LevETIRAcetam (Lexi-Drugs)

Drug Shortages

One or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information:

ASHP: http://www.ashp.org/menu/DrugShortages

Pronunciation

(lee va tye RA se tam)

Brand Names: US

Keppra; Keppra XR; Roweepra; Roweepra XR; Spritam [DSC]

Brand Names: Canada

Abbott-Levetiracetam [DSC]; ACT Levetiracetam; APO-Levetiracetam; Auro-Levetiracetam; BIO-Levetiracetam; DOM-Levetiracetam; JAMP-Levetiracetam; Keppra; NAT-Levetiracetam; PHL-Levetiracetam [DSC]; PMS-Levetiracetam; Priva-Levetiracetam; PRO-Levetiracetam-250; PRO-Levetiracetam-500; PRO-Levetiracetam-750; RAN-Levetiracetam; SANDOZ Levetiracetam; VAN-Levetiracetam

Pharmacologic Category

Anticonvulsant, Miscellaneous

Dosing: Adult

Note: When switching between oral and IV formulations, the total daily dose should be the same.

Craniotomy, seizure prophylaxis (alternative agent for phenytoin) (off-label use): IV, Oral: 1,000 mg/day in 2 divided doses is commonly used; a dosage range of 500 to 3,000 mg/day has been studied. After induction of anesthesia, administer first dose (eg, 500 to 1,000 mg IV [Paisansathan 2018]); subsequently, adjust dose based on response and tolerability (Fuller 2013; Iuchi 2015; Pourzitaki 2016).

Focal (partial) onset seizures and generalized onset seizures (FDA approved for juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures; may be used off-label for other seizure types):

Oral:

Immediate release (tablets, oral solution, tablets for oral suspension): Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose based on response and tolerability to the maximum recommended dose of 1,500 mg twice daily

Extended release (FDA approved only for focal [partial] onset seizures): Initial: 1,000 mg once daily; increase every 2 weeks by 1,000 mg/day based on response and tolerability to a maximum of 3,000 mg once daily

Note: In patients with epilepsy, oral loading doses of 1,500 to 2,000 mg (immediate release) have been well tolerated and may be useful for more rapidly achieving serum concentrations associated with seizure control (Betts 2000; Koubeissi 2008); however, the necessity of an oral loading dose has not been established.

IV: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose based on response and tolerability to a maximum of 1,500 mg twice daily.

Note: Additional benefit of oral or IV doses greater than 3,000 mg/day has not been established; however, oral doses of 4,000 mg/day have been studied in patients with refractory epilepsy but may be associated with a greater incidence of somnolence (Betts 2000; Striano 2005).

Status epilepticus (off-label use): IV: 1,000 to 3,000 mg administered at a rate of 2 to 5 mg/kg/minute (NCS [Brophy 2012]) or 40 to 60 mg/kg as a single dose infused over 15 minutes in combination with a parenteral benzodiazepine. Maximum dose: 4,500 mg. (AES [Glauser 2016]; Drislane 2018; Gaspard 2018).

Subarachnoid hemorrhage (short-term seizure prophylaxis) (off-label use): IV:

Loading dose: 20 mg/kg (rounded to the nearest 250 mg) over 60 minutes (Szaflarski 2010)

Maintenance dose: 1,000 mg over 15 minutes every 12 hours for 7 days; may be increased to a maximum dose of 1,500 mg every 12 hours if necessary (Szaflarski 2010)

Traumatic brain injury (severe acute) (short-term seizure prophylaxis) (off-label use): IV:

Loading dose: 20 mg/kg (rounded to the nearest 250 mg) over 60 minutes (Szaflarski 2010)

Maintenance dose: 1,000 mg over 15 minutes every 12 hours for 7 days; may be increased to a maximum dose of 1,500 mg every 12 hours if necessary (Szaflarski 2010)

Dosing: Geriatric

Refer to adult dosing; consider lowering initial dose by 30% to 50% and increasing gradually (eg, ≤125 mg/week) due to reduced drug clearance (Contin 2012; Theitler 2017).

Dosing: Renal Impairment: Adult

Note: The manufacturer’s labeling recommends estimating CrCl using the Cockcroft-Gault formula adjusted for BSA as follows: CrCl (mL/minute/1.73 m2) = CrCl (mL/minute)/BSA (m2) x 1.73

Immediate-release and IV formulations:

CrCl >80 mL/minute/1.73 m2: 500 to 1,500 mg every 12 hours

CrCl 50 to 80 mL/minute/1.73 m2: 500 to 1,000 mg every 12 hours

CrCl 30 to 50 mL/minute/1.73 m2: 250 to 750 mg every 12 hours

CrCl <30 mL/minute/1.73 m2: 250 to 500 mg every 12 hours

End-stage renal disease (ESRD) requiring hemodialysis: Dialyzable (50%); 500 to 1,000 mg every 24 hours; supplemental dose of 250 to 500 mg is recommended posthemodialysis

Peritoneal dialysis: 500 to 1,000 mg every 24 hours (Aronoff 2007)

Continuous renal replacement therapy (CRRT): 250 to 750 mg every 12 hours (Aronoff 2007)

Extended-release tablets:

CrCl >80 mL/minute/1.73 m2: 1,000 to 3,000 mg every 24 hours

CrCl 50 to 80 mL/minute/1.73 m2: 1,000 to 2,000 mg every 24 hours

CrCl 30 to 50 mL/minute/1.73 m2: 500 to 1,500 mg every 24 hours

CrCl <30 mL/minute/1.73 m2: 500 to 1,000 mg every 24 hours

ESRD requiring hemodialysis: Use of immediate-release formulation is recommended.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary

Dosing: Pediatric

Note: Use oral solution in infants and children ≤20 kg. Parenteral IV therapy should be temporary and transitioned to oral when able; when switching from oral to IV formulation, the total daily dose should be the same.

Myoclonic seizures with juvenile myoclonic epilepsy: Children ≥12 years and Adolescents: IV, Oral (immediate release: Tablets, oral solution [eg, Keppra], or tablets for oral suspension [Spritam]): Initial 500 mg twice daily; increase dosage every 2 weeks by 500 mg/dose twice daily, to the recommended dose of 1,500 mg twice daily. Efficacy of doses <3,000 mg/day has not been studied.

