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Side Effects & Adverse Reactions

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including KEPPRA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 7 shows absolute and relative risk by indication for all evaluated AEDs.

Table 7 Risk by indication for antiepileptic drugs in the pooled analysis
Indication	Placebo Patients with Events Per 1000 Patients	Drug Patients with Events Per 1000 Patients	Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients	Risk Difference: Additional Drug Patients with Events Per 1000 Patients
Epilepsy	1.0	3.4	3.5	2.4
Psychiatric	5.7	8.5	1.5	2.9
Other	1.0	1.8	1.9	0.9
Total	2.4	4.3	1.8	1.9

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing KEPPRA or any other AED must balance the risk of suicidal thoughts or behaviors with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.

Neuropsychiatric Adverse Events

Partial Onset Seizures

Adults

In adults experiencing partial onset seizures, KEPPRA use is associated with the occurrence of central nervous system adverse events that can be classified into the following categories: 1) somnolence and fatigue, 2) coordination difficulties, and 3) behavioral abnormalities.

In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.8% of KEPPRA-treated patients reported somnolence, compared to 8.4% of placebo patients. There was no clear dose response up to 3000 mg/day. In a study where there was no titration, about 45% of patients receiving 4000 mg/day reported somnolence. The somnolence was considered serious in 0.3% of the treated patients, compared to 0% in the placebo group. About 3% of KEPPRA-treated patients discontinued treatment due to somnolence, compared to 0.7% of placebo patients. In 1.4% of treated patients and in 0.9% of placebo patients the dose was reduced, while 0.3% of the treated patients were hospitalized due to somnolence.

In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 14.7% of treated patients reported asthenia, compared to 9.1% of placebo patients. Treatment was discontinued in 0.8% of treated patients as compared to 0.5% of placebo patients. In 0.5% of treated patients and in 0.2% of placebo patients the dose was reduced.

A total of 3.4% of KEPPRA-treated patients experienced coordination difficulties, (reported as either ataxia, abnormal gait, or incoordination) compared to 1.6% of placebo patients. A total of 0.4% of patients in controlled trials discontinued KEPPRA treatment due to ataxia, compared to 0% of placebo patients. In 0.7% of treated patients and in 0.2% of placebo patients the dose was reduced due to coordination difficulties, while one of the treated patients was hospitalized due to worsening of pre-existing ataxia.

Somnolence, asthenia and coordination difficulties occurred most frequently within the first 4 weeks of treatment.

In controlled trials of patients with epilepsy experiencing partial onset seizures, 5 (0.7%) of KEPPRA-treated patients experienced psychotic symptoms compared to 1 (0.2%) placebo patient. Two (0.3%) KEPPRA-treated patients were hospitalized and their treatment was discontinued. Both events, reported as psychosis, developed within the first week of treatment and resolved within 1 to 2 weeks following treatment discontinuation. Two other events, reported as hallucinations, occurred after 1-5 months and resolved within 2-7 days while the patients remained on treatment. In one patient experiencing psychotic depression occurring within a month, symptoms resolved within 45 days while the patient continued treatment. A total of 13.3% of KEPPRA patients experienced other behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.) compared to 6.2% of placebo patients. Approximately half of these patients reported these events within the first 4 weeks. A total of 1.7% of treated patients discontinued treatment due to these events, compared to 0.2% of placebo patients. The treatment dose was reduced in 0.8% of treated patients and in 0.5% of placebo patients. A total of 0.8% of treated patients had a serious behavioral event (compared to 0.2% of placebo patients) and were hospitalized.

Pediatric Patients

In pediatric patients experiencing partial onset seizures, KEPPRA is associated with somnolence, fatigue, and behavioral abnormalities.

In the double-blind, controlled trial in children with epilepsy experiencing partial onset seizures, 22.8% of KEPPRA-treated patients experienced somnolence, compared to 11.3% of placebo patients. The design of the study prevented accurately assessing dose-response effects. No patient discontinued treatment for somnolence. In about 3.0% of KEPPRA-treated patients and in 3.1% of placebo patients the dose was reduced as a result of somnolence.

Asthenia was reported in 8.9% of KEPPRA-treated patients, compared to 3.1% of placebo patients. No patient discontinued treatment for asthenia, but asthenia led to a dose reduction in 3.0% of KEPPRA-treated patients compared to 0% of placebo patients.

A total of 37.6% of the KEPPRA-treated patients experienced behavioral symptoms (reported as agitation, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesia, nervousness, neurosis, and personality disorder), compared to 18.6% of placebo patients. Hostility was reported in 11.9% of KEPPRA-treated patients, compared to 6.2% of placebo patients. Nervousness was reported in 9.9% of KEPPRA-treated patients, compared to 2.1% of placebo patients. Depression was reported in 3.0% of KEPPRA-treated patients, compared to 1.0% of placebo patients.

A total of 3.0% of KEPPRA-treated patients discontinued treatment due to psychotic and nonpsychotic adverse events, compared to 4.1% of placebo patients. Overall, 10.9% of KEPPRA-treated patients experienced behavioral symptoms associated with discontinuation or dose reduction, compared to 6.2% of placebo patients.

Myoclonic Seizures

During clinical development, the number of patients with myoclonic seizures exposed to KEPPRA was considerably smaller than the number with partial seizures. Therefore, under-reporting of certain adverse events was more likely to occur in the myoclonic seizure population. In adult and adolescent patients experiencing myoclonic seizures, KEPPRA is associated with somnolence and behavioral abnormalities. It is expected that the events seen in partial seizure patients would occur in patients with JME.

In the double-blind, controlled trial in adults and adolescents with juvenile myoclonic epilepsy experiencing myoclonic seizures, 11.7% of KEPPRA-treated patients experienced somnolence compared to 1.7% of placebo patients. No patient discontinued treatment as a result of somnolence. In 1.7% of KEPPRA-treated patients and in 0% of placebo patients the dose was reduced as a result of somnolence.

