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Voriconazole Intravenous for Adults
Who can administer
May be administered by registered competent doctor or nurse/midwife
Important information
- Reserve antimicrobial: Restricted for indications in the antimicrobial prescribing guidelines, or following approval by microbiology/infectious diseases
- Voriconazole has high oral bioavailability so switching to oral therapy is appropriate when clinically indicated (see BNF for doses)
- There are numerous, potentially life-threatening interactions with antimicrobials, anticoagulants and transplant rejection drugs for example - check the manufacturer's SPC (or the BNF if the SPC is not available)
- If possible, avoid any drugs known to prolong the QT interval
- See under 'Dose' for adjustments required in renal impairment
- Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected if necessary, prior to and during voriconazole therapy
Available preparations
Voriconazole 200mg vial
Reconstitution
Water for injections
19ml per 200mg vial
This produces a solution with a concentration of 200mg in 20ml
Dilute further prior to administration
Infusion fluids
Sodium Chloride 0.9% or Glucose 5%
Methods of intravenous administration
Intermittent intravenous infusion
- Final concentration of infusion must be between 0.5 and 5mg/ml - use the following table as guidance
| Dose | Volume of infusion |
|---|---|
| Less than 140mg | 100ml |
| 140 to 500mg | 100 to 250ml |
| Greater than 500mg | 250ml |
| Administer at a rate as dictated by table below | |
Rate of administration
- Maximum rate of administration is 3mg/kg/hour - for simplicity use the following guidance
| Rate of administration | Administration time |
|---|---|
| Doses of 4mg/kg | 90 minutes |
| Doses of 6mg/kg | 120 minutes |
| Doses over 6mg/kg (on Micro/ID advice only) | 180 minutes |
Dose in adults
Loading dose (day 1)
- Give 6mg/kg every twelve hours for the first twenty-four hours (two doses)
Maintenance dose (day 2 onwards)
- Give 4mg/kg every twelve hours
- If patient is unable to tolerate treatment at this dose, then decrease the dose to 3mg/kg every twelve hours
Renal impairment
- The manufacturers advise avoiding the intravenous form if possible where eGFR 50ml/minute/1.73m2 or less due to the risk of accumulation of toxic 'additive' (vehicle), unless the benefit outweighs risk
Hepatic impairment
- In mild to moderate hepatic cirrhosis (Child-Pugh score A and B), give usual loading dose, and then halve maintenance dose
- For severe hepatic cirrhosis (Child-Pugh score C), no information available. Manufacturer advises only to use in patients with severe hepatic impairment if potential benefit outweighs risk
- There is limited data on the safety of voriconazole in patients with abnormal LFTs (AST, ALT, ALP, or total bilirubin >5 times the upper limit of normal)
Monitoring
- Infusion related reactions, predominantly flushing and nausea, have been observed during administration of the intravenous formulation of voriconazole. Depending on the severity of symptoms, consideration should be given to stopping treatment
- Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected if necessary, prior to and during voriconazole therapy
- Monitor serum creatinine in all patients
- Monitor liver function before starting treatment, then at least weekly for one month, and then monthly during treatment. Consider treatment discontinuation if LFTs become markedly elevated
- Monitor pancreatic function - serum amylase or lipase
- Drug levels should be measured weekly, or as per Micro/ID - not routinely performed in house- sent to Bristol (ref 1)
Storage
Store below 250C
References
Voriconazole (Fresenius Kabi) May 2021
1: AST advice Nov 2021
Therapeutic classification
Antifungal agent