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

Interactions
PK
Renal impairment
References

Valaciclovir

Generic name
Valaciclovir
Brand name
ATC Code
J05AB11

Pharmacokinetics in children

The following pharmacokinetic parameters (aciclovir) have been observed after a single oral dose of 25 mg/kg valaciclovir in immunocompetent children [Kimberlin 2010]:

  1-2 months 3-5 months 6-11 months 1 year 2-5 years
n= 9 9 7 9 12
Cmax (mg/l) 7 5.2 4.9 4.9 6.5
t½ (hour) 2 1.8 1.3 1.3 1.5
Cl (ml/min/h) 11 21.6 21.9 21.2 14.9

The following pharmacokinetic parameters (aciclovir) have been observed in children 1 to 18 years old after oral administration of valaciclovir [Nadal 2002, Bomgaars 2008, Kimberlin 2010, Eksborg 2002, Simon 2002]:

  Immunocompetent Immunocompromised
Vd (l/kg)
 3.01-3.79 1.34-3.49
Cmax (mg/l)
 10 mg/kg: 2.41
20 mg/kg: 4.38
500 mg: 3.16		 250 mg: 4.11
500 mg: 5.12-5.27
Tmax (h)
 1.15-1.88 1.41-2.62
t½ (h)
 1.3-2.1 1.35-2.51
Cl (ml/min/kg)
 11-25.5 9.1-19
F (%)
 45-51% 45-64%

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

No information is present at this moment.

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Available formulations

No information is present at this moment.

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Dosages

HSV infection
VZV and HSV infection in immunocompromised patients
  • Oral
    • 1 month up to 18 years
      [7]
      • 60 mg/kg/day in 3 doses. Max: 3.000 mg/day.
Cold sores
  • Oral
    • 12 years up to 18 years
      [12]
      • 4.000 mg/day in 2 doses. Start treatment within 24-48 hours.
      • Duration of treatment:

        1 day
Prophylaxis for CMV in organ transplants
  • Oral
    • 1 month up to 12 years
      [12]
      • 1.000 mg/m²/day in 3 doses. Max: 2.000 mg/dose.
    • 12 years up to 18 years
      [12]
      • 8.000 mg/day in 4 doses.
      • Duration of treatment:

        90 days
Prevention of recurrent genital herpes
  • Oral
    • 12 years up to 18 years
      [12]
      • 500 mg/day in 1 dose In very frequent recurrences (more than 10 years without treatment): 500 mg/day in 2 doses.
      • Duration of treatment:

        Reassess treatment after 6-12 months
Prophylaxis for VZV and HSV infections after stem cell transplants
  • Oral
    • ≥ 1 month and < 40 kg
      [13]
      • 20 mg/kg/day in 2 doses. Max: 1.000 mg/day.
    • ≥ 40 kg
      [13]
      • 1.000 mg/day in 2 doses.
Shingles
  • Oral

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Renal impaiment in children > 3 months

Adjustments per indication, as follows:
(Source: KNMP (Royal Dutch Pharmacists Association) on Renal Function Disorders, SmPC Zelitrex)

HSV infections, shingles, VZV and HSV infections in immunocompromised patients:
GFR 50-80 ml/min/1.73m²: Adjustment not necessary
GFR 30-50 ml/min/1.73m²: 100% of the normal dose each time and the interval between two doses: 12 hours
GFR 10-30 ml/min/1.73m²: 100% of the normal dose each time and the interval between two doses: 24 hours
GFR < 10 ml/min/1.73m²: 50% of the normal dose each time and the interval between two doses: 24 hours

Prevention of recurrent genital herpes:  
GFR 50-80 ml/min/1.73m²: Adjustment not necessary
GFR 30-50 ml/min/1.73m²: Adjustment not necessary
GFR 10-30 ml/min/1.73m²: 50% of the normal dose each time and the interval between two doses: 24 hours
GFR < 10 ml/min/1.73m²: 50% of the normal dose each time and the interval between two doses: 24 hours

Cold sores:
GFR 50-80 ml/min/1.73m²: Adjustment not necessary
GFR 30-50 ml/min/1.73m²: 50% of the normal dose each time and the interval between two doses: 12 hours
GFR 10-30 ml/min/1.73m²: 25% of the normal dose each time and the interval between two doses: 12 hours
GFR < 10 ml/min/1.73m²: 25% of the normal dose, one-time only

