Please wait while the formulary information is being retrieved.
Drug overview for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic):
Generic name: levetiracetam in sodium chloride, iso-osmotic
Drug class: Anticonvulsants
Therapeutic class: Central Nervous System Agents
Levetiracetam, a pyrrolidine derivative, is an anticonvulsant.
No enhanced Uses information available for this drug.
Generic name: levetiracetam in sodium chloride, iso-osmotic
Drug class: Anticonvulsants
Therapeutic class: Central Nervous System Agents
Levetiracetam, a pyrrolidine derivative, is an anticonvulsant.
No enhanced Uses information available for this drug.
DRUG IMAGES
LEVETIRACETAM-NACL 1,000MG/100
The following indications for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic) have been approved by the FDA:
Indications:
Myoclonic epilepsy adjunct treatment
Partial epilepsy treatment adjunct
Tonic-clonic epilepsy treatment adjunct
Professional Synonyms:
Adjunct medication therapy for myoclonic epilepsy
Grand mal epilepsy treatment adjunct
Partial onset seizures treatment adjunct
Partial seizures treatment adjunct
Tonic-clonic seizures treatment adjunct
Indications:
Myoclonic epilepsy adjunct treatment
Partial epilepsy treatment adjunct
Tonic-clonic epilepsy treatment adjunct
Professional Synonyms:
Adjunct medication therapy for myoclonic epilepsy
Grand mal epilepsy treatment adjunct
Partial onset seizures treatment adjunct
Partial seizures treatment adjunct
Tonic-clonic seizures treatment adjunct
The following dosing information is available for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic):
Levetiracetam therapy should not be discontinued abruptly.
When switching from oral to IV levetiracetam therapy, the initial total daily dosage of IV levetiracetam should be equivalent to the daily dose and frequency of oral levetiracetam. At the completion of the IV treatment period, the patient may be switched back to oral levetiracetam at the equivalent daily dose and frequency that was administered IV.
In adults 16 years of age and older, the recommended initial oral dosage of levetiracetam for adjunctive therapy of partial seizures is 1 g daily (administered as 500 mg twice daily as conventional tablets or oral solution, or 1 g once daily as extended-release tablets). Dosage may be increased in increments of 1 g daily at 2-week intervals up to the maximum recommended dosage of 3 g daily. However, some clinicians reportedly have initiated therapy with oral dosages of 2-4 g daily.
Dosages exceeding 3 g daily have been used in open-label studies for periods of 6 months or longer; however, the manufacturers state that there is no evidence that these higher dosages provide additional therapeutic benefit.
When oral therapy is temporarily not feasible, levetiracetam may be administered by IV infusion at the same dosages recommended for conventional oral preparations.
When conventional oral preparations of levetiracetam are used in pediatric patients, the manufacturer recommends that children weighing 20 kg or less receive the oral solution; children weighing more than 20 kg may receive either the immediate-release tablets or oral solution. Extended-release levetiracetam tablets are indicated for use only in pediatric patients 12 years of age and older.
In pediatric patients 1 to younger than 6 months of age, the recommended initial oral dosage of levetiracetam for adjunctive therapy of partial seizures is 14 mg/kg daily, administered as 7 mg/kg twice daily (as immediate-release preparations). Dosage should be increased in increments of 14 mg/kg daily at 2-week intervals up to the recommended dosage of 42 mg/kg daily, given as 21 mg/kg twice daily. In the clinical trial, the mean daily dosage was 35 mg/kg in this age group; efficacy of lower dosages has not been established.
In pediatric patients 6 months to younger than 4 years of age, the recommended initial oral dosage of levetiracetam is 20 mg/kg daily, administered as 10 mg/kg twice daily (as immediate-release preparations). Dosage should be increased in increments of 20 mg/kg daily at 2-week intervals up to the recommended dosage of 50 mg/kg daily, given as 25 mg/kg twice daily. Dosage may be reduced if the patient is unable to tolerate a dosage of 50 mg/kg daily.
In the clinical trial, the mean daily dosage was 47 mg/kg in this age group.
In pediatric patients 4 years to younger than 16 years of age, the recommended initial oral dosage of levetiracetam is 20 mg/kg daily, administered as 10 mg/kg twice daily (as immediate-release preparations). Dosage should be increased in increments of 20 mg/kg daily at 2-week intervals up to the recommended dosage of 60 mg/kg daily, given as 30 mg/kg twice daily. Dosage may be reduced if the patient is unable to tolerate a dosage of 60 mg/kg daily.
In the clinical trial, the mean daily dosage was 44 mg/kg and the maximum daily dosage was 3 g daily. If levetiracetam immediate-release tablets are used in pediatric patients weighing 20-40 kg, the recommended initial dosage is 500 mg daily, given as 250 mg twice daily; dosage may be increased in increments of 500 mg daily every 2 weeks up to a maximum of 1.5 g daily, given as 750 mg twice daily.