Partial onset seizures:

Infants 1 to <6 months: IV, Oral (immediate release: Solution): Initial: 7 mg/kg/dose twice daily; increase dosage every 2 weeks by 7 mg/kg/dose twice daily as tolerated, to the recommended dose of 21 mg/kg/dose twice daily; effectiveness of lower doses has not been established; during clinical trials, the mean daily dose was 35 mg/kg/day

Infants ≥6 months and Children <4 years: IV, Oral (immediate release: Solution or tablets): Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily, as tolerated, to the recommended dose of 25 mg/kg/dose twice daily; may reduce daily dose if not tolerated; during clinical trials, the mean daily dose was 47 mg/kg/day

Children ≥4 years and Adolescents <16 years:

IV: Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily, as tolerated, to a maximum of 30 mg/kg/dose twice daily; maximum daily dose: 3,000 mg/day; may reduce daily dose if not tolerated; during clinical trials, the mean daily dose was 44 mg/kg/day; in older pediatric patients and adults (eg, weight >50 kg), an initial fixed dose of 500 mg twice daily is suggested.

Oral:

Immediate release:

Weight-directed dosing: Oral solution: Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily, as tolerated, to a maximum of 30 mg/kg/dose twice daily; maximum daily dose: 3,000 mg/day; may reduce daily dose if not tolerated; during clinical trials, the mean daily dose was 44 mg/kg/day; in older pediatric patients and adults (eg, weight >50 kg), an initial fixed dose of 500 mg twice daily is suggested.

Fixed dosing: Tablet (immediate release [eg, Keppra] or for oral suspension [Spritam]):

20 to 40 kg: Initial: 250 mg twice daily; increase every 2 weeks by 250 mg twice daily to the maximum recommended dose of 750 mg twice daily

>40 kg: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg twice daily to the maximum recommended dose of 1,500 mg twice daily. Additional benefit with doses >3,000 mg/day has not been shown.

Extended release (eg, Elepsia XR; Keppra XR): Children ≥12 years and Adolescents: Initial: 1,000 mg once daily; may increase every 2 weeks by 1,000 mg/day to a maximum of 3,000 mg once daily

Adolescents ≥16 years:

IV: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose twice daily, if tolerated, to a maximum dose of 1,500 mg twice daily. Efficacy of doses >3,000 mg/dayhas not been established.

Oral:

Immediate release (tablets, oral solution [eg, Keppra], tablets for oral suspension [Spritam]): Initial: 500 mg twice daily; increase every 2 weeks by 500 mg twice daily to the maximum recommended dose of 1,500 mg twice daily. Efficacy of doses >3,000 mg/day has not been studied.

Extended release (eg, Elepsia XR, Keppra XR): Initial: 1,000 mg once daily; increase every 2 weeks by 1,000 mg/day to a maximum of 3,000 mg once daily

Status epilepticus, refractory:

Neurocritical care guidelines (NCS [Brophy 2012]): Limited data available: Infants, Children, and Adolescents: IV: 20 to 60 mg/kg as a single dose; initiate maintenance therapy based upon clinical response and type of seizure disorder; Note: Maximum dose in adults is 3,000 mg/dose

American epilepsy society guidelines (AES [Glauser 2016]): Limited data available: Infants, Children, and Adolescents: IV: 60 mg/kg as a single dose; maximum dose: 4,500 mg/dose; initiate maintenance therapy based upon clinical response and type of seizure disorder

Tonic-clonic seizures; primary generalized:

Children ≥6 years and Adolescents <16 years:

IV: Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily to the recommended dose of 30 mg/kg/dose twice daily. Efficacy of doses <60 mg/kg/day has not been established. In older pediatric patients and adults (eg, weight >50 kg), an initial fixed dose of 500 mg twice daily is suggested.

Oral: Immediate release:

Weight-directed: Oral solution or tablets: Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily to the recommended dose of 30 mg/kg/dose twice daily. Efficacy of doses <60 mg/kg/day has not been established. In pediatric patients and adults (eg, weight >50 kg), an initial fixed dose of 500 mg twice daily is suggested.

Fixed-dosing: Orally disintegrating tablets [Spritam]:

20 to 40 kg: Initial: 250 mg twice daily; increase every 2 weeks by 250 mg twice daily to the maximum recommended dose of 750 mg twice daily

>40 kg: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg twice daily to the maximum recommended dose of 1,500 mg twice daily. Efficacy of doses <3,000 mg/day has not been established.

Adolescents ≥16 years: IV, Oral (immediate release: Solution or tablets [eg, Keppra], tablets for oral suspension [Spritam]): Initial: 500 mg twice daily; increase dosage every 2 weeks by 500 mg/dose twice daily to the recommended dose of 1,500 mg twice daily. Efficacy of doses <3,000 mg/day has not been established.

Dosing: Renal Impairment: Pediatric

Infants, Children, and Adolescents <16 years: There are no dosage adjustments provided in the manufacturer’s labeling; clearance is decreased and correlates with creatinine clearance. Some have recommended the following for immediate-release tablets, oral solution, and IV formulations (Aronoff 2007):

GFR <50 mL/minute/1.73 m2: Administer 50% of the dose.

Hemodialysis: Dialyzable (50%); administer 50% of normal dose every 24 hours; a supplemental dose after hemodialysis is recommended.

CAPD: Administer 50% of normal dose.

CRRT: Administer 50% of normal dose.

Adolescents ≥16 years:

IV, Oral (immediate release [tablets, oral solution] and tablets for oral suspension [Spritam]):

CrCl >80 mL/minute/1.73 m2: 500 to 1,500 mg every 12 hours

CrCl 50 to 80 mL/minute/1.73 m2: 500 to 1,000 mg every 12 hours

CrCl 30 to 50 mL/minute/1.73 m2: 250 to 750 mg every 12 hours

CrCl <30 mL/minute/1.73 m2: 250 to 500 mg every 12 hours

End-stage renal disease patients using dialysis: Dialyzable (50%); 500 to 1,000 mg every 24 hours; a supplemental dose of 250 to 500 mg following dialysis is recommended

Peritoneal dialysis: 500 to 1,000 mg every 24 hours (Aronoff 2007)

CRRT: 250 to 750 mg every 12 hours (Aronoff 2007)

Oral extended release (Elepsia XR, Keppra XR): There are no pediatric-specific recommendations provided in the manufacturer’s labeling; based on experience in adult patients, dosage adjustment suggested.

Dosing: Hepatic Impairment: Pediatric

No dosage adjustment necessary

Use: Labeled Indications

Focal (partial) onset:

Immediate-release tablets/oral solution/tablets for oral suspension: Adjunctive therapy in the treatment of focal (partial) onset seizures in adults and children 1 month and older (Keppra) or 4 years and older and more than 20 kg (Spritam) with epilepsy.

