Epilepsy/Seizures

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Medications

Medications can be divided into older medications (called first-generation anticonvulsants) and more recently developed medications (second-generation anticonvulsants).

First-Generation Anticonvulsants
Phenytoin (Dilantin®)—This is one of the more commonly used agents and often is considered the first-line drug to treat partial and generalized tonic-clonic (grand mal) seizures and status epilepticus.

Phenytoin is thought to work by suppressing electrical activity in brain nerve cells. It can be given orally or intravenously (IV), and a newer form of the drug, fosphenytoin (Cerebryx®), can be injected into muscle. The oral form has the benefit of once-a-day dosing.

Phenytoin drug levels need to be monitored with liver function testing and a complete blood count (CBC). The therapeutic concentration recommended is between 10-20mg/L. Phenytoin interacts with many other medications, and its level can fluctuate when other drugs are taken.

Side effects associated with its use include:

• Anemia
• Excessive hair growth (hirsuitism/hypertrichosis)
• Imbalance
• Lethargy
• Overgrowth of the gums (gingival hyperplasia)
• Peripheral weakness (neuropathy) with long-term use

Carbamazepine (Tegretol®/Carbatrol®)—This drug is commonly prescribed for the treatment of partial and generalized tonic-clonic (grand mal) seizures. The mechanism by which it works is not well understood. In oral form, it can be taken 2 to 3 times a day; a recent development of the drug in sustained-release form allows for twice-a-day dosing.

Carbamazepine levels must be monitored. The recommended therapeutic level is between 8-12mg/L. Liver function tests and CBC also must be checked routinely. Carbamazepine can affect the levels of a number of other drugs in the body, and its level can fluctuate when other agents are taken.

Side effects include drowsiness, imbalance, nausea, anemia, and low, white blood cell count (neutropenia).

Phenobarbital —This drug is used to treat both partial and generalized seizures. It also is used as part of the protocol after phenytoin use in status epilepticus as well as in neonatal epilepsy. It is available in oral and intravenous forms.

Levels need to be monitored. The recommended therapeutic level is 15-40mg/L. A complete blood analysis also should be routinely conducted. Phenobarbital can cause changes in the metabolism of other drugs through its actions on liver enzymes.

Possible side effects include drowsiness, cognitive impairment, and irritability.

Valproate (Depakote®)—This is prescribed for partial seizures, generalized tonic-clonic (grand mal) seizures, absence (petit mal) seizures, and myoclonic epilepsy. Its mechanism of action is thought to be related to the effect of a brain substance known as GABA (gamma-aminobutyric acid). It is available in oral form and must be taken 2 to 3 times per day for adequate dosing.

Drug levels must be monitored, as well as liver function and blood count. The drug's suggested therapeutic window is 50-100mg/L. Side effects include liver damage (hepatotoxicity), nausea, weight gain, hair loss (alopecia), and tremor.

Second-Generation Anticonvulsants
Topiramate (Topamax®)—This drug is used with other anticonvulsant drugs in the treatment of partial seizures and generalized tonic-clonic seizures in adults and children aged 2 to 16. Its precise mechanism of action is unknown, but its anticonvulsant activity may be due in part to increasing GABA (gamma-aminobutyric acid), a neurotransmitter that inhibits excitation of nerve cells in the brain. It is available in oral form, including sprinkles for children, and is taken twice daily. There are few drug interactions between topiramate and other medications or other anticonvulsants.

Side effects include drowsiness, nausea, dizziness, and coordination problems. Children may have difficulty concentrating and may become aggressive. Acute glaucoma and visual abnormality, a potentially very serious complication, has been reported in a small number of patients. If abnormal visual symptoms occur, patients should notify a physician immediately.

Gabapentin (Neurontin®)—This drug is indicated for the adjunct treatment of partial seizures, with or without secondary generalization. Although it is structurally related to the substance GABA (gamma-aminobutyric acid), it does not interact with GABA receptors in the brain, and its mechanism of action is unknown. It is available in oral form and is taken 3 times daily.

No laboratory monitoring of liver, kidney, or blood (hematologic) function is necessary. Side effects include fatigue, dizziness, and imbalance.