If levetiracetam immediate-release tablets are used in pediatric patients weighing more than 40 kg, the recommended initial dosage is 1 g daily, given as 500 mg twice daily; dosage may be increased in increments of 1 g daily every 2 weeks up to a maximum of 3 g daily, given as 1.5 g twice daily.
In pediatric patients 12 years of age and older, the recommended initial dosage of levetiracetam (as extended-release tablets) is 1 g once daily. Dosage may be increased in increments of 1 g daily at 2-week intervals up to the maximum recommended dosage of 3 g daily.
When oral therapy is temporarily not feasible, levetiracetam may be administered by IV infusion at the same dosages recommended for conventional oral preparations.
The recommended initial dosage of oral levetiracetam as adjunctive therapy for primary generalized tonic-clonic seizures in adults 16 years of age and older is 1 g daily, given as 500 mg twice daily (as immediate-release preparations). Dosage should be increased in increments of 1 g daily at 2-week intervals up to the recommended dosage of 3 g daily, given as 1.5 g twice daily.
Efficacy of dosages lower than 3 g daily has not been established.
When oral therapy is temporarily not feasible, levetiracetam may be administered by IV infusion at the same dosages recommended above.
The recommended initial dosage of oral levetiracetam as adjunctive therapy for primary generalized tonic-clonic seizures in pediatric patients 6 to younger than 16 years of age is 20 mg/kg daily, given as 10 mg/kg twice daily (as immediate-release preparations). Children weighing 20 kg or less should receive the oral solution; children weighing more than 20 kg may receive either the tablets (administered whole) or the oral solution. Dosage should be increased in increments of 20 mg/kg daily at 2-week intervals up to the recommended dosage of 60 mg/kg daily, given as 30 mg/kg twice daily.
Efficacy of dosages lower than 60 mg/kg daily has not been established.
When oral therapy is temporarily not feasible, levetiracetam may be administered by IV infusion at the same dosages recommended above.
When switching from oral to IV levetiracetam therapy, the initial total daily dosage of IV levetiracetam should be equivalent to the daily dose and frequency of oral levetiracetam. At the completion of the IV treatment period, the patient may be switched back to oral levetiracetam at the equivalent daily dose and frequency that was administered IV.
In adults 16 years of age and older, the recommended initial oral dosage of levetiracetam for adjunctive therapy of partial seizures is 1 g daily (administered as 500 mg twice daily as conventional tablets or oral solution, or 1 g once daily as extended-release tablets). Dosage may be increased in increments of 1 g daily at 2-week intervals up to the maximum recommended dosage of 3 g daily. However, some clinicians reportedly have initiated therapy with oral dosages of 2-4 g daily.
Dosages exceeding 3 g daily have been used in open-label studies for periods of 6 months or longer; however, the manufacturers state that there is no evidence that these higher dosages provide additional therapeutic benefit.
When oral therapy is temporarily not feasible, levetiracetam may be administered by IV infusion at the same dosages recommended for conventional oral preparations.
When conventional oral preparations of levetiracetam are used in pediatric patients, the manufacturer recommends that children weighing 20 kg or less receive the oral solution; children weighing more than 20 kg may receive either the immediate-release tablets or oral solution. Extended-release levetiracetam tablets are indicated for use only in pediatric patients 12 years of age and older.
In pediatric patients 1 to younger than 6 months of age, the recommended initial oral dosage of levetiracetam for adjunctive therapy of partial seizures is 14 mg/kg daily, administered as 7 mg/kg twice daily (as immediate-release preparations). Dosage should be increased in increments of 14 mg/kg daily at 2-week intervals up to the recommended dosage of 42 mg/kg daily, given as 21 mg/kg twice daily. In the clinical trial, the mean daily dosage was 35 mg/kg in this age group; efficacy of lower dosages has not been established.
In pediatric patients 6 months to younger than 4 years of age, the recommended initial oral dosage of levetiracetam is 20 mg/kg daily, administered as 10 mg/kg twice daily (as immediate-release preparations). Dosage should be increased in increments of 20 mg/kg daily at 2-week intervals up to the recommended dosage of 50 mg/kg daily, given as 25 mg/kg twice daily. Dosage may be reduced if the patient is unable to tolerate a dosage of 50 mg/kg daily.
In the clinical trial, the mean daily dosage was 47 mg/kg in this age group.
In pediatric patients 4 years to younger than 16 years of age, the recommended initial oral dosage of levetiracetam is 20 mg/kg daily, administered as 10 mg/kg twice daily (as immediate-release preparations). Dosage should be increased in increments of 20 mg/kg daily at 2-week intervals up to the recommended dosage of 60 mg/kg daily, given as 30 mg/kg twice daily. Dosage may be reduced if the patient is unable to tolerate a dosage of 60 mg/kg daily.
