Active Ingredient: Voriconazole
Voriconazole, is a broad-spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above for the treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 6 milligrams voriconazole per kilogram of body weight, once every 12 hours, over the duration of 24 hours. Afterwards, intravenous, 4 milligrams voriconazole per kilogram of body weight, 2 times daily.
Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected, if necessary, prior to initiation and during voriconazole therapy.
It is recommended that voriconazole is administered at a maximum rate of 3 mg/kg per hour over 1 to 3 hours.
Therapy must be initiated with the specified loading dose regimen of either intravenous 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%), switching between intravenous and oral administration is appropriate when clinically indicated.
Detailed information on dosage recommendations is provided in the following table:
| Intravenous | |
| Loading dose regimen (first 24 hours) | 6 mg/kg every 12 hours |
| Maintenance dose (after first 24 hours) | 4 mg/kg twice daily |
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.
If patient is unable to tolerate intravenous treatment at 4 mg/kg twice daily, reduce the dose to 3 mg/kg twice daily.
If patient response to treatment is inadequate, the maintenance dose may be increased to 300 mg twice daily for oral administration. For patients less than 40 kg the oral dose may be increased to 150 mg twice daily.
If patient is unable to tolerate treatment at a higher dose reduce the oral dose by 50 mg steps to the 200 mg twice daily (or 100 mg twice daily for patients less than 40 kg) maintenance dose.
For:
Regimen A, in the case that patient weight is ≥ 40 kg :
Oral, 400 milligrams voriconazole, once every 12 hours, over the duration of 24 hours. Afterwards, oral, 200 milligrams voriconazole, 2 times daily.
Regimen B, in the case that patient weight is < 40 kg :
Oral, 200 milligrams voriconazole, once every 12 hours, over the duration of 24 hours. Afterwards, oral, 100 milligrams voriconazole, 2 times daily.
Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected, if necessary, prior to initiation and during voriconazole therapy.
Therapy must be initiated with the specified loading dose regimen of either intravenous 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%), switching between intravenous and oral administration is appropriate when clinically indicated.
Detailed information on dosage recommendations is provided in the following table:
| Oral | ||
| Patients 40 kg and above | Patients less than 40 kg | |
| Loading dose regimen (first 24 hours) | 400 mg every 12 hours | 200 mg every 12 hours |
| Maintenance dose (after first 24 hours) | 200 mg twice daily | 100 mg twice daily |
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.
If patient response to treatment is inadequate, the maintenance dose may be increased to 300 mg twice daily for oral administration. For patients less than 40 kg the oral dose may be increased to 150 mg twice daily.
If patient is unable to tolerate treatment at a higher dose, reduce the oral dose by 50 mg steps to the 200 mg twice daily (or 100 mg twice daily for patients less than 40 kg) maintenance dose.
For:
Regimen A, in the case that patient age in years is ≤ 14 and patient weight is < 50 kg :
Intravenous, 9 milligrams voriconazole per kilogram of body weight, once every 12 hours, over the duration of 24 hours. Afterwards, oral, 9 milligrams voriconazole per kilogram of body weight, 2 times daily.
Regimen B, in the case that patient age in years is ≤ 14 and patient weight is > 50 kg :
Oral, 400 milligrams voriconazole, once every 12 hours, over the duration of 24 hours. Afterwards, oral, 200 milligrams voriconazole, 2 times daily.
Regimen C, in the case that patient age in years is ≥ 15 and patient weight is < 40 kg :
Oral, 200 milligrams voriconazole, once every 12 hours, over the duration of 24 hours. Afterwards, oral, 200 milligrams voriconazole, 2 times daily.
Regimen D, in the case that patient age in years is ≥ 15 and patient weight is ≥ 40 kg :
Oral, 400 milligrams voriconazole, once every 12 hours, over the duration of 24 hours. Afterwards, oral, 200 milligrams voriconazole, 2 times daily.
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:
| Intravenous | Oral | |
| Loading Dose Regimen (first 24 hours) | 9 mg/kg every 12 hours | Not recommended |
| Maintenance Dose (after first 24 hours) | 8 mg/kg twice daily | 9 mg/kg twice daily (a maximum dose of 350 mg twice daily) |
Note: Based on a population pharmacokinetic analysis in 112 immunocompromised paediatric patients aged 2 to <12 years and 26 immunocompromised adolescents aged 12 to <17 years.
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.
These oral dose recommendations for children are based on studies in which voriconazole was administered as the powder for oral suspension. Bioequivalence between the powder for oral suspension and tablets has not been investigated in a paediatric population. Considering the assumed limited gastro-enteric transit time in paediatric patients, the absorption of tablets may be different in paediatric compared to adult patients. It is therefore recommended to use the oral suspension formulation in children aged 2 to <12.
