Interaksi Nefazodon dan Triazolam

• Concomitant administration of strong cytochrome P450 (CYP 3A) enzyme inhibitors (e.g., ketoconazole, itraconazole, nefazodone, lopinavir, ritonavir) [see Warnings and Precautions (5.8) , Drug Interactions (7.1) ].

• Concomitant use with medications that significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP 3A) including ketoconazole, itraconazole, nefazodone, and several human immunodeficiency virus (HIV) protease inhibitors ( 4 , 5.8 , 17 )

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.

The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam (see WARNINGS and PRECAUTIONS ), and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together.

Because not all commercially available dosage forms of triazolam permit a sufficient dosage reduction, the coadministration of triazolam and nefazodone should be avoided for most patients, including the elderly.

Because not all commercially available dosage forms of triazolam permit sufficient dosage reduction, coadministration of triazolam with nefazodone should be avoided for most patients, including the elderly.

In particular, the combined use of nefazodone with triazolam should be avoided for most patients, including the elderly.

Interaction with Triazolobenzodiazepines Interaction studies of nefazodone with two triazolobenzodiazepines, i.e., triazolam and alprazolam, metabolized by cytochrome P450 3A4, have revealed substantial and clinically important increases in plasma concentrations of these compounds when administered concomitantly with nefazodone.