Levetiracetam
Levetiracetam Uses, Dosage, Side Effects, Food Interaction and all others data.
The exact mechanism of anticonvulsant effect is unknown but does not involve inhibitory and excitatory neurotransmission. Stereo-selective binding of Levetiracetam was confined to synaptic plasma membranes in the central nervous system with no binding occurring in peripheral tissue.
Studies show that levetiracetam affects intraneuronal Ca levels by partial inhibition of N-type Ca currents and by reducing the release of Ca from intraneuronal stores; facilitates GABA-ergic inhibitory transmission through displacement of negative modulators; reduces delayed rectifier K current; and/or binds to synaptic proteins which modulate neurotransmitter release.
Levetiracetam appears to prevent seizure activity via the selective inhibition of hypersynchronized epileptiform burst firing without affecting normal neuronal transmission, though the exact mechanism through which this occurs is unclear. The therapeutic index of levetiracetam is wide, making it relatively unique amongst other anti-epileptic medications.
Anti-epileptic drugs, including levetiracetam, may increase the risk of suicidal ideation or behaviour - patients taking levetiracetam should be monitored for the emergence or worsening of depressive symptoms, suicidal ideation, and behavioural abnormalities.
| Trade Name | Levetiracetam |
| Availability | Prescription only |
| Generic | Levetiracetam |
| Levetiracetam Other Names | Levetiracetam, Levetiracetame, Levetiracetamum |
| Related Drugs | gabapentin, clonazepam, lamotrigine, diazepam, pregabalin, Lyrica, topiramate, Keppra, Topamax, Valium |
| Weight | 100mg/ml, 1000mg, 250mg, 500mg, 750mg, , 250mg |
| Type | Oral Solution, Oral Tablet, Dispersible, Extended Release, Intravenous, Tablet |
| Formula | C8H14N2O2 |
| Weight | Average: 170.212 Monoisotopic: 170.105527699 |
| Protein binding | Levetiracetam and its metabolites are largely unbound to plasma proteins (15,11,13 |
| Groups | Approved |
| Therapeutic Class | Adjunct anti-epileptic drugs |
| Manufacturer | Intrapharm Laboratories Limited, Actavis Indonesia |
| Available Country | United Kingdom, United States, Netherlands, Indonesia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Levetiracetam is used for an adjunctive therapy for:
- Partial Onset Seizures
- Myoclonic Seizures In Patients with Juvenile Myoclonic Epilepsy
- Primary Generalized Tonic-Clonic Seizures
Levetiracetam injection is an alternative for adult patients (16 years and older) when oral administration is temporarily not feasible.
Levetiracetam is also used to associated treatment for these conditions: Epilepsies, Grand mal Generalized tonic-clonic seizure, Partial-Onset Seizures, Myoclonic seizures
How Levetiracetam 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. Levetiracetam 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.
Levetiracetam 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
Levetiracetam 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-
Levetiracetam injection is for intravenous use only and must be diluted prior to administration. Levetiracetam 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 Levetiracetam 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).
Levetiracetam 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.
Levetiracetam 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
Levetiracetam 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
Levetiracetam is rapidly and nearly completely absorbed following oral administration, with a reported absolute oral bioavailability of essentially 100%. Tmax is approximately 1.3 hours after dosing, and Cmax is 31 μg/mL following a single 1000mg dose and 43 μg/mL following repeated dosing. Co-administration of levetiracetam with food delays Tmax by approximately 1.5 hours and decreases Cmax 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 Levetiracetam in breast feeding women are available. Data from animals indicate that Levetiracetam is secreted into milk.Therefore Levetiracetam 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. Levetiracetam 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
You find simplified version here Levetiracetam
Levetiracetam contains Levetiracetam see full prescribing information from innovator Levetiracetam Monograph, Levetiracetam MSDS, Levetiracetam FDA label
FAQ
What is Levetiracetam used for?
Levetiracetam is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formulation or by injection into a vein.
How safe is Levetiracetam?