Extended-release tablets: Adjunctive therapy in the treatment of focal (partial) onset seizures in adults and adolescents 12 years and older with epilepsy.

IV: Adjunctive therapy in the treatment of focal (partial) onset seizures in adults and children 1 month and older with epilepsy.

Generalized onset:

Juvenile myoclonic epilepsy:

Immediate-release tablets/oral solution/tablets for oral suspension: Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years and older with juvenile myoclonic epilepsy.

IV: Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years and older with juvenile myoclonic epilepsy.

Primary generalized tonic-clonic seizures:

Immediate-release tablets/oral solution/tablets for oral suspension: Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years and older with idiopathic generalized epilepsy.

IV: Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years and older with idiopathic generalized epilepsy.

Use: Off-Label: Adult

  Craniotomy, seizure prophylaxisLevel of Evidence [B]

Data from a systematic review and meta-analysis support the use of levetiracetam as an alternative to phenytoin for seizure prophylaxis during craniotomy and in the postoperative period Ref.

  Status epilepticusLevel of Evidence [G]

Based on the Neurocritical Care Society guidelines for the evaluation and management of status epilepticus and the American Epilepsy Society guideline for the treatment of convulsive status epilepticus, the use of levetiracetam is an effective and recommended treatment option for urgent control of status epilepticus. However, benzodiazepines continue to be the agents of choice for initial therapy.

  Subarachnoid hemorrhage (short-term seizure prophylaxis)Level of Evidence [C, G]

According to current guidelines for the management of subarachnoid hemorrhage (SAH), prophylactic anticonvulsants may be considered following hemorrhage; however, data presented from 2 prospective trials present inconclusive results. Levetiracetam may be considered following SAH in patients who have a history of seizure disorder, aneurysm in the middle cerebral artery, intracerebral hematoma, infarction, and intractable hypertension. Additional randomized, controlled trials further evaluating levetiracetam for prophylaxis of seizures following SAH are necessary before it can be routinely recommended. Access Full Off-Label Monograph

  Traumatic brain injury, severe acute (short-term seizure prophylaxis)Level of Evidence [B]

Data from a meta-analysis that included 1 randomized, controlled trial and 7 cohort studies support the use of intravenous levetiracetam for early seizure prophylaxis following severe traumatic brain injury Ref.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

American Academy of Neurology and American Epilepsy Society, “Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy,” 2018

American Academy of Neurology and American Epilepsy Society, “Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy, “ 2018

American Epilepsy Society, “Treatment of Convulsive Status Epilepticus in Children and Adults,” January 2016

Administration: IV

For IV use only; infuse over 15 minutes.

Administration: Injectable Detail

pH: 5.5

Administration: Oral

Administer without regard to meals.

Oral solution: Administer with a calibrated measuring device (not a household teaspoon or tablespoon).

Tablet (immediate release and extended release): Only administer as whole tablet; do not crush, break or chew.

Tablet for oral suspension: Remove from blister by peeling back the foil (do not push tablet through the foil). Place whole tablet on the tongue with dry hand, follow with a sip of liquid and swallow only after tablet disintegrates. Do not swallow tablets intact. Partial tablets should not be administered. Tablet disintegrates in a mean time of 11 seconds (ranging from 2 to 27 seconds) in the mouth when taken with a sip of liquid.

Alternatively, allow whole tablet to disperse in a small volume of liquid (one tablespoon or enough to cover the tablet) in a cup; consume entire contents immediately; resuspend any residue by adding an additional small volume of liquid and swallow the full amount.

Administration: Pediatric

Oral: May be administered without regard to meals

Immediate release and extended release tablets: Swallow tablets whole; do not break, crush, or chew.

Oral solution: Administer with calibrated measuring device (not household teaspoon or tablespoon).

Tablets for oral suspension (Spritam): Remove from blister by peeling back the foil (do not push tablet through the foil). Place whole tablet on the tongue with dry hand; follow with a sip of liquid and swallow only after tablet disintegrates; do not swallow intact tablet. Partial/split tablets should not be administered. Tablet disintegrates in a mean time of 11 seconds (ranging from 2 to 27 seconds) in the mouth when taken with a sip of liquid.

Alternatively, allow whole tablet to disperse in a small volume of liquid (eg, 15 mL or enough to cover the tablet[s]) in a cup; consume entire contents immediately; resuspend any residue in cup by adding an additional small volume of liquid and swallow the full amount

Parenteral: IV: Vials must be diluted prior to use. Do not use if solution contains particulate matter or is discolored. Discard unused portions; does not contain preservative. Infuse over 15 minutes; in status epilepticus a rate of 2 to 5 mg/kg/minute has been recommended (NCS [Brophy 2012]). Others have safely used a 1:1 dilution infused over 5 to 6 minutes (with doses up to 60 mg/kg) through a peripheral site in patients 4 to 32 years of age (Wheless 2009).

Storage/Stability

Oral solution, tablets, tablets for oral suspension: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Premixed solution for infusion: Store at 20°C to 25°C (68°F to 77°F).

Vials for injection: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Admixed solution in NS, LR, or D5W is stable for 4 hours in PVC bags kept at room temperature (Note: The manufacturer’s labeling for Keppra injection previously stated the admixed solution is stable for 24 hours in PVC bags at room temperature; this was changed to 4 hours as of April 2016 although there was no change in the formulation (Personal Communication, UCB, Inc. 2016). The manufacturer’s labeling for generic levetiracetam injectable products may have differing recommendations; refer to individual manufacturer’s labeling for details.

Preparation for Administration: Adult

Vials for injection: Must dilute dose in 100 mL of NS, LR, or D5W. If a smaller volume is required (eg, pediatric patients) the amount of diluent should be calculated to not exceed a maximum levetiracetam concentration of 15 mg/mL of diluted solution.

Preparation for Administration: Pediatric

Parenteral: IV: Vials: Dilute dose in 100 mL of NS, LR, or D5W; if smaller diluent volume required (eg, pediatric patients), dilute dose in a compatible diluent to maximum final concentration of 15 mg/mL. A 1:1 dilution of drug from vial with D5W or NS has also been safely used in patients ≥4 years (Wheless 2009).