In the clinical trial, the mean daily dosage was 44 mg/kg and the maximum daily dosage was 3 g daily. If levetiracetam immediate-release tablets are used in pediatric patients weighing 20-40 kg, the recommended initial dosage is 500 mg daily, given as 250 mg twice daily; dosage may be increased in increments of 500 mg daily every 2 weeks up to a maximum of 1.5 g daily, given as 750 mg twice daily.
If levetiracetam immediate-release tablets are used in pediatric patients weighing more than 40 kg, the recommended initial dosage is 1 g daily, given as 500 mg twice daily; dosage may be increased in increments of 1 g daily every 2 weeks up to a maximum of 3 g daily, given as 1.5 g twice daily.
In pediatric patients 12 years of age and older, the recommended initial dosage of levetiracetam (as extended-release tablets) is 1 g once daily. Dosage may be increased in increments of 1 g daily at 2-week intervals up to the maximum recommended dosage of 3 g daily.
When oral therapy is temporarily not feasible, levetiracetam may be administered by IV infusion at the same dosages recommended for conventional oral preparations.
The recommended initial dosage of oral levetiracetam as adjunctive therapy for primary generalized tonic-clonic seizures in adults 16 years of age and older is 1 g daily, given as 500 mg twice daily (as immediate-release preparations). Dosage should be increased in increments of 1 g daily at 2-week intervals up to the recommended dosage of 3 g daily, given as 1.5 g twice daily.
Efficacy of dosages lower than 3 g daily has not been established.
When oral therapy is temporarily not feasible, levetiracetam may be administered by IV infusion at the same dosages recommended above.
The recommended initial dosage of oral levetiracetam as adjunctive therapy for primary generalized tonic-clonic seizures in pediatric patients 6 to younger than 16 years of age is 20 mg/kg daily, given as 10 mg/kg twice daily (as immediate-release preparations). Children weighing 20 kg or less should receive the oral solution; children weighing more than 20 kg may receive either the tablets (administered whole) or the oral solution. Dosage should be increased in increments of 20 mg/kg daily at 2-week intervals up to the recommended dosage of 60 mg/kg daily, given as 30 mg/kg twice daily.
Efficacy of dosages lower than 60 mg/kg daily has not been established.
When oral therapy is temporarily not feasible, levetiracetam may be administered by IV infusion at the same dosages recommended above.
Levetiracetam is administered orally (as immediate-release tablets, extended-release tablets, or oral solution). The drug also may be administered by IV infusion in patients in whom oral therapy is temporarily not feasible. Commercially available levetiracetam conventional (immediate-release) tablets, extended-release tablets, oral solution, and IV formulations have been shown to be bioequivalent.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| LEVETIRACETAM-NACL 500 MG/100 | Maintenance | Adults infuse 100 milliliters (500 mg) over 15 minute(s) by intravenous route 2 times per day |
| LEVETIRACETAM-NACL 1,000MG/100 | Maintenance | Adults infuse 100 milliliters (1,000 mg) over 15 minute(s) by intravenous route 2 times per day |
| LEVETIRACETAM-NACL 1,500MG/100 | Maintenance | Adults infuse 100 milliliters (1,500 mg) over 15 minute(s) by intravenous route 2 times per day |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| LEVETIRACETAM-NACL 1,000MG/100 | Maintenance | Adults infuse 100 milliliters (1,000 mg) over 15 minute(s) by intravenous route 2 times per day |
| LEVETIRACETAM-NACL 1,500MG/100 | Maintenance | Adults infuse 100 milliliters (1,500 mg) over 15 minute(s) by intravenous route 2 times per day |
| LEVETIRACETAM-NACL 500 MG/100 | Maintenance | Adults infuse 100 milliliters (500 mg) over 15 minute(s) by intravenous route 2 times per day |
The following drug interaction information is available for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic):
There are 0 contraindications.
There are 0 severe interactions.
