posaconazole (Noxafil)

Indications

• prevention of invasive fungal infections in immunocompromised hosts (>= 13 years of age)
  • aspergillosis
  • Candida infections

Contraindications

• concurrent use of ergot alkaloids, pimozide, cisapride, quinidine

Pregnancy category: C

pregnancy category = c

Dosage

• 200 mg (one teaspoon) TID
• delayed release tablet also available

40 mg/mL oral suspension, 4-ounces

* oral suspension & delayed release dosing not the same dosage adjustment rqwuired

Pharmacokinetics

• food increases absorption
• metabolized by glucuronidation
• posaconazole inhibits CYP3A4

elimination via liver

1/2life = >40 hours

Monitor

• liver function test baseline & during treatment

Adverse effects

• nausea/vomiting (30-38%)
• headache (28%)
• abnormal liver function tests, hepatitis (uncommon)

Drug interactions

• rifabutin & phenytoin can diminish posaconazole levels via enzyme induction
• cimetidine can diminish posaconazole absorption by increasing gastric pH
  • other H2 blockers & proton pump inhibitors do not seem to interact
• posaconazole inhibits CYP3A4 substrates thus may increase levels of pharmaceuticals metabolized by CYP3A4
  • diminish dose of tacrolimus 66% & monitor trough
  • diminish dose of cyclosporine 25% & monitor trough
• monitor WBC & for uveitis when used with rifabutin
• phenytoin levels should be monitored with concomitant use
• monitor for hypoglycemia when used with glipizide
• NO interaction with zidovudine, lamivudine, ritonavir, indinavir

• drug interaction(s) of antibiotics with warfarin

Laboratory

• posaconazole in hair
• posaconazole in serum/plasma

Mechanism of action

• inhibits synthesis of ergosterol
• inhibits lanosterol 14-alpha-demethylase

More general terms

• antifungal agent
• triazole; pyrrodiazole

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=468595
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=147912