00 mg QD × 10 days 200 mg (tablets) QD × 10 days† ↓ 41%
(0.59; 0.44-0.79) ↓ 50%
(0.50; 0.36-0.71)
In vitro studies with human hepatic microsomes and clinical studies indicate that posaconazole is an inhibitor primarily of CYP3A4. A clinical study in healthy volunteers also indicates that posaconazole is a strong CYP3A4 inhibitor as evidenced by a >5-fold increase in midazolam AUC. Therefore, plasma concentrations of drugs predominantly metabolized by CYP3A4 may be increased by posaconazole. A summary of the drugs studied clinically, for which plasma concentrations were affected by posaconazole, is provided in Table 16 [see Contraindications (4) and Drug Interactions (7.1) including recommendations].
Table 16: Summary of the Effect of Posaconazole on Coadministered Drugs in Healthy Volunteers and Patients
Coadministered Drug
(Postulated Mechanism of Interaction is Inhibition of CYP3A4 by posaconazole)
Coadministered Drug Dose/Schedule
Posaconazole Dose/Schedule
Effect on Bioavailability of Coadministered Drugs
Change in Mean Cmax
(ratio estimate*; 90% CI of the ratio estimate)
Change in Mean AUC
(ratio estimate*; 90% CI of the ratio estimate)
* Ratio Estimate is the ratio of coadministered drug plus posaconazole to coadministered drug alone for Cmax or AUC.† The tablet refers to a non-commercial tablet formulation without polymer.‡ The mean terminal half-life of midazolam was increased from 3 hours to 7 to 11 hours during coadministration with posaconazole.
Sirolimus 2-mg single oral dose 400 mg (oral suspension) BID × 16 days ↑ 572%
(6.72; 5.62-8.03) ↑ 788%
(8.88; 7.26-10.9)
Cyclosporine Stable maintenance dose in heart transplant recipients 200 mg (tablets) QD × 10 days† ↑ cyclosporine whole blood trough concentrations
Cyclosporine dose reductions of up to 29% were required
Tacrolimus 0.05-mg/kg single oral dose 400 mg (oral suspension) BID × 7 days ↑ 121%
(2.21; 2.01-2.42) ↑ 358%
(4.58; 4.03-5.19)
Simvastatin 40-mg single oral dose 100 mg (oral suspension) QD × 13 days Simvastatin
↑ 841%
(9.41, 7.13-12.44)
Simvastatin Acid
↑ 817%
(9.17, 7.36-11.43) Simvastatin
↑ 931%
(10.31, 8.40-12.67)
Simvastatin Acid
↑634%
(7.34, 5.82-9.25)
200 mg (oral suspension) QD × 13 days Simvastatin
↑ 1041%
(11.41, 7.99-16.29)
Simvastatin Acid
↑851%
(9.51, 8.15-11.10) Simvastatin
↑ 960%
(10.60, 8.63-13.02)
Simvastatin Acid
↑748%
(8.48, 7.04-10.23)
Midazolam 0.4-mg single IV dose‡ 200 mg (oral suspension) BID × 7 days ↑ 30%
(1.3; 1.13-1.48) ↑ 362%
(4.62; 4.02-5.3)
0.4-mg single IV dose‡ 400 mg (oral suspension) BID × 7 days ↑62%
(1.62; 1.41-1.86) ↑524%
(6.24; 5.43-7.16)
2-mg single oral dose‡ 200 mg (oral suspension) QD × 7 days ↑ 169%
(2.69; 2.46-2.93) ↑ 470%
(5.70; 4.82-6.74)
2-mg single oral dose‡ 400 mg (oral suspension) BID × 7 days ↑ 138%
(2.38; 2.13-2.66) ↑ 397%
(4.97; 4.46-5.54)
Rifabutin 300 mg QD × 17 days 200 mg (tablets) QD × 10 days† ↑ 31%
(1.31; 1.10-1.57) ↑ 72%
(1.