There are 4 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Apixaban/Levetiracetam SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of the interaction is unknown. Levetiracetam may decrease the efficacy of apixaban. CLINICAL EFFECTS: Concurrent use of levetiracetam may result in decreased effectiveness of apixaban. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of levetiracetam in patients receiving apixaban should be approached with caution. Consider alternative anticonvulsants in patients maintained on apixaban. If concurrent use is warranted, monitor patients closely for decreased response to apixaban. DISCUSSION: A nested case-control study of 100,168 patients on apixaban, dabigatran, edoxaban, or rivaroxaban were reviewed for stroke (CVA)/systemic emboli in patients with atrial fibrillation or recurrent thromboembolism in patients with thromboembolism. The primary outcome of CVA/systemic embolism with concurrent use of levetiracetam resulted in an odds ratio (95% CI) of 2.38 (1.19-4.75) and a propensity score adjusted odds ratio (95% CI) of 2.26 (1.13-4.54) compared to controls.(5) A population-based retrospective cohort study of 8746 patients on apixaban, dabigatran, edoxaban, or rivaroxaban were evaluated for occurrence of first ischemic stroke with concurrent antiseizure medications. Antiseizure medications that induce CYP3A4 or P-gp were associated with an increased risk of ischemic stroke (annual incidence rate of 5.5% vs 3.9%, adjusted hazard ratio 1.28). The annual incidence rates of ischemic stroke (valproate: 5.1%; levetiracetam: 6.0%; control: 3.9%) and venous thromboembolism (valproate: 3.7%; levetiracetam: 3.8%; control: 3.0%) were higher among valproate and levetiracetam users but were not statistically different from controls.(6) In a case report, a 54 year old man with a complicated medical history including paroxysmal atrial fibrillation, heart failure, and epilepsy who was on levetiracetam 500 mg twice daily was started on dabigatran 150 mg twice daily, taken simultaneously with levetiracetam. On day 10 of dabigatran, trough levels were normal but Cmax was subtherapeutic. Separation of dabigatran administration to 4 hours before levetiracetam resulted in an increase of Cmax from 88 ng/mL to 101 ng/mL. Over 32 months of follow-up, no hemorrhagic or ischemic events occurred.(7) A retrospective study of 320 patients with atrial fibrillation on DOAC therapy for secondary stroke prevention compared the incidence of ischemic stroke or TIA in patients on concomitant CYP3A4 and P-gp inducing medications (n=43), P-gp inducing medications (n=13), or no interacting medications (n=264). Twenty of the patients were on levetiracetam. There was no statistically significant difference between any of the groups.(8) A small prospective cohort study of 19 patients on the combination of levetiracetam and DOACs (8 patients on dabigatran, 9 patients on apixaban, 4 patients on rivaroxaban) did not find a significant correlation between levetiracetam and DOAC concentrations. One patient who was on low-dose apixaban had low apixaban levels, and there were no thromboembolic events in the 1388 +/- 994 days of follow-up.(9) |
ELIQUIS |
| Dabigatran/Levetiracetam SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of the interaction is unknown. Levetiracetam may decrease the efficacy of dabigatran. CLINICAL EFFECTS: Concurrent use of levetiracetam may result in decreased effectiveness of dabigatran. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of levetiracetam in patients receiving dabigatran should be approached with caution. Consider alternative anticonvulsants in patients maintained on dabigatran. If concurrent use is warranted, monitor patients closely for decreased response to dabigatran. DISCUSSION: A nested case-control study of 100,168 patients on apixaban, dabigatran, edoxaban, or rivaroxaban were reviewed for stroke (CVA)/systemic emboli in patients with atrial fibrillation or recurrent thromboembolism in patients with thromboembolism. The primary outcome of CVA/systemic embolism with concurrent use of levetiracetam resulted in an odds ratio (95% CI) of 2.38 (1.19-4.75) and a propensity score adjusted odds ratio (95% CI) of 2.26 (1.13-4.54) compared to controls.(4) A population-based retrospective cohort study of 8746 patients on apixaban, dabigatran, edoxaban, or rivaroxaban were evaluated for occurrence of first ischemic stroke with concurrent antiseizure medications. Antiseizure medications that induce CYP3A4 or P-gp were associated with an increased risk of ischemic stroke (annual incidence rate of 5.5% vs 3.9%, adjusted hazard ratio 1.28). The annual incidence rates of ischemic stroke (valproate: 5.1%; levetiracetam: 6.0%; control: 3.9%) and venous thromboembolism (valproate: 3.7%; levetiracetam: 3.8%; control: 3.0%) were higher among valproate and levetiracetam users but were not statistically different from controls.(5) In a case report, a 54 year old man with a complicated medical history including paroxysmal atrial fibrillation, heart failure, and epilepsy who was on levetiracetam 500 mg twice daily was started on dabigatran 150 mg twice daily, taken simultaneously with levetiracetam. On day 10 of dabigatran, trough levels were normal but Cmax was subtherapeutic. Separation of dabigatran administration to 4 hours before levetiracetam resulted in an increase of Cmax from 88 ng/mL to 101 ng/mL. Over 32 months of follow-up, no hemorrhagic or ischemic events occurred.(6) A retrospective study of 320 patients with atrial fibrillation on DOAC therapy for secondary stroke prevention compared the incidence of ischemic stroke or TIA in patients on concomitant CYP3A4 and P-gp inducing medications (n=43), P-gp inducing medications (n=13), or no interacting medications (n=264). Twenty of the patients were on levetiracetam. There was no statistically significant difference between any of the groups.(7) A small prospective cohort study of 19 patients on the combination of levetiracetam and DOACs (8 patients on dabigatran, 9 patients on apixaban, 4 patients on rivaroxaban) did not find a significant correlation between levetiracetam and DOAC concentrations. One patient who was on low-dose apixaban had low apixaban levels, and there were no thromboembolic events in the 1388 +/- 994 days of follow-up.(8) |
