Nurses Compass
Drug Guide
Posaconazole
Classification
Therapeutic: Antifungal
Pharmacological: Azole antifungal
FDA Approved Indications
- Prophylaxis of invasive Aspergillus and Candida infections in immunocompromised patients at high risk
- Treatment of oropharyngeal candidiasis in patients who are refractory or intolerant to conventional therapy
Mechanism of Action
Posaconazole inhibits fungal cytochrome P450 enzyme 14α-sterol demethylase, leading to decreased ergosterol synthesis and increased membrane permeability, which inhibits fungal growth.
Dosage and Administration
Adult: Varies by formulation and indication; typical dose for prophylaxis is 300 mg twice on day 1, then 300 mg once daily; for oral suspension, taken with food.
Pediatric: Safety and efficacy established for pediatric patients 13 years and older; dosing tailored to body weight and specific indication.
Geriatric: Use with caution; no specific dosage adjustment required but monitor for adverse effects.
Renal Impairment: No dose adjustment necessary, but caution advised; monitor renal function.
Hepatic Impairment: Use with caution; dosing adjustments may be necessary; monitor liver function.
Pharmacokinetics
Absorption: Poorly absorbed in fasting state; absorption significantly increased when taken with a high-fat, high-calorie meal.
Distribution: Wide distribution; high plasma protein binding (~98%).
Metabolism: Metabolized mainly by UDP-glucuronidation and also by CYP3A4.
Excretion: Primarily via feces; minor renal excretion.
Half Life: Approximately 25-31 hours in healthy volunteers.
Contraindications
- Hypersensitivity to posaconazole or other azole antifungals.
Precautions
- Liver function impairment; drug interactions via CYP3A4 inhibitors or inducers; QT prolongation risk; cautions in pregnancy and breastfeeding.
Adverse Reactions - Common
- Nausea (Common)
- Vomiting (Common)
- Headache (Common)
- Fever (Common)
Adverse Reactions - Serious
- QT prolongation and serious cardiac arrhythmias (Rare)
- Liver enzyme elevations and hepatitis (Rare)
- SHS (Severe hypersensitivity reactions) (Rare)
Drug-Drug Interactions
- CYP3A4 inhibitors and inducers (e.g., ritonavir, ketoconazole, rifampin)
- Other QT prolonging agents
Drug-Food Interactions
N/ADrug-Herb Interactions
N/ANursing Implications
Assessment: Monitor liver function tests, renal function, and signs of adverse reactions.
Diagnoses:
- Risk for infection due to immunosuppression
- Potential for drug interactions
Implementation: Administer with food to enhance absorption; monitor for signs of hepatotoxicity and drug interactions.
Evaluation: Evaluate patient's response; monitor for adverse effects, especially liver function and cardiac status.
Patient/Family Teaching
- Take medication with food to improve absorption.
- Report signs of liver problems (jaundice, dark urine).
- Inform about potential cardiac side effects and to report palpitations or dizziness.
- Adhere strictly to dosing schedule.
Special Considerations
Black Box Warnings:
- QT prolongation and serious cardiac arrhythmias,
Genetic Factors: Consider CYP3A4 genetic polymorphisms affecting metabolism.
Lab Test Interference: May elevate serum lipids and liver enzymes.
Overdose Management
Signs/Symptoms: Nausea, vomiting, dizziness, abnormal heart rhythms.
Treatment: Supportive care; activated charcoal may be considered within 1 hour of ingestion; no specific antidote.
Storage and Handling
Storage: Store at room temperature, away from moisture and heat.
Stability: Warms to room temperature; unopened vials and powder mix kits stable as per package insert.