Gabapentin

Generic name
Gabapentin
Brand name
ATC Code
N02BF01
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Gabapentin

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

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

The following farmacokinetic parameters were observed (Haig et al. 2001, Ouellet et al. 2001, Tallian et al. 2004):

  Single dose   Steady state
Age 1 mnd-4 years 5-12 years 1 months-13 years
Cmax (µg/ml) 3.7 ± 1.3 (10 mg/kg) 4.5 ± 1.2 (10 mg/kg) 2.6 ± 1.7 (mean 17 mg/kg/day)
Tmax (h) 2.1 ± 0.9 2.5 ± 0.9 1.6 ± 1.0
t½ (h) 4.3 ± 1.7 4.7 ± 0.6 5.5 ± 0.8
Cl/F (ml/min/kg) 6.0 (2.3-13.5) 4.0 (1.7-7.5) 8.3 ± 4.7 (2.0-18.7)
Vd/F (l/kg) 2.7 (1.07-6.26) 1.8 (1.08-2.90) 3.0 (2.5-4.1)

Young children have a higher renal clearance and a larger volume of distribution. Therefore young children may need higher doses. However it has not been demonstrated that the effect is predicted by the plasma concentration. Gabapentin dose should be adjusted individually based on tolerance and efficacy. 

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

Neuropathic pain and other neuropathic symptoms
  • Oral
    • 1 month up to 18 years

      • Days 1 and 2:     5 mg/kg/day in a single dose before going to bed
        Days 3 and 4: 10 mg/kg/day in 2 doses
        Day 5:                15 mg/kg/day in 3 doses.
        After Day 5, titrate depending on the effect. Maximum 35 mg/kg/day in 3 doses

        When discontinuing treatment: slowly secrease the dose over 1 week. 

        • The effect on neuropathic pain has been demonstrated in one study (Brown 2016) and in various case reports. In individual cases, gabapentin can provide a solution for neuropathic pain, when other options are not effective.
        • Gabapentin should be prescribed by a specialist with experience in the field of neuropathic pain in children. The dose must be determined individually.
Epilepsy
  • Oral
    • 3 years up to 12 years
      • Initial dose: 10 - 15 mg/kg/day in 3 doses.
      • Maintenance dose: Increase the initial dose depending on effect over approximately 3 days to 15 - 50 mg/kg/day in 3 doses. Max: 70 mg/kg/day.

      • The effective dose is generally between 25 and 40 mg/kg/day. Younger children may need higher doses. The dosing interval between two doses should not exceed 12 hours.

        When discontinuing treatment: slowly secrease the dose over 1 week. 

    • 12 years up to 18 years

      • Initial dose:
        Day 1:300 mg/day in 1 dose
        Day 2: 600 mg/day in 2 doses
        Day 3: 900 mg/day in 3 doses.
        Maintenance dose: further increase of the dose up to 3600 mg/day may be indicated based on efficacy.

        When discontinuing treatment: slowly secrease the dose over 1 week. 

      • The dosing interval between two doses must not exceed 12 hours.
        Alternative tiatration regimen: start 900 mg / day in 3 doses, depending on the effect, increase if necessary every 2-3 days by 300 mg / day to a maximum of 3600 mg / day.

Renal impaiment in children > 3 months

  • When the creatinine clearance is 50-80 ml/min/1.73m²:   66.7% of the normal dose each time at a dosage interval of 8 hours
  • When the creatinine clearance is 30-50 ml/min/1.73m²: 33% of the normal dose each time at a dosage interval of 8 hours
  • When the creatinine clearance is 10-30 ml/min/1.73m²: 16.7% of the normal dose each time at a dosage interval of 8 hours
  • Where the creatinine clearance is < 10 ml/min/1.73m²: generalized recommendations cannot be given

1. Phasing-in stage: adjust the dose to be given each time, frequency as normal for the phasing-in stage
2. If the clearance is above 60 ml/min, the same dose may be adopted as for normal renal function. This is in line with the American product information.
3. Except while phasing in, 3 times daily administration of gabapentin is preferred to achieve a stable level. However, the half-life increases, so that gabapentin can also be given in 1 or 2 doses in the maintenance phase in the event of reduced renal function.

Information
In reduced renal function, half-life and AUC of gabapentin increase and the plasma clearance and renal clearance decrease. The risk of side effects is elevated as a result

Clinical consequences
side-effects include sleepiness, dizziness, ataxia, tiredness and fever.

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

Common (1-10%): respiratory tract infection, middle ear infection, convulsions and bronchitis. Aggressive behavior and hyperkinesia (SmPC).