Lamotrigine (Lamictal®)—This drug is used for the adjunct treatment of partial seizures. Its precise mechanism of action is unknown. It is presently available in oral form and is taken twice daily. No laboratory monitoring of drug levels are necessary.

Side effects include headache, nausea, dizziness, and skin rash. The appearance of the potentially life-threatening skin rash, particularly for patients who also are taking valproate (Depakote®), should be reported immediately to a physician.

Tiagabine (Gabitril®)—This drug is indicated for adjunct therapy in adults with partial seizures. Its mechanism of action may be related to its effect on the brain substance GABA (gamma-aminobutyric acid). It is available in oral form and should be given in divided doses 2 to 4 times daily.

No laboratory monitoring of tiagabine levels are necessary. Its metabolism may be altered when taken with other anticonvulsants. Side effects include dizziness and somnolence.

Levetiracetam (Keppra®)—This drug is approved for use in adults and children 4 years of age and older as adjunct therapy for the treatment of partial seizure disorders. It is available in tablet form and as an oral solution for patients who prefer a liquid or cannot swallow tablets. Side effects can include fatigue, imbalance, and behavioral changes, which often dissipate after the first month of treatment.

Oxcarbazepine (Trileptal®)—This drug is indicated for monotherapy (used alone) and adjunct therapy (in addition to other medications) in adults who have partial seizures and as adjunct therapy in children aged 4 and older who have partial seizures. When used as monotherapy, Trileptal causes very few of the side effects associated with other AEDs.

Side effects are usually mild or moderate and include the following:

• Abdominal pain, nausea, vomiting
• Dizziness
• Double vision
• Drowsiness, fatigue
• Loss of coordination, abnormal gait

Zonisamide (Zonegram®)—This drug is approved for use in adults as adjunct therapy for partial seizures. It has however, been used fairly extensively in other countries for use in other seizure types including generalized seizures, myoclonic seizures, and absence seizures. Side effects can include dizziness, imbalance, and fatigue. Patients who are allergic to sulfonamide drugs should not use zonisamide because it is a derivative of this class of drug.

Ethosuximide (Zarontin®)—This agent is used to treat absence (petit mal) seizures. It is thought to work by suppressing brain cell activity that is associated with lapses of consciousness. It is given orally and is available as a tablet or flavored syrup.

Ethosuximide levels need to be monitored to ensure that the therapeutic concentration of 40 to 100 mcg/mL is maintained. Complete blood count (CBC), urinalysis, and liver function tests also should be performed routinely to monitor for possible adverse effects.

Potential side effects produced by ethosuximide include the following:

• Gastrointestinal–nausea and vomiting, abdominal pain, cramps, diarrhea, weight loss
• Genitourinary–vaginal bleeding, blood in urine (microscopic hematuria)
• Hematological–bone marrow suppression
• Integumentary–excessive hair growth (hirsutism ), skin rash, systemic lupus erythematous (SLE)
• Neurological–headache, dizziness, sleep disturbances, aggression, incoordination, fatigue, inability to concentrate

Primidone (Mysoline®)—This drug is a barbiturate that contains phenobarbitol. It is used to control generalized tonic-clonic (grand mal) seizures and partial seizures and is used in adults and children over 8 years old.

The effective concentration of primidone in the body is 5-12 mcg/mL. This is achieved with 250 mg tablets taken 3 to 4 times daily. The dosage may be increased, but should not exceed 500 mg taken 4 times daily.

Potential side effects include:

• Blurred vision
• Fatigue
• Incoordination
• Nausea and vomiting
• Sexual impotence (erectile dysfunction)
• Vertigo
• Weight loss

Primidone is not known to interact with other drugs. It is present in breast milk and is associated with neonatal hemorrhage and coagulation defects similar to vitamin K deficiency. Patients hypersensitive to phenobarbital should not take primidone.

Pregabalin (Lyrica®)—This drug is approved for use in adults as adjunct therapy for partial onset seizures. Lyrica, which is also used to treat diabetic peripheral neuropathy and postherpetic neuralgia, can be taken 2 or 3 times a day.

Side effects include the following:

• Blurred vision
• Difficulty concentrating
• Dizziness
• Dry mouth
• Peripheral edema (swelling)
• Somnolence (excessive sleepiness)

Epilepsy/Seizures, Medications, Side Effects reprinted with permission from neurologychannel.com
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