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

Interactions
PK
Renal impairment
References

Sildenafil

Generic name
Sildenafil
Brand name
ATC Code
G04BE03

Pharmacokinetics in children

Tmax = approx. 1 hour

Cmax: after 20 mg oral: 49, 104 and 165 ng/ml for patients of 70, 20 and 10 kg respectively
Cmax: after 10 mg given orally: 24, 53 and 85 ng/ml for patients of 70, 20 and 10 kg respectively

T½ (children 10-70 kg) = 4.2-4.4 hours

Neonates (intravenous):
Large inter-individual variability.
Clearance: 0.84 l/h (~8.05 l/h/70 kg) and 2.58 l/h (~24.7 l/h/70 kg) at 1 day old and 7 days old respectively.
Total volume of distribution: 22.4 l (~456 l/70 kg)
T½: 55.9 h (1 day old) and 47.7 h (7 days old)

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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

Pulmonary arterial hypertension
  • Oral
    • 1 month up to 18 years
      • 1.5 - 6 mg/kg/day in 3 doses. Max: 8 mg/kg/day. Titrate the dose depending on the effect.

      • Caution:
        The dosage above is the most widely used, effective dosage in studies. However, Pfizer has issued a safety warning for the use of doses higher than the authorized doses (30 mg in 3 doses in children ≤ 20 kg and 60 mg in 3 doses in children > 20 kg), due to the increased incidence of mortality observed during studies. A direct relationship with the use of sildenafil has however not been established

  • Intravenous
    • Premature neonates: Gestational age 34 weeks up to 37 weeks
      • Initial dose: ONLY IN THE ACUTE PHASE   0.4 mg/kg/dose, continuous infusion over 3 hours.
      • Maintenance dose: 1.6 mg/kg/day, continuous infusion.

      • Sildenafil should be prescribed by paediatric cardiologists, intensive care specialists or neonatologists who are properly familiar with the use of this drug in children.

    • Term neonate
      • Initial dose: 0.4 mg/kg/dose, continuous infusion over 3 hours.
      • Maintenance dose: 1.6 mg/kg/day, continuous infusion.

      • Sildenafil should be prescribed by paediatric cardiologists, intensive care specialists or neonatologists who are properly familiar with the use of this drug in children.

    • Term neonate
      • Initial dose: 0.4 mg/kg/dose, continuous infusion over 3 hours.
      • Maintenance dose: 1.6 mg/kg/day, continuous infusion.

      • Sildenafil should be prescribed by paediatric cardiologists, intensive care specialists or neonatologists who are properly familiar with the use of this drug in children.
Chronic Lung Disease (CLD)
  • Oral
    • Premature neonates: Gestational age < 37 weeks
      • Initial dose: 1.5 mg/kg/day in 3 doses.
      • Maintenance dose: 0.5 - 6 mg/kg/day in 3 doses.
    • Premature neonates: Gestational age < 37 weeks
      [26]
      • Initial dose: 1.5 mg/kg/day in 3 doses.
      • Maintenance dose: 0.5 - 6 mg/kg/day in 3 doses.

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Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

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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

Vomiting, nausea, abdominal pain, dyspepsia and coughing, headaches, flushing, muscle ache, diarrhoea, changes in vision, increased erection, hypotension, pyrexia, infection of the upper respiratory tract, bronchitis, pharyngitis, runny nose, pneumonia and bronchopneumonia, rhinitis, influenza, epistaxis, cardiac failure, right ventricular failure, viral or other gastroenteritis, fainting, chest pain, tooth cavities, cardiogenic shock, urinary tract infection, dyspnoea, haemoptysis, cardiac arrest, pleural effusion, convulsions, coronary artery disease, reduced tolerance to exertion, hypoxia, reduced oxygen saturation, pulmonary bleeding, respiratory failure and stridor.

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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

In pulmonary hypertension (especially resulting from a connective tissue disease) an increased risk of bleeding can occur when vitamin K antagonists are already used. In children with pulmonary hypertension who use a dosage higher than the recommended dose in increase in the number of fatalities was observed. When sudden vision disorders occur, stop the treatment and immediately have a specialist eye examination done. Sildenafil also inhibits PD-6 in addition to PD-5 in the retina. Care is recommended in premature infants due to an increased risk of retinopathies

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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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Acidifiers
G04BA01
Drugs for urinary frequency and incontinence
G04BD04
G04BD04
G04BD06
G04BD08
G04BD07
G04BD09
Drugs used in erectile dysfunction
G04BE08
Other urologicals
G04BX16
OTHER UROLOGICALS
G04BX16

