Details About Overdose or Poisoning Generic Salt ::  Phenytoin And Fosphenytoin

Phenytoin and Fosphenytoin

    

Drug Pharmacology ::

I. Pharmacology.The neuronal membrane-stabilizing actions of phenytoin make this apopular drug for sustained control of acute and chronic seizuredisorders and a useful drug for certain cardiac arrhythmias. Because ofthe relatively slow onset of anticonvulsant action, phenytoin usuallyis administered after diazepam. At serum concentrations consideredtherapeutic for seizure control, phenytoin acts similarly to lidocaineto reduce ventricular premature depolarization and suppress ventriculartachycardia. After intravenous administration, peak therapeutic effectsare attained within 1 hour. The therapeutic serum concentration forseizure control is 10–20 mg/L. Elimination is nonlinear, with anapparent half-life averaging 22 hours. Fosphenytoin, a prodrugof phenytoin for intravenous use, is converted to phenytoin afterinjection, with a conversion half-life of 8–32 minutes.

Drug Indications ::

Indications

   

A.Control of generalized tonic-clonic seizures or status epilepticus.However, benzodiazepines (Benzodiazepines [Diazepam, Lorazepam, andMidazolam]) and phenobarbital (Phenobarbital) are generally moreeffective for treating drug-induced seizures.

Control of cardiac arrhythmias, particularly those associated with digitalis intoxication.

Drug Contra-Indications ::

III. Contraindications. Known hypersensitivity to phenytoin or other hydantoins.

Drug Adverse Effects ::

IV. Adverse effects.

   

Rapid intravenous phenytoin administration (greater than 50 mg/min inadults or 1 mg/kg/min in children) may produce hypotension, AV block,and cardiovascular collapse, probably owing to the propylene glycoldiluent. Fosphenytoin is readily soluble and does not contain propyleneglycol, and a hypotensive response is not common.

Extravasation of phenytoin may result in local tissue necrosis andsloughing. Phenytoin may induce the “purple glove syndrome” (edema,discoloration, and pain) after peripheral IV administration. This canoccur hours after infusion, in the absence of clinical signs ofextravasation, and can lead to limb ischemia and necrosis from acompartment syndrome. Risk factors include elderly patients receivinglarge multiple doses, use of small IV catheters, high infusion rates,and use of the same catheter site for two or more IV push doses.Extravasation problems have not been observed with fosphenytoin.

Drowsiness, ataxia, nystagmus, and nausea may occur.

Use in pregnancy.No assigned FDA category. Congenital malformations (fetal hydantoinsyndrome) and hemorrhagic disease of the newborn have occurred withchronic use. However, this does not preclude its acute, short-term usein a seriously symptomatic patient (see Table III–1).

Drug or laboratory interactions.

   

The various drug interactions associated with chronic phenytoin dosing(ie, accelerated metabolism of other drugs) are not applicable to itsacute emergency use.

.Extracorporeal removal methods (eg, hemoperfusion and repeat-doseactivated charcoal) will enhance phenytoin clearance. Supplementaldosing may be required during such procedures to maintain therapeuticlevels.

Drug Dose Management ::

Dosage and method of administration.

   

Parenteral.

   

1. Phenytoin.Administer a loading dose of 15–20 mg/kg IV slowly at a rate not toexceed 50 mg/min (1 mg/kg/min in children). It may be diluted in 50–150mL of normal saline with the use of an in-line filter. Phenytoin hasbeen administered via the intraosseous route in children. Do not administer by the intramuscular route.

2. Fosphenytoin.Dosage is based on the phenytoin equivalent: 750 mg of fosphenytoin isequivalent to 500 mg of phenytoin. (For example, a loading dose of 1 gphenytoin would require a dose of 1.5 g fosphenytoin.) Dilute twofoldto 10-fold in 5% dextrose or normal saline and administer no fasterthan 225 mg/min.

Maintenance oral phenytoin dose.Give 5 mg/kg/d as a single oral dose of capsules or twice daily forother dosage forms and in children. Monitor serum phenytoin levels.

Drug Chemical Formulations ::

Formulations.

   

Parenteral. Phenytoinsodium, 50 mg/mL, 2- and 5-mL ampules and vials. Fosphenytoin sodium(Cerebyx), 150 mg (equivalent to 100 mg phenytoin) in 2-mL vials or 750mg (equivalent to 500 mg phenytoin) in 10-mL vials.

Oral. Phenytoin sodium (Dilantin and others), 30-mg and 50-mg chewable tablets and 100-mg capsule.

The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is six vials (50 mg/mL, 5 mL each) or the equivalent.

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