Non-psychotic behavioral disorders (reported as aggression and irritability) occurred in 5% of the KEPPRA-treated patients compared to 0% of placebo patients. Non-psychotic mood disorders (reported as depressed mood, depression, and mood swings) occurred in 6.7% of KEPPRA-treated patients compared to 3.3% of placebo patients. A total of 5.0% of KEPPRA-treated patients had a reduction in dose or discontinued treatment due to behavioral or psychiatric events (reported as anxiety, depressed mood, depression, irritability, and nervousness), compared to 1.7% of placebo patients.

Primary Generalized Tonic-Clonic Seizures

During clinical development, the number of patients with primary generalized tonic-clonic epilepsy exposed to KEPPRA was considerably smaller than the number with partial epilepsy, described above. As in the partial seizure patients, behavioral symptoms appeared to be associated with KEPPRA treatment. Gait disorders and somnolence were also described in the study in primary generalized seizures, but with no difference between placebo and KEPPRA treatment groups and no appreciable discontinuations. Although it may be expected that drug related events seen in partial seizure patients would be seen in primary generalized epilepsy patients (e.g. somnolence and gait disturbance), these events may not have been observed because of the smaller sample size.

In patients 6 years of age and older experiencing primary generalized tonic-clonic seizures, KEPPRA is associated with behavioral abnormalities.

In the double-blind, controlled trial in patients with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures, irritability was the most frequently reported psychiatric adverse event occurring in 6.3% of KEPPRA-treated patients compared to 2.4% of placebo patients. Additionally, non-psychotic behavioral disorders (reported as abnormal behavior, aggression, conduct disorder, and irritability) occurred in 11.4% of the KEPPRA-treated patients compared to 3.6% of placebo patients. Of the KEPPRA-treated patients experiencing non-psychotic behavioral disorders, one patient discontinued treatment due to aggression. Non-psychotic mood disorders (including anger, apathy, depression, mood altered, mood swings, negativism, and tearfulness) occurred in 12.7% of KEPPRA-treated patients compared to 8.3% of placebo patients. No KEPPRA-treated patients discontinued or had a dose reduction as a result of these events. One patient experienced delusional behavior that required the lowering of the dose of KEPPRA.

In a long-term open label study that examined patients with various forms of primary generalized epilepsy, along with the non-psychotic behavioral disorders, 2 of 192 patients studied exhibited psychotic-like behavior. Behavior in one case was characterized by auditory hallucinations and suicidal thoughts and led to KEPPRA discontinuation. The other case was described as worsening of pre-existent schizophrenia and did not lead to drug discontinuation.

Withdrawal Seizures

Antiepileptic drugs, including KEPPRA, should be withdrawn gradually to minimize the potential of increased seizure frequency.

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Legal Issues

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Manufacturer Warnings

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FDA Labeling Changes

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Uses

KEPPRA is indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.

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History

There is currently no drug history available for this drug.

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Other Information

KEPPRA is an antiepileptic drug available as 250 mg (blue), 500 mg (yellow), 750 mg (orange), and 1000 mg (white) tablets and as a clear, colorless, grape-flavored liquid (100 mg/mL) for oral administration.

The chemical name of levetiracetam, a single enantiomer, is (-)-(S)-α-ethyl-2-oxo-1-pyrrolidine acetamide, its molecular formula is C8H14N2O2 and its molecular weight is 170.21. Levetiracetam is chemically unrelated to existing antiepileptic drugs (AEDs). It has the following structural formula:

Levetiracetam is a white to off-white crystalline powder with a faint odor and a bitter taste. It is very soluble in water (104.0 g/100 mL). It is freely soluble in chloroform (65.3 g/100 mL) and in methanol (53.6 g/100 mL), soluble in ethanol (16.5 g/100 mL), sparingly soluble in acetonitrile (5.7 g/100 mL) and practically insoluble in n-hexane. (Solubility limits are expressed as g/100 mL solvent.)

KEPPRA tablets contain the labeled amount of levetiracetam. Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, polyethylene glycol 3350, polyethylene glycol 6000, polyvinyl alcohol, talc, titanium dioxide, and additional agents listed below:

   250 mg tablets: FD&C Blue #2/indigo carmine aluminum lake
   500 mg tablets: iron oxide yellow
   750 mg tablets: FD&C yellow #6/sunset yellow FCF aluminum lake, iron oxide red

KEPPRA oral solution contains 100 mg of levetiracetam per mL. Inactive ingredients: ammonium glycyrrhizinate, citric acid monohydrate, glycerin, maltitol solution, methylparaben, potassium acesulfame, propylparaben, purified water, sodium citrate dihydrate and natural and artificial flavor.

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Keppra Manufacturers

Ucb Farchim S.a.

Keppra | Ucb Farchim S.a.

KEPPRA is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.
Partial Onset Seizures Adults 16 Years And Older
In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose (see CLINICAL STUDIES), a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.
Pediatric Patients Ages 4 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 52 mg/kg. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. Table 15 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

