistat has no influence on the ability to drive and use machines.