Levetiracetam extended-release tablets are indicated as adjunctive therapy in the treatment of partial onset seizures in patients 12 years of age and older with epilepsy.
Levetiracetam is an antiepileptic drug available as 500 mg and 750 mg (blue and white to off-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:
Levetiracetam, USP is a white to off-white crystalline powder with a faint odor and a bitter taste. It is very soluble in water (104 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 contain the labeled amount of levetiracetam. Inactive ingredients: povidone, hypromellose, amino methacrylate copolymer, colloidal silicon dioxide, magnesium stearate, talc, silicified microcrystalline cellulose, crospovidone, sodium lauryl sulfate, FD&C Blue #1 aluminum lake, ethyl cellulose aqueous dispersion, dibutyl sebacate, triethyl citrate, polysorbate 20, polyvinyl alcohol, polyethylene glycol, and polysorbate 80. The imprinting ink contains shellac glaze, iron oxide black, N-butyl alcohol, propylene glycol, and ammonium hydroxide.
Levetiracetam extended-release tablet is administered once daily.
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.
2.2 Dosage Adjustment 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, creatine 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:
Then CLcr is adjusted for body surface area (BSA) as follows:
Table 1: Dosage Adjustment Regimen for Adult Patients with Renal Impairment
Group
Creatinine Clearance (mL/min/1.73m2)
Dosage (mg)
Frequency
Normal
> 80
1,000 to 3,000
Every 24 hours
Mild
50 to 80
1,000 to 2,000
Every 24 hours
Moderate
30 to 50
500 to 1,500
Every 24 hours
Severe
< 30
500 to 1,000
Every 24 hours
The usual initial dosage of timolol maleate is 10 mg twice a day, whether used alone or added to diuretic therapy. Dosage may be increased or decreased depending on heart rate and blood pressure response. The usual total maintenance dosage is 20 to 40 mg per day. Increases in dosage to a maximum of 60 mg per day divided into two doses may be necessary. There should be an interval of at least 7 days between increases in dosages.
Timolol maleate tablets may be used with a thiazide diuretic or with other antihypertensive agents. Patients should be observed carefully during initiation of such concomitant therapy.
Myocardial Infarction
The recommended dosage for long-term prophylactic use in patients who have survived the acute phase of a myocardial infarction is 10 mg given twice daily (see CLINICAL PHARMACOLOGY).
Migraine
The usual initial dosage of timolol maleate is 10 mg twice a day. During maintenance therapy the 20 mg daily dosage may be administered as a single dose. Total daily dosage may be increased to a maximum of 30 mg, given in divided doses, or decreased to 10 mg once per day, depending on clinical response and tolerability. If a satisfactory response is not obtained after 6 to 8 weeks use of the maximum daily dosage, therapy with timolol should be discontinued.