KEPPRA is given orally with or without food.
Table 15: KEPPRA Tablet Weight-Based Dosing Guide For Children Daily Dose
Patient Weight 20 mg/kg/day
(BID dosing) 40 mg/kg/day
(BID dosing) 60 mg/kg/day
(BID dosing) 20.1-40 kg 500 mg/day
(1 x 250 mg
tablet BID) 1000 mg/day
(1 x 500 mg
tablet BID) 1500 mg/day
(1 x 750 mg
tablet BID) >40 kg 1000 mg/day
(1 x 500 mg
tablet BID) 2000 mg/day
(2 x 500 mg
tablets BID) 3000 mg/day
(2 x 750 mg
tablets BID)
The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients based on a daily dose of 20 mg/kg/day, 40 mg/kg/day or 60 mg/kg/day:
Total daily dose (mL/day) = Daily dose (mg/kg/day) x patient weight (kg) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 100 mg/mL
A household teaspoon or tablespoon is not an adequate measuring device. It is recommended that a calibrated measuring device be obtained and used. Healthcare providers should recommend a device that can measure and deliver the prescribed dose accurately, and provide instructions for measuring the dosage.
Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
Primary Generalized Tonic-Clonic Seizures Adults 16 Years And Older
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.
Pediatric Patients Ages 6 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. See Table 14 for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.
Adult Patients With Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 16. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:
CLcr = [140-age (years)] x weight (kg) (x 0.85 for female patients) - - - - - - - - - - - - - - - - - - - - - - 72 x serum creatinine (mg/dL) Table 16: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance
(mL/min) Dosage
(mg) Frequency 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. Normal > 80 500 to 1,500 Every 12 h Mild 50 – 80 500 to 1,000 Every 12 h Moderate 30 – 50 250 to 750 Every 12 h Severe < 30 250 to 500 Every 12 h ESRD patients using dialysis ---- 500 to 1,000 1Every 24 h

No Recall
Ucb Farchim S.a.

Keppra | Ucb Farchim S.a.

KEPPRA is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.
Partial Onset Seizures Adults 16 Years And Older
In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose (see CLINICAL STUDIES), a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.
Pediatric Patients Ages 4 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 52 mg/kg. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. Table 15 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

KEPPRA is given orally with or without food.
Table 15: KEPPRA Tablet Weight-Based Dosing Guide For Children Daily Dose
Patient Weight 20 mg/kg/day
(BID dosing) 40 mg/kg/day
(BID dosing) 60 mg/kg/day
(BID dosing) 20.1-40 kg 500 mg/day
(1 x 250 mg
tablet BID) 1000 mg/day
(1 x 500 mg
tablet BID) 1500 mg/day
(1 x 750 mg
tablet BID) >40 kg 1000 mg/day
(1 x 500 mg
tablet BID) 2000 mg/day
(2 x 500 mg
tablets BID) 3000 mg/day
(2 x 750 mg
tablets BID)
The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients based on a daily dose of 20 mg/kg/day, 40 mg/kg/day or 60 mg/kg/day:
Total daily dose (mL/day) = Daily dose (mg/kg/day) x patient weight (kg) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 100 mg/mL
A household teaspoon or tablespoon is not an adequate measuring device. It is recommended that a calibrated measuring device be obtained and used. Healthcare providers should recommend a device that can measure and deliver the prescribed dose accurately, and provide instructions for measuring the dosage.
Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
Primary Generalized Tonic-Clonic Seizures Adults 16 Years And Older
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.
Pediatric Patients Ages 6 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. See Table 14 for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.
Adult Patients With Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 16. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:
CLcr = [140-age (years)] x weight (kg) (x 0.85 for female patients) - - - - - - - - - - - - - - - - - - - - - - 72 x serum creatinine (mg/dL) Table 16: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance
(mL/min) Dosage
(mg) Frequency 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. Normal > 80 500 to 1,500 Every 12 h Mild 50 – 80 500 to 1,000 Every 12 h Moderate 30 – 50 250 to 750 Every 12 h Severe < 30 250 to 500 Every 12 h ESRD patients using dialysis ---- 500 to 1,000 1Every 24 h

No Recall
Rebel Distributors Corp

Keppra | Rebel Distributors Corp

KEPPRA is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.
Partial Onset Seizures Adults 16 Years And Older
In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose (see CLINICAL STUDIES), a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.
Pediatric Patients Ages 4 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 52 mg/kg. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. Table 15 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

KEPPRA is given orally with or without food.
Table 15: KEPPRA Tablet Weight-Based Dosing Guide For Children Daily Dose
Patient Weight 20 mg/kg/day
(BID dosing) 40 mg/kg/day
(BID dosing) 60 mg/kg/day
(BID dosing) 20.1-40 kg 500 mg/day
(1 x 250 mg
tablet BID) 1000 mg/day
(1 x 500 mg
tablet BID) 1500 mg/day
(1 x 750 mg
tablet BID) >40 kg 1000 mg/day
(1 x 500 mg
tablet BID) 2000 mg/day
(2 x 500 mg
tablets BID) 3000 mg/day
(2 x 750 mg
tablets BID)
The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients based on a daily dose of 20 mg/kg/day, 40 mg/kg/day or 60 mg/kg/day:
Total daily dose (mL/day) = Daily dose (mg/kg/day) x patient weight (kg) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 100 mg/mL
A household teaspoon or tablespoon is not an adequate measuring device. It is recommended that a calibrated measuring device be obtained and used. Healthcare providers should recommend a device that can measure and deliver the prescribed dose accurately, and provide instructions for measuring the dosage.
Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
Primary Generalized Tonic-Clonic Seizures Adults 16 Years And Older
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.
Pediatric Patients Ages 6 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. See Table 14 for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.
Adult Patients With Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 16. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:
CLcr = [140-age (years)] x weight (kg) (x 0.85 for female patients) - - - - - - - - - - - - - - - - - - - - - - 72 x serum creatinine (mg/dL) Table 16: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance
(mL/min) Dosage
(mg) Frequency 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. Normal > 80 500 to 1,500 Every 12 h Mild 50 – 80 500 to 1,000 Every 12 h Moderate 30 – 50 250 to 750 Every 12 h Severe < 30 250 to 500 Every 12 h ESRD patients using dialysis ---- 500 to 1,000 1Every 24 h

No Recall
Stat Rx Usa Llc

Keppra | Stat Rx Usa Llc

KEPPRA is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.
Partial Onset Seizures Adults 16 Years And Older
In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose (see CLINICAL STUDIES), a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.
Pediatric Patients Ages 4 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 52 mg/kg. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. Table 15 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

