PHENYTOIN

Posology 92mg of phenytoin is equivalent to 100mg of phenytoin sodium. Dosage should be individually titrated as there may be wide variability in phenytoin serum levels with equivalent dosage. Phenytoin should be introduced in small doses with gradual increments until control is achieved or until toxic effects appear.

The clinically effective plasma phenytoin concentration is 10- 20μg/ml (40-80μmol/1) but some patients are satisfactorily controlled at concentrations outside this range. With recommended dosage a period of seven to ten days may be required to achieve steady state serum levels with Phenytoin and changes in dosage should not be carried out at intervals shorter than seven to ten days.

Maintenance of treatment should be the lowest dose of anticonvulsant consistent with control of seizures.

Adults:

Initially 3 to 4mg/kg/day with subsequent dosage adjustment as necessary. For most adults a satisfactory maintenance dose will be 200 to 500 mg daily in single or divided doses. Exceptionally, a daily dose outside this range may be indicated.

Dosage should normally be adjusted according to serum levels where assay facilities exist.

Children and Infants:

Initially 5mg/kg/day in 2 or 3 divided doses. A suggested maintenance dose is 4 to 8mg/kg daily in divided doses. Maximum dosage is 300mg daily.

Neonates:

In neonates the absorption of phenytoin following oral administration is variable and the metabolism of phenytoin may be depressed. It is therefore very important to monitor serum levels in the neonate.

Administration in liver disorders:

A reduced dose should be used to avoid toxicity.

Elderly:

As with adults the dosage of phenytoin should be titrated to the patient's individual requirements using the same guidelines. The usual adult dose unless serum albumin is low or hepatic or renal dysfunction is present. As older people tend to receive multiple drug therapies, the possibility of drug interactions should be borne in mind.

The following adverse reactions have been reported with phenytoin (frequency unknown-cannot be estimated from available data): Immune system reactions: Anaphylactoid reaction and anaphylaxis.

Central Nervous System:

Adverse reactions in this body system are common and are usually dose-related. Reactions include nystagmus, ataxia, slurred speech, decreased co-ordination and mental confusion. 4). Dizziness, insomnia, transient nervousness, motor twitchings, taste perversion, headaches paraesthesia, somnolence and vertigo have also been observed.

There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs. There are occasional reports of irreversible cerebellar dysfunction associated with severe phenytoin overdosage.

A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy. 4).

Dermatological System:

Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash is the most common; dermatitis is seen more rarely. Other more serious and rare forms have included bullous, exfoliative or purpuric dermatitis, lupus erythematosus.

4).

Connective Tissue System:

Coarsening of the facial features, enlargement of the lips, gingival hyperplasia, hirsutism, hypertrichosis, Peyronie's Disease and Dupuytren's contracture may occur rarely.

Haematopoietic System:

Haematopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leucopenia, granulocytopenia, agranulocytosis, pancytopenia with or without bone marrow suppression, and aplastic anaemia.

General Phenytoin is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence seizures are present together, combined drug therapy is needed. Phenytoin is not indicated for seizures due to hypoglycaemia or other metabolic causes.

Phenytoin may precipitate or aggravate absence seizures and myoclonic seizures. Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. When, in the judgement of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative anti-epileptic medication arises, this should be done gradually.

However, in the event of an allergic or hypersensitivity reaction, rapid substitution of alternative therapy may be necessary. In this case, alternative therapy should be an anti-epileptic drug not belonging to the hydantoin chemical class.

Acute alcohol intake may increase phenytoin serum levels while chronic alcoholism may decrease serum levels. Herbal preparations containing St. 5). Suicide Suicidal ideation and behaviour have been reported in patients treated with anti- epileptic agents in several indications.

A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for phenytoin sodium.

Therefore patients should be monitored for sings 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 behaviour emerge.

Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms (HSS/DRESS) Hypersensitivity Syndrome (HSS) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking anticonvulsant drugs, including phenytoin.

1. Acute intermittent porphyria. Co-administration of phenytoin is contraindicated with delavirdine due to the potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.