Levetiracetam Flashcards
What are the indications of levetiracetam?
Monotherapy of focal seizures with or without secondary generalisation
Adjunctive therapy of focal seizures with or without secondary generalisation
Adjunctive therapy of myoclonic seizures and tonic-clonic seizures
Convulsive status epilepticus (on expert advice)
What is the pharmacodynamic of levetiracetam?
Prevents seizure activity by selectively inhibiting hypersynchronised epileptiform burst firing
Does not affect normal neuronal transmission
Exact mechanism unclear but believed to bind to synaptic vesicle protein 2A (SV2A) in the presynaptic neuron, which may inhibit neurotransmitter release - this action does not appear to affect normal neurotransmission
Also indirectly affects GABAergic neurotransmission
In vitro it inhibits N-type calcium channels
What is SV2A?
Synaptic vesicle protein 2A
A membrane bound protein found on synaptic vesicles
Found throughout the CNS
What is the pharmacokinetic of levetiracetam?
Bioavailability = 100% (oral)
Protein binding = < 10%
Half-life = 6-8 hours
Metabolism = minimal, 24% by CYP enzymes in liver
Excretion = 66% kidney via urine (as unchanged drug), 0.3% of total dose via faeces
Has a wide therapeutic index, which is unlike the other antiepileptics
What are the common/very common side effects of levetiracetam?
Blocked nose or itchy throat
Increased risk of infection
Drowsiness
Dizziness
N+V
Agitation/increased aggression
Headaches
Reduced appetite
GI discomfort
Vertigo
Tremor
Insomnia
What are the uncommon side effects of levetiracetam?
Alopecia
Concentration impaired
Confusion
Hallucination
Memory impairment
Muscle weakness
Myalgia
Paraesthesia
Psychotic disorder
Suicidal behaviours
Thrombocytopenia/leucopenia
Vision disorders
Weight changes
What are the rare/very rare side effects of levetiracetam?
AKI
Pancreatitis
QT interval prolongation
Rhabdomyolysis
Seizures exacerbated
Delirium
Encephalopathy
Abnormal gait
Hyponatraemia
Neutropenia
Severe cutaneous adverse reactions (SCARs)
Abnormal thinking
What is the frequency unknown side effects of levetiracetam?
Neuroleptic malignant syndrome
What is neuroleptic malignant syndrome?
Life-threatening neurologic emergency associated with the use of antipsychotic (neuroleptic) agents
Characterized by a distinctive clinical syndrome of:
- mental status change
- rigidity
- fever
- dysautonomia (i.e., dysfunction of the autonomic nervous system)
Can levetiracetam be used in pregnancy?
Yes
But it needs to be monitored
What should you advise patients on levetiracetam about driving?
If the drug makes them sleepy they should not drive or use tools or machines
What is the usual dose of levetiracetam used to treat epilepsy in adults and older children (aged 12 years and over)?
250mg to 3000mg OD/BD
Exact dose may depend on weight
What is the usual dose of levetiracetam used to treat epilepsy in children (aged 1 month to 11 years)?
PO
1-5 months = 7mg/kg OD
6 months to 17 years (body weight up to 50kg) = 10mg/kg OD intially then increased in steps of 10mg/kg BD (max per dose is 30mg/kg BD) - dose to be increased every 2 weeks
What is the usual dose of levetiracetam used to treat epilepsy in children (aged 1 month to 11 years)?
PO
1-5 months = 7mg/kg OD
6 months to 17 years (body weight up to 50kg) = 10mg/kg OD intially then increased in steps of 10mg/kg BD (max per dose is 30mg/kg BD) - dose to be increased every 2 weeks
What forms does levetiracetam come in?
Tablets
Liquid
Granules
How would you advise patients to take levetiracetam tablets?
Swallow the tablets whole with a drink of water, milk or juice
Do not chew them
How would you advise patients to take levetiracetam oral solution?
The liquid dose can be taken by itself or mixed into a glass of water, milk or juice
The liquid levetiracetam comes with syringe to measure the doses. If you do not have one ask your pharmacist
Do not use a kitchen teaspoon to measure the doses as it will not measure the right amount
How would you advise patients to take levetiracetam granules?
Granules can be taken straight from the packet or mixed with food or water
Do not chew them because they can sometimes taste bitter
Drink some water after you have taken the granules
What should you advise patients on levetiracetam not to do?
Never stop suddenly as this can cause seizures
Coming off the drug should be done very slowly and may take a few months
What should patients do if they forget to take a dose of levetiracetam?
For once a day users
Take the missed dose as soon as they remember unless it is less than 12 hours before the next dose
If so, they should leave out the missed dose and take the next dose at the usual time
For 2ce a day users
Take the missed dose as soon as they remember unless it is less than 8 hours before the next dose
If so, they should skip the missed dose and take the next dose at the usual time
They should not take 2 doses at the same time
If they forget regularly, advice them to set an alarm to help remind them or ask their pharmacist for other ways to help them remember to take their medications
What should patients do if they take more than the prescribed dose?
If they have taken more than the prescribed dose and they feel:
- sleepy or less alert
- agitated or aggressive
Call 111
If they need to go to A&E they should ask someone else to drive them or call an ambulance and take the levetiracetam packet & any remaining medication
If they:
- have problems breathing
- lose consciousness
Call 999
What are the significant drug interactions for levetiracetam?
Levetiracetam + methotrexate = reduced methotrexate clearance
Levetiracetam is a non-enzyme inducing drug - unlikely to affect any form of contraception
Sources
https://www.nhs.uk/medicines/levetiracetam/
https://bnf.nice.org.uk/drugs/levetiracetam/
https://go.drugbank.com/drugs/DB01202
https://epilepsysociety.org.uk/living-epilepsy/women-and-epilepsy/contraception-and-epilepsy#:~:text=Enzyme%2Dinducing%20AEDs%20may%20make%20some%20methods%20of%20contraception%20less%20effective.&text=Enzyme%2Dinducing%20AEDs%20may%20affect,down%20hormones%20in%20the%20body.