KEPPRA is given orally with or without food.
Table 15: KEPPRA Tablet Weight-Based Dosing Guide For Children Daily Dose
Patient Weight 20 mg/kg/day
(BID dosing) 40 mg/kg/day
(BID dosing) 60 mg/kg/day
(BID dosing) 20.1-40 kg 500 mg/day
(1 x 250 mg
tablet BID) 1000 mg/day
(1 x 500 mg
tablet BID) 1500 mg/day
(1 x 750 mg
tablet BID) >40 kg 1000 mg/day
(1 x 500 mg
tablet BID) 2000 mg/day
(2 x 500 mg
tablets BID) 3000 mg/day
(2 x 750 mg
tablets BID)
The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients based on a daily dose of 20 mg/kg/day, 40 mg/kg/day or 60 mg/kg/day:
Total daily dose (mL/day) = Daily dose (mg/kg/day) x patient weight (kg) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 100 mg/mL
A household teaspoon or tablespoon is not an adequate measuring device. It is recommended that a calibrated measuring device be obtained and used. Healthcare providers should recommend a device that can measure and deliver the prescribed dose accurately, and provide instructions for measuring the dosage.
Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
Primary Generalized Tonic-Clonic Seizures Adults 16 Years And Older
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.
Pediatric Patients Ages 6 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. See Table 14 for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.
Adult Patients With Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 16. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:
CLcr = [140-age (years)] x weight (kg) (x 0.85 for female patients) - - - - - - - - - - - - - - - - - - - - - - 72 x serum creatinine (mg/dL) Table 16: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance
(mL/min) Dosage
(mg) Frequency 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. Normal > 80 500 to 1,500 Every 12 h Mild 50 – 80 500 to 1,000 Every 12 h Moderate 30 – 50 250 to 750 Every 12 h Severe < 30 250 to 500 Every 12 h ESRD patients using dialysis ---- 500 to 1,000 1Every 24 h

No Recall
Cardinal Health

Keppra | Cardinal Health

2.1 General Information
KEPPRA injection is for intravenous use only and must be diluted prior to administration. KEPPRA injection (500 mg/5 mL) should be diluted in 100 mL of a compatible diluent [see Dosage and Administration (2.7)] and administered intravenously as a 15-minute IV infusion.

Product with particulate matter or discoloration should not be used.

Any unused portion of the KEPPRA injection vial contents should be discarded.
2.2 Initial Exposure to KEPPRA
KEPPRA can be initiated with either intravenous or oral administration.

Partial Onset Seizures

In clinical trials of oral KEPPRA, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose [see Clinical Studies (14.1)], a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies with KEPPRA tablets for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy

Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.

Primary Generalized Tonic-Clonic Seizures

Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.
2.3 Replacement Therapy
When switching from oral KEPPRA, the initial total daily intravenous dosage of KEPPRA should be equivalent to the total daily dosage and frequency of oral KEPPRA and should be administered as a 15-minute intravenous infusion following dilution in 100 mL of a compatible diluent.
2.4 Switching to Oral Dosing
At the end of the intravenous treatment period, the patient may be switched to KEPPRA oral administration at the equivalent daily dosage and frequency of the intravenous administration.
2.5 Dosing Instructions
KEPPRA injection is for intravenous use only and must be diluted prior to administration. One vial of KEPPRA injection contains 500 mg levetiracetam (500 mg/5 mL). See Table 1 for the recommended preparation and administration of KEPPRA injection to achieve a dose of 500 mg, 1000 mg, or 1500 mg.
Table 1: Preparation and Administration of KEPPRA Injection Dose Withdraw Volume Volume of Diluent Infusion Time 500 mg 5 mL (5 mL vial) 100 mL 15 minutes 1000 mg 10 mL (two 5 mL vials) 100 mL 15 minutes 1500 mg 15 mL (three 5 mL vials) 100 mL 15 minutes
For example, to prepare a 1000 mg dose, dilute 10 mL of KEPPRA injection in 100 mL of a compatible diluent [see Dosage and Administration (2.7)] and administer intravenously as a 15-minute infusion.
2.6 Adult Patients with Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 2. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:
1. For female patients CLcr= [140-age (years)] x weight (kg) x 1 0.85 - - - - - - - - - - - - - - - - - - - - - 72 x serum creatinine (mg/dL) Table 2: Dosing Adjustment Regimen for Adult Patients with Impaired Renal Function 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. Group Creatinine Clearance
(mL/min) Dosage
(mg) Frequency Normal > 80 500 to 1,500 Every 12 h Mild 50 – 80 500 to 1,000 Every 12 h Moderate 30 – 50 250 to 750 Every 12 h Severe < 30 250 to 500 Every 12 h ESRD patients using dialysis ---- 500 to 1,000 1Every 24 h 2.7 Compatibility and Stability
KEPPRA injection was found to be physically compatible and chemically stable when mixed with the following diluents and antiepileptic drugs for at least 24 hours and stored in polyvinyl chloride (PVC) bags at controlled room temperature 15-30°C (59-86°F).

Diluents
Sodium chloride (0.9%) injection, USP
Lactated Ringer’s injection
Dextrose 5% injection, USP

Other Antiepileptic Drugs
Lorazepam
Diazepam
Valproate sodium

There is no data to support the physical compatibility of KEPPRA injection with antiepileptic drugs that are not listed above.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

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Pd-rx Pharmaceuticals, Inc.

Keppra | Pd-rx Pharmaceuticals, Inc.

KEPPRA is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy.

KEPPRA is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy.
Partial Onset Seizures Adults 16 Years And Older
In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose (see CLINICAL STUDIES), a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.
Pediatric Patients Ages 4 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 52 mg/kg. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. Table 15 below provides a guideline for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.