Compatibility

See Trissel’s IV Compatibility Database

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, rhinitis, rhinorrhea, insomnia, abdominal pain, pharyngitis, nausea, vomiting, lack of appetite, or flu-like symptoms. Have patient report immediately to prescriber signs of angioedema, signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), signs of infection, seizures, hallucinations, severe loss of strength and energy, severe dizziness, severe headache, passing out, change in balance, abnormal gait, severe fatigue, bruising, bleeding, agitation, irritability, panic attacks, mood changes, behavioral changes, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Keppra: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021035s099,021505s038lbl.pdf#page=28

Keppra XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022285s025lbl.pdf#page=21

Spritam: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM487803.pdf

Contraindications

Hypersensitivity (eg, anaphylaxis, angioedema) to levetiracetam or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression (impaired coordination, ataxia, abnormal gait, weakness, fatigue, dizziness, and somnolence), which may impair physical or mental abilities. Symptoms occur most commonly during the first month of therapy. Patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Dermatologic reactions: Severe reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported in adults and children. Onset is usually within ~2 weeks of treatment initiation, but may be delayed (>4 months); recurrence following rechallenge has been reported. Levetiracetam should be discontinued if there are any signs of a hypersensitivity reaction or unspecified rash; if signs or symptoms suggest SJS or TEN, do not resume therapy and consider alternative treatment.

• Hematologic effects: Decreases in red blood cell counts, hemoglobin, hematocrit, white blood cell counts, and neutrophils and increases in eosinophils have been observed. Cases of, agranulocytosis, pancytopenia, and thrombocytopenia have also been reported.

• Hypersensitivity reactions: Potentially life-threatening hypersensitivity reactions, including anaphylaxis, angioedema, hypotension, hives, rash and respiratory distress may occur after the first dose or at any time during treatment. If signs or symptoms of anaphylaxis or angioedema occur, discontinue levetiracetam immediately. If a clear alternative etiology for the symptoms cannot be determined, discontinue permanently.

• Hypertension: Isolated elevations in diastolic blood pressure measurements have been reported in children <4 years; however, no observable differences were noted in mean diastolic measurements of children receiving levetiracetam vs placebo. Similar effects have not been observed in older children and adults.

• Psychiatric symptoms: Psychosis, paranoia, hallucinations and behavioral symptoms (including aggression, agitation, anger, anxiety, apathy, confusion, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personality disorder) may occur; dose reduction or discontinuation may be required.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.

Disease-related concerns:

• Renal impairment: Use caution with renal impairment; dosage adjustment may be necessary. In patients with ESRD requiring hemodialysis, it is recommended that immediate-release formulations be used instead of ER formulations.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Children may have increased incidence of psychiatric symptoms; dose reduction or discontinuation may be required.

Other warnings/precautions:

• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Geriatric Considerations

In a study of 16 older adults (61-88 years of age) receiving levetiracetam daily and with creatinine clearances ranging from 30-74 mL/minute, a decrease in creatinine clearance (38%) and a 2.5 hour longer half-life were recorded in the elderly compared to younger adults. The authors concluded that the difference was due to renal function. Other studies show no overall difference in safety and efficacy, although larger numbers in studies are needed to verify efficacy. Levetiracetam has demonstrated a low incidence of cognitive effects. When using the drug in elderly, it is essential to base the dose on estimated creatinine clearance and adjust appropriately.

Warnings: Additional Pediatric Considerations

Incidence of behavioral abnormalities is higher in children (37.6%) than adults (13.3%); dosage reductions may be required. In clinical trials, pediatric patients 4 to <16 years, when compared with placebo, had statistically significant decreases in WBC and neutrophil counts; in one clinical trial, possible clinically significant decreases in WBCs were observed, but no difference in neutrophil counts was observed. Isolated elevations in diastolic blood pressure (DBP) measurements have been reported in infants and children 1 month to <4 years of age receiving levetiracetam; however, no difference was noted in mean diastolic measurements of these patients vs placebo group; monitor blood pressure in infants and children <4 years. Similar effects have not been observed in older children and adults. In pediatric clinical trials, the most frequently reported adverse reactions in pediatric patients 4 to <16 years of age were fatigue, aggression, nasal congestion, decreased appetite, and irritability and in younger pediatric patients (1 month to <4 years of age) were somnolence and irritability; additionally, children may experience a higher frequency of certain adverse effects than adults, including the following: Behavioral abnormalities (37.6% vs 13.3%), aggression/hostility (10% vs 2%), vomiting (reported in children only, 15%), and cough (9% vs 2%).

A retrospective chart review of 280 neonates who had received either phenobarbital, levetiracetam, or both for treatment of neonatal seizures evaluated neurodevelopment. A subset of the study group (n=67) had a Bayley Scales of Infant Development (BSID) completed at 24 months corrected age. Based on the analysis of cumulative exposures, the investigators observed that increased levetiracetam exposure was associated with a significant decrease in BSID cognitive (2.2 points) and motor (2.6 points) scores for every 300 mg/kg of levetiracetam exposure and no increased incidence of cerebral palsy was observed; however, increased neonatal exposure to phenobarbital was associated with larger significant reductions in BSID cognitive and motor scores (8 to 9 points) and an increased probability for the development of cerebral palsy. Since most patients received both drugs and thus were included in both evaluation groups and due to the retrospective design, a direct causality between levetiracetam exposure and negative cognitive and motor outcomes could not be confirmed (Maitre 2013).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse effects were observed in animal reproduction studies. Levetiracetam crosses the placenta and can be detected in the newborn following delivery (Johannessen 2005; Lopez-Fraile 2009; Tomson 2007). An increase in the overall rate of major congenital malformations has not been observed following maternal use of levetiracetam. Available studies have not been large enough to determine if there is an increased risk of specific birth defects (Hernandez-Diaz 2012; Mawhinney 2013; Mølgaard-Nielsen 2011; Vajda 2012). In general, maternal polytherapy with antiepileptic drugs may increase the risk of congenital malformations; monotherapy with the lowest effective dose is recommended. Newborns of women taking antiepileptic medications may be at an increased risk of SGA and a 1 minute APGAR score <7 (Harden 2009). Plasma concentrations of levetiracetam gradually decrease during pregnancy, especially during the third trimester, due to physiologic changes which occur; patients should be monitored during pregnancy and postpartum.

A registry is available for women exposed to levetiracetam during pregnancy: Pregnant women may enroll themselves into the North American Antiepileptic Drug (AED) Pregnancy Registry (888-233-2334 or http://www.aedpregnancyregistry.org/).

Breast-Feeding Considerations

Levetiracetam is present in breast milk.

The relative infant dose (RID) of levetiracetam is 7.9% when calculated using data derived from the highest breast milk concentration located and compared to a weight-adjusted maternal dose of 1,000 to 3,000 mg/day.

