Levetiracetam Er

FDA Drug Information • Also known as: Levetiracetam Er

Brand Names: Levetiracetam Er
Route: ORAL
Dosage Form: TABLET, FILM COATED, EXTENDED RELEASE
Product Type: HUMAN PRESCRIPTION DRUG

Description

Levetiracetam extended-release tablets USP are an antiepileptic drug available as 500 mg and 750 mg (white) extended-release tablets 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: [Levetiracretam 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.) Levetiracetam extended-release tablets USP contain the labeled amount of levetiracetam, USP. Inactive ingredients: hypromellose, hydroxypropylcellulose, colloidal silicon dioxide, magnesium stearate, polyvinyl alcohol-partially hydrolyzed, macrogol/peg 3350, talc, and titanium dioxide. FDA approved dissolution test specifications differ from USP. The medication is combined with a drug release controlling polymer that provides a drug release at a controlled rate. The biologically inert components of the tablet may occasionally remain intact during GI transit and will be eliminated in the feces as a soft, hydrated mass.

What Is Levetiracetam Er Used For?

Levetiracetam extended-release tablets are indicated for the treatment of partial-onset in patients 12 years of age and older.

Dosage and Administration

2.1 Recommended Dosing For adults and adolescent patients, the recommended dosing for monotherapy and adjunctive therapy is the same; as outlined below. Adults and Adolescents 12 Years of Age and Older Weighing 50 kg or More Initiate treatment with a dose of 1,000 mg once daily. The once daily dosage may be adjusted in increments of 1,000 mg every 2 weeks to a maximum recommended daily dose of 3,000 mg/day once daily. Administration Levetiracetam extended-release tablets are administered once daily. Levetiracetam extended-release tablets should be swallowed whole. The tablets should not be chewed, broken, or crushed. 2.2 Dosage Adjustments in Adult Patients with Renal Impairment Levetiracetam extended-release tablets 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 2] [clcr 2] Table 1: Dosage Adjustment Regimen For Adult Patients With Impaired Renal Function Group Creatinine Clearance (mL/min/1.73m2) Dosage (mg) Frequency Normal > 80 1,000 to 3,000 Every 24 hours Mild 50 – 80 1,000 to 2,000 Every 24 hours Moderate 30 – 50 500 to 1500 Every 24 hours Severe < 30 500 to 1,000 Every 24 hours 2.3 Discontinuation of Levetiracetam Extended-release Tablets Avoid abrupt withdrawal from levetiracetam extended-release tablets in order to reduce the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.7)].

Side Effects (Adverse Reactions)

The following adverse reactions are discussed in more details in other sections of labeling:

Behavioral abnormalities and Psychotic Symptoms [see Warnings and Precautions (5.1)]

Suicidal Behavior and Ideation [see Warnings and Precautions (5.2)]

Somnolence and Fatigue [see Warnings and Precautions (5.3)]

Anaphylaxis and Angioedema [see Warnings and Precautions (5.4)]

Serious Dermatological Reactions [see Warnings and Precautions (5.5)]

Coordination Difficulties [see Warnings and Precautions (5.6)]