KEPPRA is given orally with or without food.
Table 15: KEPPRA Tablet Weight-Based Dosing Guide For Children Daily Dose
Patient Weight 20 mg/kg/day
(BID dosing) 40 mg/kg/day
(BID dosing) 60 mg/kg/day
(BID dosing) 20.1-40 kg 500 mg/day
(1 x 250 mg
tablet BID) 1000 mg/day
(1 x 500 mg
tablet BID) 1500 mg/day
(1 x 750 mg
tablet BID) >40 kg 1000 mg/day
(1 x 500 mg
tablet BID) 2000 mg/day
(2 x 500 mg
tablets BID) 3000 mg/day
(2 x 750 mg
tablets BID)
The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients based on a daily dose of 20 mg/kg/day, 40 mg/kg/day or 60 mg/kg/day:
Total daily dose (mL/day) = Daily dose (mg/kg/day) x patient weight (kg) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 100 mg/mL
A household teaspoon or tablespoon is not an adequate measuring device. It is recommended that a calibrated measuring device be obtained and used. Healthcare providers should recommend a device that can measure and deliver the prescribed dose accurately, and provide instructions for measuring the dosage.
Myoclonic Seizures In Patients 12 Years Of Age And Older With Juvenile Myoclonic Epilepsy
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
Primary Generalized Tonic-Clonic Seizures Adults 16 Years And Older
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.
Pediatric Patients Ages 6 To <16 Years
Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg BID). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤ 20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution. See Table 14 for tablet dosing based on weight during titration to 60 mg/kg/day. Only whole tablets should be administered.
Adult Patients With Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 16. To use this dosing table, an estimate of the patient's creatinine clearance (CLcr) in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the following formula:
CLcr = [140-age (years)] x weight (kg) (x 0.85 for female patients) - - - - - - - - - - - - - - - - - - - - - - 72 x serum creatinine (mg/dL) Table 16: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance
(mL/min) Dosage
(mg) Frequency 1 Following dialysis, a 250 to 500 mg supplemental dose is recommended. Normal > 80 500 to 1,500 Every 12 h Mild 50 – 80 500 to 1,000 Every 12 h Moderate 30 – 50 250 to 750 Every 12 h Severe < 30 250 to 500 Every 12 h ESRD patients using dialysis ---- 500 to 1,000 1Every 24 h

No Recall
Physicians Total Care, Inc.

Keppra | Physicians Total Care, Inc.

2.1 Important Administration Instructions
KEPPRA is given orally with or without food. The KEPPRA dosing regimen depends on the indication, age group, dosage form (tablets or oral solution), and renal function.

Prescribe the oral solution for pediatric patients with body weight ≤ 20 kg. Prescribe the oral solution or tablets for pediatric patients with body weight above 20 kg.

When using the oral solution, in pediatric patients, dosing is weight-based (mg per kg) using a calibrated measuring device (not a household teaspoon or tablespoon).

KEPPRA tablets should be swallowed whole. KEPPRA tablets should not be chewed or crushed.
2.2 Partial Onset Seizures
Adults 16 Years And Older

In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose [see Clinical Studies (14.1)], a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients

1 Month To < 6 Months

Treatment should be initiated with a daily dose of 14 mg/kg in 2 divided doses (7 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 14 mg/kg to the recommended daily dose of 42 mg/kg (21 mg/kg twice daily). In the clinical trial, the mean daily dose was 35 mg/kg in this age group. The effectiveness of lower doses has not been studied.

6 Months To <4 Years:

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased in 2 weeks by an increment of 20 mg/kg to the recommended daily dose of 50 mg/kg (25 mg/kg twice daily). If a patient cannot tolerate a daily dose of 50 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 47 mg/kg in this age group.

4 Years To < 16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical efficacy trial, the mean daily dose was 44 mg/kg. The maximum daily dose was 3000 mg/day.

For KEPPRA tablet dosing in pediatric patients weighing 20 to 40 kg, treatment should be initiated with a daily dose of 500 mg given as twice daily dosing (250 mg twice daily). The daily dose should be increased every 2 weeks by increments of 500 mg to a maximum recommended daily dose of 1500 mg (750 mg twice daily).

For KEPPRA tablet dosing in pediatric patients weighing more than 40 kg, treatment should be initiated with a daily dose of 1000 mg/day given as twice daily dosing (500 mg twice daily). The daily dose should be increased every 2 weeks by increments of 1000 mg/day to a maximum recommended daily dose of 3000 mg (1500 mg twice daily).

KEPPRA Oral Solution Weight-Based Dosing Calculation For Pediatric Patients

The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients:
Total daily dose (mL/day) =   Daily dose (mg/kg/day) × patient weight (kg) ----------------------------------------- 100 mg/mL 2.3 Myoclonic Seizures In Patients 12 Years of Age and Older With Juvenile Myoclonic Epilepsy
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
2.4 Primary Generalized Tonic-Clonic Seizures
Adults 16 Years And Older

Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.

Pediatric Patients Ages 6 To <16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution [see Dosage and Administration (2.1)]. Only whole tablets should be administered.
2.5 Adult Patients With Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this an estimate of the patient's creatinine clearance (CLcr) in mL/min must first be calculated using the following formula:
CLcr=   [140-age (years)] × weight (kg) -----------------------------------------   (× 0.85 for female patients) 72 × serum creatinine (mg/dL)
Then CLcr is adjusted for body surface area (BSA) as follows:
CLcr (mL/min/1.73m2)=     CLcr (mL/min) ----------------------------   × 1.73   BSA subject (m2) Table 1: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function * Following dialysis, a 250 to 500 mg supplemental dose is recommended. Group Creatinine Clearance
(mL/min/1.73m2) Dosage
(mg) Frequency Normal > 80 500 to 1,500 Every 12 hours Mild 50 – 80 500 to 1,000 Every 12 hours Moderate 30 – 50 250 to 750 Every 12 hours Severe < 30 250 to 500 Every 12 hours ESRD patients using dialysis ---- 500 to 1,000* Every 24 hours*

No Recall
Remedyrepack Inc.

