Valganciclovir

Generic name
Valganciclovir
Brand name
ATC Code
J05AB14
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Valganciclovir

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

Valganciclovir is a prodrug of ganciclovir. It is well absorbed from the gastrointestinal tract and rapidly and extensively metabolised to ganciclovir.

Bioavailability of ganciclovir (when valganciclovir is administered orally) is approximately 60% in all patient populations. The resulting concentration of ganciclovir after administration of oral valganciclovir is comparable to the concentration of ganciclovir after intravenous administration of ganciclovir. Adults: 1800 mg orally (valganciclovir) corresponds to 10 mg/kg intravenously (ganciclovir) in 2 doses

The following table shows pharmacokinetic parameters in adults (mean + SD) compared to the paediatric population for prophylaxis of CMV infection after organ transplantation. The single daily dose of valganciclovir (900mg) in this study was calculated based on the body surface area:

PK Parameter

Adults*

Children and adolescents
 

≥18 years
(n=160)

<4 months
(n=14)

4 months- ≤2 years
(n=17)

>2 years - <12 years
(n=21)

≥12 years - 16 years

(n=25)

AUC0 – 24h (μg ∙ h/ml)

46,3 ± 15,2

68,1 ± 19,8

64,3 ± 29,2

59,2 ± 15,1

50,3 ± 15,0

AUC0 – 24h-range

15,4 – 116,1

34 – 124

34 – 152

36 – 108

22 – 93

Cmax (μg/mL)

5,3 ± 1,5

10,5 ± 3,36

10,3 ± 3,3

9,4 ± 2,7

8,0 ± 2,4

Clearance (L/h)

12,7 ± 4,5

1,25 ± 0,473

2,5 ± 2,4

4,5 ± 2,9

6,4 ± 2,9

t1/2 (h)

6,5 ± 1,4

1,97 ± 0,185

3,1 ±1,4

4,1 ± 1,3

5,5 ± 1,1

* data from study report PV 16000

The following table shows pharmacokinetic parameters (mean + SD) in newborns and infants for the therapy of congenital CMV infection:

PK Parameter

16 mg/kg valganciclovir twice daily
(n=19)

16 mg/kg valganciclovir twice daily
(n=100)

AUC0 – 12h (μg ∙ h/ml)

38,2 ± 42,7

20,85 ± 5,40

Cmax (μg/mL)

5,44 ± 4,04

-

t1/2 (h)

2,98 ± 1,26

2,98 ± 1,12

SmPC Valcyte

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

(Congenital) CMV infection
  • Oral
    • Term neonate
      • 32 mg/kg/day in 2 doses.

      • Dose adjustment depending on the effect (CMV viral load) and/or ganciclovir plasma concentration.

    • 1 month up to 18 years
      [28] [35] [40]
      • 32 mg/kg/day in 2 doses.

      • Dose adjustment depending on the effect (CMV viral load) and/or ganciclovir plasma concentration.
Treatment of CMV infection after organ and stem cell transplantation
  • Oral
    • 1 month up to 18 years
      [16] [37]
      • 32 mg/kg/day in 2 doses.

      • Dose adjustment depending on the effect (CMV viral load) and/or ganciclovir plasma concentration.
Preemptive therapy of CMV in organ and stem cell transplants

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2
100 percentage of single dose and dosing interval : 24 uur
GFR 30-50 ml/min/1.73 m2
Dose adjustment depending on concentration, interval between 2 doses is 48 hours
GFR 10-30 ml/min/1.73 m2
Dose adjustment depending on concentration, interval between 2 doses is 48 hours
GFR < 10 ml/min/1.73 m2
Dose adjustment depending on concentration, interval between 2 doses is 48-96 hours

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Lower incidence of nausea, constipation and rejection of the donor organ. Higher incidences of upper respiratory tract infection, vomiting and pyrexia. [Vaudry 2009: side effects in italic: possibly not related to treatment and it concerns a cross-study comparison]

The most commonly reported adverse reactions in paediatric clinical trials were diarrhoea, nausea, neutropenia, leucopenia and anaemia. The overall safety profile in children and adolescents after organ transplantation was comparable to adults. [SmPC Valcyte]

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Determine the creatinine level twice a week.

Ganciclovir oral CANNOT be converted 1:1 to valganciclovir oral. The bioavailability of valganciclovir is about 10 times higher.

Potentially carcinogenic and teratogenic.

[SmPC Valcyte]

Therapeutic Drug Monitoring
Similar to ganciclovir -> There is no agreement yet on whether to routinely perform TDM due to the lack of PK/PD data. According to the NVZA, the evidence level for performing TDM is 4 (Level 4: do not perform routine TDM. Consider performing TDM selectively only in special cases, for example, to investigate toxicity, ineffectiveness/compliance or the effect of pharmacokinetic interactions) [NVZA monograph Ganciclovir].. TDM in special populations with unpredictable PK/PD profiles, i.e. patients with unstable renal function, younger children, or patients with suspected resistance may be considered . Despite the uncertainty surrounding the benefits of TDM in general, it may provide some guidance in these cases.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

DIRECT ACTING ANTIVIRALS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Nucleosides and nucleotides excl. reverse transcriptase inhibitors
J05AB01
J05AB12
J05AB06
J05AB16
J05AB04
J05AB11
Phosphonic acid derivatives
J05AD01
Protease inhibitors
J05AE08
J05AE10
J05AE07
J05AE02
J05AE04
J05AE03
J05AE01
Nucleoside and nucleotide reverse transcriptase inhibitors
J05AF06
J05AF02
J05AF09
J05AF10
J05AF05
J05AF04
J05AF07
J05AF13
J05AF13
J05AF01
Non-nucleoside reverse transcriptase inhibitors
J05AG06
J05AG03
J05AG04
J05AG01
J05AG05
Neuraminidase inhibitors
J05AH02
J05AH01
Antivirals for treatment of HIV infections, combinations
J05AR02
J05AR20
J05AR13
J05AR25
J05AR18
J05AR19
J05AR03
J05AR09
J05AR10
Other antivirals
J05AX28
J05AX12
J05AX07
J05AX09
J05AX08
J05AX24
ANTIVIRALS FOR TREATMENT OF HIV INFECTIONS, COMBINATIONS
J05AR02
J05AR20
J05AR13
J05AR25
J05AR18
J05AR19
J05AR03
J05AR09
J05AR10
Integrase inhibitors
J05AJ04
Antivirals for treatment of HCV infections
J05AP54
J05AP57
J05AP51
J05AP08
J05AP55

References

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Changes

Therapeutic Drug Monitoring


Overdose