Elepsia XR

ELEPSIA XR — levetiracetam tablet, extended release
Sun Pharma Advanced Research Company Limited

1 Elepsia XR Indications and Usage

ELEPSIA XR is indicated as adjunctive therapy for the treatment of partial-onset seizures in patients 12 years of age and older.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing

ELEPSIA XR is administered orally once daily.

Initiate treatment with a dose of 1000 mg once daily. The once daily dosage may be adjusted in increments of 1000 mg every 2 weeks, to a maximum recommended daily dose of 3000 mg/day.

ELEPSIA XR should be taken whole; do not split or cut tablets.

2.2 Dosage Adjustment in Adult Patients with Renal Impairment

ELEPSIA XR is not recommended for use in patients with moderate or severe renal impairment. Recommended doses and adjustment for patients with mild renal impairment 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:

image description
(click image for full-size original)

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

image description
(click image for full-size original)

Table 1: Dosing Adjustment Regimen for Adult Patients with Impaired Renal Function

Group

Creatinine Clearance (mL/min/1.73m 2 )

Dosage (mg)

Frequency

Normal

greater than 80

1000 to 3000

Every 24 hours

Mild

50 to 80

1000 to 2000

Every 24 hours

2.3 Discontinuation of ELEPSIA XR

When discontinuing ELEPSIA XR, reduce the dosage gradually and avoid abrupt discontinuation because of the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.7)].

3 Elepsia XR Dosage Forms and Strengths

Extended-release tablets:

  • 1000 mg: oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on blue layer; imprinted with “574” with black ink on one side and plain on the other side.
  • 1500 mg: oval biconvex, coated, blue and white to off-white, bilayer tablet with drilled portal on blue layer; imprinted with “575” with black ink on one side and plain on the other side.

4 CONTRAINDICATIONS

ELEPSIA XR is contraindicated in patients with a hypersensitivity to levetiracetam. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.4)].

5 Elepsia XR Warnings and Precautions

5.1 Behavioral Abnormalities and Psychotic Symptoms

ELEPSIA XR may cause behavioral abnormalities and psychotic symptoms. Patients treated with ELEPSIA XR should be monitored for psychiatric signs and symptoms.

Behavioral Abnormalities

Levetiracetam Extended-Release Tablets
A total of 7% of levetiracetam extended-release tablets-treated patients experienced non-psychotic behavioral disorders (reported as irritability and aggression), compared to 0% of placebo-treated patients. Irritability was reported in 7% of levetiracetam extended-release tablet-treated patients. Aggression was reported in 1% of levetiracetam extended-release tablet-treated patients.

No patient discontinued treatment or had a dose reduction as a result of these adverse reactions.

The number of patients exposed to levetiracetam extended-release tablets was considerably smaller than the number of patients exposed to immediate-release levetiracetam tablets in controlled trials. Therefore, certain adverse reactions observed in the immediate-release levetiracetam controlled trials will likely to occur in patients receiving ELEPSIA XR.

Immediate-Release Levetiracetam Tablets
A total of 13% of adult patients and 38% of pediatric patients (4 to 16 years of age) treated with immediate-release levetiracetam tablets experienced non-psychotic behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, and personality disorder), compared to 6% and 19% of adult and pediatric patients on placebo. A randomized, double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of immediate-release levetiracetam tablets as adjunctive therapy in pediatric patients (4 to 16 years of age). An exploratory analysis suggested a worsening in aggressive behavior in patients treated with immediate-release levetiracetam tablets in that study [see Use in Specific Populations (8.4)].

A total of 1.7% of adult patients treated with immediate-release levetiracetam tablets discontinued treatment due to behavioral adverse reactions, compared to 0.2% of placebo-treated patients. The treatment dose was reduced in 0.8% of adult patients treated with immediate-release levetiracetam tablets, compared to 0.5% of placebo-treated patients. Overall, 11% of pediatric patients treated with immediate-release levetiracetam tablets experienced behavioral symptoms associated with discontinuation or dose reduction, compared to 6.2% of placebo-treated pediatric patients.

One percent of adult patients and 2% of pediatric patients (4 to 16 years of age) treated with immediate-release levetiracetam tablets experienced psychotic symptoms, compared to 0.2% and 2%, respectively, in adult and pediatric placebo-treated patients. In the controlled study that assessed the neurocognitive and behavioral effects of immediate-release levetiracetam tablets in pediatric patients 4 to 16 years of age, 1.6% levetiracetam -treated patients experienced paranoia, compared to no placebo-treated patients. There were 3.1% patients treated with immediate-release levetiracetam tablets who experienced confusional state, compared to no placebo-treated patients [see Use in Specific Populations (8.4)].

Psychotic Symptoms

Immediate-Release Levetiracetam Tablets One percent of immediate-release levetiracetam tablets-treated adult patients experienced psychotic symptoms, compared to 0.2% of placebo-treated patients.

Two (0.3%) immediate-release levetiracetam tablets-treated adult patients were hospitalized and their treatment was discontinued due to psychosis. Both events, reported as psychosis, developed within the first week of treatment and resolved within 1 to 2 weeks following treatment discontinuation. There was no difference between drug and placebo-treated patients in the incidence of pediatric patients who discontinued treatment due to psychotic and non-psychotic adverse reactions.

5.2 Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including ELEPSIA XR, 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 to 100 years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs.

Table 2: 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

3.4

3.5

2.4

Psychiatric

5.7

8.5

1.5

2.9

Other

1

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 ELEPSIA XR or any other AED must balance the risk of suicidal thoughts or behavior 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.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.