Carbamazepine inactivates sodium channels and inhibits the creation of rapid action potentials. It can be used to treat generalized and focal seizures and other illnesses such as trigeminal neuralgia and bipolar disease. It is effective for adults with focal seizures, likely effective in children with focal seizures, and potentially effective in both kids and adults in generalized-onset tonic-clonic seizures. This drug has many drug-to-drug interactions.
The initial starting dose is 2-3 mg/kg per day, which is most typically given two to four times a day, two times a day for the extended-release form, and 3 to 4 times a day for the immediate release form. The dose can be increased every week to 10 mg/kg day. Levels should be checked at three, six and nine weeks.
Side effects include nausea, vomiting, rash, itch, diarrhea, dizziness, vision change, lethargy, headache, and fluid retention. Also, lower testosterone levels and increased rates of sexual dysfunction may be seen. Hyponatremia may be seen, and it is recommended to measure the level at the start of therapy and then when therapeutic levels are reached. Serious side effects include liver failure, Stevens-Johnson syndrome/toxic epidermal necrolysis, agranulocytosis, aplastic anemia, pancreatitis, and lupus syndrome.
Gabapentin appears to inhibit inward calcium currents and reduces neurotransmitter release. It also affects the transport of gamma-aminobutyric acid (GABA). It is used for add-on therapy for focal seizures. It is excreted in the urine, and dosage adjustment is needed in those with renal insufficiency.
This drug has very few drug interactions. Typically, the dose is started at 100-300 mg a day and is titrated up to a maximum of 1800 mg per day split three times a day.
Common side effects include sedation, weight gain, ataxia, and dizziness. Serious side effects include respiratory depression and multiorgan hypersensitivity*.
|*Certain seizure drugs can cause a hypersensitivity syndrome, which has the potential to be life-threatening. It is a delayed (typically occurring in the first few weeks of starting a drug) hypersensitivity reaction associated with rash, fever, and multiorgan involvement.|
Lacosamide inactivates voltage-dependent sodium channels, which stabilizes the neuronal membrane. It is approved as monotherapy or adds on therapy for focal-onset seizures. Its recommended starting dose is 50-100 mg two times a day to a maximum of 400 mg per day.
Side effects include dizziness, ataxia, vertigo, nausea, headache, diplopia, and poor coordination. Syncope has been reported in a small percentage of patients with diabetic neuropathy and those receiving doses of more than 400 mg per day. Serious side effects include neutropenia, multiorgan hypersensitivity, and atrioventricular block.
Lamotrigine has multiple mechanisms of action, including inactivating the voltage-dependent sodium channels. It may also affect neurons that synthesize aspartate and glutamate. It is approved for focal-onset seizures and as adjunctive therapy for generalized tonic-clonic seizures and Lennox-Gastaut syndrome (LGS). It is often thought of as an alternative to valproate with fewer side effects.
Pregnancy and oral contraceptives can affect serum levels. This drug interacts with many other seizure drugs, including valproate, phenytoin, and carbamazepine. The typical starting dose is 25 mg every day and slowly increased. The maximum dose is dependent on other drugs that the patient takes, including valproate, carbamazepine, phenytoin, rifampin, and some protease inhibitors.
Side effects include nausea, rash, dizziness, fatigue, sleepiness, and diplopia. The rash is common and most likely to occur in those who have the dose increased too quickly. Serious side effects include Stevens-Johnson syndrome/toxic epidermal necrolysis, multiorgan hypersensitivity, and aseptic meningitis.
Levetiracetam is a commonly used drug, and the mechanism of action is unknown. It is a drug with broad-spectrum antiseizure properties. Drug interactions are minimal with levetiracetam, as it is independent of the CYP system.
It is started at 250-500 mg two times a day and is often very effective at reducing seizures after the first day. It may be titrated to 4000 mg a day, but 3000 mg a day has similar efficacy and less sedation.
An intravenous form is available, but it is no more bioavailable than oral form. Levels of the drugs do not need to be monitored but may be monitored in renal insufficiency, pregnancy, or to monitor for adherence.
Side effects include somnolence, dizziness, agitation, irritability, fatigue, and upper respiratory tract infection. These side effects are more common during the initial phase of therapy. Serious side effects include Stevens-Johnson syndrome/toxic epidermal necrolysis, pancytopenia, and psychosis.
Oxcarbazepine is like carbamazepine and blocks voltage-sensitive sodium channels and affects high voltage calcium channels. In adults, it is indicated for monotherapy or adjunctive therapy in the treatment of partial seizures. It has fewer drug-to-drug interactions when compared to carbamazepine. Dosing for adults is with 300-600 mg per day and may be increased to 900 to 3000 mg per day in divided doses.
Side effects include dizziness, vertigo, rash, ataxia, diplopia, sedation, nausea, headache, and hyponatremia. Serious side effects include Stevens-Johnson syndrome/toxic epidermal necrolysis, multiorgan hypersensitivity, agranulocytosis, and pancytopenia.
|Carbamazepine and oxcarbazepine are the two seizures drugs most likely to cause hyponatremia. It is more likely to be seen older adults, those on diuretics, those with high serum levels of the seizure drug, and those on polytherapy for seizures. Baseline sodium levels should be checked, and then once levels are therapeutic, sodium levels should be rechecked. If the patient develops any indication of hyponatremia such as headaches, lethargy, confusion, then the sodium levels should be checked.|
Phenobarbital works on the GABA receptor to extend GABAs effect. It is the oldest anti-epileptic and is indicated for generalized and focal seizures. It is metabolized in the liver and should be used with caution in those with hepatic impairment. It is a schedule IV-controlled substance and available in intravenous, intramuscular, and oral form. This drug has abuse potential, and it is dosed 1-5 mg/kg/day, and blood levels should be monitored.
