LEVETIRACETAM

brands

Class

• Anticonvulsant, synaptic vesicle protein SV2A modulator

LEVETIRACETAM commonly prescribed for

(Bold for FDA approved)

How LEVETIRACETAM works

• Binds to synaptic vesicle protein SV2A, which is involved in synaptic vesicle exocytosis

• Opposes the activity of negative modulators of GABA- and glycine-gated currents and partially inhibits N-type calcium currents in neuronal cells

How long until LEVETIRACETAM works

• Should reduce seizures by 2 weeks

• Not yet clear if it has mood-stabilizing effects in bipolar disorder or antineuralgic actions in chronic neuropathic pain, but some patients may respond and if so, would be expected to show clinical effects starting by 2 weeks although it may take several weeks to months to optimize clinical effects

Notable Side Effects

• Sedation, dizziness, ataxia, asthenia

• Hematologic abnormalities (decrease in red blood cell count and hemoglobin)

Life Threatening Side Effects

• Rare severe dermatologic reactions (Stevens–Johnson syndrome, toxic epidermal necrolysis)

• Activation of suicidal ideation and acts (rare)

• Changes in behavior (aggression, agitation, anxiety, hostility)

• Rare activation of suicidal ideation and behavior (suicidality)

weight gain

unusual

sedation

common

What to do about LEVETIRACETAM side effects

• Wait

• Wait

• Wait

• Take more of the dose at night to reduce daytime sedation

• Lower the dose

• Switch to another agent

usual dosage range

• 1000–3000 mg/day in 2 doses

Dosage Forms

• Tablet 250 mg, 500 mg, 750 mg, 1000 mg

• Extended-release tablet 500 mg, 750 mg, 1000 mg, 1500 mg

• Tablet for suspension 250 mg, 500 mg, 750 mg, 1000 mg

• Oral solution 100 mg/mL

• Intravenous injection 500 mg/5 mL

• Intravenous injection (levetiracetam in sodium chloride) 500 mg/100 mL, 1000 mg/100 mL, 1500 mg/100 mL

long term use

• Safe

habit forming

• No

Renal Impairment

• Recommended dose for patients with mild impairment may be between 500 mg and 1500 mg twice a day

• Recommended dose for patients with moderate impairment may be between 250 mg and 750 mg twice a day

• Recommended dose for patients with severe impairment may be between 250 mg and 500 mg twice a day

• Patients on dialysis may require doses between 500 mg and 1000 mg once a day, with a supplemental dose of 250–500 mg following dialysis

Hepatic Impairment

• Dose adjustment usually not necessary

Cardiac Impairment

• No specific recommendations

Elderly

• Some patients may tolerate lower doses better

• Elderly patients may be more susceptible to adverse effects

Children and Adolescents

• Safety and efficacy not established under age 16

• Children may require higher doses than adults; dosing should be adjusted according to weight

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

• Taper drug if discontinuing

• Seizures, even mild seizures, may cause harm to the embryo/fetus

• Lack of convincing efficacy for treatment of bipolar disorder or chronic neuropathic pain suggests risk/benefit ratio is in favor of discontinuing levetiracetam during pregnancy for these indications

• For bipolar patients, given the risk of relapse in the postpartum period, moodstabilizer treatment, especially with agents with better evidence of efficacy than levetiracetam, should generally be restarted immediately after delivery if patient is unmedicated during pregnancy

• For bipolar patients, levetiracetam should generally be discontinued before anticipated pregnancies

• Atypical antipsychotics may be preferable to levetiracetam if treatment of bipolar disorder is required during pregnancy

• Bipolar symptoms may recur or worsen during pregnancy and some form of treatment may be necessary

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or bottle feed

• If drug is continued while breast feeding, infant should be monitored for possible adverse effects

• If infant becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Bipolar disorder may recur during the postpartum period, particularly if there is a history of prior postpartum episodes of either depression or psychosis

• Relapse rates may be lower in women who receive prophylactic treatment for postpartum episodes of bipolar disorder

• Atypical antipsychotics and anticonvulsants such as valproate may be safer than levetiracetam during the postpartum period when breast feeding