In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).

The RID of levetiracetam was calculated using an average milk:maternal plasma ratio of 1.05, providing an estimated daily infant dose via breast milk of ~2.4 mg/kg/day. This average milk:maternal plasma ratio was calculated using samples collected from 11 mother-infant pairs 4 to 23 days’ postpartum following maternal administration of oral levetiracetam 1,000 to 3,000 mg/day. Concomitant maternal medications included lamotrigine, carbamazepine, tiagabine, clobazam, and/or oxcarbazepine which may have impacted maternal plasma concentrations. Levetiracetam was detected in the plasma of the breastfed infants (Tomson 2007).

Adverse effects, including hypotonia, sedation, vomiting, weight loss, and poor suckling have been reported in breastfed infants (Kramer 2002; Paret 2014). Insufficient lactation and subsequent discontinuation of breastfeeding has also been reported (Paret 2014).

Breastfeeding is not recommended by the manufacturer. Infants exposed to levetiracetam via breast milk should be monitored for adverse effects and for achievement of developmental milestones. Maternal plasma concentrations should be monitored postpartum.

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Incidences are for all indications and populations (adults and children) unless otherwise specified.

>10%:

Cardiovascular: Increased blood pressure (diastolic; infants and children: 17%)

Central nervous system: Behavioral problems (includes aggression, agitation, anger, anxiety, apathy, depersonalization, emotional lability, irritability, neurosis; children and adolescents: 7% to 38%; adults: 7% to 13%), headache (14% to 19%), psychotic symptoms (infants and children: 17%; adults: 1%), drowsiness (8% to 15%; immediate release 4,000 mg/day, no titration: 45%; serious [patients hospitalized]: <1%), irritability (infants, children, and adolescents: 6% to 12%), fatigue (10% to 11%)

Gastrointestinal: Vomiting (children and adolescents: 15%)

Infection: Infection (13%)

Neuromuscular & skeletal: Weakness (15%)

Respiratory: Nasopharyngitis (7% to 15%)

1% to 10%:

Central nervous system: Aggressive behavior (children and adolescents: 10%; adults: 1%), dizziness (5% to 9%), pain (7%), lethargy (children and adolescents: 6%), insomnia (children and adolescents: 5%), depression (3% to 5%), vertigo (3% to 5%), emotional lability (2% to 5%), agitation (children and adolescents: 4%), nervousness (4%), ataxia (partial-onset seizures: 3%; includes abnormal gait, incoordination), falling (children and adolescents: 3%), mood changes (children and adolescents: 3%), confusion (2% to 3%), amnesia (2%), anxiety (2%), hostility (2%), paranoia (children and adolescents: 2%), paresthesia (2%), sedation (children and adolescents: 2%)

Gastrointestinal: Upper abdominal pain (children and adolescents: 9%), decreased appetite (children and adolescents: 8%), diarrhea (6% to 8%), nausea (5%), anorexia (3% to 4%), constipation (children and adolescents: 3%), gastroenteritis (children and adolescents: 2%)

Hematologic & oncologic: Eosinophilia (children and adolescents: 9%), bruise (children and adolescents: 3%), decreased white blood cell count (3%), decreased neutrophils (2%)

Infection: Influenza (3% to 8%)

Neuromuscular & skeletal: Neck pain (2% to 8%), arthralgia (children and adolescents: 2%), joint sprain (children and adolescents: 2%)

Ophthalmic: Conjunctivitis (children and adolescents: 2%), diplopia (2%)

Otic: Otalgia (children and adolescents: 2%)

Respiratory: Nasal congestion (children and adolescents: 9%), cough (2% to 9%), pharyngolaryngeal pain (children and adolescents: 7%), pharyngitis (6% to 7%), rhinitis (2% to 4%), sinusitis (2%)

Miscellaneous: Head trauma (children and adolescents: 4%)

<1%, postmarketing and/or case reports: Abnormal hepatic function tests, acute renal failure, agranulocytosis, alopecia, anaphylaxis, angioedema, blurred vision, choreoathetosis, decreased hematocrit, decreased hemoglobin, decreased red blood cells, disturbance in attention, DRESS syndrome, dyskinesia, eczema, equilibrium disturbance, erythema multiforme, granulomatous interstitial nephritis (Chau 2012), hepatic failure, hepatitis, hyperkinesia, hyponatremia, leukopenia, memory impairment, myalgia, myasthenia, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression in some cases), panic attack, personality disorder, pruritus, psychosis, skin rash, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies, thrombocytopenia, toxic epidermal necrolysis, weight loss

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

None known.

Drug Interactions 

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Brivaracetam: LevETIRAcetam may diminish the therapeutic effect of Brivaracetam. Specifically, the therapeutic effect of brivaracetam may be diminished and/or negligible when given to patients already receiving levetiracetam. Risk D: Consider therapy modification

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

CarBAMazepine: LevETIRAcetam may enhance the adverse/toxic effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Fosphenytoin-Phenytoin: May decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification

Methotrexate: LevETIRAcetam may increase the serum concentration of Methotrexate. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

Orlistat: May decrease the serum concentration of Anticonvulsants. Risk C: Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

OXcarbazepine: May decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

PHENobarbital: May decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Primidone: May decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Food Interactions

Food may delay, but does not affect the extent of absorption. Management: Administer without regard to meals.

Monitoring Parameters

CNS depression (impaired coordination, ataxia, abnormal gait, weakness, fatigue, dizziness, and somnolence); psychiatric and behavioral symptoms (aggression, agitation, anger, anxiety, apathy, confusion, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, suicidal thoughts and personality disorder); diastolic blood pressure in children 1 month to <4 years; CBC (in patients who experience significant weakness, pyrexia, recurrent infections or coagulation disorders).

Reference Range

Timing of serum samples: Draw trough just before next dose.

Laboratory alert level: 50 mcg/mL (SI: 294 mcmol/L) (AGNP [Hiemke 2018])

Therapeutic reference range: Note: There is no clear correlation with therapeutic levels and efficacy or tolerability; base dosing on therapeutic response as opposed to serum concentrations. However, therapeutic drug levels may be useful in elderly patients, neonates, pregnant women, and patients on enzyme-inducing drugs or with renal insufficiency due to the wide range of alterations in clearance (Sourbron 2018).

