Phenytoin Sodium

Introduction

Phenytoin is an anticonvulsant medication used primarily in the treatment of:

• Tonic-clonic seizures; focal seizures. A period of 5-10 days may be required to achieve anticonvulsant effects.
• Treatment of seizures during or following neurosurgery or severe head injury;
• Status epilepticus;
• Trigeminal neuralgia if carbamazepine inappropriate;
• Abnormal heart rhythm such as ventricular tachycardia and atrial tachycardia.

Pronunciation

Phenytoin sodium 100mg

Phenytoin sodium 30mg

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Phenytoin Sodium Cap 30mg	PHEN31	P1S1S3
Phenytoin Sodium Extended
Release Cap 100mg	PHEN86	P1S1S3

Mechanism of Action

Anticonvulsant medication. It is a sodium channel blocker. It binds to sodium channels and suppresses repetitive neuronal firing.

Dosage

Doses may be expressed in terms of phenytoin or phenytoin sodium; phenytoin 92 mg is equivalent to about 100 mg phenytoin sodium.

As phenytoin has a narrow therapeutic index, need to monitor plasma-phenytoin concentration.

Anticonvulsant effect: 10-20 micrograms/mL (40 to 80 micromoles/litre)

Antiarrhythmic effect: 10-20 micrograms/mL (40 to 80 micromoles/litre)

By mouth, initially 3-4 mg/kg daily or 150 – 300 mg daily (as a single dose or in 2 divided doses) increased gradually as necessary to 600 mg daily. The suggested minimum interval between increments has ranged from about 7 to 10 days. A usual maintenance dose is 200 – 500 mg daily.

For doses in children.

To lessen gastric irritation, phenytoin should be taken with or after food.

As with other antiepileptics, withdrawal of phenytoin therapy or transition to or from another type of antiepileptic therapy should be made gradually to avoid precipitating an increase in seizure frequency.

Side Effects

Common side effects include:

• CNS-related effects such as headaches, dizziness, tremor, transient nervousness and insomnia;
• Gastrointestinal disturbances, such as nausea , vomiting, stomach pain, loss of appetite and constipation.
• Enlargement of the gums and tenderness (maintain good oral hygiene)
• Acne, increased hair growth and coarsening of facial appearance, may be particularly undesirable in adolescents and women.

Potentially serious side effects include:

• Self-harm
• Liver problems
• Bone marrow suppression
• Low blood pressure: severe low blood pressure and abnormal heartbeat rhythms can be seen with rapid infusion of IV phenytoin
• Toxic epidermal necrolysis

Phenytoin toxicity may be manifested as:

• Syndrome of cerebellar, vestibular, and ocular effects, notably nystagmus, double vision, slurred speech, and ataxia
• Mental confusion
• Dyskinesias
• hyperglycaemia

Neurological: Phenytoin may accumulate in the cerebral cortex over long periods of time which can cause atrophy of the cerebellum. The degree of atrophy is related to the duration of phenytoin treatment and is not related to dosage of the medication.

Blood: Phenytoin blocks the gut absorption of folate in food, thereby causing folate deficiency, and thus megaloblastic anaemia. Other side effects may include agranulocytosis, aplastic anaemia, decreased white blood cell count, and a low platelet count.

Skin: Hypertrichosis, purple glove syndrome, rash, exfoliative dermatitis, itching, excessive hairiness, and coarsening of facial features cab be seen in those taking phenytoin. Also, phenytoin has been linked to the life-threatening skin reactions Stevens-Johnson syndrome and toxic epidermal necrolysis. Test for HLA-B*1502 allele in individuals of Han Chinese or Thai origin (avoid unless no alternative – risk of Stevens-Johnson syndrome in presence of HLA-B*1502 allele).

Immune system: phenytoin has been known to cause drug-induced lupus.

Psychological: Phenytoin may increase risk of suicidal thoughts or behaviour.

Bone: phenytoin has been associated with decreased bone density (osteoporosis) and increased bone fractures.

Pharmacokinetics

Oral bioavailability	Phenytoin is largely insoluble at the acid pH of the stomach, most being absorbed from the upper intestine.
Onset of action	It has a very variable, dose-dependent half-life, but the mean plasma half-life appears to be about 22 hours at steady state; because phenytoin inhibits its own metabolism it may sometimes be several weeks before a steady-sate plasma-phenytoin concentration is attained.
Metabolism	Phenytoin is metabolized in the liver. It undergoes enterohepatic recycling.
Elimination half-life	Excreted in the urine.

Drug Management

Monitoring

• recognize signs of blood, liver, or skin toxicity. Seek immediate medical attention if symptoms such as fever, sore throat, rash, blistering, mouth ulcers, bruising or bleeding develop.
• Patients with heart failure should be weighed regularly to detect fluid retention.
• Patients with pre-existing cardiac conduction disorders should be carefully monitored.
• 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 plasma monitoring is advisable with combination therapy. A potentially serious type of interaction may occur because phenytoin metabolism is saturable: toxic concentrations of phenytoin can develop in patients given drugs that inhibit phenytoin metabolism even to quite a minor degree. Phenytoin itself is also a potent enzyme inducer, and induces the metabolism of many drugs, including some antibiotics, anticoagulants, corticosteroids, quinidine, and sex hormones (notably, oral contraceptives).

Drugs given with phenytoin	Potential Effect
Antacids (such as Magnesium Trisilicate Mixture)	Absorption of phenytoin reduced by antacids
Anti-arrhythmics: amiodarone	Inhibit metabolism of phenytoin, leading to increased plasma-phenytoin concentration, and increased risk of toxicity
Antibiotics: Clarithromycin, metronidazole, chloramphenicol, Isoniazid trimethoprim	Inhibit metabolism of phenytoin, leading to increased plasma-phenytoin concentration, and increased risk of toxicity