The FDA has approved a rapidly disintegrating tablet formulation of the antiepileptic drug levetiracetam (Spritam – Aprecia) for adjunctive treatment of partialonset, myoclonic, and primary generalized tonicclonic seizures. Oral and intravenous formulations of levetiracetam (Keppra, and generics) have been available for years. Although approved by the FDA only as adjunctive therapy, levetiracetam is commonly used as monotherapy for partial-onset and generalized seizures and may also be effective in treating absence seizures and seizures of Lennox-Gastaut syndrome.

The FDA has approved a new extended-release capsule formulation of topiramate (Qudexy XR – Upsher Smith), which can be opened and sprinkled on food for patients who have difficulty swallowing tablets or capsules, for treatment of epilepsy. Qudexy XR was marketed as a branded drug in March 2014 and as a generic drug four months later. An earlier extended-release formulation (Trokendi XR) must be swallowed whole.

Trokendi XR is approved for initial monotherapy in patients ≥10 years old with partial-onset seizures or primary generalized tonic-clonic seizures and for adjunctive therapy in patients ≥6 years old with partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome. Qudexy XR has been approved for the same indications, but the indication for adjunctive therapy has been extended to children ≥2 years old. Topiramate has been available for many years in immediate-release formulations (Topamax, and others) for the same indications for patients ≥2 years old. Trokendi XR and Qudexy XR both appear to be bioequivalent to immediate-release formulations of topiramate; whether they are bioequivalent to one another has not been established.

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The FDA has approved ezogabine (ee-ZOE-ga-been; Potiga – GSK/Valeant) for oral adjunctive treatment of partial-onset seizures in adults. Ezogabine is available in Europe as retigabine (Trobalt).

The FDA has approved vigabatrin (vye gá ba trin; Sabril – Lundbeck) for oral use as add-on therapy for complex partial seizures in adults who are refractory to several antiepileptic drugs and as monotherapy for infantile spasms. Vigabatrin has been available in other countries for many years. Because of its potential for retinal toxicity, it will be available in the US only through a restricted distribution program called SHARE (Support, Help and Resources for Epilepsy). Prescribers and pharmacists distributing the drug must register, and patients must undergo visual field testing.

The FDA has approved lacosamide (Vimpat - UCB Pharma) for oral or intravenous (IV) use as add-on therapy in adults with partial-onset seizures.

Rufinamide (Banzel - Eisai), a triazole derivative structurally unrelated to other marketed antiepileptic drugs (AEDs), has been approved by the FDA for treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients ≥4 years old.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only as adjunctive therapy for partial seizures may also be effective for other types of seizures and as monotherapy. Studies suggest that when used for the appropriate seizure type, antiepileptic drugs are roughly equivalent in efficacy. The choice of a drug is usually based on factors such as ease of use, adverse effects and cost.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only as adjunctive therapy for partial seizures may also be effective for other types of seizures and as monotherapy.

Pregabalin (Lyrica - Pfizer), a structural analog of gamma-aminobutyric acid (GABA) similar to gabapentin (Neurontin - Pfizer, and others), which recently became available generically, has been approved by the FDA for treatment of neuropathic pain associated with postherpetic neuralgia (PHN) and diabetic peripheral neuropathy (DPN), and for adjunctive treatment of partial onset seizures in adults with epilepsy.

Gabapentin (Neurontin - Pfizer), which has been available in the US since 1994, is approved by the FDA only for treatment of partial epilepsy and postherpetic neuralgia, but is widely used off-label for a number of other indications, especially neuropathic pain syndromes. According to one report, among Medicaid recipients in Florida receiving gabapentin, 71% of prescriptions were for chronic pain and 8% for seizures and neuralgia ("The Pink Sheet" February 2, 2004; 66:30).

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only for adjunctive therapy are probably also effective as monotherapy. Many of the drugs used to treat epilepsy interact with each other (see table beginning on page 63) and with other drugs; for interactions with other drugs, see The Medical Letter Handbook of Adverse Drug Interactions, 2003. The treatment of status epilepticus is not included here.

Topiramate (Topamax - Ortho-McNeil) has been approved by the US Food and Drug Administration (FDA) for oral use as an adjunct to other drugs in adult patients with partial seizures. Since this diagnostic category includes the largest number of patients with refractory epilepsy, new drugs with antiepileptic activity are usually tried first for this indication. Topiramate (toe pyre' a mate) is a structurally unique agent chemically related to the D-enantiomer of fructose.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become intolerable. If seizures continue and further increases in dosage appear inadvisable because of adverse effects, at least one and sometimes a second alternative drug should be tried before considering use of two drugs at the same time. All of these drugs interact with each other and with other drugs; for details see The Medical Letter Handbook of Adverse Drug Interactions, 1995. The treatment of status epilepticus is not included here.

Lamotrigine (la mo tri jeen; Lamictal - Burroughs Wellcome), a phenyltriazine derivative, has been approved by the US Food and Drug Administration for use in addition to other antiepileptic drugs in adults with partial seizures. Since this diagnostic category includes the largest number of patients with intractable epilepsy, new drugs with antiepileptic activity are usually tried first for this indication. Lamotrigine was first marketed abroad in 1990 and is now available in more than 50 other countries.

Gabapentin (Neurontin - Parke-Davis), a cyclohexane acetic acid derivative, has been approved by the US Food and Drug Administration for use in addition to other antiepileptic drugs in patients with partial (focal) seizures with or without secondary generalization. Since this diagnostic category includes the largest number of patients with intractable epilepsy, new drugs with antiepileptic activity are generally tried first for this indication.

Felbamate (Felbatol - Wallace Laboratories), a phenyl dicarbamate structurally similar to meprobamate (Equanil, and others), was recently approved by the US Food and Drug Administration for use alone or with other drugs in adults with partial seizures with or without secondary generalization. It was also approved for use in addition to other drugs in children with the multiple types of seizures associated with the Lennox-Gastaut syndrome, a severe epileptic encephalopathy.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become intolerable. If seizures continue and further increases in dosage appear inadvisable because of adverse effects or high serum concentrations of the drug, at least one and sometimes a second alternative drug should be tried before considering use of two drugs at the same time. The drugs of choice and alternative drugs for treatment of the most common types of epileptic seizures are listed below.