Detailed information on dosage recommendations is provided in the following table:
| Oral | ||
| Patients 40 kg and above | Patients less than 40 kg | |
| Loading dose regimen (first 24 hours) | 400 mg every 12 hours | 200 mg every 12 hours |
| Maintenance dose (after first 24 hours) | 200 mg twice daily | 100 mg twice daily |
If patient response to treatment is inadequate, the dose may be increased by 1 mg/kg steps (or by 50 mg steps if the maximum oral dose of 350 mg was used initially). If patient is unable to tolerate treatment, reduce the dose by 1 mg/kg steps (or by 50 mg steps if the maximum oral dose of 350 mg was used initially).
For:
Regimen A, in the case that patient age in years is ≤ 14 and patient weight is < 50 kg :
Intravenous, 9 milligrams voriconazole per kilogram of body weight, once every 12 hours, over the duration of 24 hours. Afterwards, intravenous, 8 milligrams voriconazole per kilogram of body weight, 2 times daily.
Regimen B, in the case that patient age in years is ≤ 14 and patient weight is > 50 kg :
Intravenous, 6 milligrams voriconazole, once every 12 hours, over the duration of 24 hours. Afterwards, intravenous, 4 milligrams voriconazole, 2 times daily.
Regimen C, in the case that patient age in years is ≥ 15 and patient weight is < 40 kg :
Intravenous, 200 milligrams voriconazole, once every 12 hours, over the duration of 24 hours. Afterwards, intravenous, 100 milligrams voriconazole, 2 times daily.
Regimen D, in the case that patient age in years is ≥ 15 and patient weight is ≥ 40 kg :
Intravenous, 400 milligrams voriconazole, once every 12 hours, over the duration of 24 hours. Afterwards, intravenous, 200 milligrams voriconazole, 2 times daily.
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:
| Intravenous | |
| Loading Dose Regimen (first 24 hours) | 9 mg/kg every 12 hours |
| Maintenance Dose (after first 24 hours) | 8 mg/kg twice daily |
Note: Based on a population pharmacokinetic analysis in 112 immunocompromised paediatric patients aged 2 to <12 years and 26 immunocompromised adolescents aged 12 to <17 years.
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.
Detailed information on dosage recommendations is provided in the following table:
| Intravenous | |
| Loading dose regimen (first 24 hours) | 6 mg/kg every 12 hours |
| Maintenance dose (after first 24 hours) | 4 mg/kg twice daily |
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.
For:
Intravenous, 9 milligrams voriconazole per kilogram of body weight, once every 12 hours, over the duration of 24 hours. Afterwards, oral, 9 milligrams voriconazole per kilogram of body weight, 2 times daily.
The recommended dosing regimen is as follows:
| Intravenous | Oral | |
| Loading Dose Regimen (first 24 hours) | 9 mg/kg every 12 hours | Not recommended |
| Maintenance Dose (after first 24 hours) | 8 mg/kg twice daily | 9 mg/kg twice daily (a maximum dose of 350 mg twice daily) |
Note: Based on a population pharmacokinetic analysis in 112 immunocompromised paediatric patients aged 2 to <12 years and 26 immunocompromised adolescents aged 12 to <17 years.
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.
These oral dose recommendations for children are based on studies in which voriconazole was administered as the powder for oral suspension. Bioequivalence between the powder for oral suspension and tablets has not been investigated in a paediatric population. Considering the assumed limited gastro-enteric transit time in paediatric patients, the absorption of tablets may be different in paediatric compared to adult patients. It is therefore recommended to use the oral suspension formulation in children aged 2 to <12.
If patient response to treatment is inadequate, the dose may be increased by 1 mg/kg steps (or by 50 mg steps if the maximum oral dose of 350 mg was used initially). If patient is unable to tolerate treatment, reduce the dose by 1 mg/kg steps (or by 50 mg steps if the maximum oral dose of 350 mg was used initially).
Use in paediatric patients aged 2 to <12 years with hepatic or renal insufficiency has not been studied.
For:
Intravenous, 9 milligrams voriconazole per kilogram of body weight, once every 12 hours, over the duration of 24 hours. Afterwards, intravenous, 8 milligrams voriconazole per kilogram of body weight, 2 times daily.
The recommended dosing regimen is as follows:
| Intravenous | Oral | |
| Loading Dose Regimen (first 24 hours) | 9 mg/kg every 12 hours | Not recommended |
| Maintenance Dose (after first 24 hours) | 8 mg/kg twice daily | 9 mg/kg twice daily (a maximum dose of 350 mg twice daily) |
Note: Based on a population pharmacokinetic analysis in 112 immunocompromised paediatric patients aged 2 to <12 years and 26 immunocompromised adolescents aged 12 to <17 years.
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.
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.
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