Phenobarbital Sopharma

The treatment and control of all forms of epilepsy, except absence seizures. Phenobarbital Sopharmarbital should only be used in the treatment of febrile convulsions in exceptional circumstances.

Adults: 60-180mg at night

Child: 5-8mg/kg daily

Elderly: Phenobarbital Sopharmarbital clearance diminishes in the elderly. Therefore the dose of Phenobarbital Sopharmarbital is usually lower in elderly patients.

The dose of Phenobarbital Sopharmarbital should be adjusted to meet the needs of individual patients. This usually requires plasma concentration of 15 to 40 micrograms/ml (65 to 170 micromoles/litre).

Method of Administration

For oral administration

Phenobarbital Sopharmarbital should not be given to patients with:

- Known hypersensitivity to Phenobarbital Sopharmarbital, other barbiturates or other ingredients in the tablet

- Acute intermittent porphyia

- Severe respiratory depression

- Severe renal or hepatic impairment

Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomized placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behavior. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Phenobarbital Sopharmarbital.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behavior emerge.

Steven-Johnson syndrome and toxic epidermal necrolysis

Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of Phenobarbital Sopharmarbital. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment.

If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present, Phenobarbital Sopharmarbital treatment should be discontinued. The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis.

If the patient has developed SJS or TEN with the use of Phenobarbital Sopharmarbital, Phenobarbital Sopharmarbital must not be re-started in this patient at any time.

Care should be used in the following situations:

- Patients with the rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose - galactose malabsorption should not take this medicine

- Respiratory depression (avoid if severe)

- Young, debilitated or senile patients

- Renal impairment

- Existing liver disease

- Sudden withdrawal should be avoided as severe withdrawal syndrome (rebound insomnia, anxiety, tremor, dizziness, nausea, fits and delirium) may be precipitated

- Acute chronic pain - paradoxical excitement may be induced or important symptoms masked.

- Prolonged use may result in dependence of the alcohol-barbiturate type. Care should be taken in treating patients with a history of drug abuse or alcoholism.

Phenobarbital Sopharmarbital may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Patients should be advised to make sure they are not affected before undertaking any potentially hazardous tasks.

- Blood and the lymphatic system disorders: megaloblastic anaemia (due to folate deficiency), agranulocytosis, thrombocytopenia.

- Musculoskeletal and connective tissue disorders: Dupuytren's contracture, frozen shoulder, arthralgia, osteomalacia, rickets.

There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with Phenobarbital Sopharmarbital. The mechanism by which Phenobarbital Sopharmarbital affects bone metabolism has not been identified.

- Reproductive and breast disorders: Peyronie's disease.

- Psychiatric disorders: paradoxical reaction (unusual excitement), hallucinations, restlessness and confusion in the elderly, mental depression, memory and cognitive impairment, drowsiness, lethargy.

- Nervous system disorders: hyperactivity, behavioural disturbances in children, ataxia, nystagmus.

- Cardiac disorders: hypotension.

- Respiratory disorders: respiratory depression.

- Hepato-bilary: hepatitis, cholestasis.

- Skin and subcutaneous tissue disorders: allergic skin reactions (maculopapular morbilliform or scarlatiniform rashes), other skin reactions such as exfoliative dermatitis, erythema multiforme.

Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported.

Frequency: very rare

- General disorders and administration site conditions: antiepileptic hypersensitivity syndrome (features include fever, rash, lymphadenopathy, lymphocytosis, eosinophilia, haematological abnormalities, hepatic and other organ involvement including renal and pulmonary systems which may become life threatening).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard

Toxicity varies between patients; tolerance will develop with chronic use. Features of poisoning are to be expected after ingestion of 1g in adults.

Features:

Drowsiness, dysarthria, ataxia, nystagmus and disinhibition. There may also be coma, cardiovascular collapse, cardiac arrest, hypotension, hypotonia, hyporeflexia, hypothermia, hypotension and respiratory depression.

Barbiturates decrease gut motility, which may lead to slow onset and worsening of symptoms or cyclical improvement and worsening of symptoms.

Management:

Consider activated charcoal (50g for an adult, 10-15g for a child under 5 years) if more than 10mg/kg body weight of Phenobarbital Sopharmarbital has been ingested within 1 hour, provided the airway can be protected. Repeat dose activated charcoal is the best method of enhancing elimination of Phenobarbital Sopharmarbital in symptomatic patients. In severe hypotension dopamine or dobutamine can be used. Treat rhabdomyolysis with urinary alkalinistion. Haemodialysis or haemofiltration may be required for cases of acute renal or severe hyperkalaemia.

Charcoal haemoperfusion is the treatment of choice for the majority of patients with severe barbiturate poisoning who fail to improve, or who deteriorate despite good supportive care.

ATC CODE: N03A A02

Phenobarbital Sopharmarbital is a long-acting barbiturate, which because of its depressant effect on the motor cortex, is used in the treatment of epilepsy.

Phenobarbital Sopharmarbital has a widespread depressant action on cerebral function. It has sedative effects and has some protective action against all varieties of human partial and generalised epilepsy, with the exception of absence seizures. Phenobarbital Sopharmarbital is also effective in preventing seizures in the corresponding experimental animal models of epilepsy. In different studies Phenobarbital Sopharmarbital appears to have had inconsistent effects in suppressing experimental epileptic foci, and epileptic after-discharges, but it inhibits synaptic transmission, at least in the spinal cord. The drug's probable biochemical mechanism of action is through prolonging the opening time of Cl^- ion channels in postsynaptic neuronal membranes. This effect causes membrane hyperpolarisation and thus impairs nerve impulse propagation. Phenobarbital Sopharmarbital also decreases intraneuronal Na⁺ concentrations, and inhibits Ca²⁺ influx into depolarised synaptosomes. It raises brain serotonin levels, and inhibits noradrenaline (norepinephrine) reuptake into synaptosomes. These additional biochemical actions may contribute towards the anticonvulsant effects of the drug.

Absorption - Phenobarbital Sopharmarbital is readily absorbed from the gastrointestinal tract, although it is relatively lipid - insoluble; peak concentrations are reached in about 2 hours after oral administration.

Distribution - Phenobarbital Sopharmarbital is about 45 to 60% bound to plasma proteins. Phenobarbital Sopharmarbital crosses the placental barrier and is distributed into breast milk.

Metabolism - the plasma half life is about 75 to 120 hours in adults but is greatly prolonged in neonates, and shorter (about 21 to 75 hours) in children. There is considerable interindividual variation in Phenobarbital Sopharmarbital kinetics. Phenobarbital Sopharmarbital in only partly metabolised in the liver.

Elimination - about 25% of a dose is excreted in the urine unchanged at normal urinary pH.

There is no preclinical safety data of relevance to a prescriber which is additional to that already included in other sections of the SPC.

None known.

No specific instructions. All medicines should be stored out of the reach of children.