Interactions : אינטראקציות

4.5      Interaction with other medicinal products and other forms of interaction
Contra-indicated combinations (see also section 4.3):

Other retinoids: risk of symptoms suggestive of hypervitaminosis A.

Vitamin A: risk of symptoms suggestive of hypervitaminosis A for daily doses greater than 10,000 IU.

Tetracyclines: risk of intracranial hypertension (pseudotumour cerebri).

The effect of food on the bioavailability of tretinoin has not been characterised. Since the bioavailability of retinoids, as a class, is known to increase in the presence of food, it is recommended that Vesanoid/Tretinoin be administered with a meal or shortly thereafter.

As tretinoin is metabolised by the hepatic P450 system, there is the potential for alteration of pharmacokinetic parameters in patients administered concomitant medications that are also inducers or inhibitors of this system.

Medications that generally induce hepatic P450 enzymes include rifampicin, glucocorticoids, phenobarbital and pentobarbital.

Medications that generally inhibit hepatic P450 enzymes include ketoconazole, cimetidine, erythromycin, verapamil, diltiazem and ciclosporin. Increased toxicity of tretinoin (e.g. pseudotumour cerebri, hypercalcaemia) was reported when azole antifungals (e.g. fluconazole, voriconazole, posaconazole) were administered. This appears to be the result of a pharmacokinetic interaction mainly involving CYP3A4.
Combination with other strong CYP3A4 inhibitors (protease inhibitors or macrolides, e.g. clarithromycin), may also trigger tretinoin toxicity. A dose reduction of tretinoin should be considered if necessary.

Cases of fatal thrombotic complications have been reported rarely in patients concomitantly treated with tretinoin and antifibrinolytic agents such as tranexamic acid, aminocaproic acid and aprotinin (see section 4.4). Therefore, caution should be exercised when administering tretinoin concomitantly with these agents.

There are no data on a possible pharmacokinetic interaction between tretinoin and daunorubicin, idarubicin or cytarabine.