BRAND NAMES
 MECHANISM OF ACTION
Posaconazole is a triazole antifungal. It inhibits lanosterol 14α-demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol.
Ergosterol is an essential component of the fungal cell membrane. The inhibition of its synthesis results in accumulation of toxic 14α-methylated sterols and the production of a defective cell membrane with altered permeability and leakage of cellular contents.
Unlike, Voriconazole that causes reversible visual disturbances immediately after usage, Posaconazole doesn’t show this problem.
Posaconazole crosses the BBB and is actually more similar to Voriconazole than the other azoles. It is metabolized and used for invasive aspergillosis.
- Injection, delayed-release tablets, and oral suspension are indicated for Prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy.
- Oral suspension is indicated for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole.
|Indication||Dose and Duration of Therapy|
Loading dose: 300 mg Posaconazole injection
intravenously twice a day on the first day.
Maintenance dose: 300 mg 'Posaconazole 'injection
intravenously once a day thereafter. Duration of
therapy is based on recovery from neutropenia
Delayed-Release Tablets † :
Loading dose: 300 mg (three 100 mg
delayed-release tablets) twice a day on the first
Maintenance dose: 300 mg (three 100 mg
delayed-release tablets) once a day, starting on
the second day. Duration of therapy is based
on recovery from neutropenia or
Oral Suspension‡ : 200 mg (5 mL) three times
a day. Duration of therapy is based on recovery
from neutropenia or immunosuppression.
Oral Suspension‡ :
Loading dose: 100 mg (2.5 mL) twice a day on the first day.
Maintenance dose: 100 mg (2.5 mL) once a day for 13 days.
Oral Suspension‡ : 400 mg (10 mL) twice a day. Duration of therapy is based on the severity of the patient’s underlying disease and
- Do not administer to persons with known hypersensitivity to posaconazole or other azole antifungal agents.
- Do not coadminister posaconazole with the following drugs; posaconazole increases concentrations of:
- Sirolimus: Concomitant administration of Posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity
- CYP3A4 substrates that prolong the QT interval (pimozide, quinidine): can result in QTc interval prolongation and cases of torsades de pointes
- HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4 (e.g., atorvastatin, lovastatin, and simvastatin): is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis
- Ergot alkaloids: Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism
 WARNINGS AND PRECAUTIONS
- Calcineurin Inhibitor Toxicity: Posaconazole increases concentrations of cyclosporine or tacrolimus; reduce dose of cyclosporine and tacrolimus and monitor concentrations frequently.
- Arrhythmias and QTc Prolongation: Posaconazole has been shown to prolong the QTc interval and cause cases of torsades de pointes. Administer with caution to patients with potentially proarrhythmic conditions. Do not administer with drugs known to prolong QTc interval and metabolized through CYP3A4 (See contraindications). Correct K+, Mg++, and Ca++ before starting Posaconazole.
- Hepatic Toxicity: Elevations in Liver function tests (e.g., mild to moderate elevations in alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase, total bilirubin, and/or clinical hepatitis) may occur. Discontinuation should be considered in patients who develop abnormal LFTs or monitor Liver function tests during treatment.
- Posaconazole injection should be avoided in patients with moderate or severe renal impairment (creatinine clearance <50 mL/min), unless an assessment of the benefit/risk to the patient justifies the use of Posaconazole injection.
- Midazolam: Posaconazole can prolong hypnotic/sedative effects. Monitor patients and benzodiazepine receptor antagonists should be available.
Rifabutin, phenytoin, efavirenz, cimetidine, esomeprazole*
Avoid coadministration unless
the benefit outweighs the risks
Other drugs metabolized by CYP3A4
Consider dosage adjustment
and monitor for adverse effects
Monitor digoxin plasma
Monitor for breakthrough fungal
*The drug interactions with esomeprazole and metoclopramide do not apply to posaconazole tablets.
 PREGNANCY AND LACTATION
- Pregnancy Category C: (US): Based on animal data, may cause fetal harm.
- Nursing Mothers: Discontinue drug or nursing, taking in to consideration the importance of drug to the mother.
 SIDE EFFECTS
Common treatment-emergent adverse reactions in studies with posaconazole are diarrhea, nausea, fever, vomiting, headache, coughing, and hypokalemia.
 RELATED LINKS
|Ergosterol target : Cell membrane target||Azoles (lanosterol 14 alpha-demethylase inhibitors) : Ergosterol inhibitors||Imidazoles||Topical: Bifonazole • Clotrimazole • Econazole • Fenticonazole • Ketoconazole • Isoconazole • Miconazole • Sertaconazole • Tioconazole|
|Triazoles|| Topical: Fluconazole • Terconazole|
Systemic: Fluconazole • Itraconazole • Posaconazole • Voriconazole
|Polyene antimycotics (ergosterol binding; they form pores in the membrane)|| Topical: Nystatin |
Systemic: Amphotericin B
|Allylamines (squalene epoxidase inhibitors) : Ergosterol inhibitors|| Topical: Amorolfine • Naftifine • Terbinafine |
|Echinocandins (β-glucan synthase inhibitors) : Cell wall target||Anidulafungin • Caspofungin • Micafungin|
|Pyrimidine analogues / Thymidylate synthase inhibitors : Nucleic acid inhibitors||Flucytosine|