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References

  1. Baquero H, et al., Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study, Pediatrics, 2006, 117, 1077-83
  2. Leibovitch L, et al., Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension., Drugs, 2007, 67, 57-73
  3. Namachivayam P, et al., Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children., Am J Respir Crit Care Med, 2006, 174, 1042-7
  4. Noori S, et al., Cardiovascular effects of sildenafil in neonates and infants with congenital diaphragmatic hernia and pulmonary hypertension., Neonatology, 2007, 91, 92-100
  5. Shah PS, et al., Sildenafil for pulmonary hypertension in neonates., Cochrane Database Syst Rev, 2007, 18, CD005494
  6. Travadi JN, et al., Phosphodiesterase inhibitors for persistent pulmonary hypertension of the newborn: a review., Pediatr Pulmonol, 2003, 36, 529-35
  7. Nemoto S, et al, Oral sildenafil for persistent pulmonary hypertension early after congenital cardiac surgery in children, Eur J Cardiothorac Surg, 2010, Jul;38(1), 71-7
  8. Reinhardt Z, et al, Sildenafil in the management of the failing Fontan circulation, Cardiol Young, 2010, Oct;20(5), 522-5
  9. Apitz C, et al, Pharmacokinetic and hemodynamic responses to oral sildenafil during invasive testing in children with pulmonary hypertension, J Am Coll Cardiol, 2010, Apr 6;55(14), 1456-62
  10. Uhm JY, et al, Postoperative use of oral sildenafil in pediatric patients with congenital heart disease, Pediatr Cardiol, 2010, May;31(4), 515-20
  11. Huddleston AJ, et al, Sildenafil for the treatment of pulmonary hypertension in pediatric patients, Pediatr Cardiol, 2009, Oct;30(7), 871-82
  12. Spillers J., PPHN: is sildenafil the new nitric? A review of the literature, Adv Neonatal Care, 2010, Apr;10(2), 69-7
  13. Kehat R, et al, Ocular findings of oral sildenafil use in term and near-term neonates, J AAPOS, 2010, Apr;14(2), 159-62
  14. Ahsman MJ, et al, Sildenafil exposure in neonates with pulmonary hypertension after administration via a nasogastric tube, Arch Dis Child Fetal Neonatal Ed, 2010, Mar;95(2), F109-14
  15. Vargas-Origel A, et al, The use of sildenafil in persistent pulmonary hypertension of the newborn, Am J Perinatol, 2010, Mar;27(3), 225-30
  16. Mourani PM, et al, Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease., J Pediatr., 2009, Mar;154(3), 379-84, 84 e1-2
  17. Mukherjee A, et al, Population pharmacokinetics of sildenafil in term neonates: evidence of rapid maturation of metabolic clearance in the early postnatal period., Clin Pharmacol Ther., 2009, Jan;85(1), 56-63
  18. Pfizer Limited, SPC Revatio (EU/1/05/318/001, EU/1/05/318/002 en EU/1/05/318/003) 03-04-2012, www.geneesmiddeleninformatiebank.nl
  19. Beghetti M, et al, Sildenafil for the treatment of pulmonary hypertension in children, Expert Rev Cardiovasc Ther., 2014, Oct;12(10), 1157-84
  20. Steinhorn RH, et al, Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension., J Pediatr, 2009, Dec;155(6), 841-7
  21. Maxey DM, et al, Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients., Pediatr Cardiol, 2013, Oct;34(7), 1628-36
  22. Stocker C, et al, Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery, Intensive Care Med, 2003, 29, 1996-2003
  23. Schulze-Neick I, et al, Intravenous Sildenafil Is a Potent Pulmonary Vasodilator in Children With Congenital Heart Disease, Circulation, 2003, 108[suppl II], II-167-II-173
  24. Lammers AE, et al, Intravenous sildenafil as an effective treatment of pulmonary hypertensive crises during acute intestinal malabsorption, Cardiol Young, 2006, 16, 84-6
  25. Fraisse A, et al, Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease, Intensive Care Med., 2011, 37, 502-9
  26. Werkgroep Neonatale Farmacologie NVK sectie Neonatologie, Expert opinie, 28 maart 2018
  27. Cochius-den Otter SCM, et al., Pharmacokinetic modeling of intravenous sildenafil in newborns with congenital diaphragmatic hernia., Eur J Clin Pharmacol., 2020, Feb;76(2), 219-227.

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