e)
Change in 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.† In 5 subjects, the Cmax and AUC decreased substantially (range: -27% to -53% and -33% to -51%, respectively) when Noxafil was administered via an NG tube compared to when Noxafil was administered orally. It is recommended to closely monitor patients for breakthrough fungal infections when Noxafil is administered via an NG tube because a lower plasma exposure may be associated with an increased risk of treatment failure.
400-mg single dose with a high-fat meal relative to fasted state (n=12)
5 minutes before high-fat meal ↑96%
(1.96; 1.48-2.59) ↑111%
(2.11; 1.60-2.78)
During high-fat meal ↑339%
(4.39; 3.32-5.80) ↑382%
(4.82; 3.66-6.35)
20 minutes after high-fat meal ↑333%
(4.33; 3.28-5.73) ↑387%
(4.87; 3.70-6.42)
400 mg BID and 200 mg QID for 7 days in fasted state and with liquid nutritional supplement (BOOST®) ( n=12) 400 mg BID with BOOST ↑65%
(1.65; 1.29-2.11) ↑66%
(1.66; 1.30-2.13)
200 mg QID with BOOST No Effect No Effect
Divided daily dose from 400 mg BID to 200 mg QID for 7 days regardless of fasted conditions or with BOOST (n=12) Fasted state ↑136%
(2.36; 1.84-3.02) ↑161%
(2.61; 2.04-3.35)
With BOOST ↑137%
(2.37; 1.86-3.04) ↑157%
(2.57; 2.00-3.30)
400-mg single dose with carbonated acidic beverage (ginger ale) and/or proton pump inhibitor (esomeprazole) (n=12) Ginger ale ↑92%
(1.92; 1.51-2.44) ↑70%
(1.70; 1.43-2.03)
Esomeprazole ↓32%
(0.68; 0.53-0.86) ↓30%
(0.70; 0.59-0.83)
400-mg single dose with a prokinetic agent (metoclopramide 10 mg TID for 2 days) + BOOST or an antikinetic agent (loperamide 4-mg single dose) + BOOST (n=12) With metoclopramide + BOOST ↓21%
(0.79; 0.72-0.87) ↓19%
(0.81; 0.72-0.91)
With loperamide + BOOST ↓3%
(0.97; 0.88-1.07) ↑11%
(1.11; 0.99-1.25)
400-mg single dose either orally with BOOST or via an NG tube with BOOST (n=16) Via NG tube† ↓19%
(0.81; 0.71-0.91) ↓23%
(0.77; 0.69-0.86)
Concomitant administration of posaconazole oral suspension with drugs affecting gastric pH or gastric motility results in lower posaconazole exposure. (See Table 14.)
Table 14: The Effect of Concomitant Medications that Affect the Gastric pH and Gastric Motility on the Pharmacokinetics of Posaconazole Oral Suspension in Healthy Volunteers
Coadministered Drug (Postulated Mechanism of Interaction)
Coadministered Drug Dose/Schedule
Posaconazole Dose/Schedule
Effect on Bioavailability of Posaconazole
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 drug interactions associated with the oral suspension are also relevant for the delayed-release tablet with the exception of Esomeprazole and Metoclopramide.
Cimetidine
(Alteration of gastric pH)
