SODIUM VALPROATE (VALPROIC ACID)

Antiepileptic medicine

Dosage Forms

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Enteric coated tablet

500 mg

Tablet (crushable)

100 mg

Syrup

200 mg/5 ml

Uses

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  • Epilepsy
  • Manic episodes associated with bipolar disorder
  • Nodding disease

Dose and Duration

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To be taken after a meal
Treatment of epilepsy

Adult and child over 12 years: 600 mg daily in 2 divided doses, increased by 200 mg every 3 days until control is achieved. Usual dose range 1000–2000 mg daily i.e. 20–30 mg/kg daily (max 2500 mg per day).

Child 1 month–12 years: 10–15 mg/kg (max 600 mg) daily in 1–2 divided doses; usual maintenance dose 25–30 mg/kg daily in 2 divided doses.

Neonate: 20 mg/kg once daily; usual maintenance dose 10 mg/kg every 12 hours.

Manic episodes associated with bipolar disorder

Adult: 750 mg daily in 2–3 divided doses, increased according to response, usual dose 1–2 g daily.

Contra-indications

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  • Family history of severe hepatic dysfunction
  • Acute porphyria
  • Active liver disease
  • Pancreatitis
  • Hypersensitivity

Side Effects

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  • Nausea, gastric irritation, diarrhoea
  • Weight gain
  • Thrombocytopenia, anaemia
  • Transient hair loss
  • Liver damage with increased liver enzymes
  • Tremor, extrapyramidal disorder
  • Stupor, somnolence, memory impairment, headache
  • Convulsion
  • Nystagmus
  • Hyponatremia
  • Hypersensitivity
  • Dysmenorrhoea
  • Haemorrhage
  • Deafness

Interactions

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  • Amitriptyline (antagonism of the anticonvulsant effect)
  • Chloroquine (possibly increased risk of convulsions)
  • Chlorpromazine (antagonism of anticonvulsant effect)
  • Clomipramine (antagonism of anticonvulsant effect)
  • Fluphenazine (antagonism of anticonvulsant effect)
  • Mefloquine (antagonism of anticonvulsant effect)
  • Olanzapine (increased risk of side effects)
  • Orlistat (possible increased risk of convulsions)
  • Cimetidine (increased plasma concentration of valproate)
  • Lamotrigine (increased concentration of lamotrigine)
  • Haloperidol (antagonism of anticonvulsant effect)
  • Imipenem (reduced plasma concentration of valproate)

Patient Instructions

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  • Do not remove tablets from the foil until immediately before they are to be taken
  • The crushable tablet can be crushed and mixed with cold soft food or drink and taken immediately
  • Take your medication after a meal
  • The enteric coated tablet should not be crushed or chewed but swallowed whole with a glass of water
  • Seek immediate medical attention if blood or liver disorders signs such as loss of seizure control, weakness, anorexia, oedema, vomiting, abdominal pain, drowsiness, jaundice, or spontaneous bruising or bleeding develop
  • Seek immediate medical attention if symptoms of pancreatitis such as abdominal pain, nausea and vomiting develop

Pregnancy

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  • Can be used

Breast-feeding

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  • Can be used

⚠️ Caution

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  • Avoid sudden withdrawal. Reduce dose gradually over at least 1 month when stopping valproate
  • Valproate is associated with the high risk congenital malformations and growth delays when used in the 1ˢᵗ and 3ʳᵈ trimesters. Only prescribe in pregnancy if there are no safer alternatives and after careful discussion of risks with patient. Risk of teratogenicity is greater if more than one antiepileptic is used; folic acid may reduce risk of neural tube defects. Give effective contraception in women of child-bearing potential.
  • Reduce dose in mild to moderate renal impairment
  • Avoid use in hepatic impairment due to risk of hepatotoxicity and hepatic failure usually in the first 6 months
  • Monitor liver function before and during first 6 months of therapy in patients most at risk of hepatic impairment
  • Care should be taken when switching between different brands of valproate in the treatment of epilepsy
  • Discontinue use if patient develops pancreatitis
  • Assess risk of bleeding before starting, and also before major surgery or anticoagulant therapy
  • Valproate may cause false positive urine ketone test