Phenobarbitone

Phenobarbital(中文: 苯巴比妥), also known as phenobarbitone or phenobarb, is a medication of the barbiturate type. It is used to control all forms of epilepsy except absence seizures. It is also used as part of the emergency management of acute seizures including status epilepticus. It usually begins working within 5 minutes when used intravenously and 30 minutes when administered by mouth. Its effects last for between 4 hours and 2 days.

Pronunciation

Phenobarbitone 30mg

Phenobarbitone 60mg

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Phenobarbitone Tablet 30mg	PHEN08	P1S1S3
Phenobarbitone Tablet 60mg	PHEN09	P1S1S3

Mechanism of Action

Anticonvulsant medication. It binds to GABAa receptor subunits. Through this interaction, phenobarbitone increases the flow of chloride ions into the neuron which decreases the excitability of the post-synaptic neuron. Furthermore, direct blockade of excitatory glutamate signaling also contribute to the hypnotic/anticonvulsant effect.

Dosage

The dose should be adjusted to the needs of the individual patient to achieve control of seizures; this usually requires plasma concentrations of 15 to 40 micrograms/ml. However, plasma-drug concentration monitoring is less useful than with other drugs because tolerance occurs.

Epilepsy

By Mouth ADULT: 60 – 180 mg once daily, dose to be taken at night CHILD 1 month – 11 years: Initially 1 – 1.5 mg/kg twice daily, then Increased in steps of 2 mg/kg daily as required; Maintenance 2.5 – 4 mg/kg in 1 – 2 times daily CHILD 12 – 17 years: 60 – 180 mg once daily, dose to be taken at night

Status epilepticus

By intravenous injection ADULT: 10 mg/kg (max. per dose 1g), dose to be administered at a rate not more than 100 mg/minute, injection to be diluted 1 in 10 with water for injections. By slow intravenous injection CHILD 1 month – 11 years: Initially 20 mg/kg, dose to be administered at a rate no faster than 1 mg/kg/minute, then 2.5 – 5 mg/kg 1 -2 times a day CHILD 12 – 17 years: Initially 20 mg/kg (max. per dose 1g), dose to be administered at a rate no faster than 1 mg/kg/minute, then 300 mg twice daily

Side Effects

Adverse drug reactions associated with the use of topiramate include:

Very common (>10% incidence)	sedation hypnosis
Common (1-10% incidence)	Central nervous systems effects, such as dizziness, nystagmus and ataxia Hyperactivity in the elderly and in children hepatitis Impaired cognition Impaired memory Depression Prolonged use can occasionally result in folate deficiency At high doses typical barbiturate-induced respiratory depression may become severe
Rare (<0.1% of incidence)	Stevens-Johnson syndrome Suicidal ideation Toxic epidermal necrolysis

Phenobarbitone therapy

Overdose

Overdosage can prove fatal; toxic effects include:

• Coma
• Slow or shallow breathing, weak pulse
• Hypotension
• Renal failure

Pharmacokinetics

Oral bioavailability	Phenobarbitone is rapidly absorbed after oral doses.
Onset of action	Peak plasma concentrations occur 8 to 12 hours after oral doses.
Metabolism	Phenobarbitone is metabolized by the liver, and induces many isoenzymes of the cytochrome P450 system.
Elimination half-life	It is excreted primarily by the kidneys. It remains in the body for a very long term The elimination half-life is about 75 hours to 120 hours in adult. Phenobarbitone kinetics show considerable interindividual variation

Drug Management

Monitoring

• Plasma-phenobarbital concentration for optimum response is 15 – 40 mg/litre
• Long-term therapy has an adverse effect on Bone Mass Density. Suggest monitoring indices of bone health, and preventing falls in patients on long-term therapy
• changes in mood, the development or worsening depression, and/or any thoughts or behaviour of suicide.

Drug interaction

There are complex interactions between antiepileptics, and toxicity may be enhanced. Plasma monitoring is often advisable with combination therapy.

Drugs given with phenobarbitone	Potential Effects
Alcohol	Increased sedative effect
Antibiotics: METRONIDAZOLE, DOXYCYCLINE, CHLORAMPHENICOL, RIFAMPICIN	Phenobarbitone accelerates their metabolism of metronidazole (reduced effect)
Anticoagulants APIXABAN RIVAROXABAN
Phenobarbitone possibly reduces plasma concentration, recommends to monitor signs of thrombosis
Antidepressants PAROXETINE MIANSERIN TRICYCLICS	Phenobarbitone reduces their plasma concentration
Antifungals ITRACONAZOLE GRISEOFULVIN	Phenobarbitone reduces their plasma concentration
Antipsychotics HALOPERIDOL CHLORPROMAZINE ARIPIPRAZOLE CLOZAPINE	Phenobarbitone reduces their plasma concentration Avoid concomitant use or consider increasing the dose of antipsychotics
Anxiolytics and Hypnotics	Increased sedative effect
CICLOSPORIN	Phenobarbitone accelerates metabolism of CICLOSPORIN (reduced effect)
Corticosteroids	Phenobarbitone accelerates metabolism of CORTICOSTEROIDS (reduced effect)
OESTROGENS	Phenobarbitone accelerates metabolism of OESTROGENS (leading to reduced oral contraceptive effect, other contraceptive method must be used)
Thyroid Hormones	Phenobarbitone accelerates the metabolism of THYROID HORMONES (may increase dosage of thyroxine in hypothyroidism)