7.8 Phenytoin
 
Phenytoin induces UDP-glucuronidase and decreases posaconazole plasma concentrations. Phenytoin is also metabolized by CYP3A4. Therefore, coadministration of phenytoin with posaconazole increases phenytoin plasma concentrations [see Clinical Pharmacology (12.3)]. Concomitant use of posaconazole and phenytoin should be avoided unless the benefit to the patient outweighs the risk. However, if concomitant administration is required, close monitoring for breakthrough fungal infections is recommended and frequent monitoring of phenytoin concentrations should be performed while coadministered with posaconazole and dose reduction of phenytoin should be considered.

7.9 Gastric Acid Suppressors/Neutralizers

Posaconazole Delayed-Release Tablet:
 
No clinically relevant effects on the pharmacokinetics of posaconazole were observed when posaconazole delayed-release tablets are concomitantly used with antacids, H2-receptor antagonists and proton pump inhibitors [see Clinical Pharmacology (12.3)]. No dosage adjustment of posaconazole delayed-release tablets is required when posaconazole delayed-release tablets are concomitantly used with antacids, H2-receptor antagonists and proton pump inhibitors.

Posaconazole Oral Suspension:
 
Cimetidine (an H2-receptor antagonist) and esomeprazole (a proton pump inhibitor) when given with posaconazole oral suspension results in decreased posaconazole plasma concentrations [see Clinical Pharmacology (12.3)]. It is recommended to avoid concomitant use of cimetidine and esomeprazole with posaconazole oral suspension unless the benefit outweighs the risks. However, if concomitant administration is required, close monitoring for breakthrough fungal infections is recommended.
 
No clinically relevant effects were observed when posaconazole oral suspension is concomitantly used with antacids and H2-receptor antagonists other than cimetidine. No dosage adjustment of posaconazole oral suspension is required when posaconazole oral suspension is concomitantly used with antacids and H2-receptor antagonists other than cimetidine.

7.10 Vinca Alkaloids
 
Most of the vinca alkaloids are substrates of CYP3A4. Posaconazole may increase the plasma concentrations of vinca alkaloids (e.g., vincristine and vinblastine) which may lead to neurotoxicity. Therefore, it is recommended that dose adjustment of the vinca alkaloid be considered.

7.11 Calcium Channel Blockers Metabolized by CYP3A4
 
Posaconazole may increase the plasma concentrations of calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, diltiazem, nifedipine, nicardipine, felodipine). Frequent monitoring for adverse reactions and toxicity related to calcium channel blockers is recommended during coadministration. Dose reduction of calcium channel blockers may be needed.

7.12 Digoxin
 
Increased plasma concentrations of digoxin have been reported in patients receiving digoxin and posaconazole. Therefore, monitoring of digoxin plasma concentrations is recommended during coadministration.

7.13 Gastrointestinal Motility Agents

Posaconazole Delayed-Release Tab