Side effects include nausea, rash, mood changes, sedation, tolerance, dependence, and reduced concentration. Chronic use may be associated with frozen shoulder, bone problems, Dupuytren's contractures, and plantar fibromatosis. Serious side effects include liver failure, agranulocytosis, and Stevens-Johnson syndrome/toxic epidermal necrolysis.
Phenytoin works by blocking the sodium channels, thereby reducing synaptic transmission. It is another older drug that was first used in the 1930s. It can be used for those with generalized and focal seizures as well as for status epilepticus.
Phenytoin interacts with many drugs, which can affect phenytoin levels. Phenytoin is available as an oral agent and an intravenous agent. The maintenance dose is typically 300-400 mg a day in 2-3 divided doses. The loading dose may be 15mg/kg in three divided diseases. Target doses should control seizures without significant side effects, which generally correlates with a serum concentration between 10-20 mcg/mL. Caution must be used with dosing as small changes in dose may cause significant changes in drug levels.
Side effects include rash, reduced bone density, gingival hypertrophy, folic acid depletion, an increase in body hair, slurred speech, ataxia, confusion, and double vision. If they develop a rash with phenytoin, they are more likely to get a rash with carbamazepine. Serious side effects include agranulocytosis, liver failure, Stevens-Johnson syndrome/toxic epidermal necrolysis, aplastic anemia, adenopathy, neuropathy, and lupus syndrome.
Pregabalin is similar to gabapentin. It binds to the alpha-2-delta subunit of the calcium channel and affects glutamate, substance P, and noradrenaline.
It is used as an adjunctive treatment for focal seizures. It does not have significant interactions with other drugs used to manage seizures and overall, very few drug interactions. It is dosed 150 mg a day in 2 to 3 divided doses, and the dose may be increased up to 600 mg a day.
Side effects include ataxia, dizziness, sedation, weight gain, vision change, tremor, impaired concentration, peripheral edema, and dry mouth. It may also cause euphoria and is classified as a Schedule V controlled substance. Serious side effects include angioedema, hypersensitivity reactions, and rhabdomyolysis.
Topiramate works through multiple mechanisms, including affecting the sodium channels and the GABA(A) receptor. It is indicated for monotherapy for primary generalized tonic-clonic seizures as well as focal-onset seizures. It may also be used for adjunctive therapy for Lennox-Gastaut syndrome. The dosage is started at 50 mg/day and increased in 50 mg increments every week to a maximum of 400 mg a day divided twice per day.
Side effects include weight loss, fatigue, dizziness, cognitive impairment, sedation, paresthesia, depression, kidney stones, reduced appetite, nervousness, mood disturbance, and tremor. Serious side effects include hyperthermia, acute myopia, glaucoma, and kidney stones.
Valproate blocks sodium channels, as well as the calcium channels. It also affects the GABA system. It has a broad spectrum of activity and is used in both focal and generalized seizures. It is metabolized in the liver, and the dose may need to be decreased in those with hepatic insufficiency. It is also bound to protein, so those with low albumin in the blood may have elevated levels despite a low serum value.
Dosing is between 10-15 mg/kg and may be increased weekly. Serum levels should be checked in about one to two weeks after starting the drug.
Side effects include tremor, hair loss, nausea, vomiting, dizziness, easy bruising, weight gain, and may increase alanine aminotransferase levels. In rare situations, it may cause elevated ammonia levels leading to encephalopathy, acute liver injury, or pancreatitis. It can also cause thrombocytopenia and elevations in thyrotropin (TSH) levels. It has a high rate of teratogenicity when compared to other anti-seizure drugs.
Serious side effects include liver failure, agranulocytosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, aplastic anemia, and pancreatitis.
Zonisamide blocks the sodium and calcium channels and is indicated for generalized and focal seizures. It is mainly metabolized in the liver. It interacts with multiple other anti-seizure drugs. It is dosed at 100 to 200 mg per day in two doses. To minimize side effects starting at 25 mg a day and increase it 25 mg a week until the patient is on 100 mg twice day can be tried. The dose is increased at two-week intervals to a typical dose of 400-600 mg/day.
Common side effects include fatigue, dizziness, somnolence, mental status changes, ataxia, anorexia, nausea, concentration problems, and depression. Serious side effects include Stevens-Johnson syndrome/toxic epidermal necrolysis, aplastic anemia, agranulocytosis, nephrolithiasis, acute myopia, glaucoma, hyperammonemia, and encephalopathy.
- To avoid danger, patients on these drugs should not drive or participate in activities requiring alertness.
- Patients with a seizure history should carry an ID card or medic alert bracelet that includes the drugs they take.
- Patients should take the drug with food or milk to decrease GI symptoms.
- Patients on prolonged therapy should have an adequate intake of Vitamin D foods and sufficient exposure to sunlight.
- Since the liver metabolizes some anticonvulsants, caution the patient to report any jaundice immediately.
- Caution the patient to take the drug as prescribed. Abrupt discontinuation may precipitate seizures and status epilepticus.
- Alcohol intake may increase drug levels leading to toxicity. When taking barbiturates, the patient should abstain from alcohol or psychotropic drugs unless directed by a physician.
- Patients should use good oral hygiene, including flossing daily to control gingival hyperplasia.
- Be sure to check required laboratory tests.
- Monitor the patient for changes in behavior.
- Monitor for hepatotoxicity.
- Monitor therapeutic range.
- When giving an anticonvulsant IV, frequently observe for signs of infiltration at the IV site since these drugs can destroy soft tissue. Continuously monitor vital signs closely during IV infusion and for 1 hour following completion. A cardiac monitor should be used. Watch for respiratory depression.