Voriconazole Kabi Dosage/Direction for Use

Posology: Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected, if necessary, prior to initiation and during voriconazole therapy (see Precautions).
It is recommended that Voriconazole Kabi is administered at a maximum rate of 3 mg/kg per hour over 1 to 3 hours.
Treatment: Adults: Therapy must be initiated with the specified loading dose regimen of either intravenous Voriconazole Kabi or oral voriconazole to achieve plasma concentrations on Day 1 that are close to steady state. On the basis of the high oral bioavailability (96%; see Pharmacology: Pharmacokinetics under Actions), switching between intravenous and oral administration is appropriate when clinically indicated.
Detailed information on dosage recommendations is provided in the following table: See Table 6.

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Duration of treatment: Treatment duration should be as short as possible depending on the patient's clinical and mycological response. Long term exposure to voriconazole greater than 180 days (6 months) requires careful assessment of the benefit-risk balance (see Precautions and Pharmacology: Pharmacodynamics under Actions). Clinical data to establish the safety of intravenously administered hydroxypropylbetadex in long term treatment are limited (see Pharmacology: Pharmacokinetics under Actions).
Dosage adjustment (adults): If patient is unable to tolerate intravenous treatment at 4 mg/kg twice daily, reduce the dose to 3 mg/kg twice daily.
In case of use as prophylaxis, refer as follows.
Children (2 to <12 years) and young adolescents with low body weight (12 to 14 years and <50 kg): Voriconazole should be dosed as children as these young adolescents may metabolise voriconazole more similarly to children than to adults.
The recommended dosing regimen is as follows: See Table 7.

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It is recommended to initiate the therapy with intravenous regimen, and oral regimen should be considered only after there is a significant clinical improvement. It should be noted that an 8 mg/kg intravenous dose will provide voriconazole exposure approximately 2-fold higher than a 9 mg/kg oral dose.
All other adolescents (12 to 14 years and ≥50 kg; 15 to 17 years regardless of body weight): Voriconazole should be dosed as adults.
Dosage adjustment (Children [2 to <12 years] and young adolescents with low body weight [12 to 14 years and <50 kg]): If patient response to treatment is inadequate, the intravenous dose may be increased by 1 mg/kg steps.
If patient is unable to tolerate treatment, reduce the intravenous dose by 1 mg/kg steps.
Use in paediatric patients aged 2 to <12 years with hepatic or renal insufficiency has not been studied (see Adverse Reactions and Pharmacology: Pharmacokinetics under Actions).
Prophylaxis in adults and children: Prophylaxis should be initiated on the day of transplant and may be administered for up to 100 days.
Prophylaxis should be as short as possible depending on the risk for developing invasive fungal infection (IFI) as defined by neutropenia or immunosuppression. It may only be continued up to 180 days after transplantation in case of continuing immunosuppression or graft versus host disease (GvHD) (see Pharmacology: Pharmacodynamics under Actions).
Dosage: The recommended dosing regimen for prophylaxis is the same as for treatment in the respective age groups. Please refer to the treatment tables as previously mentioned.
Duration of prophylaxis: The safety and efficacy of voriconazole use for longer than 180 days has not been adequately studied in clinical trials.
Use of voriconazole in prophylaxis for greater than 180 days (6 months) requires careful assessment of the benefit-risk balance (see Precautions and Pharmacology: Pharmacodynamics under Actions). Clinical data to establish the safety of intravenously administered hydroxypropylbetadex in long term treatment are limited (see Pharmacology: Pharmacokinetics under Actions).
The following instructions apply to both treatment and prophylaxis: Dosage adjustment: For prophylaxis use, dose adjustments are not recommended in the case of lack of efficacy or treatment-related adverse events. In the case of treatment-related adverse events, discontinuation of voriconazole and use of alternative antifungal agents must be considered (see Precautions and Adverse Reactions).
Dosage adjustments in case of co-administration: Rifabutin or phenytoin may be coadministered with voriconazole if the maintenance dose of voriconazole is increased to 5 mg/kg intravenously twice daily, see Precautions and Interactions.
Efavirenz may be coadministered with voriconazole if the maintenance dose of voriconazole is increased to 400 mg every 12 hours and the efavirenz dose is reduced by 50%, i.e. to 300 mg once daily. When treatment with voriconazole is stopped, the initial dosage of efavirenz should be restored (see Precautions and Interactions).
Elderly: No dose adjustment is necessary for elderly patients (see Pharmacology: Pharmacokinetics under Actions).
Renal impairment: In patients with moderate to severe renal dysfunction (creatinine clearance <50 ml/min), accumulation of the intravenous vehicle, hydroxypropylbetadex, occurs. Oral voriconazole should be administered to these patients, unless an assessment of the risk benefit to the patient justifies the use of intravenous voriconazole. Serum creatinine levels should be closely monitored in these patients and, if increases occur, consideration should be given to changing to oral voriconazole therapy (see Pharmacology: Pharmacokinetics under Actions). Use in patients who are not undergoing haemodialysis is not recommended.
Voriconazole is haemodialysed with a clearance of 121 ml/min. A 4-hour haemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment.
The intravenous vehicle, hydroxypropylbetadex, is haemodialysed with a clearance of 37.5 ± 24 ml/min.
Hepatic impairment: It is recommended that the standard loading dose regimens be used but that the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis (Child-Pugh A and B) receiving voriconazole (see Pharmacology: Pharmacokinetics under Actions).
Voriconazole has not been studied in patients with severe chronic hepatic cirrhosis (Child-Pugh C).
There is limited data on the safety of voriconazole in patients with abnormal liver function tests (aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase [ALP], or total bilirubin >5 times the upper limit of normal).
Voriconazole has been associated with elevations in liver function tests and clinical signs of liver damage, such as jaundice, and must only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk. Patients with severe hepatic impairment must be carefully monitored for drug toxicity (see Adverse Reactions).
Paediatric population: The safety and efficacy of voriconazole in children below 2 years has not been established. Currently available data are described in Adverse Reactions and Pharmacology: Pharmacodynamics under Actions, but no recommendation on a posology can be made.
Clinical data to establish the safety of intravenously administered hydroxypropylbetadex in the paediatric population are limited.
Method of administration: Voriconazole Kabi requires reconstitution and dilution (see Special precautions for disposal and other handling under Cautions for Usage) prior to administration as an intravenous infusion. Not for bolus injection.