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Clinically important adverse drug reactions of AEDs

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Five commonest ADRs with AEDs

• Ataxia• Dizziness• Fatigue• Nausea• Somnolence

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Predictable Dose Dependent Reactions• Sedation – phenobarbitone,

primidone, benzodiazepines (all drugs to some extent)

• Nystagmus, ataxia, incoordination, dysarthria (cerebellar signs) – phenytoin, primidone, carbamazepine

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Nystagmus

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Nystagmus

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Unpredictable idiosyncratic reactions

• Aplastic anaemia, hepatotoxicity - Felbamate

• Stevens Johnsons syndrome - Lamotrigine

• Hepatotoxicity - Valproate• Bone marrow suppression -

Carbamazepine

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7Hepatic necrosis

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12Aplastic anaemia

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Chronic toxicity• Sexual dysfunction, Dupuytren’s

contracture – Phenobarbitone, primidone

• Coarse facies, gingival hyperplasia, hypertrichosis, megaloblastic anaemia, folate defieciency - Phenytoin

• Weight gain, polycystic ovary disease - Valproate

• Bradykinesia, parkinsonian syndrome - Ethosuximide

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14Dupuytren’s contracture

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Gingival hyperplasia

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Gum Hyperplasia - phenytoin

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Megaloblastic anemia Blood smear

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21Megaloblasts in marrow

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Delayed toxicity

• Neural tube defects (1% risk) - Valproate, Carbamazepine

• Increased risk of cleft lip and palate, cardiac anomalies, CNS anomalies – all drugs

• Fetal hydantoin syndrome - phenytoin

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Antiepileptic Therapy & Pregnancy• Antiepileptic medication should not be discontinued in pregnant epileptic women, for whom medication is necessary for prevention of major seizures.

• 4-6% of infants of mothers with epilepsy have malformations

• Most teratogenic – Valproate, phenytoin

• Spina bifida, neural tube defect – Valproate, carbamazepine

• Incidence of malformations greatest with phenytoin plus phenobarbitone compared to Phenobarbitone alone

• Phenytoin, Phenobarbitone, Primidone - Deficiency of vitamin K dependent clotting factor in newborn

• Folate supplementation 0.4mg/day

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Proconvulsant effects of AEDs

• Carbamazepine can induce Juvenile Myoclonic Epilepsy.

• Phenobarbitone can induce tonic seizures in children with Lennox Gastaut syndrome, can aggravate absence seizures.

• Ethosuximide worsens atonic seizures in children with juvenile myoclonic epilepsy.

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COMMONLY USED ANTIEPILEPTICS DURING PREGNANCY AND THEIR POTENTIAL TOXIC EFFECTS

Drug Potential fetal /neonatal effects

1. Carbamazepine Facial dysmorphism, neural tube

defects, hypoplasia of distal phalanges

2. Phenobarbital Neonatal withdrawal, neonatal coagulopathy

3. Phenytoin Facial clefting hypoplasia of distal

phalanges, hypertelorism, neonatal coagulopathy

4. Primidone Neonatal withdrawal, neonatal coagulopathy

5. Valproic acid Facial dysmorphism, neural tube defects

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Side effects of newer AEDs

Drug Common S.E. Rare S.E.Felbamate Anorexia, nausea,

insomnia, headacheAplastic anemia, Hepatic failure

Fosphenytoin Paraesthesia, pruritus, ataxia, nystagmus

Severe rash,

Steven Johnson’s Syndrome (SJS).

Gabapentin Drowsiness, fatigue, dizziness, nausea, ataxia

None known

Lamotrigine Rash, tremor, dizziness, nausea, headache, weight gain

Severe rash,

SJS.

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Cost of Common AEDs

Rs./tab Rs/day• Carbamazepine - 200mg 1.65 4.95• Phenytoin - 100mg 1.05 3.15• Phenobarbitone - 30mg 0.30 3.00• Sodium valproate - 200mg 1.90 14.25• Clonazepam - 0.5mg 1.30 20.80• Clobazam - 5mg 2.80 16.00• Lamotrigine - 25mg 2.75 22.00

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