Keppra | Remedyrepack Inc.

KEPPRA is given orally with or without food. The KEPPRA dosing regimen depends on the indication, age group, dosage form (tablets or oral solution), and renal function.

Prescribe the oral solution for pediatric patients with body weight ≤ 20 kg. Prescribe the oral solution or tablets for pediatric patients with body weight above 20 kg.

When using the oral solution, in pediatric patients, dosing is weight-based (mg per kg) using a calibrated measuring device (not a household teaspoon or tablespoon).

KEPPRA tablets should be swallowed whole. KEPPRA tablets should not be chewed or crushed.

Adults 16 Years And Older

In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose [see Clinical Studies (14.1)], a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients

1 Month To < 6 Months

Treatment should be initiated with a daily dose of 14 mg/kg in 2 divided doses (7 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 14 mg/kg to the recommended daily dose of 42 mg/kg (21 mg/kg twice daily). In the clinical trial, the mean daily dose was 35 mg/kg in this age group. The effectiveness of lower doses has not been studied.

6 Months To <4 Years:

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased in 2 weeks by an increment of 20 mg/kg to the recommended daily dose of 50 mg/kg (25 mg/kg twice daily). If a patient cannot tolerate a daily dose of 50 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 47 mg/kg in this age group.

4 Years To < 16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical efficacy trial, the mean daily dose was 44 mg/kg. The maximum daily dose was 3000 mg/day.

For KEPPRA tablet dosing in pediatric patients weighing 20 to 40 kg, treatment should be initiated with a daily dose of 500 mg given as twice daily dosing (250 mg twice daily). The daily dose should be increased every 2 weeks by increments of 500 mg to a maximum recommended daily dose of 1500 mg (750 mg twice daily).

For KEPPRA tablet dosing in pediatric patients weighing more than 40 kg, treatment should be initiated with a daily dose of 1000 mg/day given as twice daily dosing (500 mg twice daily). The daily dose should be increased every 2 weeks by increments of 1000 mg/day to a maximum recommended daily dose of 3000 mg (1500 mg twice daily).

KEPPRA Oral Solution Weight-Based Dosing Calculation For Pediatric Patients

The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients:
Total daily dose (mL/day) =   Daily dose (mg/kg/day) × patient weight (kg) ----------------------------------------- 100 mg/mL

Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.

Adults 16 Years And Older

Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.

Pediatric Patients Ages 6 To <16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution [see Dosage and Administration (2.1)]. Only whole tablets should be administered.

KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this an estimate of the patient's creatinine clearance (CLcr) in mL/min must first be calculated using the following formula:
CLcr=   [140-age (years)] × weight (kg) -----------------------------------------   (× 0.85 for female patients) 72 × serum creatinine (mg/dL)
Then CLcr is adjusted for body surface area (BSA) as follows:
CLcr (mL/min/1.73m2)=     CLcr (mL/min) ----------------------------   × 1.73   BSA subject (m2) Table 1: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance
(mL/min/1.73m2) Dosage
(mg) Frequency Normal > 80 500 to 1,500 Every 12 hours Mild 50 – 80 500 to 1,000 Every 12 hours Moderate 30 – 50 250 to 750 Every 12 hours Severe < 30 250 to 500 Every 12 hours ESRD patients using dialysis ---- 500 to 1,000* Every 24 hours1

1 Following dialysis, a 250 to 500 mg supplemental dose is recommended.

No Recall
Rxpak Division Of Mckesson Corporation

Keppra | Rxpak Division Of Mckesson Corporation

2.1 Important Administration Instructions
KEPPRA is given orally with or without food. The KEPPRA dosing regimen depends on the indication, age group, dosage form (tablets or oral solution), and renal function.

Prescribe the oral solution for pediatric patients with body weight ≤ 20 kg. Prescribe the oral solution or tablets for pediatric patients with body weight above 20 kg.

When using the oral solution, in pediatric patients, dosing is weight-based (mg per kg) using a calibrated measuring device (not a household teaspoon or tablespoon).

KEPPRA tablets should be swallowed whole. KEPPRA tablets should not be chewed or crushed.
2.2 Partial Onset Seizures
Adults 16 Years and Older

In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing were shown to be effective. Although in some studies there was a tendency toward greater response with higher dose [see Clinical Studies (14.1)], a consistent increase in response with increased dose has not been shown.

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. Doses greater than 3000 mg/day have been used in open-label studies for periods of 6 months and longer. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients

1 Month to < 6 Months

Treatment should be initiated with a daily dose of 14 mg/kg in 2 divided doses (7 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 14 mg/kg to the recommended daily dose of 42 mg/kg (21 mg/kg twice daily). In the clinical trial, the mean daily dose was 35 mg/kg in this age group. The effectiveness of lower doses has not been studied.

6 Months to <4 Years:

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased in 2 weeks by an increment of 20 mg/kg to the recommended daily dose of 50 mg/kg (25 mg/kg twice daily). If a patient cannot tolerate a daily dose of 50 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 47 mg/kg in this age group.

4 Years to < 16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical efficacy trial, the mean daily dose was 44 mg/kg. The maximum daily dose was 3000 mg/day.

For KEPPRA tablet dosing in pediatric patients weighing 20 to 40 kg, treatment should be initiated with a daily dose of 500 mg given as twice daily dosing (250 mg twice daily). The daily dose should be increased every 2 weeks by increments of 500 mg to a maximum recommended daily dose of 1500 mg (750 mg twice daily).

For KEPPRA tablet dosing in pediatric patients weighing more than 40 kg, treatment should be initiated with a daily dose of 1000 mg/day given as twice daily dosing (500 mg twice daily). The daily dose should be increased every 2 weeks by increments of 1000 mg/day to a maximum recommended daily dose of 3000 mg (1500 mg twice daily).