Epilepsy: 12 to 46 mcg/mL (SI: 70 to 270 mcmol/L) (AGNP [Hiemke 2018]; ILAE [Patsalos 2008])

Advanced Practitioners Physical Assessment/Monitoring

Monitor for CNS depression, psychiatric abnormalities, or behavioral abnormalities. Monitor therapeutic effectiveness (seizure activity, type, duration) at beginning of therapy and throughout. Teach patient seizure safety precautions.

Nursing Physical Assessment/Monitoring

Monitor therapeutic response (seizure activity, force, type, duration) at beginning of therapy and periodically throughout. Monitor for CNS depression (somnolence and fatigue), behavioral abnormalities (psychosis, hallucinations, psychotic depression), and other behavioral symptoms (agitation, anger, aggression, irritability, hostility, anxiety, apathy, emotional lability, depersonalization, and depression). Observe and teach seizure/safety precautions.

Product Availability

Elepsia XR: FDA approved December 2018; anticipated availability is currently unknown. Information pertaining to this product within the monograph is pending revision. Consult the prescribing information for additional information.

Dosage Forms Considerations

Note: Tablets for oral suspension and soluble disintegrating tablet both refer to Spritam.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Keppra: 500 mg/5 mL (5 mL)

Generic: 500 mg/100 mL (100 mL); 1000 mg/100 mL (100 mL); 1500 mg/100 mL (100 mL); 500 mg/5 mL (5 mL)

Solution, Intravenous [preservative free]:

Generic: 500 mg/100 mL (100 mL); 1000 mg/100 mL (100 mL); 1500 mg/100 mL (100 mL); 500 mg/5 mL (5 mL)

Solution, Oral:

Keppra: 100 mg/mL (473 mL) [gluten free, lactose free; contains acesulfame potassium, methylparaben, propylparaben; grape flavor]

Generic: 100 mg/mL (5 mL, 473 mL, 500 mL)

Tablet, Oral:

Keppra: 250 mg [scored; contains fd&c blue #2 (indigotine)]

Keppra: 500 mg [scored]

Keppra: 750 mg [scored; contains fd&c yellow #6 (sunset yellow)]

Keppra: 1000 mg [scored]

Roweepra: 500 mg

Roweepra: 500 mg [scored; contains corn starch]

Roweepra: 750 mg [contains corn starch, fd&c yellow #6 aluminum lake]

Roweepra: 1000 mg [contains corn starch]

Generic: 250 mg, 500 mg, 750 mg, 1000 mg

Tablet Disintegrating Soluble, Oral:

Spritam: 250 mg [DSC]

Spritam: 250 mg [DSC] [spearmint flavor]

Spritam: 500 mg [DSC]

Spritam: 500 mg [DSC] [spearmint flavor]

Spritam: 750 mg [DSC]

Spritam: 750 mg [DSC] [spearmint flavor]

Spritam: 1000 mg [DSC]

Spritam: 1000 mg [DSC] [spearmint flavor]

Tablet Extended Release 24 Hour, Oral:

Keppra XR: 500 mg, 750 mg

Roweepra XR: 500 mg, 750 mg

Generic: 500 mg, 750 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Keppra: 250 mg, 500 mg, 750 mg

Generic: 250 mg, 500 mg, 750 mg, 1000 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N03AX14
Generic Available (US)

May be product dependent

Pricing: US

Solution (Keppra Intravenous)

500 mg/5 mL (per mL): $12.73

Solution (Keppra Oral)

100 mg/mL (per mL): $1.82

Solution (levETIRAcetam in NaCl Intravenous)

500 mg/100 mL (per mL): $0.22 – $0.41

1000 mg/100 mL (per mL): $0.36 – $0.67

1500 mg/100 mL (per mL): $0.48 – $0.95

Solution (levETIRAcetam Intravenous)

500 mg/5 mL (per mL): $0.92 – $3.00

Solution (levETIRAcetam Oral)

100 mg/mL (per mL): $0.15 – $0.73

Tablet, 24-hour (Keppra XR Oral)

500 mg (per each): $8.56

750 mg (per each): $12.85

Tablet, 24-hour (levETIRAcetam ER Oral)

500 mg (per each): $0.89 – $4.47

750 mg (per each): $1.34 – $6.68

Tablet, 24-hour (Roweepra XR Oral)

500 mg (per each): $4.44

750 mg (per each): $6.67

Tablets (Keppra Oral)

250 mg (per each): $7.72

500 mg (per each): $9.44

750 mg (per each): $12.79

1000 mg (per each): $18.88

Tablets (levETIRAcetam Oral)

250 mg (per each): $0.06 – $3.26

500 mg (per each): $0.09 – $3.52

750 mg (per each): $0.13 – $4.77

1000 mg (per each): $0.19 – $7.04

Tablets (Roweepra Oral)

500 mg (per each): $3.51

750 mg (per each): $4.76

1000 mg (per each): $4.76

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

The precise mechanism by which levetiracetam exerts its antiepileptic effect is unknown. However, several studies have suggested the mechanism may involve one or more of the following central pharmacologic effects: inhibition of voltage-dependent N-type calcium channels; facilitation of GABA-ergic inhibitory transmission through displacement of negative modulators; reduction of delayed rectifier potassium current; and/or binding to synaptic proteins which modulate neurotransmitter release.

Pharmacodynamics/Kinetics

Absorption: Oral: Rapid and almost complete

Immediate release: Food decreases Cmax by 20% and delays time to Cmax (Tmax) by 1.5 hours

Extended release: Intake of a high-fat, high-calorie breakfast before the administration results in a higher Cmax and longer median Tmax; the median Tmax is 2 hours longer in the fed state

Distribution: Vd: Similar to total body water

Infants and Children <4 years: 0.63 ± 0.08 L/kg (Glauser 2007)

Children 6 to 12 years: 0.72 ± 0.12 L/kg (Pellock 2001)

Adults: 0.5 to 0.7 L/kg

Protein binding: <10%

Metabolism: Not extensive; 24% of dose is metabolized by enzymatic hydrolysis of acetamide group (major metabolic pathway; hydrolysis occurs primarily in the blood; not cytochrome P450 dependent); two minor metabolites (one via hydroxylation of 2-oxo-pyrrolidine ring and one via opening of the 2-oxo-pyrrolidine ring in position 5) are also formed; metabolites are inactive and renally excreted

Bioavailability: 100%; bioavailability of extended release tablets is similar to immediate release tablets; tablets, oral solution, and injection are bioequivalent

Half-life elimination: Increased in patients with renal impairment:

Infants and Children <4 years: 5.3 ± 1.3 hours (Glauser 2007)