Prevention of CMV infection after organ transplant:
GFR 50-80 ml/min/1.73m²: Adjustment not necessary
GFR 30-50 ml/min/1.73m²: 750 mg/m²/day in 2 doses
GFR 10-30 ml/min/1.73m²: 500 mg/m²/day in a single dose
GFR < 10 ml/min/1.73m²: 250 mg/m²/day in a single dose

Clinical consequences

Risk of neurological reactions, including confusion and hallucinations.
In clinical studies in immunocompromised patients, renal insufficiency, microangiopathic haemolytic anaemia and thrombocytopenia were reported when using high doses (8 g per day).
A ´case control study showed that the group of patients with neurological symptoms had a smaller average creatinine clearance and that the levels of aciclovir and the metabolite 9-carboxymethoxymethyl guanine were higher on average compared to the group of patients without neurological symptoms. This study also included people with a creatinine clearance of less than 10 ml/min.
If the trough level is insufficient, the antiviral effect may possibly not be sufficient; this can cause resistance.

Patients on dialysis

In haemodialysis, administer after the dialysis.

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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

Nausea and vomiting.
According FDA the side effects are the same as in adults, both the incidence and intensity.

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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.

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Interactions

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

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Nucleosides and nucleotides excl. reverse transcriptase inhibitors
J05AB01
J05AB04
J05AB14
Protease inhibitors
J05AE10
J05AE03
Nucleoside and nucleotide reverse transcriptase inhibitors
J05AF10
J05AF05
J05AF01
Non-nucleoside reverse transcriptase inhibitors
J05AG01
Neuraminidase inhibitors
J05AH02
Antivirals for treatment of HIV infections, combinations
J05AR02
J05AR10
Other antivirals
J05AX12
J05AX08
ANTIVIRALS FOR TREATMENT OF HIV INFECTIONS, COMBINATIONS
J05AR02
J05AR10
Antivirals for treatment of HCV infections
J05AP57
J05AP08
J05AP55

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References

  1. Hartwig NC, et al, Vademecum pediatrische antimicrobiele therapie, 2005
  2. Souza PM, et al, Bilateral herpetic keratoconjunctivitis., Ophthalmology, 2003, Mar;110(3), 493-6.
  3. Schwartz GS, Oral acyclovir for the management of herpes simplex virus keratitis in children, Ophthalmology, 2000, Feb;107(2), 278-82
  4. Nadal D, et al, An investigation of the steady-state pharmacokinetics of oral valacyclovir in immunocompromised children, J Infect Dis, 2002, Oct 15;186 Suppl 1, S123-30
  5. Zeng L, et al, Population pharmacokinetics of acyclovir in children and young people with malignancy after administration of intravenous acyclovir or oral valacyclovir, Antimicrob Agents Chemother, 2009, Jul;53(7), 2918-27
  6. Bomgaars L, et al, Valacyclovir and acyclovir pharmacokinetics in immunocompromised children, Pediatr Blood Cancer, 2008, Oct;51(4), 504-8
  7. Kimberlin DW, et al, Pharmacokinetics and safety of extemporaneously compounded valacyclovir oral suspension in pediatric patients from 1 month through 11 years of age, Clin Infect Dis, 2010, Jan 15;50(2), 221-8
  8. Eksborg S, et al, Pharmacokinetics of acyclovir in immunocompromized children with leukopenia and mucositis after chemotherapy: can intravenous acyclovir be substituted by oral valacyclovir?, Med Pediatr Oncol, 2002, Apr;38(4), 240-6
  9. Simon MW, et al, Pharmacokinetics and safety of valaciclovir in children with Epstein-Barr virus illness, Drugs R D, 2002, 3(6), 365-73
  10. Kimberlin DW., Herpes simplex virus infections in neonates and early childhood, Semin Pediatr Infect Dis, 2005, Oct;16(4), 271-81
  11. Spruance SL, et al, High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies, Antimicrob Agents Chemother, 2003, Mar;47(3), 1072-80
  12. GlaxoSmithKline BV, SpC Zelitrex (RCG 21719 en 18065) 07-04-2014, www.geneesmiddeleninformatiebank.nl
  13. Erard V et al. , One-year acyclovir prophylaxis for preventing varicella-zoster virus disease after hematopoietic cell transplantation: no evidence of rebound varicella-zoster virus disease after drug discontinuation., Blood., 2007 , Oct 15;110(8), 3071-7
  14. Kechagia IA et al., Extrapolation of valacyclovir posology to children based on pharmacokinetic modelling, Pediatr Infect Dis J., 2015 Dec, 34(12), 1342-8

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Changes

Changes