Generic Phenytoin Research Articles

Switching between phenytoin generics in patients with epilepsy may lead to increased risk of breakthrough seizure: chart analysis and practice recommendations.

The Food and Drug Administration (FDA) only requires bioequivalence testing of generic substitutions in order for them to be deemed equivalen to the original product. There may be a large difference of bioavailability among the generic drugs that especially have a narrow therapeutic index, and this may affect clinical outcomes. We aimed to determine whether switching from generic-to-generic equivalent anti-epileptic drugs (AEDs) in patients with epilepsy is associated with clinical outcomes. We performed a retrospective study using the electronic medical records of a tertiary hospital. Adults with a history of epilepsy who used a generic phenytoin and whose therapy was switched to another generic phenytoin between January 2012 and June 2013 were included (n = 80). We compared the drug concentration of phenytoin and seizure events before and after the switch. After switching their generic phenytoin, 33 out of 80 patients (41%) suffered from increasing seizure events (pre-interchange period, 0.44 ± 0.97; post-interchange period, 1.24 ± 2.05; p < 0.0001). The number of medical visits for acute seizure significantly increased in the post-interchange period. The phenytoin serum concentration of all the patients was lesser in the post-interchange period than in the pre-interchange period. (pre-interchange period, 12.79 μg/mL; post-interchange period, 6.36 μg/mL; p < 0.0001). Among the patients with drug resistant epilepsy (DRE), 17 patients (84.2%) had increasing seizure events in the post-interchange period. We confirmed that there was a significant difference in bioavailability between generic phenytoin. Therefore, when using or switching generic anti-epileptic drugs, therapeutic drug monitoring must be done, and the patients' condition must be considered.

Clinical Outcomes Associated with Brand-to-Generic Phenytoin Interchange

Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. However, little within-patient evidence exists examining such interchanges. To compare within-patient seizure control before and after the interchange of a branded to a single-source generic phenytoin among patients with seizures in a managed care organization. This was a pre-post, self-controlled, retrospective study. Adults with a history of seizure who used Dilantin Kapseals 100 mg extended phenytoin sodium, USP, capsules and whose therapy was interchanged to Taro Pharmaceuticals' AB-rated generic extended phenytoin sodium capsules, USP, 100 mg between July 2007 and May 2008 were included. Study outcomes included the comparisons of the proportions of patients with at least emergency department (ED) visit/inpatient hospitalization and medical office visit/nonoffice consultation for acute seizure in the 6 months before and after interchange. Outcomes were confirmed with manual chart reviews and adjusted for potential confounding medication use. A total of 222 patients were included in the study. Patients were primarily middle-aged (mean 56 years), equally mixed by sex (47% female); most had nonintractable seizures. The majority of patients (~70%) were on phenytoin as monotherapy and had equivalent rates of purchases for potentially confounding medications in both pre- and postinterchange time periods (all p > 0.05). Low serum concentrations were detected more often in the postinterchange study period (adjusted p < 0.001). Despite this, there were low proportions of patients with confirmed seizure events that resulted in an ED visit/inpatient hospitalization in both pre- and postinterchange periods (both 6.3%, adjusted p = 0.937). The proportion of patients with confirmed seizure events diagnosed at a medical office visit was not significantly different between the preinterchange and postinterchange periods (12.2% vs 11.3%, adjusted p = 0.545). No increased proportion of seizures was observed within patients when branded phenytoin was interchanged to an AB-rated, single-source, generic equivalent. More rigorous studies should be conducted to more thoroughly evaluate patient tolerability and drug efficacy when antiepileptic drugs are interchanged from brand to generic formulations.

Antiepileptic Drugs: All Ages

Antiepileptic Drugs: All Ages

Lower phenytoin serum levels in persons switched from brand to generic phenytoin

Lower phenytoin serum levels in persons switched from brand to generic phenytoin

Lower phenytoin serum levels in persons switched from brand to generic phenytoin

After generic phenytoin (PHT) was marketed, the authors identified eight adult patients (ages 34 to 49) whose seizures increased enough to require intervention after switching to generic PHT. The mean total PHT concentration on brand (before generic) was 17.7 ± 5.3 mg/L, decreased to 12.5 ± 2.7 mg/L with generic, and increased to 17.8 ± 3.9 mg/L after brand was re-introduced. Brand and generic PHT do not yield equivalent concentrations in some patients and substitution should not be permitted without physician notification.

Lower phenytoin serum levels in persons switched from brand to generic phenytoin

After generic phenytoin (PHT) was marketed, the authors identified eight adult patients (ages 34 to 49) whose seizures increased enough to require intervention after switching to generic PHT. The mean total PHT concentration on brand (before generic) was 17.7 +/- 5.3 mg/L, decreased to 12.5 +/- 2.7 mg/L with generic, and increased to 17.8 +/- 3.9 mg/L after brand was re-introduced. Brand and generic PHT do not yield equivalent concentrations in some patients and substitution should not be permitted without physician notification.

Prescribing antiepileptic drugs: should patients be switched on the basis of cost?

To assess the costs of switching from one antiepileptic drug (AED) to another, all associated direct and indirect costs, not only drug acquisition costs, must be considered. The perspective of the healthcare system evaluated in cost-effectiveness analysis is of crucial importance. Multiple clinical factors can influence clinical decisions regarding switching AEDs. The economic cost of poorly controlled epilepsy is enormous and the most cost-effective intervention is an AED that provides total seizure control. Cost-minimisation studies have evaluated costs associated with various medications. If only efficacy and adverse events were considered, then the 'older' AEDs were generally more cost effective than the 'newer' AEDs. Most studies only examine very specific clinical situations and are not suitable for establishing general clinical recommendations. The pharmacoeconomics of AED choice is highly country specific. While switching to generic formulations is, in general, cost effective, some changes may be detrimental and more costly than remaining on the trade name preparation. For example, as a result of differences in bioavailability and possible loss of seizure control, changing patients to generic phenytoin and carbamazepine can be problematic. Fosphenytoin may only be cost effective in certain clinical situations compared with intravenous phenytoin. Seizure control should not be sacrificed on the basis of costs alone, as the major endpoint in treating epilepsy with AEDs is seizure control without adverse effects. Switching AEDs in clinical practice still depends on the individual clinical situation and choosing AED therapy solely on the basis of initial acquisition costs is unlikely to be cost effective in the long-term care of patients with epilepsy.