Phenytoin Sodium

Phenytoin( 中文: 苯妥英) 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

Drug Names

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.

By mouth	initially 5 mg/kg daily in 2 divided doses, usual dose range 4-8 mg/kg daily (max. 300 mg daily)

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
Doxycycline	Phenytoin accelerates metabolism of doxycycline (reduced doxycycline plasma concentration and thus its drug effect)
Rifamycins	Accelerate metabolism of phenytoin, thus reduced phenytoin plasma concentration and its drug effect.
Anticoagulants: Apixaban, Dabigatran, rivaroxaban warfarin	Phenytoin possibly reduces their plasma concentration, thus anticoagulant effect; Avoid concomitant use and monitor signs of thrombosis.
Antidepressants: Fluoxetine, sertraline	Increase plasma concentration of phenytoin, and increased risk of toxicity
Antiepileptics: Carbamazepine Clonazepam, lamotrigine, topiramate, valproate, oxcarbazepine	Carbamazepine may lowers or raise plasma-phenytoin concentration. Phenytoin often lowers their plasma concentration.
Antifungals: Miconazole, fluconazole	Plasma concentration of phenytoin increased, consider reducing dose of phenytoin
Antipsychotics: aripiprazole clozapine Haloperidol Quetiapine	Phenytoin accelerates their metabolism and reduced their plasma concentration. Avoid concomitant use or increase the dose
Anxiolytics: Clonazepam diazepam	Phenytoin often reduces plasma concentration of clonazepam. Plasma concentration of phenytoin increased or decreased by diazepam.
corticosteroids	Phenytoin accelerates metabolism of corticosteroids (reduced effect)
Diuretics: frusemide	Phenytoin antagonizes effects of frusemide
Lithium	Neurotoxicity may occur when phenytoin given with lithium
Oestrogens	Phenytoin accelerates metabolism of oestrogens, thus reduce contraceptive effect
Orlistat	Possible increased risk of convulsions when antiepileptics given with orlistat
Progesterones	Phenytoin accelerates metabolism of progesterones, thus reduce contraceptive effect
Theophylline	Plasma concentration of both drugs reduced when phenytoin given with theophylline.
Thyroid hormones	Phenytoin accelerates metabolism of thyroid hormones (may increase thyroxine dosage in hypothyroidism)
Ulcer-healing drugs: Cimetidine Esomeprazole, omeprazole	Metabolism of phenytoin inhibited by cimetidine, thus increase plasma-phenytoin concentration, and increased risk of toxicity. Effects of phenytoin enhanced by esomeprazole and omeprazole.

Caution

• Avoid abrupt withdrawal
• Caution in diabetic patients because of the potential effects phenytoin on blood sugar
• Genotype test for HLA-B*1502 allele in Han Chinese of Thai origin (avoid phenytoin unless no alternative – risk of Stevens-Johnson syndrome in presence of HLA-B*1502 allele);
• may exacerbate absence and myoclonic seizures
• consider vitamin D supplement for immobilized patients or who have inadequate sun exposure or dietary intake of calcium
• enteral feeding (interrupt feeding for 2 hours before and after dose)

Contraindications

• AV conduction abnormalities
• History of bone-marrow depression
• Acute porphyria

Hepatic impairment

Phenytoin is metabolized in the liver and should be given with care to patients with impaired liver function. Reduce dose to avoid toxicity.

Renal impairment

Can begin with standard dose and adjust as needed

Pregnancy

Women of child-bearing potential should discuss with a specialist the impact of both epilepsy, and its treatment, on the outcome of pregnancy. There is an increased risk of teratogenicity associated with the use of antiepileptic drug (especially if used during the first trimester)

Breast-feeding

Use during breast feeding is not recommended.

Epilepsy and driving

Driving by patients with epilepsy is generally regulated. Also, antiepileptic drugs may produce CNS-related adverse effects, including dizziness and drowsiness, that could impair a patient’s ability to drive a vehicle or operate machinery, particularly during the initial stages of therapy.

FAQ

How should I take the tablet?

To lessen gastric irritation, take preferably with or after food.

What should I avoid while taking?

Avoid abruptly discontinue the medication.

What happen if I overdose?

Contact your primary care doctor. If emergency situation, call 999

What happen if I miss a dose?

Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.