Interaction entre Fluconazole et Triazolam

Strong CYP 3A Inhibitors Triazolam is contraindicated in patients receiving strong inhibitors of CYP 3A such as ketoconazole, itraconazole, nefazodone, ritonavir, indinavir, nelfinavir, saquinavir, and lopinavir [see Contraindications (4) , Drug Interactions (7.1) ] .

Prevention or management Do not administer triazolam with a strong CYP3A4 inhibitor [see Contraindications (4) , Warnings and Precautions (5.8) ].

Moderate and Weak CYP 3A Inhibitors Triazolam should be used with caution in patients receiving moderate or weak inhibitors of CYP 3A.

• Use with CYP 3A4 Inhibitors : Increased risk of adverse reactions ( 4 , 5.8 , 7.1 )

Strong Inhibitors of CYP 3A Clinical implication Concomitant use of triazolam with strong CYP3A inhibitors has a profound effect on the clearance of triazolam, resulting in increased concentrations of triazolam and increased risk of adverse reactions [see Clinical Pharmacology (12.3) ].

Triazolam Fluconazole increases the AUC of triazolam (single dose) by approximately 50%, C max by 20% to 32%, and increases t½ by 25% to 50 % due to the inhibition of metabolism of triazolam.

Dosage adjustments of triazolam may be necessary.

Short-acting benzodiazepines Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects.

If short-acting benzodiazepines, which are metabolized by the cytochrome P450 system, are concomitantly administered with fluconazole, consideration should be given to decreasing the benzodiazepine dosage, and the patients should be appropriately monitored.