DABIGATRAN ETEXILATE, PRADAXA |
| Edoxaban/Levetiracetam SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of the interaction is unknown. Levetiracetam may decrease the efficacy of edoxaban. CLINICAL EFFECTS: Concurrent use of levetiracetam may result in decreased effectiveness of edoxaban. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of levetiracetam in patients receiving edoxaban should be approached with caution. Consider alternative anticonvulsants in patients maintained on edoxaban. If concurrent use is warranted, monitor patients closely for decreased response to edoxaban. DISCUSSION: A nested case-control study of 100,168 patients on apixaban, dabigatran, edoxaban, or rivaroxaban were reviewed for stroke (CVA)/systemic emboli in patients with atrial fibrillation or recurrent thromboembolism in patients with thromboembolism. The primary outcome of CVA/systemic embolism with concurrent use of levetiracetam resulted in an odds ratio (95% CI) of 2.38 (1.19-4.75) and a propensity score adjusted odds ratio (95% CI) of 2.26 (1.13-4.54) compared to controls.(4) A population-based retrospective cohort study of 8746 patients on apixaban, dabigatran, edoxaban, or rivaroxaban were evaluated for occurrence of first ischemic stroke with concurrent antiseizure medications. Antiseizure medications that induce CYP3A4 or P-gp were associated with an increased risk of ischemic stroke (annual incidence rate of 5.5% vs 3.9%, adjusted hazard ratio 1.28). The annual incidence rates of ischemic stroke (valproate: 5.1%; levetiracetam: 6.0%; control: 3.9%) and venous thromboembolism (valproate: 3.7%; levetiracetam: 3.8%; control: 3.0%) were higher among valproate and levetiracetam users but were not statistically different from controls.(5) In a case report, a 54 year old man with a complicated medical history including paroxysmal atrial fibrillation, heart failure, and epilepsy who was on levetiracetam 500 mg twice daily was started on dabigatran 150 mg twice daily, taken simultaneously with levetiracetam. On day 10 of dabigatran, trough levels were normal but Cmax was subtherapeutic. Separation of dabigatran administration to 4 hours before levetiracetam resulted in an increase of Cmax from 88 ng/mL to 101 ng/mL. Over 32 months of follow-up, no hemorrhagic or ischemic events occurred.(6) A retrospective study of 320 patients with atrial fibrillation on DOAC therapy for secondary stroke prevention compared the incidence of ischemic stroke or TIA in patients on concomitant CYP3A4 and P-gp inducing medications (n=43), P-gp inducing medications (n=13), or no interacting medications (n=264). Twenty of the patients were on levetiracetam. There was no statistically significant difference between any of the groups.(7) A small prospective cohort study of 19 patients on the combination of levetiracetam and DOACs (8 patients on dabigatran, 9 patients on apixaban, 4 patients on rivaroxaban) did not find a significant correlation between levetiracetam and DOAC concentrations. One patient who was on low-dose apixaban had low apixaban levels, and there were no thromboembolic events in the 1388 +/- 994 days of follow-up.(8) |
SAVAYSA |
| Rivaroxaban/Levetiracetam SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of the interaction is unknown. Levetiracetam may decrease the efficacy of rivaroxaban. CLINICAL EFFECTS: Concurrent use of levetiracetam may result in decreased effectiveness of rivaroxaban. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of levetiracetam in patients receiving rivaroxaban should be approached with caution. Consider alternative anticonvulsants in patients maintained on rivaroxaban. If concurrent use is warranted, monitor patients closely for decreased response to rivaroxaban. DISCUSSION: A nested case-control study of 100,168 patients on apixaban, dabigatran, edoxaban, or rivaroxaban were reviewed for stroke (CVA)/systemic emboli in patients with atrial fibrillation or recurrent thromboembolism in patients with thromboembolism. The primary outcome of CVA/systemic embolism with concurrent use of levetiracetam resulted in an odds ratio (95% CI) of 2.38 (1.19-4.75) and a propensity score adjusted odds ratio (95% CI) of 2.26 (1.13-4.54) compared to controls.(4) A population-based retrospective cohort study of 8746 patients on apixaban, dabigatran, edoxaban, or rivaroxaban were evaluated for occurrence of first ischemic stroke with concurrent antiseizure medications. Antiseizure medications that induce CYP3A4 or P-gp were associated with an increased risk of ischemic stroke (annual incidence rate of 5.5% vs 3.9%, adjusted hazard ratio 1.28). The annual incidence rates of ischemic stroke (valproate: 5.1%; levetiracetam: 6.0%; control: 3.9%) and venous thromboembolism (valproate: 3.7%; levetiracetam: 3.8%; control: 3.0%) were higher among valproate and levetiracetam users but were not statistically different from controls.