PHENYTOIN ELSAAD
-
Chemical Name:
Phenytoin Soduim -
Therapeutic Category:
Central nervous system drugs -
Pharmacologic Category:
Anticonvulsant, Hydantoin -
Pharmaceutical Form:
Ampoule -
Composition:
Phenytoin Soduim 250mg/5ml
PHENYTOIN ELSaad
Injection (Ampoule)
Phenytoin Sodium
1-PHARMACOLOGY:
Phenytoin is used in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase (grand mal) seizures.
2-PHARMACOKINETICS:
The plasma half-life after IV administration ranges from 10 to 15 hours. Optimum control without clinical signs of toxicity occurs most often with serum levels between 10 to 20 mcg/ml.
A fall in plasma levels may occur when patients are changed from oral to IM administration. The drop is caused by slower absorption, as compared to oral administration, due to poor water solubility of phenytoin. IV administration is the preferred route for producing therapeutic serum levels.
There are occasions when IM administration may be required, i.e. postoperatively, in comatose patients, for GI upsets. During these periods, a sufficient dose must be administered intramuscularly to maintain the plasma level within the therapeutic range.
A short-term (one-week) study indicates that patients do not experience the expected drop in blood levels when crossed over to the IM route if the phenytoin IM dose is increased by 50% over the previously established oral dose.
Most of the drug is excreted in the bile as inactive metabolites, which are then reabsorbed from the intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion.
3-INDICATIONS:
PHENYTOIN ELSaad is indicated in the following cases:
- Treatment of grand mal of epilepsy in adults and children as monotherapy or in association.
- In prophylaxis of epileptic convulsions induced by cranial neurosurgical interventions when oral administration is impossible.
- In ventricular arrhythmias due to digitalis intoxication.
4-CONTRAINDICATIONS:
PHENYTOIN ELSaad is contraindicated in those patients who are hypersensitive to phenytoin or other hydantoins.
5-PRECAUTIONS:
- Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. When, in the judgment of the clinician, the need for dosage reduction discontinuation, or substitution of alternative antiepileptic 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 antiepileptic drug not belonging to the hydantoin chemical class.
- In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every effort should be made to achieve seizure control using alternative antiepileptic drugs.
- Acute alcoholic intake may increase phenytoin serum levels while chronic alcoholic use may decrease serum levels.
- Caution should be exercised in using this medication in patients suffering from porphyria.
- An increase in seizure frequency during pregnancy occurs in a high proportion of patients, because of altered phenytoin absorption or metabolism. Periodic measurement of serum phenytoin levels is particularly valuable in the management of a pregnant epileptic patient .
- Phenytoin appears to be secreted in low concentrations in human milk.
- Neonatal coagulation defects have been reported within the first 24 hours in babies born to epileptic mothers receiving phenobarbital and/or phenytoin. Vitamin K has been shown to prevent or correct this defect and has been recommended to be given to the mother before delivery and to the neonate after birth.
- Hypotension usually occurs when the drug is administered rapidly by the IV route.
- Patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity.
- Phenytoin should be discontinued if a skin rash appears.
- Phenytoin may also raise the serum glucose level in diabetic patients.
- Osteomalacia has been associated with phenytoin therapy and is considered to be due to phenytoin's interference with Vitamin D metabolism.
- Phenytoin is not indicated for seizures due to hypoglycemic or other metabolic causes. Appropriate diagnostic procedures should be performed as indicated.
- Phenytoin is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence (petit mal) seizures are present, combined drug therapy is needed.
- Patients taking phenytoin should be advised of the importance of adhering strictly to the prescribed dosage regimen.
- The importance of good dental hygiene should be stressed in order to minimize the development of gingival hyperplasia.
- The addition of Phenytoin injection, to IV infusion is not recommended due to lack of solubility and resultant precipitation.
- Each injection of Phenytoin should be followed by an injection of sterile saline through the same needle or IV catheter to avoid venous irritation due to the alkalinity of the solution.
- Subcutaneous or perivascular injection of Phenytoin should be avoided.
- Intramuscular injection for treatment of especially should be avoided.
- Dilution with glucose solution should be avoided.
- Injection should be discontinued in case of hypotension.
6-DRUG INTERACTIONS:
Serum level determinations for phenytoin are especially helpful when possible drug interactions are suspected.
Drugs which may increase phenytoin serum levels include: Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, diazepam, dicumarol, disulfiram, estrogens, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide, trazodone.
Drugs which may decrease phenytoin serum levels include: Carbamazepine, chronic alcohol abuse, reserpine, and sucralfate.
Drugs which may either increase or decrease phenytoin serum levels include: Phenobarbital, sodium valproate, and valproic acid.
