BNF for Children 2011-2012

224 4.8.1 Control of the epilepsies BNFC 2011–20124 Central nervous systemPhenobarbital (Non-proprietary) 3Tablets, phenobarbital 15 mg, net price 28-tab pack =95p; 30 mg, 28-tab pack = 96p; 60 mg, 28-tab pack =71p. Label: 2, 8, counselling, driving (see notes above)Elixir, phenobarbital 15 mg/5 mL in a suitable flavouredvehicle, containing alcohol 38%, net price100 mL = 78p. Label: 2, 8, counselling, driving (seenotes above)Note Some hospitals supply alcohol-free formulations ofvarying phenobarbital strengthsInjection, phenobarbital sodium 15 mg/mL, net price1-mL amp = £1.64; 30 mg/mL, 1-mL amp = £2.04;60 mg/mL, 1-mL amp = £2.14; 200 mg/mL, 1-mLamp = £2.00Excipients include propylene glycol (see Excipients, p. 2)Note Must be diluted before intravenous administration (seeAdministration)PRIMIDONECautions see Phenobarbital; interactions: see p. 215and Appendix 1 (primidone)Hepatic impairment reduce dose, may precipitatecomaRenal impairment see PhenobarbitalPregnancy see PhenobarbitalBreast-feeding see PhenobarbitalSide-effects see Phenobarbital; also nausea, visualdisturbances; less commonly vomiting, headache,dizziness; rarely psychosis, lupus erythematosus,arthralgia; also reported Dupuytren’s contracturePharmacokinetics monitor plasma concentrationsof derived phenobarbital. Optimum range as forphenobarbitalIndication and doseAll forms of epilepsy except absence seizures(but see notes above). By mouthChild under 2 years initially 125 mg daily atbedtime, increased by 125 mg every 3 daysaccording to response; usual maintenance, 125–250 mg twice dailyChild 2–5 years initially 125 mg daily at bedtime,increased by 125 mg every 3 days according toresponse; usual maintenance, 250–375 mg twicedailyChild 5–9 years initially 125 mg daily at bedtime,increased by 125 mg every 3 days according toresponse; usual maintenance, 375–500 mg twice adayChild 9–18 years initially 125 mg daily at bedtime,increased by 125 mg every 3 days to 250 mgtwice daily, then increased according to responseby 250 mg every 3 days to max. 750 mg twice dailyMysoline c (Acorus) ATablets, scored, primidone 50 mg, net price 100-tabpack = £12.60; 250 mg, 100-tab pack = £12.60.Label: 2, 8, counselling, driving (see notes above)PhenytoinPhenytoin is effective for tonic-clonic, focal, and neonatalseizures but it may worsen myoclonus. It has anarrow therapeutic index and the relationship betweendose and plasma-drug concentration is non-linear; smalldosage increases in some children may produce largeincreases in plasma concentration with acute toxic sideeffects.Similarly, a few missed doses or a small changein drug absorption may result in a marked change inplasma concentration. Monitoring of plasma concentrationimproves dosage adjustment. Symptoms of phenytointoxicity include nystagmus, diplopia, slurredspeech, ataxia, confusion, and hyperglycaemia.Phenytoin may cause coarsening of the facial appearance,acne, hirsutism, and gingival hyperplasia and somay be particularly undesirable in adolescent patients.When only parenteral administration is possible,fosphenytoin (section 4.8.2), a pro-drug of phenytoin,may be convenient to give. Whereas phenytoin shouldbe given intravenously only, fosphenytoin may also begiven by intramuscular injection.PHENYTOINCautions see notes above; cross-sensitivity reportedwith cabamazepine; avoid abrupt withdrawal; HLA-B*1502 allele in individuals of Han Chinese or Thaiorigin – avoid unless essential (increased risk of Stevens–Johnsonsyndrome); manufacturer recommendsblood counts (but evidence of practical value uncertain);consider vitamin D supplementation in patientsthat are immobilised for long periods or who haveinadequate sun exposure or dietary intake of calcium;enteral feeding (interrupt feeding for 2 hours beforeand after dose; more frequent monitoring may benecessary); avoid in acute porphyria (section 9.8.2);interactions: see p. 215 and Appendix 1 (phenytoin)Blood or skin disorders Children and their carers should betold how to recognise signs of blood or skin disorders, andadvised to seek immediate medical attention if symptomssuch as fever, rash, mouth ulcers, bruising, or bleedingdevelop. Leucopenia which is severe, progressive, or associatedwith clinical symptoms requires withdrawal (ifnecessary under cover of a suitable alternative)Hepatic impairment reduce dosePregnancy changes in plasma-protein binding makeinterpretation of plasma-phenytoin concentrationsdifficult—monitor unbound fraction; see alsoPregnancy, p. 216Breast-feeding small amounts present in milk, but notknown to be harmful; see also Breast-feeding, p. 217Side-effects nausea, vomiting, constipation; drowsiness,insomnia, transient nervousness, tremor,paraesthesia, dizziness, headache, anorexia; gingivalhypertrophy and tenderness (maintain good oralhygiene); rash (discontinue; if mild reintroduce cautiouslybut discontinue immediately if recurrence),acne, hirsutism, coarsening of facial appearance;rarely hepatoxicity (discontinue immediately and donot readminister), peripheral neuropathy, dyskinesia,lymphadenopathy, osteomalacia (see Cautions), blooddisorders (including megaloblastic anaemia, leucopenia,thrombocytopenia, and aplastic anaemia),polyarteritis nodosa, lupus erythematosus, Stevens-Johnson syndrome, and toxic epidermal necrolysis;also reported polyarthropathy, pneumonitis, interstitialnephritis; suicidal ideationPharmacokinetics therapeutic plasma-phenytoinconcentrations reduced in first 3 months of lifebecause of reduced protein bindingTrough plasma concentration for optimumresponse:Neonate–3 months, 6–15 mg/litre (25–60 micromol/litre)