Furthermore, hostility, emotional lability and an increase in epileptic seizures have been reported (Appleton 1999 and 2001, Mills JKA 2012, Tallian 2004, SmPC).

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

Target for therapeutic drug monitoring: through level 2-20 mg/L (NVZA TDM Gabapentine)

The effects of long-term treatment for epilepsia (longer than 36 weeks) with gabapentin on the learning ability, intelligence and development of children and adolescents have not been sufficiently studied. The benefits of such extended therapy must therefore be weighed against the potential risks.

Interactions

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

OTHER ANALGESICS AND ANTIPYRETICS

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

Anilides
N02BE01
N02BE51

References

  1. Gallowy KS et al, Pain and symptom control in terminally ill children, Pediatr Clin North Am, 2000, 47, 711-46.
  2. Haig GM, et al, Single-dose gabapentin pharmacokinetics and safety in healthy infants and children, J Clin Pharmacol, 2001, 41, 507-14
  3. Hauer JM, et al, Gabapentin successfully manages chronic unexplained irritability in children with severe neurologic impairment., Pediatrics, 2007, 119, 519-22.
  4. Lauder GR, et al, Neuropathic pain following multilevel surgery in children with cerebral palsy: a case series and review, Paediatr Anaesth, 2005, 15, 412-20
  5. Tallian KB, et al, Pharmacokinetics of gabapentin in paediatric patients with uncontrolled seizures., J Clin Pharm Ther, 2004, 29, 511-5
  6. Drs.T.G. de Leeuw (anaesthesioloog), Expert opinion
  7. Phizer BV, SmPC Neurontin (RVG 22481) 18 sept 2014, Geraadpleegd 25 okt 2014
  8. Gatti G et al., Plasma gabapentin concentrations in children with epilepsy: influence of age, relationship with dosage, and preliminary observations on correlation with clinical response., Ther Drug Monit., 2003, 25(1), 54-60
  9. Mills JKA et al., Retention rate of gabapentin in children with intractable epilepsies at 1 year., Seizure, 2012, 21, 28-31
  10. Anghelescu DL et al., Neuropathic pain during treatment for childhood acute lymphoblastic leukemia., Pediatr Blood Cancer., 2011, 57(7), 1147-53
  11. Appleton R et al., Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week multicenter, double-blind, placebo-controlled study., Epilepsia., 1999, 40, 1147-1154
  12. Nonoda Y et al., The efficacy of gabapentin in children of partial seizures and the blood levels., Brain Dev, 2013, 36(3), 194-202
  13. Hauer JM et al., Treatment with gabapentin associated with resolution of apnea in two infants with neurologic impairment., J Palliat Med., 2013, Apr;16(4), 455-8
  14. Edwards L et al. , Gabapentin Use in the Neonatal Intensive Care Unit., J Pediatr., 2016, 169, 310-2
  15. Boesen ML et al. , Newborn with severe epidermolysis bullosa: to treat or not to treat? , BMJ Case Rep., 2016
  16. Allegaert K, et al., Gabapentin as part of multimodal analgesia in a newborn with epidermolysis bullosa. , Paediatr Anaesth., 2010, 20(10), 973-3
  17. Haney AL et al., Gabapentin therapy for pain and irritability in a neurologically impaired infant., Pharmacotherapy, 2009, 29(8), 997-1001
  18. Brown SC et al., A randomized controlled trial of amitriptyline versus gabapentin for complex regional pain syndrome type I and neuropathic pain in children., Scand J Pain, 2016, 13, 156-63
  19. Shapiro DY et al., Gabapentin as add-on therapy for refractory partial seizures in children 1-36 months of age: a novel short-term, placebo-controlled trial., Epilepsia., 2000, 41(7), 106
  20. Appleton R et al., Gabapentin as add-on therapy with refractory partial seizures: a 24-week, multicenter, open-label study., Dev Med Child Neurol., 2001, 43(4), 269-73
  21. Ouellet D et al., Population pharmacokinetics of gabapentin in infants and children, Epilepsy Res , 2001, 47(3), 229-41
  22. Boesen ML et al., Newborn with severe epidermolysis bullosa: to treat or not to treat?, BMJ Case Rep., 2016
  23. Edwards L et al., Gabapentin Use in the Neonatal Intensive Care Unit., J Pediatr., 2016, 169, 310-2
  24. Allegaert K, et al., Gabapentin as part of multimodal analgesia in a newborn with epidermolysis bullosa., Paediatr Anaesth., 2010, 20(10), 973-3
  25. Ouellet D et al., Population pharmacokinetics of gabapentin in infants and children, Epilepsy Res, 2001, 47(3), 229-41

Changes

Therapeutic Drug Monitoring


Overdose