Tricyclic antidepressants may precipitate seizures in susceptible patients and phenytoin dosage may need to be adjusted.
Drugs whose efficacy is impaired by phenytoin include: Corticosteroids, coumarin anticoagulants, digitoxin, doxycycline, furosemide, oral contraceptives, quinidine, rifampin, theophylline, vitamin D.
7-ADVERSE REACTIONS:
Central Nervous System: Nystagmus, ataxia, slurred speech, decreased coordination, mental confusion, dizziness, insomnia, transient nervousness, motor twitchings, and headache.
There have also been rare reports of phenytoin induced dyskinesias, similar to those induced by phenothiazine and other neuroleptic drugs.
Gastrointestinal System: Nausea, vomiting, constipation, toxic hepatitis and liver damage.
Integumentary System: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes.
Other more serious forms included bullous, exfoliative or purpuric dermatitis, lupus erythematosus, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Hemopoietic System: Thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia. While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy.
Connective Tissue System: Enlargement of the lips, gingival hyperplasia, hypertrichosis.
Cardiovascular: Periarteritis nodosa.
The most notable signs of toxicity associated with the IV use of this drug are cardiovascular collapse and/or central nervous system depression. Hypotension does occur when the drug is administered rapidly by the IV route. The rate of administration is very important; it should not exceed 50 mg per minute in adults, and 1 to 3 mg/kg/min in neonates. At this rate, toxicity should be minimized.
Severe cardiotoxic reactions and fatalities have been reported with atrial and ventricular conduction depression and ventricular fibrillation. Severe complications are most commonly encountered in elderly or gravely ill patients.
Local irritation, inflammation.
8-DOSAGE AND ADMINISTRATION:
The addition of Phenytoin Injection, IV infusion is not recommended due to lack of solubility and resultant precipitation.
Not to exceed 50 mg per minute, intravenously in adults, and not exceeding 1 to 3 mg/kg/min in neonates. There is a relatively small margin between full therapeutic effect and minimally toxic doses of this drug.
In the treatment of status epilepticus, the IV route is preferred because of the delay in absorption of phenytoin when administered intramuscularly.
Status Epilepticus:
Adults: 18 mg/kg
Children: 10 to 15 mg/kg
Neonates: 8 to 12 mg/kg
Elderly: 10 to 15 mg/kg
In case of insufficiency of the dose follow up doses of 5 mg/kg can be used but, not more than 30 mg/kg/24 hours supported by continuous monitoring of plasma concentration.
Intravenous rate: 1 mg/kg/min but not more than 50 mg/min for adults and children and 25 mg/min for elderly.
This will require approximately 20 to 60 minutes.
Neurosurgery and cranial trauma:
Phenytoin is indicated for prophylaxis of epilepsy in Neurosurgery and cranial trauma when oral administration is impossible.
In patients not previously stabilized orally, the charging dose is the as established followed by doses calculated according to the plasma concentrations.
In patients previously stabilized orally, the charging dose is 9 mg/kg followed by doses calculated according to the plasma concentrations.
Cardiac arrhythmias caused by overdosage with cardiac glycosides:
200 to 1000 mg slow I.V injection at uniform rate not more than 50 mg/min.
Method of administration:
Direct intravenous administration can be used but it is better to be diluted with intravenous solution of sodium chloride to approximate concentration of 5 mg/kg.
Phenytoin Injection should be injected slowly and directly into a large vein through a large IV catheter.
Continuous monitoring of the electrocardiogram and blood pressure is essential especially in elderly. The patient should be observed for signs of respiratory depression.
9-OVERDOSAGE:
The initial symptoms are nystagmus, ataxia, dysarthria, tremor, hyperreflexia, lethargy, nausea, vomiting.
The patient may become comatose and hypotensive. Death is due to respiratory and circulatory depression.
There are marked variations among individuals with respect to phenytoin plasma levels where toxicity may occur.
Treatment is non specific since there is no known antidote.
The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed. Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins.
Total exchange transfusion has been used in the treatment of severe intoxication in children.
10-PACKAGING & COMPOSITION:
PHENYTOIN ELSaad – Injection: A pack of 5 or 25 ampoules of 5 mL. Each ampoule 5 mL contains 250 mg Phenytoin Sodium.
11-STORAGE CONDITIONS:
Store PHENYTOIN ELSaad – Injection at temperature below 25°C. Upon refrigeration, a precipitate might form; this will dissolve again after the solution is allowed to stand at room temperature. The solution is still suitable for use. Use only a clear solution.
Note: A faint yellow color may be develop, but has no effect on the potency of the solution.
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