Levetiracetam is proving to be safe and well-tolerated. So far, it appears to have a favourable safety profile in special populations, such as children, the elderly, and patients with hepatic dysfunction.
How does Levetiracetam work?
Levetiracetam work by help to control certain types of seizures (eg, partial seizures, myoclonic seizures, or tonic-clonic seizures) in the treatment of epilepsy. This medicine cannot cure epilepsy and will only work to control seizures for as long as you continue to use it.
How quickly does Levetiracetam work?
Levetiracetam should take effect within 1 to 2 hours; however, effects may not be visibly obvious and therefore laboratory tests may need to be done to evaluate whether the medication is working.
What are the common side effects of Levetiracetam?
The most common side effects of Levetiracetam are headaches, feeling sleepy and a blocked nose or itchy throat.
Is Levetiracetam safe during pregnancy?
Levetiracetam is one such AED which is supposed to be effective in controlling seizures during pregnancy and relatively free of teratogenic side effects.
Is Levetiracetam safe during breastfeeding?
Levels of Levetiracetam in milk can be relatively high in some women and can occasionally cause sedation and other adverse effects in their breastfed infants. If Levetiracetam is required by the mother, it is not necessarily a reason to discontinue breastfeeding.
Can I drink alcohol with Levetiracetam?
Alcohol can increase the nervous system side effects of Levetiracetam such as dizziness, drowsiness, and difficulty concentrating. You should avoid or limit the use of alcohol while being treated with Levetiracetam.
Can I drive after taking Levetiracetam?
feeling drowsy, sleepy or dizzy as your body gets used to Levetiracetam, these side effects should wear off. Do not drive, ride a bike, or operate machinery until you feel more alert.
When should be taken of Levetiracetam?
Levetiracetam is usually taken twice a day, about 12 hours apart. Swallow the tablets whole. They may have a bitter taste when the pill is crushed. People who have trouble swallowing the pills whole can break the tablets in half, mix the tablet with food, or use the liquid form.
Can I take Levetiracetam on an empty stomach?
You can take Levetiracetam with or without food.
How long does Levetiracetam stay in my system?
It can take about 44 hours for Levetiracetam to be out of ones system. The elimination half-life of a medication is the time it takes for blood levels of the medication to be reduced by half. It takes approximately 5.5 x elimination half-life for a medicine to be out of your system.
Can Levetiracetam be stopped?
Do not stop taking Levetiracetam without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. If you suddenly stop taking Levetiracetam, your seizures may become worse. Your doctor will probably decrease your dose gradually.
How do I stop taking Levetiracetam ?
If you need to stop the Levetiracetam, you should do so by reducing by 1 tablet each day until you are off the medicine. No blood monitoring is needed while on Levetiracetam.
Can Levetiracetam cause liver damage?
A single case of acute liver failure attributed to Levetiracetam has been published.
Is Levetiracetam hard on my kidneys?
Levetiracetam is a widely used drug that has been reported to be generally tolerable and effective; however, it has the potential to negatively affect renal function.
Does Levetiracetam affect blood pressure?
Levetiracetam has been associated with an increase in blood pressure.
Is Levetiracetam used for dementia?
The anti-epileptic drug Levetiracetam can reduce abnormal brainwave activity and reverse memory deficits in a mouse model of Alzheimer's disease.
What happen if I overdose of Levetiracetam?
Overdose symptoms may include extreme drowsiness, agitation, aggression, shallow breathing, weakness, or fainting.
What happens if I miss a dose?
If you take Levetiracetam and miss a dose once a day take the missed dose as soon as you remember. If it's less than 12 hours before the next dose is due, leave out the missed dose and take your next dose as normal.
Who should not take Levetiracetam?
Some people have thoughts about suicide while taking Levetiracetam.Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor. Seizures may increase if you stop using Levetiracetam suddenly.
What should I avoid while taking Levetiracetam ?
Avoid driving or hazardous activity until you know how Levetiracetam will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.
