Citazar^®

Citazar is an antiepileptic drug. The precise mechanism(s) by which Levetiracetam exerts its antiepileptic effect is unknown. A saturable and stereoselective neuronal binding site in brain tissue has been described for Citazar. Experimental data indicate that this binding site is the synaptic vesicle protein SV2A, thought to be involved in the regulation of vesicle exocytosis. Although the molecular significance of Citazar binding to synaptic vesicle protein SV2A is not understood. These findings suggest that the interaction of Citazar with the SV2A protein may contribute to the antiepileptic mechanism of action of the drug.

No Data

Citazar is indicated for-
• The treatment of partial-onset seizures in patients 1 month of age and older.
• Adjunctive therapy for the treatment of:

✔ Myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy.
✔ Primary generalized tonic-clonic seizures in patients 6 years of age and older with idiopathic generalized epilepsy.

Route of administration: Citazar can be administered in either oral or intravenous route. Citazar injection is used only as an alternative for patients when oral administration is temporarily not feasible. Citazar tablets should be swallowed whole and should not be chewed or crushed.

Partial-onset seizures (Monotherapy or adjunctive therapy)

Adults 16 years of age and older
Initiate treatment with 500 mg twice daily. Increase 500 mg twice daily every 2 weeks to a maximum recommended 1500 mg twice daily.

Pediatric patients

*Daily dose should be increased every 2 weeks.

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

Myoclonic seizures in adults and pediatric patients 12 years and older
Initiate with 500 mg twice daily; increase by 500 mg twice daily every 2 weeks upto recommended dose of 1500 mg twice daily.

Primary generalized tonic-clonic seizures
• 6 years to < 16 years: 10 mg/kg twice daily, increase by 10 mg/kg twice daily every 2 weeks to recommended dose of 30 mg/kg twice daily.
• Adults 16 years and older: 500 mg twice daily, increase by 500 mg twice daily every 2 weeks to recommended dose of 1500 mg twice daily.

Switching from or to oral Citazar
When switching from or to oral Citazar, the total daily dosage/frequency of Citazar injection should be equivalent to those of oral Citazar

Renal impairment
Dosage adjustment regimen for adult patients with renal impairment

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

Dosage adjustment for infants, children and adolescent patients weighing less than 50 kg with impaired renal function:

1. Citazar oral solution should be used for doses under 250 mg, for doses not multiple of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets.
2. A 10.5 mg/kg (0.105 mL/kg) loading dose is recommended on the first day of treatment with Citazar.
3. A 15 mg/kg (0.15 mL/kg) loading dose is recommended on the first day of treatment with Citazar.
4. Following dialysis, a 3.5 to 7 mg/kg (0.035 to 0.07 mL/kg) supplemental dose is recommended.
5. Following dialysis, a 5 to 10 mg/kg (0.05 to 0.10 mL/kg) supplemental dose is recommended.

Avoid abrupt withdrawal from Citazar in order to reduce the risk of increased seizure frequency and status epilepticus. 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.

Preparation and administration instructions for IV injection
Citazar 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 Citazar concentration of 15 mg per mL of diluted solution. Consideration should also be given to the total daily fluid intake of the patient. Citazar injection should be administered as a 15-minute IV infusion. Citazar injection may be mixed with the following diluents and antiepileptic drugs and may be stored in polyvinyl chloride (PVC) bags. The diluted solution should not be stored for more than 4 hours at controlled room temperature (15°C-30°C). Any unused portion of the Citazar injection ampoule contents should be discarded.

Adults
Recommended preparation and administration of Citazar injection for adults

For example, to prepare a 1000 mg dose, dilute 10 mL of Citazar injection in 100 mL of a compatible diluent and administer intravenously as a 15-minute infusion.

Pregnancy: Prolonged experience with levetiracetam in pregnant women has not identified a drug-associated risk of major birth defects or miscarriage. Decrease in levetiracetam plasma concentrations has been observed during pregnancy. This decrease is more pronounced during the third trimester. Dose adjustments may be necessary to maintain clinical response.

Lactation: Levetiracetam is excreted in human milk. There are no data on the effects of levetiracetam on the breastfed infant or the effects on milk production.

Use in children and adolescents
Safety and effectiveness of levetiracetam for the treatment of partial-onset seizures in pediatric patients below the age of 1 month; adjunctive therapy for the treatment of myoclonic seizures in pediatric patients below the age of 12 years; and adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in pediatric patients below the age of 6 years have not been established.

Behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability and aggressive behavior have been observed. Monitor for somnolence, fatigue and co-ordination difficulties and advise patients not to drive or operate machinery until they have gained sufficient experience on levetiracetam. Discontinue levetiracetam at the first sign of rash unless clearly not drug related. Monitor for ataxia, abnormal gait, incoordination and hematologic abnormalities. Levetiracetam must be gradually withdrawn to avoid withdrawal seizures.

The most common side effects are-
Adult patients: Somnolence, asthenia, infection and dizziness.
Pediatric patients: Fatigue, aggression, nasal congestion, decreased appetite and irritability.

It is contraindicated in patients with history of known hypersensitivity to levetiracetam or any other components of this product.

Drug interaction with medication: No significant interaction with other drugs has been reported with levetiracetam.
Drug interaction with food and others: Not applicable.

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 overdoses in postmarketing use. There is no specific antidote for overdose with levetiracetam. 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. Standard hemodialysis procedures result in significant clearance of levetiracetam (approximately 50% in 4 hours) and should be considered in cases of overdose.

No Data

Store in a cool and dry place. Protect from light.

Citazar 250 Tablet: Each coated tablet contains Levetiracetam USP 250 mg.
Citazar 500 Tablet: Each coated tablet contains Levetiracetam USP 500 mg.
Citazar Injection: Each 5 mL ampoule contains Levetiracetam USP 500 mg.
Citazar Oral Solution: Each 5 mL solution contains Levetiracetam USP 500 mg.

Storage
Store below 30°C in a dry place, protected from light. Keep away from the reach of children.

Packing
Citazar 250 Tablet: Carton of 20 tablets in blister pack.
Citazar 500 Tablet: Carton of 10 tablets in blister pack.
Citazar Injection: Carton of 10 ampoules in plastic tray.
Citazar Oral Solution: Carton of 50 mL bottle.