(5) In a case report, a 69-year-old male on rivaroxaban for nonvalvular atrial fibrillation experienced transient ischemic attacks while on concurrent levetiracetam. During concurrent use of levetiracetam, rivaroxaban levels were subtherapeutic. After tapering off levetiracetam, rivaroxaban levels were within therapeutic range and the transient ischemic attacks resolved.(6) In a case report, a 54 year old man with a complicated medical history including paroxysmal atrial fibrillation, heart failure, and epilepsy who was on levetiracetam 500 mg twice daily was started on dabigatran 150 mg twice daily, taken simultaneously with levetiracetam. On day 10 of dabigatran, trough levels were normal but Cmax was subtherapeutic. Separation of dabigatran administration to 4 hours before levetiracetam resulted in an increase of Cmax from 88 ng/mL to 101 ng/mL. Over 32 months of follow-up, no hemorrhagic or ischemic events occurred.(7) A retrospective study of 320 patients with atrial fibrillation on DOAC therapy for secondary stroke prevention compared the incidence of ischemic stroke or TIA in patients on concomitant CYP3A4 and P-gp inducing medications (n=43), P-gp inducing medications (n=13), or no interacting medications (n=264). Twenty of the patients were on levetiracetam. There was no statistically significant difference between any of the groups.(8) A small prospective cohort study of 19 patients on the combination of levetiracetam and DOACs (8 patients on dabigatran, 9 patients on apixaban, 4 patients on rivaroxaban) did not find a significant correlation between levetiracetam and DOAC concentrations. One patient who was on low-dose apixaban had low apixaban levels, and there were no thromboembolic events in the 1388 +/- 994 days of follow-up.(9) |
RIVAROXABAN, XARELTO |
The following contraindication information is available for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic):
Drug contraindication overview.
Levetiracetam is contraindicated in patients with known hypersensitivity to the drug.
Levetiracetam is contraindicated in patients with known hypersensitivity to the drug.
There are 0 contraindications.
There are 6 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic kidney disease stage 2 (mild) GFR 60-89 ml/min |
| Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Depression |
| Suicidal ideation |
There are 4 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Ataxia |
| Gait abnormality |
| Hallucinations |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
The following adverse reaction information is available for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic):
Adverse reaction overview.
Adverse effects occurring in 1% or more of adults receiving oral levetiracetam (as conventional preparations) for adjunctive management of partial seizures include somnolence, asthenia, headache, infection, dizziness, pain, pharyngitis, depression, nervousness, rhinitis, anorexia, ataxia, vertigo, amnesia, anxiety, emotional lability, hostility, paresthesia, increased cough, sinusitis, and diplopia. Adverse effects occurring in 2% or more of pediatric patients older than 4 years of age receiving oral levetiracetam (as conventional preparations) for adjunctive management of partial seizures include headache, vomiting, nasopharyngitis, somnolence, fatigue, aggression, upper abdominal pain, cough, nasal congestion, decreased appetite, dizziness, pharyngolaryngeal pain, abnormal behavior, dizziness, irritability, diarrhea, lethargy, insomnia, head injury, anorexia, agitation, constipation, influenza, contusion, fall, depression, altered mood, ear pain, conjunctivitis, gastroenteritis, rhinitis, joint sprain, arthralgia, neck pain, sedation, labile affect, anxiety, confusional state, and mood swing. The most common adverse effects in patients younger than 4 years of age were somnolence and irritability.
The adverse effect profile of levetiracetam (as conventional preparations) in patients with myoclonic seizures or primary generalized tonic-clonic seizures is generally similar to that of patients with partial seizures. Adverse effects occurring in 5% or more of patients receiving extended-release levetiracetam tablets for adjunctive management of partial seizures include influenza, somnolence, irritability, nasopharyngitis, dizziness, and nausea. Adverse effects associated with IV levetiracetam generally appear to be consistent with those associated with oral administration of the drug.
Adverse effects occurring in 1% or more of adults receiving oral levetiracetam (as conventional preparations) for adjunctive management of partial seizures include somnolence, asthenia, headache, infection, dizziness, pain, pharyngitis, depression, nervousness, rhinitis, anorexia, ataxia, vertigo, amnesia, anxiety, emotional lability, hostility, paresthesia, increased cough, sinusitis, and diplopia. Adverse effects occurring in 2% or more of pediatric patients older than 4 years of age receiving oral levetiracetam (as conventional preparations) for adjunctive management of partial seizures include headache, vomiting, nasopharyngitis, somnolence, fatigue, aggression, upper abdominal pain, cough, nasal congestion, decreased appetite, dizziness, pharyngolaryngeal pain, abnormal behavior, dizziness, irritability, diarrhea, lethargy, insomnia, head injury, anorexia, agitation, constipation, influenza, contusion, fall, depression, altered mood, ear pain, conjunctivitis, gastroenteritis, rhinitis, joint sprain, arthralgia, neck pain, sedation, labile affect, anxiety, confusional state, and mood swing. The most common adverse effects in patients younger than 4 years of age were somnolence and irritability.
