Budget Impact Analysis of Extended-Release Phenytoin Capsules Compared With Immediate-Release Phenytoin Capsules for Patients With Epilepsy in Thailand.

OBJECTIVES: There was higher frequency of breakthrough seizures during immediate-release phenytoin capsule usage than during extended-release phenytoin capsule usage by epilepsy patients. This study aimed to estimate the total budget of using extended-release phenytoin compared with immediate-release phenytoin capsules. METHODS: A decision tree model was developed for 3 scenarios in Thailand where (1) extended-release phenytoin, (2) immediate-release phenytoin, and (3) both forms, as per the market share, were prescribed. All parameters were derived from the literature reviews and hospital database and analyzed from payer and societal perspectives. RESULTS: Of 95 613 patients receiving phenytoin, the total budget impact of scenarios 1 to 3 ranged from $45 214 915 to $50 209 357, $104 298 093 to $111 846 317, and $61 167 373 to $66 851 336 from payer and societal perspectives, respectively. CONCLUSION: Prescribing extended-release phenytoin showed the lowest total budget impact in Thailand. A healthcare policy recommendation developed from this research would help in solving the antiepileptic drug issue.

Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend(®) SF PH4 oral suspensions.

The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

The safety and efficacy of fosphenytoin for the treatment of status epilepticus.

Fosphenytoin, a water-soluble prodrug of the antiepileptic drug phenytoin, is entirely and rapidly converted to this antiepileptic drug. The mechanism of action of fosphenytoin is related to the blockade of voltage-operated sodium channels. It was developed in order to obtain a phenytoin-like drug with improved water solubility. Its maximal plasma concentration is achieved within 90-190 min following intramuscular administration with bioavailability being complete after intravenous injection. The main indications for fosphenytoin are the treatment of convulsive status epilepticus and the prevention/management of seizures during neurosurgery. Adverse effects of fosphenytoin may include: cardiovascular events (hypotension, arrhythmias), paresthesias or pruritus or some central events - somnolence, headache, dizziness, nystagmus and ataxia. The incidence of purple glove syndrome (edema, discoloration and pain distal to the site of intravenous administration) is less frequent than after phenytoin. Generally, the development of fosphenytoin aimed at avoiding complications associated with parenteral use of phenytoin.

Comparative bioavailability of a generic phenytoin and Dilantin.

Generic substitution of antiepileptic drugs (AEDs) has been controversial, with many alleged instances of biologic and therapeutic inequivalence reported. The recall of a generic phenytoin (PHT) formulation used in the Veterans Administration (VA) medical system allowed us to evaluate the question of biologic equivalence systematically in a relatively large number of patients at the Bronx VA Medical Center. Serum PHT levels were 22-31% lower during the period of generic intake as compared with levels in the same patients receiving Dilantin. Review of the literature showed only one other adequately documented report of potential clinically significant inequivalence between a brand name and generic AED. Despite the apparent infrequency of generic inequivalence, several areas in which procedures for certification of therapeutic equivalence should be improved were identified.

Guidelines for phenytoin infusions.

Until recently, phenytoin sodium injection was not recommended for dilution in intravenous fluids because insolubility results in precipitation of phenytoin acid. The formation of rod-shaped crystals primarily reflects the failure to maintain the pH of the admixture above 9.5 to 10. Investigations have clarified this problem and point out that stable solutions of phenytoin sodium can be prepared which are safe for intravenous infusion provided the injection is diluted in small volumes of 0.9 percent sodium chloride or Ringer's. Lactate injection and administered freshly prepared. Specific guidelines are suggested for the preparation and administration of phenytoin sodium infusions.

Reduced seizure control due to spoiled phenytoin capsules.

Subtherapeutic phenytoin serum levels and loss of seizure control occurred in a 31-year-old man due to decreased bioavailability of oral drug. During storage at extreme temperatures, physical changes of the phenytoin capsule resulted in altered dissolution characteristics so that only 50% dissolution occurred at 180 minutes compared with 95% in 120 minutes for control capsules. Similar changes were produced in fresh capsules within seven days at high temperature and humidity. The affected patient has metabolic responses to phenytoin that produce marked fluctuations in serum levels with changes in dose. Altered phenytoin serum concentrations may occur with minor dose changes in such patients despite good compliance.