ADMINISTRATION ROUTES:
IV, PO
ALTERNATIVE NAMES:
Phenobarbital
ICU INDICATIONS:
- Status epilepticus
Treatment of status epilepticus in children should follow the Starship protocol
PRESENTATION AND ADMINISTRATION:
IV:
200 mg in 1 mL of phenobarbitone
For direct IV injection, dilute dose to at least ten times its volume with water for injection.
Inject slowly at a rate not exceeding 100 mg/min
Dilute immediately before use. Do not store diluted solution. Do not use any solution that contains a precipitate or is more than slightly discoloured.
May be given into side arm of an infusion with any of the following fluids: 0.9% sodium chloride, Hartmanns, 5% and 10% dextrose, Glucose and sodium chloride
Store at room temperature. Protect from light. Phenobarbitone is a controlled drug and is stored as such.
IM:
May be given IM but no more than 5 mL of solution at any one site
PO:
Tablets:
Phenobarbitone 15 mg and 30 mg tablets (white)
Oral Liquid:
Phenobarbitone oral liquid 10 mg/mL
DOSAGE:
IV:
Loading dose:
15 mg/kg (max 1 g) given at 100 mg/min
Can repeat loading dose to max 30 mg/kg if seizures continue
Maintenance dose:
2 - 3 mg/kg/day OD or divided BD
PO:
Maintenance dose:
300 mg OD or divided
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose in renal impairment
| GFR (ml/min) | DOSE |
|---|---|
| <10 | reduce dose by 25-50% |
| 10-20 | dose as in normal renal function; avoid very large doses |
| >20 | dose as in normal renal function |
Dose in renal replacement therapy
| MODALITY | DOSE |
|---|---|
| CAPD | reduce dose by 25-50% |
| HD | reduce dose by 25-50% |
| CVVHDF | reduce dose by 25-50% |
DOSAGE IN PAEDIATRICS:
IV:
20 - 30 mg/kg (max 1 g) over 15 min
CLINICAL PHARMACOLOGY:
Barbiturates are nonselective central nervous system (CNS) depressants which are primarily used as sedative hypnotics. They are also anticonvulsants in subhypnotic doses. Phenobarbitone stimulates inhibitory GABA-A receptors & inhibits AMPA-type glutamate receptors. It has a long half-life at around 80 hours, but may vary between 50 - 140 hours. It is around 50% protein bound and primarily metabolised in the liver. Approx 25% may be excreted in urine unchanged.
CONTRAINDICATIONS:
- Known barbiturate sensitivity
- Porphyria
- Significant hepatic impairment
- Nephritic syndrome
WARNINGS:
IV Administration
Rapid administration may cause respiratory depression, apnea, laryngospasm, or vasodilation with fall in blood pressure. Do not administer at a rate exceeding 100 mg/min.
PRECAUTIONS:
General:
Parenteral solutions of barbiturates are highly alkaline. Extreme care should be taken to avoid perivascular extravasation or intra-arterial injection. Extravascular injection may cause local tissue damage with subsequent necrosis. Consequences of intra-arterial injection may vary from transient pain to gangrene of the limb. Any complaint of pain in the limb warrants stopping the injection.
Laboratory Tests:
No tests in addition to routine ICU tests are indicated. If serum levels are measured, the recommended trough range for seizure prevention is 15 - 40 mcg/mL. Mild toxicity may be seen at > 50 mcg/mL, progressing to severe at > 65 mcg/mL.
Drug/Laboratory Test Interactions:
None noted
IMPORTANT DRUG INTERACTIONS IN ICU:
Warfarin
Phenobarbital lowers the plasma levels of warfarin and causes a decrease in anticoagulant activity as measured by the prothrombin time.
Corticosteroids
Barbiturates appear to enhance the metabolism of exogenous corticosteroids, probably through the induction of hepatic microsomal enzymes. Patients stabilised on corticosteroid therapy may require dosage adjustments if barbiturates are added to or withdrawn from their dosage regimen.
Phenytoin, Sodium Valproate
The effect of barbiturates on the metabolism of phenytoin appears to be variable. Some investigators report an accelerating effect, while others report no effect. Because the effect of barbiturates on the metabolism of phenytoin is not predictable, phenytoin and barbiturate blood levels should be monitored more frequently if these drugs are given concurrently. Sodium valproate appear to decrease barbiturate metabolism; therefore, barbiturate blood levels should be monitored and appropriate dosage adjustments made as indicated.
Central Nervous System Depressants
The concomitant use of other central nervous system depressants, including other sedatives or hypnotics, antihistamines, tranquillisers, or alcohol, may produce additive depressant effects.
ADVERSE REACTIONS:
Body as a Whole:
Hypersensitivity reactions (angioedema, skin rashes, exfoliative dermatitis), fever
Nervous System:
Agitation, headache, confusion, hyperkinesia, ataxia, CNS depression, nightmares, nervousness, psychiatric disturbance, hallucinations, insomnia, anxiety, dizziness, thinking abnormality
Respiratory System:
Hypoventilation, apnea
Cardiovascular System:
Bradycardia, hypotension, syncope
Digestive System:
Nausea, vomiting, constipation, liver damage
Haematological System:
Megaloblastic anaemia following chronic phenobarbitone use