Levexx (zydus)

Uses

Levexx (zydus) is used for an adjunctive therapy for:

• Partial Onset Seizures
• Myoclonic Seizures In Patients with Juvenile Myoclonic Epilepsy
• Primary Generalized Tonic-Clonic Seizures

Levexx (zydus) injection is an alternative for adult patients (16 years and older) when oral administration is temporarily not feasible.

Levexx (zydus) is also used to associated treatment for these conditions: Epilepsies, Grand mal Generalized tonic-clonic seizure, Partial-Onset Seizures, Myoclonic seizures

How Levexx (zydus) works

The exact mechanism through which levetiracetam exerts its anti-epileptic effects is unclear, but is thought to be unique amongst other anti-epileptic medications. Current knowledge suggests that levetiracetam’s binding to synaptic vesicle protein 2A (SV2A) is a key driver of its action. SV2A is a membrane-bound protein that is found on synaptic vesicles and is ubiquitous throughout the CNS - it appears to play a role in vesicle exocytosis and in the modulation of synaptic transmission by increasing the available amount of secretory vesicles available for neurotransmission. Stimulation of pre-synaptic SV2A by levetiracetam may inhibit neurotransmitter release, but this action does not appear to affect normal neurotransmission. This has led to the suggestion that levetiracetam exclusively modulates the function of SV2A only under pathophysiological conditions. Levexx (zydus) and related analogues showed a correlation between affinity for SV2A and anti-epileptic potency, further suggesting that action at this site contributes to the anti-epileptic activity of the drug.

Levexx (zydus) has also been shown to indirectly affect GABAergic neurotransmission (despite having no direct effect on GABAergic or glutamatergic receptors) and modulate ionic currents. Similarly, levetiracetam has been shown in vitro to inhibit N-type calcium channels. How, or even if, these actions are implicated in its anti-epileptic action have yet to be elucidated.

Dosage

Levexx (zydus) dosage

For tablet and oral solution-

Treatment should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg twice daily). Additional dosing increments may be given (1000 mg/day additional every 2 weeks) to a maximum recommended daily dose of 3000 mg.

Use in Pediatric Patients-

• 1 Month To <6 Months: Initial Daily dose 7 mg/kg twice daily &IncrementalDaily dose 21 mg/kg twice daily
• 6 Months To <4 Years: Initial Daily dose 10 mg/kg twice daily &IncrementalDaily dose 25 mg/kg twice daily
• 4 Years To <16 Years: Initial Daily dose 10 mg/kg twice daily &IncrementalDaily dose 30 mg/kg twice daily
• Adolescent with 20-40 kg body weight: Initial Daily dose 250 mg twice daily &IncrementalDaily dose 750 mg twice daily

The daily dose should be increased every 2 weeks.

Injection-

Levexx (zydus) injection is for intravenous use only and must be diluted prior to administration. Levexx (zydus) injection (500 mg/5 mL) should be diluted in 100 mL of compatible diluents and administered intravenously as a 15-minute IV infusion. Product with particulate matter or discoloration should not be used.

Dosing Instructions: Preparation and Administration-

• Dose 500 mg:Withdraw Volume5 ml,Volume of Diluent100 ml,Infusion Time15 minutes
• Dose 1000 mg:Withdraw Volume 10ml,Volume of Diluent100 ml,Infusion Time15 minutes
• Dose 1500 mg:Withdraw Volume 15 ml,Volume of Diluent 100 ml,Infusion Time15 minutes

For example, to prepare a 1000 mg dose, dilute 10 ml of Levexx (zydus) injection in 100 ml of a compatible diluents and administer intravenously as a 15-minute infusion.

Intravenous: Dilute dose in 100 mL of suitable diluent (e.g. NaCl 0.9%, lactated Ringer's or dextrose 5% inj).

Levexx (zydus) can be initiated with either intravenous or oral administration. May be taken with or without food. Oral solution may be taken directly or diluted in a glass of water.

Side Effects

Dizziness, drowsiness, irritability, sore throat, tiredness, weakness are some common adverse effects. In rare cases severe allergic reaction may happen.