KEPPRA Oral Solution Weight-Based Dosing Calculation For Pediatric Patients

The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients:

Total daily dose (mL/day) =

Daily dose (mg/kg/day) × patient weight (kg)

-----------------------------------------

100 mg/mL
2.3 Myoclonic Seizures in Patients 12 Years of Age and Older with Juvenile Myoclonic Epilepsy
Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
2.4 Primary Generalized Tonic-Clonic Seizures
Adults 16 Years and Older

Treatment should be initiated with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Dosage should be increased by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.

Pediatric Patients Ages 6 to <16 Years

Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). The daily dose should be increased every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution [see Dosage and Administration (2.1)]. Only whole tablets should be administered.
2.5 Adult Patients with Impaired Renal Function
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended doses and adjustment for dose for adults are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this an estimate of the patient's creatinine clearance (CLcr) in mL/min must first be calculated using the following formula:

CLcr=

[140-age (years)] × weight (kg)

-----------------------------------------   (× 0.85 for female patients)

72 × serum creatinine (mg/dL)

Then CLcr is adjusted for body surface area (BSA) as follows:

CLcr (mL/min/1.73m2)=

  CLcr (mL/min)

----------------------------   × 1.73

  BSA subject (m2)
Table 1: Dosing Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance
(mL/min/1.73m2) Dosage
(mg) Frequency * Following dialysis, a 250 to 500 mg supplemental dose is recommended.
Normal

> 80

500 to 1,500

Every 12 hours

Mild

50 – 80

500 to 1,000

Every 12 hours

Moderate

30 – 50

250 to 750

Every 12 hours

Severe

< 30

250 to 500

Every 12 hours

ESRD patients using dialysis

----

500 to 1,000*

Every 24 hours*

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Ucb, Inc.

Keppra | Ucb, Inc.

2.1 Important Administration Instructions
KEPPRA is given orally with or without food. The KEPPRA dosing regimen depends on the indication, age group, dosage form (tablets or oral solution), and renal function.

Prescribe the oral solution for pediatric patients with body weight ≤ 20 kg. Prescribe the oral solution or tablets for pediatric patients with body weight above 20 kg.

When using the oral solution in pediatric patients, dosing is weight-based (mg per kg) using a calibrated measuring device (not a household teaspoon or tablespoon).

KEPPRA tablets should be swallowed whole. KEPPRA tablets should not be chewed or crushed.
2.2 Dosing for Partial Onset Seizures
Adults 16 Years and Older

Initiate treatment with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients

1 Month to < 6 Months

Initiate treatment with a daily dose of 14 mg/kg in 2 divided doses (7 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 14 mg/kg to the recommended daily dose of 42 mg/kg (21 mg/kg twice daily). In the clinical trial, the mean daily dose was 35 mg/kg in this age group. The effectiveness of lower doses has not been studied.

6 Months to <4 Years:

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose in 2 weeks by an increment of 20 mg/kg to the recommended daily dose of 50 mg/kg (25 mg/kg twice daily). If a patient cannot tolerate a daily dose of 50 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 47 mg/kg in this age group.

4 Years to < 16 Years

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 44 mg/kg. The maximum daily dose was 3000 mg/day.

For KEPPRA tablet dosing in pediatric patients weighing 20 to 40 kg, initiate treatment with a daily dose of 500 mg given as twice daily dosing (250 mg twice daily). Increase the daily dose every 2 weeks by increments of 500 mg to a maximum recommended daily dose of 1500 mg (750 mg twice daily).

For KEPPRA tablet dosing in pediatric patients weighing more than 40 kg, initiate treatment with a daily dose of 1000 mg/day given as twice daily dosing (500 mg twice daily). Increase the daily dose every 2 weeks by increments of 1000 mg/day to a maximum recommended daily dose of 3000 mg (1500 mg twice daily).

KEPPRA Oral Solution Weight-Based Dosing Calculation For Pediatric Patients

The following calculation should be used to determine the appropriate daily dose of oral solution for pediatric patients:
Total daily dose (mL/day) =   Daily dose (mg/kg/day) × patient weight (kg) ----------------------------------------- 100 mg/mL 2.3 Dosing for Myoclonic Seizures in Patients 12 Years of Age and Older with Juvenile Myoclonic Epilepsy
Initiate treatment with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Increase the dosage by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
2.4 Dosing for Primary Generalized Tonic-Clonic Seizures
Adults 16 Years and Older

Initiate treatment with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Increase dosage by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.

Pediatric Patients Ages 6 to <16 Years

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied. Patients with body weight ≤20 kg should be dosed with oral solution. Patients with body weight above 20 kg can be dosed with either tablets or oral solution [see Dosage and Administration (2.1)]. Only whole tablets should be administered.
2.5 Dosage Adjustments in Adult Patients with Renal Impairment
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended dosage adjustments for adults are shown in Table 1. In order to calculate the dose recommended for patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this an estimate of the patient's creatinine clearance (CLcr) in mL/min must first be calculated using the following formula:
CLcr=   [140-age (years)] × weight (kg) -----------------------------------------   (× 0.85 for female patients) 72 × serum creatinine (mg/dL)
Then CLcr is adjusted for body surface area (BSA) as follows:
CLcr (mL/min/1.73m2)=     CLcr (mL/min) ----------------------------   × 1.73   BSA subject (m2) Table 1: Dosing Adjustment Regimen for Adult Patients with Renal Impairment Group Creatinine Clearance
(mL/min/1.73m2) Dosage (mg) Frequency * Following dialysis, a 250 to 500 mg supplemental dose is recommended. Normal > 80 500 to 1,500 Every 12 hours Mild 50 – 80 500 to 1,000 Every 12 hours Moderate 30 – 50 250 to 750 Every 12 hours Severe < 30 250 to 500 Every 12 hours ESRD patients using dialysis ---- 500 to 1,000* Every 24 hours*

No Recall
Ucb, Inc.