Children 4 to 12 years: 6 ± 1.1 hours (Pellock 2001)

Adults: ~6 to 8 hours; extended release tablet: ~7 hours

Time to peak, plasma:

Oral solution: Fasting infants and children <4 years: 1.4 ± 0.9 hours

Oral: Immediate release: Fasting adults and children: ~1 hour

Oral: Extended release: ~4 hours; median time to peak is 2 hours longer in the fed state

Excretion: Urine (66% as unchanged drug and 27% as inactive metabolites); undergoes glomerular filtration and subsequent partial tubular reabsorption

Clearance: Correlated with creatinine clearance; clearance is decreased in patients with renal dysfunction

Infants <6 months: 1.23 mL/minute/kg (Glauser 2007)

Infants and Children 6 months to 4 years: 1.57 mL/minute/kg (Glauser 2007)

Children 6 to 12 years: 1.43 mL/minute/kg; 30% to 40% higher than adults on a per kg basis (Pellock 2001)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Clearance is decreased and half-life is increased.

Hepatic function impairment: Clearance is decreased in patients with severe (Child-Pugh class C) impairment.

Geriatric: Half-life is increased and clearance is decreased.

Gender: Cmax and AUC are higher in women.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Elepsia XR

FDA Approval Date
November 30, 1999
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Paisansathan C, Ozcan MS. Anesthesia for craniotomy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 5, 2018.

Paret N, Gouraud A, Bernard N, et al. Long-term follow-up of infants exposed to levetiracetam during breastfeeding: Comparison to a control group. Birth Defects Res A Clin Mol Teratol. 2014;100:537-538.[PubMed 23911354 ]

Patsalos PN, Berry DJ, Bourgeois BF, et al. Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49(7):1239-1276. doi: 10.1111/j.1528-1167.2008.01561.x.[PubMed 18397299]

Pellock JM, Glauser TA, Bebin EM, et al, “Pharmacokinetic Study of Levetiracetam in Children,” Epilepsia, 2001, 42(12):1574-9.[PubMed 11879369]

Pourzitaki C, Tsaousi G, Apostolidou E, Karakoulas K, Kouvelas D, Amaniti E. Efficacy and safety of prophylactic levetiracetam in supratentorial brain tumour surgery: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(1):315-325. doi: 10.1111/bcp.12926.[PubMed 26945547]

Sourbron J, Chan H, Wammes-van der Heijden EA, et al. Review on the relevance of therapeutic drug monitoring of levetiracetam. Seizure. 2018;62:131-135. doi: 10.1016/j.seizure.2018.09.004.[PubMed 30237016]

Spritam (levetiracetam) [prescribing information]. East Windsor, NJ: Aprecia Pharmaceuticals; September 2018.

Striano P, Manganelli F, Boccella P, Perretti A, Striano S. Levetiracetam in patients with cortical myoclonus: a clinical and electrophysiological study. Mov Disord. 2005;20(12):1610-1614.[PubMed 16078205]

Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010;12(2):165-172.[PubMed 19898966]

Theitler J, Brik A, Shaniv D, Berkovitch M, Gandelman-Marton R. Antiepileptic drug treatment in community-dwelling older patients with epilepsy: a retrospective observational study of old- versus new-generation antiepileptic drugs. Drugs Aging. 2017;34(6):479-487. doi: 10.1007/s40266-017-0465-7.[PubMed 28478592]

Tomson T, Palm R, Källén K, et al, “Pharmacokinetics of Levetiracetam During Pregnancy, Delivery, in the Neonatal Period, and Lactation,” Epilepsia, 2007, 48(6):1111-6.[PubMed 17381438]

Vajda FJ, Graham J, Roten A, et al. Teratogenicity of the newer antiepileptic drugs–the Australian experience. J Clin Neurosci. 2012;19(1):57-59.[PubMed 22104350 ]

Yang Y, Zheng F, Xu X, Wang X. Levetiracetam versus phenytoin for seizure prophylaxis following traumatic brain injury: a systematic review and meta-analysis. CNS Drugs. 2016;30(8):677-688. doi: 10.1007/s40263-016-0365-0.[PubMed 27395404]

Brand Names: International

Azacetam (EG); Callexe (AR); Callexe XR (AR); Ceumid (CR, DO, EC, GT, HN, NI, PA, SV, UY); Citazar (BD); Desitrend (GB); Dretacen (NL); E Keppra (JP); Eletam (BD); Epictal (IN); Epilen (TW); Epiletam (RO); Epilev (HR); Epsytam (PH); Erata (BD); Eterlox (ID); Focale (TH); Iracet (BD, LK); Ivetra (PH); Julitam (PH); Kepcet (DE); Kepcitam (LB); Kepdin (PH); Keplidon (VN); Keppra (AE, AR, AT, AU, BB, BE, BG, BH, BM, BS, CH, CL, CN, CO, CR, CU, CY, CZ, DE, DK, DO, EC, EE, EG, ES, FI, FR, GB, GR, GT, HK, HN, HR, HU, ID, IE, IL, IN, IS, IT, JM, JO, KR, KW, LB, LK, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PL, PR, PT, QA, RO, RU, SA, SE, SG, SI, SK, SV, TH, TR, TT, TW, UA, VN); Keppra I.V. (AU); Keppra XR (BB); Kerron (AU); Kevesy (NL); Kevtam (AU); Kopodex (CL, CO, EC, PE, PY); Laurak (ES); Lecetam (TH); Lentira (PH); Lethira (ID); Letram (PH, ZW); Lev Desitin (CH); Levepex (EG); Levetacis (VN); Levetam (UY); Levetrim (IL); Levetstad (VN); Levicitam (UA); Levim (TW); Levipil (LK, PH); Levit (PH); Levitam (ID); Levron (AR); Malomibe (VN); Matever (BE, EE, IE, MT, SE); Nobelin (TW); Normeg (EE); Prepalepan (AT); Repitend (EE); Rivoleve (CH); Tietari (SG); Torleva (IN, LK, VN, ZW); Trund (NL); Vexlev (PH); Vitera (RO); Zitera (LB)

Levetiracetam (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(lee va tye RA se tam)

Brand Names: US

Keppra; Keppra XR; Roweepra; Roweepra XR; Spritam [DSC]