The adverse effect profile of levetiracetam (as conventional preparations) in patients with myoclonic seizures or primary generalized tonic-clonic seizures is generally similar to that of patients with partial seizures. Adverse effects occurring in 5% or more of patients receiving extended-release levetiracetam tablets for adjunctive management of partial seizures include influenza, somnolence, irritability, nasopharyngitis, dizziness, and nausea. Adverse effects associated with IV levetiracetam generally appear to be consistent with those associated with oral administration of the drug.
There are 27 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Infection |
Hostility |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Acute hepatic failure Acute pancreatitis Acute renal failure Agranulocytosis Anaphylaxis Angioedema Chorea DRESS syndrome Drug-induced psychosis Erythema multiforme Hallucinations Hepatitis Hyponatremia Leukopenia Neutropenic disorder Pancytopenia Panic disorder Rhabdomyolysis Skin rash Stevens-johnson syndrome Suicidal ideation Thrombocytopenic disorder Toxic epidermal necrolysis Worsening of seizure |
There are 52 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Anorexia Dizziness Drowsy Eosinophilia Fatigue General weakness Headache disorder Irritability Nasal congestion Pharyngitis |
Aggressive behavior Agitation Anemia Ataxia Constipation Cough Depersonalization Depression Diarrhea Diplopia Ecchymosis Hyperkinesis Indifference Influenza Insomnia Lymphocytosis Memory impairment Mood changes Neck pain Nervousness Pain Paresthesia Rhinitis Sinusitis Symptoms of anxiety Vertigo Vomiting |
| Rare/Very Rare |
|---|
|
Accidental fall Alopecia Behavioral disorders Blurred vision Disturbance of attention Dyskinesia Eczema Gastroenteritis Hypertension Muscle weakness Myalgia Obsessive-compulsive disorder Personality disorders Pruritus of skin Weight loss |
The following precautions are available for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic):
Safety and efficacy of levetiracetam immediate-release tablets, oral solution, and injection for the management of partial onset seizures have not been established in pediatric patients younger than 1 month of age. Behavioral abnormalities (e.g., paranoia, confusional state, increased aggression) have been observed in pediatric patients 4-16 years of age with partial onset seizures receiving the drug. Safety and efficacy of levetiracetam immediate-release tablets, oral solution, and injection for the management of myoclonic seizures have not been established in pediatric patients younger than 12 years of age.
Safety and efficacy of levetiracetam immediate-release tablets, oral solution, and injection for the management of primary generalized tonic-clonic seizures have not been established in pediatric patients younger than 6 years of age. Safety and efficacy of extended-release levetiracetam tablets have not been established in pediatric patients younger than 12 years of age. Use of the extended-release tablets in children 12 years of age and older is supported by a placebo-controlled study using the immediate-release preparation in patients 4-16 years of age. Safety and efficacy of levetiracetam in sodium chloride injection have not been established in pediatric patients younger than 16 years of age.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Safety and efficacy of levetiracetam immediate-release tablets, oral solution, and injection for the management of primary generalized tonic-clonic seizures have not been established in pediatric patients younger than 6 years of age. Safety and efficacy of extended-release levetiracetam tablets have not been established in pediatric patients younger than 12 years of age. Use of the extended-release tablets in children 12 years of age and older is supported by a placebo-controlled study using the immediate-release preparation in patients 4-16 years of age. Safety and efficacy of levetiracetam in sodium chloride injection have not been established in pediatric patients younger than 16 years of age.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Available data in pregnant women have not identified a drug-associated risk of major birth defects or miscarriage with levetiracetam. In animal reproduction studies, developmental toxicity (increased embryofetal and offspring mortality, increased incidences of fetal structural abnormalities, decreased embryofetal and offspring growth, neurobehavioral alterations in offspring) was observed. Seizure control during pregnancy should be carefully monitored; decreased plasma concentrations of levetiracetam may occur during pregnancy and dosage adjustments may be necessary to maintain clinical response.
A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to anticonvulsant drugs during pregnancy. Encourage women who are taking levetiracetam during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 or https://www.aedpregnancyregistry.org.
A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to anticonvulsant drugs during pregnancy. Encourage women who are taking levetiracetam during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 or https://www.aedpregnancyregistry.org.
Levetiracetam is distributed into human milk. It is not known whether the drug has any effects on the breastfed infant or on milk production. Consider the benefits of breastfeeding along with the mother's clinical need for levetiracetam and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.
