Generic
Posaconazole
4 brands available in the market
At a glance
Posaconazole is an antifungal used for treatment of invasive aspergillosis, fusariosis, chromoblastomycosis, mycetoma, and coccidioidomycosis in patients aged 13 years and above, and for prophylaxis of invasive fungal infections.
Description
Posaconazole blocks the synthesis of ergosterol, a key component of the fungal cell membrane. It inhibits the cytochrome P-450 dependent enzyme Lanosterol 14-α-demethylase responsible for conversion of lanosterol to ergosterol. This results in accumulation of methylated sterol precursors and depletion of ergosterol, weakening the structure and function of the fungal cell membrane.
Indications
- Invasive aspergillosis (refractory/intolerant to Amphotericin B or Itraconazole)
- Fusariosis (refractory/intolerant to Amphotericin B)
- Chromoblastomycosis and mycetoma (refractory/intolerant to Itraconazole)
- Coccidioidomycosis (refractory/intolerant to Amphotericin B, Itraconazole, or Fluconazole)
- Prophylaxis of invasive fungal infections in AML/MDS patients with prolonged neutropenia
- HSCT recipients on high-dose immunosuppressive therapy for GVHD
Therapeutic class
Aural Anti-fungal preparations
Pharmacological class
Triazole Antifungal
Pharmacology
Posaconazole blocks ergosterol synthesis by inhibiting the cytochrome P-450 dependent enzyme Lanosterol 14-α-demethylase. This causes accumulation of methylated sterol precursors and depletion of ergosterol, weakening the fungal cell membrane structure and function.
Mechanism of action
Disrupts fungal cell membrane by inhibiting ergosterol synthesis.
Dosage
Adult Dose (Oral/IV):
- Loading dose: 300 mg (3 tablets) twice daily on Day 1
- Maintenance dose: 300 mg (3 tablets) once daily from Day 2
- Oral suspension (prophylaxis): 200 mg three times daily
- Oral suspension (oropharyngeal candidiasis): 100 mg twice daily (Day 1), then 100 mg once daily for 13 days
- Itraconazole/fluconazole-refractory: 400 mg twice daily
Pediatric Dose (≥13 years): Same as adult
Administration
- Tablets: Take with or without food; swallow whole, do not crush, chew, or break
- Oral suspension: Take with food
- IV: Administered by healthcare professional
Missed dose
If you miss a dose, take it as soon as you remember; skip if it's almost time for next dose; do not double the dose.
Side effects
Common Side Effects:
- Diarrhea
- Nausea
- Fever
- Vomiting
- Headache
- Coughing
- Hypokalemia
Precautions & warnings
- May affect driving ability (dizziness, drowsiness, blurred vision)
- Monitor liver function tests at the start and during therapy
- Caution in pregnancy and lactation
- Avoid IV administration in moderate-severe renal impairment (eGFR <50 mL/min)
Contraindications
- Hypersensitivity to posaconazole or other azole antifungals
- Co-administration with ergot alkaloids, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine
- Co-administration with simvastatin, lovastatin, atorvastatin
Drug interactions
- CYP3A4 substrates (midazolam, triazolam, alprazolam): Increased plasma concentrations
- Rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital, efavirenz: Significantly lower posaconazole concentrations
- Tacrolimus, ciclosporin, midazolam, Ca channel blockers, digoxin: Increased plasma concentrations
- Vinca alkaloids: Increased risk of neurotoxicity
Food interactions
It is not known whether it is safe to consume alcohol with Posaconazole.
Use in pregnancy
Use in Pregnancy: May be unsafe during pregnancy; animal studies have shown harmful effects; use only if clearly needed.
Pregnancy Category: C — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Probably unsafe; limited data suggests drug may pass into breast milk; discontinue breastfeeding.
Pediatric use
Safety and efficacy not established in pediatric patients below 13 years.
Geriatric use
No dose adjustment necessary for geriatric patients.
Renal / hepatic impairment
Renal Impairment: No dose adjustment required in mild-moderate renal impairment; avoid IV administration in severe renal impairment (eGFR <50 mL/min); monitor for breakthrough fungal infections with oral formulations.
Hepatic Impairment: Caution in liver disease; monitor liver function tests.
Overdose effects
No overdose information available; consult your doctor if taken in excess.
Storage conditions
Store below 25°C; keep out of reach of children.
Chemical structure
Posaconazole