Voriconazole (PO, IV)

Criteria & Principles

Place in therapy:​

1. Treatment of the following serious systemic mycoses in patients who are intolerant of or refractory to other therapies:
   • Aspergillosis, invasive (first-line therapy)
   • Scedosporium apiospermum infection
   • Fusarium spp infection, including Fusarium solani
   • Candidal infections resistant to fluconazole but sensitive to voriconazole

Voriconazole therapy should not be considered for fungal urinary tract infections or Zygomycosis

Usual Dose & Administration

Usual Adult Dose, Loading Doses (First Two Doses)

6 mg/kg q12h x 2 doses

Usual Adult Dose, Subsequent doses

4 mg/kg q12h

ECMO

Consider higher loading doses (i.e. 7 mg/kg q12h x 2 doses) in patients on ECMO with active infection alongside therapeutic drug monitoring.

Adjustment of Dose & Administration

Renal Adjustment

Because the cyclodextrin vehicle may accumulate in patients with renal dysfunction, IV voriconazole is not routinely recommended in patients with a CrCl <50 mL/min.  Consider using the oral route in this situation.

Dose adjustments are unnecessary for renal dysfunction.

Hepatic Adjustment

Child-Pugh A or B: standard loading dose, reduce maintenance dose by one-half.

Serum Concentration Monitoring

• For patients with invasive disease, monitoring is recommended. Target trough concentration: > 1 to < 5.5 mcg/mL (Note: troughs >2 mcg/mL may be considered for select patients guided by ID consult team)
• When being used for prophylaxis, monitoring is recommended for hematologic stem cell ransplant recipient; should be considered for all others. Target trough concentration: > 1 to < 5.5 mcg/mL

Protocol for serum monitoring

• Antifungal Therapeutic Monitoring (TDM)
• Sample should be drawn immediately prior to dose on day 5-7
• 4 mL should be drawn in a lavender top tube and placed with a cold pack for transfer to the lab (refrigerate if there is a delay in transfer). 
• Specimens should be sent to central collections. Assay is performed at DUMC in the Gould Laboratory (684-5850)

Drug-Specific Information

Caution patients to avoid sun exposure as photosensitivity is associated with voriconazole use (sunscreen is NOT effective at preventing this adverse effect)

VORICONAZOLE (substrate and inhibitor of CYP2C19, CYP2C9, and CYP3A4)

	Drug	Recommendation
Contraindicated	Commonly prescribed: carbamazepine, rifabutin, rifampin, ritonavir 400mg q12h, sirolimus Less commonly prescribed: long-acting barbituates, cisapride, ergot alkaloids, pimozide, quinidine, St. John's Wort, maraviroc	Do not use
Warning/precaution	Cyclosporin	↓ cyclosporin dose to one-half and monitor levels
	Efavirenz, nevirapine	may ↓ voriconazole levels, may need to increase vori dose
	Tacrolimus	↓ tacrolimus dose by two-thirds and monitor levels
	Methadone	Monitor effect of the interacting drug and consider decreasing dose
	Omeprazole	↓ omeprazole dose by half
	Phenytoin	increase voriconazole to 5 mg/kg IV q12h or 400 mg PO q12h; reduce phenytoin dose as necessary and monitor levels
	Ritonavir (100mg q12h)	Avoid this combination unless benefits outweigh the risks
	Warfarin	Monitor INR levels
Commonly prescribed: all benzodiazepines, all calcium channel blockers, fentanyl, oxycodone and other long acting opioids, NSAIDs, oral contraceptives, statins (avoid lovastatin and simvastatin), sulfonylureas, vinca alkaloids, simeprevir		Monitor effect of drugs and consider decreasing dose when voriconazole is added

Oral bioavailablility is excellent, but there are currently no data regarding administering voriconazole via tube

Monitor for skin rashes, and visual changes. Careful monitoring of LFTs is warranted. ALL patients should have LFTs performed before starting therapy and weekly while on therapy

Restricted Use

The use of voriconazole (intravenous and oral) in both adult and pediatric* patients must be approved via an ID Consult (* Safety and efficacy in children less than 12 years has not been established)

Refer to antifungal prophylaxis protocols for exemptions to restriction.

General Notes

1. Up-to-date cost information, click here 
2. IV antimicrobials outpatient (OPAT) dosing, click here
3. Obesity dosing weight recommendations here
4. Helpful drug-drug interaction check website here 
5. When dosing guidance is provided it is important to note the following:

Fixed (ie non weight-based) doses in adults are historically based on a 70 kg patient. Specific disease states or individual patients may warrant dosages that differ from the above recommendations. Since product-specific criteria for dose adjustment based on creatinine clearance exist, consult product information regarding specific recommendations for dosage adjustment based on estimated creatinine clearance.