Keppra | Ucb, Inc.

2.1 Dosing for Partial Onset Seizures
Adults 16 Years and Older

Initiate treatment with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg. There is no evidence that doses greater than 3000 mg/day confer additional benefit.

Pediatric Patients

1 Month to < 6 Months

Initiate treatment with a daily dose of 14 mg/kg in 2 divided doses (7 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 14 mg/kg to the recommended daily dose of 42 mg/kg (21 mg/kg twice daily). In the clinical trial, the mean daily dose was 35 mg/kg in this age group. The effectiveness of lower doses has not been studied.

6 Months to < 4 Years

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose in 2 weeks by an increment of 20 mg/kg to the recommended daily dose of 50 mg/kg (25 mg/kg twice daily). If a patient cannot tolerate a daily dose of 50 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 47 mg/kg in this age group.

4 Years to < 16 Years

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 20 mg/kg to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). If a patient cannot tolerate a daily dose of 60 mg/kg, the daily dose may be reduced. In the clinical trial, the mean daily dose was 44 mg/kg. The maximum daily dose was 3000 mg/day.
2.2 Dosing for Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy
Initiate treatment with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Increase the dosage by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.
2.3 Dosing for Primary Generalized Tonic-Clonic Seizures
Adults 16 Years and Older

Initiate treatment with a dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Increase dosage by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied.

Pediatric Patients Ages 6 to <16 Years

Initiate treatment with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg twice daily). Increase the daily dose every 2 weeks by increments of 20 mg/kg (10 mg/kg twice daily) to the recommended daily dose of 60 mg/kg (30 mg/kg twice daily). The effectiveness of doses lower than 60 mg/kg/day has not been adequately studied.
2.4 Switching from Oral Dosing
When switching from oral KEPPRA, the initial total daily intravenous dosage of KEPPRA should be equivalent to the total daily dosage and frequency of oral KEPPRA.
2.5 Switching to Oral Dosing
At the end of the intravenous treatment period, the patient may be switched to KEPPRA oral administration at the equivalent daily dosage and frequency of the intravenous administration.
2.6 Preparation and Administration Instructions
KEPPRA injection is for intravenous use only and should be diluted in 100 mL of a compatible diluent prior to administration. If a smaller volume is required (e.g. pediatric patients), the amount of diluent should be calculated to not exceed a maximum levetiracetam concentration of 15 mg per mL of diluted solution. Consideration should also be given to the total daily fluid intake of the patient. KEPPRA injection should be administered as a 15-minute IV infusion. One vial of KEPPRA injection contains 500 mg levetiracetam (500 mg/5 mL).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Product with particulate matter or discoloration should not be used.

Any unused portion of the KEPPRA injection vial contents should be discarded.

Adults

See Table 1 for the recommended preparation and administration of KEPPRA injection for adults to achieve a dose of 500 mg, 1000 mg, or 1500 mg.
Table 1: Preparation and Administration of KEPPRA Injection for Adults Dose Withdraw Volume Volume of Diluent Infusion Time 500 mg 5 mL (5 mL vial) 100 mL 15 minutes 1000 mg 10 mL (two 5 mL vials) 100 mL 15 minutes 1500 mg 15 mL (three 5 mL vials) 100 mL 15 minutes
For example, to prepare a 1000 mg dose, dilute 10 mL of KEPPRA injection in 100 mL of a compatible diluent and administer intravenously as a 15-minute infusion.

Pediatric Patients

When using KEPPRA injection for pediatric patients, dosing is weight-based (mg per kg).

The following calculation should be used to determine the appropriate daily dose of KEPPRA injection for pediatric patients:
Total daily dose (mL/day) = Daily dose (mg/kg/day) × patient weight (kg) 100 mg/mL 2.7 Dosage Adjustments in Adult Patients with Renal Impairment
KEPPRA dosing must be individualized according to the patient's renal function status. Recommended dosage adjustments for adults with renal impairment are shown in Table 2. Information is unavailable for dosage adjustments in pediatric patients with renal impairment. In order to calculate the dose recommended for adult patients with renal impairment, creatinine clearance adjusted for body surface area must be calculated. To do this an estimate of the patient's creatinine clearance (CLcr) in mL/min must first be calculated using the following formula:
CLcr= [140-age (years)] × weight (kg) (× 0.85 for female patients) 72 × serum creatinine (mg/dL)
Then CLcr is adjusted for body surface area (BSA) as follows:
CLcr (mL/min/1.73m2)= CLcr (mL/min) × 1.73 BSA subject (m2) Table 2: Dosage Adjustment Regimen for Adult Patients with Renal Impairment Group Creatinine Clearance
(mL/min/1.73m2) Dosage
(mg) Frequency * Following dialysis, a 250 to 500 mg supplemental dose is recommended. Normal > 80 500 to 1,500 Every 12 hours Mild 50 – 80 500 to 1,000 Every 12 hours Moderate 30 – 50 250 to 750 Every 12 hours Severe < 30 250 to 500 Every 12 hours ESRD patients using dialysis ------- 500 to 1,000* Every 24 hours* 2.8 Compatibility and Stability
KEPPRA injection was found to be physically compatible and chemically stable when mixed with the following diluents and antiepileptic drugs for at least 24 hours and stored in polyvinyl chloride (PVC) bags at controlled room temperature 15-30°C (59-86°F).

Diluents

Sodium chloride (0.9%) injection, USP

Lactated Ringer's injection

Dextrose 5% injection, USP

Other Antiepileptic Drugs

Lorazepam

Diazepam

Valproate sodium

There is no data to support the physical compatibility of KEPPRA injection with antiepileptic drugs that are not listed above.

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