Coadministered Drug
 
Administration Arms
 
Change in Cmax
(ratio estimate*;
90% CI of the ratio estimate)
 
Change in AUC0-last
(ratio estimate*;
90% CI of the ratio estimate)

* Ratio Estimate is the ratio of coadministered drug plus posaconazole to posaconazole alone for Cmax or AUC0-last. 
Mylanta® Ultimate strength liquid (Increase in gastric pH) 25.4 meq/5 mL, 20 mL ↑6%
(1.06; 0.90 -1.26)↑ ↑4%
(1.04; 0.90 -1.20)
Ranitidine (Zantac®) (Alteration in gastric pH) 150 mg (morning dose of 150 mg Ranitidine BID) ↑4%
(1.04; 0.88 -1.23)↑ ↓3%
(0.97; 0.84 -1.12)
Esomeprazole (Nexium®) (Increase in gastric pH) 40 mg (QAM 5 days, day -4 to 1) ↑2%
(1.02; 0.88-1.17)↑ ↑5%
(1.05; 0.89 -1.24)
Metoclopramide (Reglan®) (Increase in gastric motility) 15 mg four times daily during 2 days (Day -1 and 1) ↓14%
(0.86, 0.73,1.02) ↓7%
(0.93, 0.803,1.07)
 
Posaconazole oral suspension is absorbed with a median Tmax of ~3 to 5 hours. Steady-state plasma concentrations are attained at 7 to 10 days following multiple-dose administration.
 
Following single-dose administration of 200 mg, the mean AUC and Cmax of posaconazole are approximately 3-times higher when the oral suspension is administered with a nonfat meal and approximately 4-times higher when administered with a high-fat meal (~50 gm fat) relative to the fasted state. Following single-dose administration of posaconazole oral suspension 400 mg, the mean AUC and Cmax of posaconazole are approximately 3-times higher when administered with a liquid nutritional supplement (14 gm fat) relative to the fasted state (see Table 12). In addition, the effects of varying gastric administration conditions on the Cmax and AUC of posaconazole oral suspension in healthy volunteers have been investigated and are shown in Table 13.
 
In order to assure attainment of adequate plasma concentrations, it is recommended to administer Noxafil oral suspension during or immediately following a full meal. In patients who cannot eat a full meal, Noxafil oral suspension should be taken with a liquid nutritional supplement or an acidic carbonated beverage (e.g., ginger ale).
 
Table 12: The Mean (%CV) [min-max] Posaconazole Pharmacokinetic Parameters Following Single-Dose Oral Suspension Administration of 200 mg and 400 mg Under Fed and Fasted Conditions
 
Dose (mg)
 
Cmax
(ng/mL)
 
Tmax*
(hr)
 
AUC (I)
(ng∙hr/mL)
 
CL/F
(L/hr)
 
t½
(hr)

* Median [min-max].† n=15 for AUC (I), CL/F, and t ½ ‡ The subject with Tmax of 36 hrs had relatively constant plasma levels over 36 hrs (1.7 ng/mL difference between 4 hrs and 36 hrs).§ n=10 for AUC (I), CL/F, and t ½  
 
200 mg fasted
(n=20)† 132 (50)
[45-267] 3.50
[1.5-36‡] 4179 (31)
[2705-7269] 51 (25)
[28-74] 23.5 (25)
[15.3-33.7]
200 mg nonfat
(n=20)† 378 (43)
[131-834] 4 [3-5] 10,753 (35)
[4579-17,092] 21 (39)
[12-44] 22.2 (18)
[17.4-28.7]
200 mg high fat
(54 gm fat)
(n=20)† 512 (34)