Toxicity

The oral TDLO of levetiracetam in humans is 10 mg/kg. Symptoms of levetiracetam overdose are consistent with its adverse effect profile and may include agitation, aggression, somnolence, decreased level of consciousness, respiratory depression, or coma. There is no antidote for levetiracetam overdose, therefore management should involve general supportive measures and symptomatic treatment. Hemodialysis results in significant clearance of plasma levetiracetam (approximately 50% within 4 hours) and should be considered in cases of overdose as indicated by the patient's status.

Precaution

Severe allergic reactions, abnormal thoughts; dark urine; decreased coordination; extreme dizziness, drowsiness, tiredness, or weakness; fever, chills, or persistent sore throat; hallucinations; memory loss; mouth sores; muscle or neck pain; new or worsening mental problem; mood or behavior changes; new or worsening seizures; pain, itching or redness at the injection site;suicidal thoughts or attempts; unusual bruising or bleeding; vision changes; yellowing of the skin or eyes.

Interaction

No potential drug interaction has been reported

Food Interaction

• Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Levexx (zydus) Drug Interaction

Moderate: duloxetine, pregabalin, cetirizineUnknown: aspirin, aspirin, apixaban, omega-3 polyunsaturated fatty acids, metoprolol, metoprolol, polyethylene glycol 3350, esomeprazole, acetaminophen, albuterol, levothyroxine, acetaminophen, lacosamide, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol

Levexx (zydus) Disease Interaction

Moderate: suicidal tendency, hemodialysis, renal dysfunctionMinor: hematologic abnormalities

Volume of Distribution

The volume of distribution of levetiracetam is approximately 0.5 to 0.7 L/kg.

Elimination Route

Levexx (zydus) is rapidly and nearly completely absorbed following oral administration, with a reported absolute oral bioavailability of essentially 100%. T_max is approximately 1.3 hours after dosing, and C_max is 31 μg/mL following a single 1000mg dose and 43 μg/mL following repeated dosing. Co-administration of levetiracetam with food delays T_max by approximately 1.5 hours and decreases C_max by 20%.

Half Life

The plasma half-life of levetiracetam is 6-8 hours and is not affected by dose or repeat administration. Half-life is increased in the elderly (by about 40%) and those with renal impairment.

Clearance

The total plasma clearance of levetiracetam is 0.96 mL/min/kg, with renal clearance comprising 0.6 mL/min/kg. The primary inactive metabolite of levetiracetam, L057, has a renal clearance of 4 mL/min/kg. Given the relatively high proportion of drug undergoing renal clearance, overall clearance of levetiracetam is reduced in patients with renal impairment.

Elimination Route

Approximately 66% of the administered dose of levetiracetam is excreted in the urine as unchanged drug, while only 0.3% of the total dose is excreted via the feces. The primary inactive metabolite of levetiracetam, L057, is also found in the urine as approximately 24% of the administered dose.

Pregnancy & Breastfeeding use

Pregnancy category C. No data on the use of Levexx (zydus) in breast feeding women are available. Data from animals indicate that Levexx (zydus) is secreted into milk.Therefore Levexx (zydus) is contraindicated during breast-feeding.

Special Warning

Renal Impairment: ESRD patients undergoing dialysis: Loading dose of 750 mg, followed by 500-1,000 mg once daily; supplemental dose of 250-500 mg after dialysis.

• CrCl (<30 mL/min): Dosage 250-500 mg bid.
• CrCl (30-49 mL/min): Dosage 250-750 mg bid.
• CrCl (50-79 mL/min): Dosage 500-1,000 mg bid.

Severe Hepatic Impairment: Reduce dose by 50%.

Acute Overdose

Symptoms: Somnolence, agitation, aggression, depressed level of consciousness, resp depression, coma.

Management: Symptomatic and supportive treatment. Empty the stomach by gastric lavage or induction of emesis. May perform haemodialysis.

Storage Condition

Store in a cool and dry place, protected from light and moisture. Keep out of the reach of children. Levexx (zydus) injection was found to be physically compatible and chemically stable when mixed with the following diluents and antiepileptic drugs for at least 24 hours and stored in polyvinyl chloride (PVC) bags at controlled room temperature 15-30°C

Innovators Monograph

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