Levetiracetam

Question 1

What are the indications of levetiracetam?

Answer 1

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)

Question 2

What is the pharmacodynamic of levetiracetam?

Answer 2

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

Question 3

What is SV2A?

Answer 3

Synaptic vesicle protein 2A

A membrane bound protein found on synaptic vesicles

Found throughout the CNS

Question 4

What is the pharmacokinetic of levetiracetam?

Answer 4

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

Question 5

What are the common/very common side effects of levetiracetam?

Answer 5

Blocked nose or itchy throat

Increased risk of infection

Drowsiness

Dizziness

N+V

Agitation/increased aggression

Headaches

Reduced appetite

GI discomfort

Vertigo

Tremor

Insomnia

Question 6

What are the uncommon side effects of levetiracetam?

Answer 6

Alopecia

Concentration impaired

Confusion

Hallucination

Memory impairment

Muscle weakness

Myalgia

Paraesthesia

Psychotic disorder

Suicidal behaviours

Thrombocytopenia/leucopenia

Vision disorders

Weight changes

Question 7

What are the rare/very rare side effects of levetiracetam?

Answer 7

AKI

Pancreatitis

QT interval prolongation

Rhabdomyolysis

Seizures exacerbated

Delirium

Encephalopathy

Abnormal gait

Hyponatraemia

Neutropenia

Severe cutaneous adverse reactions (SCARs)

Abnormal thinking

Question 8

What is the frequency unknown side effects of levetiracetam?

Answer 8

Neuroleptic malignant syndrome

Question 9

What is neuroleptic malignant syndrome?

Answer 9

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)

Question 10

Can levetiracetam be used in pregnancy?

Answer 10

Yes

But it needs to be monitored

Question 11

What should you advise patients on levetiracetam about driving?

Answer 11

If the drug makes them sleepy they should not drive or use tools or machines

Question 12

What is the usual dose of levetiracetam used to treat epilepsy in adults and older children (aged 12 years and over)?

Answer 12

250mg to 3000mg OD/BD

Exact dose may depend on weight

Question 13

What is the usual dose of levetiracetam used to treat epilepsy in children (aged 1 month to 11 years)?

Answer 13

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

Question 13

What is the usual dose of levetiracetam used to treat epilepsy in children (aged 1 month to 11 years)?

Answer 13

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

Question 14

What forms does levetiracetam come in?

Answer 14

Tablets

Liquid

Granules

Question 15

How would you advise patients to take levetiracetam tablets?

Answer 15

Swallow the tablets whole with a drink of water, milk or juice

Do not chew them

Question 16

How would you advise patients to take levetiracetam oral solution?

Answer 16

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

Question 17

How would you advise patients to take levetiracetam granules?

Answer 17

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

Question 18

What should you advise patients on levetiracetam not to do?

Answer 18

Never stop suddenly as this can cause seizures

Coming off the drug should be done very slowly and may take a few months

Question 19

What should patients do if they forget to take a dose of levetiracetam?

Answer 19

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

Question 20

What should patients do if they take more than the prescribed dose?

Answer 20

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

Question 21

What are the significant drug interactions for levetiracetam?

Answer 21

Levetiracetam + methotrexate = reduced methotrexate clearance

Levetiracetam is a non-enzyme inducing drug - unlikely to affect any form of contraception

Question 22

Sources

Answer 22

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.