IM Voriconazole Administration in a 78-Year-Old Patient
Voriconazole is not available as an intramuscular (IM) formulation and should never be administered via this route. Voriconazole is only available as intravenous (IV) and oral formulations 1, 2.
Available Formulations and Routes
- Intravenous formulation: Contains sulfobutylether-β-cyclodextrin (SBECD) as a vehicle, which is renally cleared 3, 4, 1
- Oral formulation: Available as tablets and oral suspension with excellent bioavailability (>90%) 3, 5, 2
Critical Considerations for a 78-Year-Old Patient
Age-Related Factors
Advanced age (>65 years) significantly increases voriconazole plasma concentrations by 80-90% compared to younger patients, though no dose adjustment is specifically required based on age alone 1. However, elderly patients warrant more cautious monitoring due to:
- Higher systemic exposure (AUC) in elderly males (61-86% higher than young males) 1
- Increased risk of drug-drug interactions, particularly with medications metabolized by CYP3A4, CYP2C19, and CYP2C9 6, 7
- Potential for QTc prolongation, especially when combined with other QT-prolonging drugs commonly used in elderly patients 6, 7
Route Selection in Elderly Patients
For a 78-year-old requiring STAT antifungal therapy, the choice between IV and oral voriconazole depends critically on renal function:
If Creatinine Clearance ≥50 mL/min:
- IV loading dose: 6 mg/kg every 12 hours for first 24 hours (420 mg IV q12h for 70 kg patient) 3
- IV maintenance: 3-4 mg/kg every 12 hours 3
- Can transition to oral when clinically appropriate 3, 5
If Creatinine Clearance <50 mL/min:
- Avoid IV formulation due to SBECD accumulation and nephrotoxicity risk 3, 4, 1
- Use oral formulation instead: Loading dose 400 mg (6 mg/kg) twice daily for 2 doses, then maintenance 200-300 mg twice daily 3, 4
- No dose adjustment needed for renal impairment with oral route 4, 1
Drug Interactions Requiring Special Attention in Elderly
Voriconazole has extensive drug-drug interactions that are particularly relevant in elderly patients who often take multiple medications 6, 7:
- Statins: Voriconazole inhibits CYP3A4 and increases statin levels, raising myopathy risk (already elevated in elderly, especially frail women >80 years) 6
- Calcium channel blockers (diltiazem, verapamil): Bidirectional interactions via CYP3A4 6
- Digoxin: Voriconazole increases digoxin levels; monitor closely and reduce digoxin dose 6
- Warfarin: Reduce warfarin dose by 50% due to CYP2C9 inhibition 6
- Immunosuppressants (cyclosporine, tacrolimus): Significant dose reductions required 6
Hepatic Function Considerations
Voriconazole is the only triazole requiring dose reduction in hepatic impairment 3, 7, 4:
- Mild to moderate hepatic impairment (Child-Pugh A or B): Reduce maintenance dose by 50% while keeping loading dose unchanged 3, 4, 1
- Severe hepatic impairment (Child-Pugh C): No data available; use with extreme caution 1
Monitoring Requirements in Elderly Patients
Therapeutic drug monitoring is essential in elderly patients due to high interpatient variability from CYP2C19 polymorphisms 3, 7, 4:
- Visual disturbances: Occur in ~30% of patients, dose-related but typically reversible 3, 7, 2, 8
- Hepatotoxicity: Monitor liver enzymes regularly 7, 9
- QTc prolongation: Baseline and periodic ECG monitoring, especially with concomitant QT-prolonging drugs 6, 7
- Photosensitivity and skin cancers: Risk increases with prolonged use 6, 7, 9
Common Pitfalls to Avoid
- Never attempt IM administration - this route does not exist for voriconazole 1, 2
- Do not use IV formulation in patients with CrCl <50 mL/min without considering oral alternative first 3, 4
- Do not overlook drug interactions - review all medications before initiating therapy 6, 7
- Do not skip therapeutic drug monitoring - elderly patients have unpredictable pharmacokinetics 3, 7, 9
- Do not forget to reduce maintenance dose by 50% in hepatic impairment 3, 4, 1