Brand Names: Canada

Keppra

What is this drug used for?
  • It is used to treat seizures.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to levetiracetam or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have kidney disease or are on dialysis.
  • If you are breast-feeding or plan to breast-feed.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of seizures. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • This drug may cause behavior changes and mental or mood problems. Talk with the doctor.
  • A very bad reaction called angioedema has happened with this drug. Sometimes, this may be life-threatening. Signs may include swelling of the hands, face, lips, eyes, tongue, or throat; trouble breathing; trouble swallowing; or unusual hoarseness. Get medical help right away if you have any of these signs.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Use with care in children. Talk with the doctor.
  • Children younger than 4 years old will need to have their blood pressure checked often. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • This drug may not work as well during pregnancy. Talk with the doctor.
  • Extended-release tablets:
  • You may see something that looks like the tablet in your stool. This is normal and not a cause for concern. If you have questions, talk with your doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • If seizures are worse or not the same after starting this drug.
  • Hallucinations (seeing or hearing things that are not there).
  • Very bad dizziness or passing out.
  • Change in balance.
  • Trouble walking.
  • Feeling very sleepy.
  • Very bad headache.
  • Patients who take this drug may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
  • Low blood cell counts have happened with this drug. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. Call your doctor right away if you have signs of infection like fever, chills, or sore throat; any unexplained bruising or bleeding; or if you feel very tired or weak.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Diarrhea.
  • Dizziness.
  • Feeling sleepy.
  • Stuffy nose.
  • Nose and throat irritation.
  • Belly pain.
  • Trouble sleeping.
  • Feeling tired or weak.
  • Headache.
  • Upset stomach or throwing up.
  • Not hungry.
  • Flu-like signs.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Take this drug at the same time of day.
  • Oral-disintegrating tablet/tablet for oral suspension:
  • Do not swallow whole. Do not chew, break, or crush.
  • Do not take chipped or broken tablets.
  • Do not push the tablet out of the foil when opening. Use dry hands to take it from the foil. Place the tablet on your tongue and follow with a sip of liquid before you swallow. Swallow only after the tablet dissolves.
  • Whole tablet(s) may also be mixed in a cup with a small amount of liquid like 1 tablespoon (15 mL) or enough to cover the drug. Let the tablet(s) dissolve all the way and drink the mixture right away. If any drug is left in the cup, rinse cup with a small amount of liquid, swirl, and drink.
  • Liquid:
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
  • All tablet products:
  • Swallow whole. Do not chew or crush.
  • Regular-release tablets:
  • You may break the tablet in half. Do not chew or crush.
  • Extended-release tablets:
  • Do not split or break tablet.
  • Check your drug when you get a new prescription to make sure you have the right drug. Call your doctor right away if you think you were given the wrong drug or if you are not sure what your drug should look like.
  • Injection:
  • It is given as an infusion into a vein over a period of time.
What do I do if I miss a dose?
  • All oral products:
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Injection:
  • Call your doctor to find out what to do.
How do I store and/or throw out this drug?
  • All oral products:
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Injection:
  • If you need to store this drug at home, talk with your doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Levetiracetam (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(lee va tye RA se tam)

Brand Names: US

Keppra; Keppra XR; Roweepra; Roweepra XR; Spritam [DSC]

Brand Names: Canada

Keppra

What is this drug used for?
  • It is used to treat seizures.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has kidney disease or is on dialysis.
  • If your child is breast-feeding a baby:
  • Talk with the doctor if your child is breast-feeding a baby or plans to breast-feed a baby.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with your child’s doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of seizures. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • This drug may cause behavior changes and mental or mood problems. Talk with the doctor.
  • A very bad reaction called angioedema has happened with this drug. Sometimes, this may be life-threatening. Signs may include swelling of the hands, face, lips, eyes, tongue, or throat; trouble breathing; trouble swallowing; or unusual hoarseness. Get medical help right away if your child has any of these signs.
  • Use with care in children. Talk with the doctor.
  • Children younger than 4 years old will need to have their blood pressure checked often. Talk with the doctor.
  • If your child is pregnant:
  • Tell the doctor if your child is pregnant or becomes pregnant. You will need to talk about the benefits and risks of your child using this drug while pregnant.
  • This drug may not work as well during pregnancy. Talk with the doctor.
  • Extended-release tablets:
  • You may see something that looks like the tablet in your child’s stool. This is normal and not a cause for concern. If you have questions, talk with your child’s doctor.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • If seizures are worse or not the same after starting this drug.
  • Hallucinations (seeing or hearing things that are not there).
  • Very bad dizziness or passing out.
  • Change in balance.
  • Trouble walking.
  • Feeling very sleepy.
  • Very bad headache.
  • Patients who take this drug may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if your child has signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes.
  • Low blood cell counts have happened with this drug. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. Call your child’s doctor right away if your child has signs of infection like fever, chills, or sore throat; any unexplained bruising or bleeding; or if your child feels very tired or weak.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Diarrhea.
  • Dizziness.
  • Feeling sleepy.
  • Stuffy nose.
  • Nose and throat irritation.
  • Belly pain.
  • Trouble sleeping.
  • Not hungry.
  • Feeling tired or weak.
  • Upset stomach or throwing up.
  • Headache.
  • Flu-like signs.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All oral products:
  • Give this drug with or without food.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Give this drug at the same time of day.
  • Oral-disintegrating tablet/tablet for oral suspension:
  • Do not let your child swallow it whole.
  • Do not let your child chew, break, or crush.
  • Do not give your child chipped or broken tablets.
  • Do not push the tablet out of the foil when opening. Use dry hands to take it from the foil. Place on your child’s tongue and have your child follow with a sip of liquid before swallowing. Have your child swallow the tablet only after it dissolves.
  • Whole tablet(s) may also be mixed in a cup with a small amount of liquid like 1 tablespoon (15 mL) or enough to cover the drug. Let the tablet(s) dissolve all the way and have your child drink the mixture right away. If any drug is left in the cup, rinse cup with a small amount of liquid, swirl, and have your child drink.
  • Liquid:
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
  • All tablet products:
  • Have your child swallow whole. Do not let your child chew or crush.
  • Regular-release tablets:
  • You may break the tablet in half. Do not let your child chew or crush.
  • Extended-release tablets:
  • Do not split or break tablet.
  • Check your child’s drug when you get a new prescription to make sure you have the right drug. Call the doctor right away if you think you were given the wrong drug or if you are not sure what your child’s drug should look like.
  • Injection:
  • It is given as an infusion into a vein over a period of time.
What do I do if my child misses a dose?
  • All oral products:
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Injection:
  • Call your child’s doctor to find out what to do.
How do I store and/or throw out this drug?
  • All oral products:
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Injection:
  • If you need to store this drug at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.