posaconazole: clinical use

Prescribing considerations

• Initiation and supervision should involve clinicians experienced in invasive fungal infection or antifungal prophylaxis.
• Specify the exact formulation on every prescription and confirm the correct product when dispensing or switching.
• Review all prescribed, over-the-counter and complementary products for CYP3A4, QT and absorption interactions.
• Consider therapeutic drug monitoring, particularly with standard oral suspension, suspected malabsorption, adherence concerns, interacting medicines, toxicity or an inadequate clinical response.
• Use intravenous formulation cautiously in moderate or severe renal impairment because its cyclodextrin vehicle can accumulate; prefer an oral formulation where clinically appropriate.
• Assess benefit and risk carefully in hepatic impairment, pro-arrhythmic conditions, severe gastrointestinal dysfunction and previous azole hypersensitivity.

Contraindications and cautions

• Hypersensitivity to posaconazole or product excipients
• Concurrent ergot alkaloids
• Concurrent terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine
• Concurrent simvastatin, lovastatin or atorvastatin
• Concurrent venetoclax during initiation or titration in chronic lymphocytic leukaemia

Monitoring

• Liver function and bilirubin before treatment and during therapy
• Potassium, magnesium and calcium, correcting clinically significant disturbances
• ECG where QT prolongation or other pro-arrhythmic risk is present
• Clinical response and evidence of breakthrough fungal infection, especially with vomiting, diarrhoea or severe renal impairment
• Posaconazole concentrations where exposure may be uncertain or optimisation is clinically important
• Concentrations and toxicity of interacting medicines such as tacrolimus, ciclosporin and sirolimus
• Serum creatinine when intravenous posaconazole is used in renal impairment

Clinical pharmacology

Posaconazole is a broad-spectrum triazole that inhibits fungal CYP51-dependent ergosterol synthesis. It is highly protein-bound, is mainly cleared through faecal elimination and glucuronidation, and is a strong CYP3A4 inhibitor.

Formulation and product differences

• Gastro-resistant tablets provide higher and more reliable exposure than standard oral suspension and can be taken without regard to food.
• Standard oral suspension has food-dependent absorption and must be shaken before use; gastric acid suppression can lower exposure.
• Gastro-resistant powder and solvent is a distinct paediatric formulation requiring preparation with dedicated equipment and must not be substituted for standard suspension.
• Intravenous concentrate contains sodium and a cyclodextrin vehicle; it requires dilution and controlled infusion by healthcare professionals.
• Oral formulations are not directly interchangeable because absorption, exposure and administration requirements differ.

Solution for infusion

Route: Intravenous

Strengths: 300 mg

Gastro-resistant tablet

Route: Oral

Strengths: 100 mg

Oral suspension

Route: Oral

Strengths: 40 mg/mL, 300 mg