Levetiracetam (Page 6 of 7)

14.2 Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy

The effectiveness of levetiracetam as adjunctive therapy in patients with juvenile myoclonic epilepsy (JME) experiencing myoclonic seizures was established in one multicenter, randomized, double-blind, placebo-controlled study, conducted at 37 sites in 14 countries. Of the 120 patients enrolled, 113 had a diagnosis of confirmed or suspected JME. Eligible patients on a stable dose of 1 antiepileptic drug (AED) experiencing one or more myoclonic seizures per day for at least 8 days during the prospective 8-week baseline period were randomized to either levetiracetam or placebo (levetiracetam N=60, placebo N=60). Patients were titrated over 4 weeks to a target dose of 3,000 mg/day and treated at a stable dose of 3,000 mg/day over 12 weeks (evaluation period). Study drug was given in 2 divided doses.The primary measure of effectiveness was the proportion of patients with at least 50% reduction in the number of days per week with one or more myoclonic seizures during the treatment period (titration + evaluation periods) as compared to baseline. Table 10 displays the results for the 113 patients with JME in this study. Of 120 patients enrolled, 113 had a diagnosis of confirmed or suspected JME. The results are displayed in Table 10.

Table 10: Responder Rate (≥50% Reduction from Baseline) in Myoclonic Seizure Days per Week for Patients with JME

	Placebo (N=59)	Levetiracetam (N=54)
Percentage of responders	23.7%	60.4%*

^* Statistically significant versus placebo

14.3 Primary Generalized Tonic-Clonic Seizures

The effectiveness of levetiracetam as adjunctive therapy in patients with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic (PGTC) seizures was established in one multicenter, randomized, double-blind, placebo-controlled study, conducted at 50 sites in 8 countries. Eligible patients on a stable dose of 1 or 2 antiepileptic drugs (AEDs) experiencing at least 3 PGTC seizures during the 8-week combined baseline period (at least one PGTC seizure during the 4 weeks prior to the prospective baseline period and at least one PGTC seizure during the 4-week prospective baseline period) were randomized to either levetiracetam or placebo. The 8-week combined baseline period is referred to as “baseline” in the remainder of this section. The population included 164 patients (levetiracetam N=80, placebo N=84) with idiopathic generalized epilepsy (predominately juvenile myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy, or epilepsy with Grand Mal seizures on awakening) experiencing primary generalized tonic-clonic seizures. Each of these syndromes of idiopathic generalized epilepsy was well represented in this patient population. Patients were titrated over 4 weeks to a target dose of 3,000 mg/day for adults or a pediatric target dose of 60 mg/kg/day and treated at a stable dose of 3,000 mg/day (or 60 mg/kg/day for children) over 20 weeks (evaluation period). Study drug was given in 2 equally divided doses per day.

The primary measure of effectiveness was the percent reduction from baseline in weekly PGTC seizure frequency for levetiracetam and placebo treatment groups over the treatment period (titration + evaluation periods). There was a statistically significant decrease from baseline in PGTC frequency in the levetiracetam-treated patients compared to the placebo-treated patients.

Table 11: Median Percent Reduction from Baseline in PGTC Seizure Frequency per Week

	Placebo (N=84)	Levetiracetam (N=78)
Percentage reduction in PGTC seizure frequency	44.6%	77.6%*

^* Statistically significant versus placebo
The percentage of patients (y-axis) who achieved ≥50% reduction in weekly seizure rates from baseline in PGTC seizure frequency over the entire randomized treatment period (titration + evaluation period) within the two treatment groups (x-axis) is presented in Figure 4.Figure 4: Responder Rate (≥50% Reduction from Baseline) in PGTC Seizure Frequency per Week

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Levetiracetam in Sodium Chloride Injection is a clear, colorless, sterile solution that is available in a single- dose 100 mL dual port bag with an aluminum overwrap. The container closure is not made with natural rubber latex. It is available in the following presentations:

Strength	Package	NDC Number
500 mg/100 mL (5 mg/mL)	1 single-dose bag	68083-152-01
	10 bags per carton	68083-152-10
1,000 mg/100 mL (10 mg/mL)	1 single-dose bag		68083-153-01
	10 bags per carton		68083-153-10
1,500 mg/100 mL (15 mg/mL)	1 single-dose bag		68083-154-01
	10 bags per carton		68083-154-10

16.2 Storage

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Psychiatric Reactions and Changes in Behavior

Advise patients and their caregivers that levetiracetam may cause changes in behavior (e.g., aggression, agitation, anger, anxiety, apathy, depression, hostility, and irritability) and psychotic symptoms [see Warnings and Precautions (5.1)].

Effects on Driving or Operating Machinery

Inform patients that levetiracetam may cause dizziness and somnolence. Inform patients not to drive or operate machinery until they have gained sufficient experience on levetiracetam to gauge whether it adversely affects their ability to drive or operate machinery [see Warnings and Precautions (5.2)].

Anaphylaxis and Angioedema

Advise patients to discontinue levetiracetam and seek medical care if they develop signs and symptoms of anaphylaxis or angioedema [see Warnings and Precautions (5.3)].

Dermatological Adverse Reactions
Advise patients that serious dermatological adverse reactions have occurred in patients treated with levetiracetam and instruct them to call their physician immediately if a rash develops [see Warnings and Precautions (5.4)].

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during levetiracetam therapy. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry if they become pregnant [see Use in Specific Populations (8.1)].
Manufactured by:

Gland Pharma Limited

D.P.Pally, Dundigal Post

Hyderabad-500043, INDIA
Revised: May 2021