Controlled clinical studies evaluating levetiracetam have not included sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger adults. No substantial differences in safety have been observed in geriatric patients relative to younger adults.
The following prioritized warning is available for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for LEVETIRACETAM-NACL (levetiracetam in sodium chloride, iso-osmotic)'s list of indications:
| Myoclonic epilepsy adjunct treatment | |
| G40.3 | Generalized idiopathic epilepsy and epileptic syndromes |
| G40.30 | Generalized idiopathic epilepsy and epileptic syndromes, not intractable |
| G40.309 | Generalized idiopathic epilepsy and epileptic syndromes, not intractable, without status epilepticus |
| G40.31 | Generalized idiopathic epilepsy and epileptic syndromes, intractable |
| G40.319 | Generalized idiopathic epilepsy and epileptic syndromes, intractable, without status epilepticus |
| G40.4 | Other generalized epilepsy and epileptic syndromes |
| G40.40 | Other generalized epilepsy and epileptic syndromes, not intractable |
| G40.409 | Other generalized epilepsy and epileptic syndromes, not intractable, without status epilepticus |
| G40.41 | Other generalized epilepsy and epileptic syndromes, intractable |
| G40.419 | Other generalized epilepsy and epileptic syndromes, intractable, without status epilepticus |
| G40.B | Juvenile myoclonic epilepsy [impulsive petit mal] |
| G40.B0 | Juvenile myoclonic epilepsy, not intractable |
| G40.B01 | Juvenile myoclonic epilepsy, not intractable, with status epilepticus |
| G40.B09 | Juvenile myoclonic epilepsy, not intractable, without status epilepticus |
| G40.B1 | Juvenile myoclonic epilepsy, intractable |
| G40.B11 | Juvenile myoclonic epilepsy, intractable, with status epilepticus |
| G40.B19 | Juvenile myoclonic epilepsy, intractable, without status epilepticus |
| G40.C | Lafora progressive myoclonus epilepsy |
| G40.C0 | Lafora progressive myoclonus epilepsy, not intractable |
| G40.C01 | Lafora progressive myoclonus epilepsy, not intractable, with status epilepticus |
| G40.C09 | Lafora progressive myoclonus epilepsy, not intractable, without status epilepticus |
| G40.C1 | Lafora progressive myoclonus epilepsy, intractable |
| G40.C11 | Lafora progressive myoclonus epilepsy, intractable, with status epilepticus |
| G40.C19 | Lafora progressive myoclonus epilepsy, intractable, without status epilepticus |
| Partial epilepsy treatment adjunct | |
| G40.0 | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset |
| G40.00 | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, not intractable |
| G40.009 | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, not intractable, without status epilepticus |
| G40.01 | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable |
| G40.019 | Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable, without status epilepticus |
| G40.1 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures |
| G40.10 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable |
| G40.109 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable, without status epilepticus |
| G40.11 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable |
| G40.119 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable, without status epilepticus |
| G40.2 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures |
| G40.20 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, not intractable |
| G40.209 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, not intractable, without status epilepticus |
| G40.21 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable |
| G40.219 | Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable, without status epilepticus |
| Tonic-clonic epilepsy treatment adjunct | |
| G40.3 | Generalized idiopathic epilepsy and epileptic syndromes |
| G40.30 | Generalized idiopathic epilepsy and epileptic syndromes, not intractable |
| G40.309 | Generalized idiopathic epilepsy and epileptic syndromes, not intractable, without status epilepticus |
| G40.31 | Generalized idiopathic epilepsy and epileptic syndromes, intractable |
| G40.319 | Generalized idiopathic epilepsy and epileptic syndromes, intractable, without status epilepticus |
| G40.4 | Other generalized epilepsy and epileptic syndromes |
| G40.40 | Other generalized epilepsy and epileptic syndromes, not intractable |
| G40.409 | Other generalized epilepsy and epileptic syndromes, not intractable, without status epilepticus |
| G40.41 | Other generalized epilepsy and epileptic syndromes, intractable |
| G40.419 | Other generalized epilepsy and epileptic syndromes, intractable, without status epilepticus |
| G40.C | Lafora progressive myoclonus epilepsy |
| G40.C0 | Lafora progressive myoclonus epilepsy, not intractable |
| G40.C01 | Lafora progressive myoclonus epilepsy, not intractable, with status epilepticus |
| G40.C09 | Lafora progressive myoclonus epilepsy, not intractable, without status epilepticus |
| G40.C1 | Lafora progressive myoclonus epilepsy, intractable |
| G40.C11 | Lafora progressive myoclonus epilepsy, intractable, with status epilepticus |
| G40.C19 | Lafora progressive myoclonus epilepsy, intractable, without status epilepticus |
Formulary Reference Tool