Hematologic Abnormalities [see Warnings and Precautions (5.8)] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Levetiracetam Extended-Release Tablets In the controlled clinical study in patients with partial-onset seizures [see CLINICAL STUDIES (14.1)], the most common adverse reactions in patients receiving levetiracetam extended-release tablets in combination with other AEDs, for events with rates greater than placebo, were irritability and somnolence. Table 3 lists adverse reactions that occurred in at least 5% of epilepsy patients receiving levetiracetam extended-release tablets in the placebo-controlled study and were numerically more common than in patients treated with placebo. In this study, either levetiracetam extended-release tablets or placebo was added to concurrent AED therapy. Table 3: Adverse Reactions in the Placebo-Controlled, Adjunctive Study in Patients Experiencing Partial-Onset Seizures Levetiracetam Extended-Release Tablets (N=77) % Placebo (N=79) % Influenza 8 4 Somnolence 8 3 Irritability 7 0 Nasopharyngitis 7 5 Dizziness 5 3 Nausea 5 3 Discontinuation or Dose Reduction in the Levetiracetam Extended-Release Tablets Controlled Clinical Study In the controlled clinical study, 5% of patients receiving levetiracetam extended-release tablets and 3% receiving placebo discontinued as a result of an adverse reaction. The adverse reactions that resulted in discontinuation and that occurred more frequently in levetiracetam extended-release tablets-treated patients than in placebo-treated patients were asthenia, epilepsy, mouth ulceration, rash, and respiratory failure. Each of these adverse reactions led to discontinuation in a levetiracetam extended-release tablets-treated patient and no placebo-treated patients. Immediate-Release Levetiracetam Tablets Table 4 lists the adverse reactions in the controlled studies of immediate-release levetiracetam tablets in adult patients experiencing partial-onset seizures [see CLINICAL STUDIES (14.2)]. Although the pattern of adverse reactions in the levetiracetam extended-release tablets study seems somewhat different from that seen in partial-onset seizure controlled studies for immediate-release levetiracetam tablets, this is possibly due to the much smaller number of patients in this study compared to the immediate-release tablet studies. The adverse reactions for levetiracetam extended-release tablets are expected to be similar to those seen with immediate-release levetiracetam tablets. Adults In controlled clinical studies of immediate-release levetiracetam tablets as adjunctive therapy to other AEDs in adults with partial-onset seizures, the most common adverse reactions, for events with rates greater than placebo, were somnolence, asthenia, infection, and dizziness. Table 4 lists adverse reactions that occurred in at least 1% of adult epilepsy patients receiving immediate-release levetiracetam tablets in placebo-controlled studies and were numerically more common than in patients treated with placebo. In these studies, either immediate-release levetiracetam tablets or placebo was added to concurrent AED therapy. Table 4: Adverse Reactions in Pooled Placebo-Controlled, Adjunctive Studies in Adults Experiencing...

Contraindications

Levetiracetam extended-releasetablets are contraindicated in patients with a hypersensitivity to levetiracetam. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.4)].

Overdosage

10.1 Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans The signs and symptoms for levetiracetam extended-release tablets overdose are expected to be similar to those seen with immediate-release levetiracetam tablets. The highest known dose of oral immediate-release levetiracetam tablets received in the clinical development program was 6,000 mg/day. Other than drowsiness, there were no adverse reactions in the few known cases of overdose in clinical trials. Cases of somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with immediate-release levetiracetam tablets overdoses in postmarketing use. 10.2 Management of Overdose There is no specific antidote for overdose with levetiracetam extended-release tablets. If indicated, elimination of unabsorbed drug should be attempted by emesis or gastric lavage; usual precautions should be observed to maintain airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the patient's clinical status. A Certified Poison Control Center should be contacted for up to date information on the management of overdose with levetiracetam extended-release tablets. 10.3 Hemodialysis Standard hemodialysis procedures result in significant clearance of levetiracetam (approximately 50% in 4 hours) and should be considered in cases of overdose. Although hemodialysis has not been performed in the few known cases of overdose, it may be indicated by the patient's clinical state or in patients with significant renal impairment.

How Supplied

16.1 How Supplied Levetiracetam extended-release 500 mg tablets, USP, are white, oval, biconvex film-coated extended-release tablets debossed with "HH" on one side and “172” on the other side. They are supplied in white HDPE bottles as follows: NDC 43547-345-06: bottles of 60 NDC 43547-345-50: bottles of 500 Levetiracetam extended-release 750 mg tablets, USP, are white, oval, biconvex film-coated extended-release tablets debossed with "HH" on one side and “173” on the other side. They are supplied in white HDPE bottles as follows: NDC 72189-510-60: bottles of 60 NDC 43547-346-50: bottles of 500

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.