Sodium Valproate

Sodium Valproate

[1 vial for IV injection $42.58; 1 tablet 52 cents]

ADMINISTRATION ROUTES:

IV, PO, NG

ALTERNATIVE NAMES: Epilim

ICU INDICATIONS:

1. seizures and seizure prophylaxis

PRESENTATION AND ADMINISTRATION:

IV

Injection (vial) 400mg (powder) plus diluent (4ml for Injection). temperature. Prepare solutions immediately before use; reconstituted solution and solution prepared for infusion may be refrigerated for use within 24 hours For direct IV injection, add diluent (4ml) to vial. Shake gently to dissolve powder. Concentration of reconstituted solution is 95mg/ml. Give required dose over 3 to 5 minutes. For intermittent infusion, prepare as for direct IV injection then add required dose to 500ml of compatible IV fluid and infuse over a convenient period. Compatible with the following IV fluids: 0.9% normal saline 5% glucose Glucose and Sodium Chloride

PO / NG:

Crushable tablets: Epilim crushable 100mg tablets (white)

Enteric coated tablets: Epilim EC 200mg tablets (lilac)

Liquids: Epilim sugar free liquid (200mg/5ml); Epilim 200mg/5ml syrup Note: for NG administration, use liquid.

DOSAGE:

IV:

Store at room

If previous oral dose satisfactory, continue at the same dose using intermittent infusion. For commencement of therapy use 400-800mg (up to 10mg/kg) followed by a continuous or repeated infusion dose of up to a maximum of 2500mg/day.

PO:

Administered in 2 divided doses. Initial dose 600mg/day. Increase by 200mg/day at 3 day intervals until control achieved. Usual dose range 1000-2000mg/day. Maximum dose 2500mg/day

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

PO, IV:

5mg/kg 8-12 hourly oral; increase to a maximum of 20mg/kg 8-12 hourly

CLINICAL PHARMACOLOGY:

Sodium valproate is an anticonvulsant. The mechanisms by which valproate exerts its therapeutic effects have not been established. It has been suggested that its activity in epilepsy is related to increased brain concentrations of gamma-aminobutyric acid (GABA).

CONTRAINDICATIONS:

1. hypersensitivity  to sodium valproate

2. hepatic disease o rdysfunction

3. urea cycle disorders

WARNINGS

Hepatotoxicity

Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid. Experience has indicated that children under the age of 2 years are at a considerably increased risk of developing fatal hepatotoxicity and this medication should only be used in this group with consideration of this risk.

Pancreatitis

Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Urea Cycle Disorders (UCD)

Valproate sodium is contraindicated in patients with known urea cycle disorders.

Post-Traumatic Seizures

There is some evidence that valproate increases the risk of death compared to phenytoin when used for seizure prophylaxis after head injury. It should not be used for this indication. Use in pregnancy

Sodium valproate is teratogenic

PRECAUTIONS

General

Sodium Valproate is NOT indicated for toxicological seizures or seizures due to hypoglycaemia. Sodium Valproate may cause thrombocytopenia.

Laboratory Tests:

The relationship between plasma concentration and clinical response is not well documented. Some patients are well controlled with serum levels outside the therapeutic range. Serum levels should only be measured if there is a specific clinical indication.

Spec Collection: SST (Yellow) or Plain (Red)

Therapeutic Range: 300-600 umol/L (trough)

Clinical value: Used primarily to detect non-compliance or suspected toxicity

General Notes: Peak: 1-4 hr post dose.

Steady State: 2-3 days.

Half life: 7-9 hr.

Recommended sampling: Pre-dose (trough) Toxic: >800 umol/L

Drug/Laboratory Test Interactions:

None known

IMPORTANT DRUG INTERACTIONS FOR THE ICU

Reduce serum levels of valproate are seen when valproate is coadministered with carbapenems or rifampicin. The concomitant use of valproic acid and clonazepam may induce absence status in patients with a history of absence type seizures. The dose of lamotrigine should be reduced when coadministered with valproate. Serious skin reactions (such as Stevens-Johnson Syndrome and toxic epidermal necrolysis) have been reported with concomitant lamotrigine and valproate administration. In patients with epilepsy, there have been reports of breakthrough seizures occurring with the combination of valproate and phenytoin. The dosage of phenytoin should be adjusted as required by the clinical situation. In an in vitro study, valproate increased the unbound fraction of warfarin by up to 32.6%. The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. Other clinically significant drug interactions are possible.

ADVERSE REACTIONS

Body as a Whole

Chest Pain, Headache, Injection Site Inflammation & Pain

Cardiovascular System

Vasodilation, hypotension

Digestive System

Abdominal Pain, Diarrhoea, Nausea, Vomiting

Nervous System

Dizziness, Euphoria, Hyperaesthesia, Nervousness, Paresthesia, Somnolence, Tremor.

Respiratory System

Pharyngitis

Critical Care Drug Manual

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