Top 100: Levetiracetam, Lamotrigine, Valporate

Question 1

What type of seizures is levetiracetam indicated for?

Answer 1

1) Monotherapy of focal seizures with or without secondary generalisation
2) Add-on therapy for myoclonic seizures and GTC seizures

Question 2

list the important side effects caused by levetiracetam

Answer 2

1) Drowsiness, weakness, dizziness, headache
2) Mood disturbance and psychiatric adverse effects are less common but more likely to cause discontinuation
3) Suicidal ideation and serious hypersensitivity reactions rarely

Question 3

who should levetiracetam be used in caution with?

Answer 3

1) Eliminated by the kidneys, so dosage reduction may be required in renal impairment
2) fetal growth should be monitored in pregnancy

Question 4

outline some of the interactions that can occur with regards to levetiracetam

Answer 4

Few clinically significant interactions, and this is one of its major advantages. Does not interact with other antiepileptic drugs, hormonal contraception, or warfarin

Question 5

how does the bioavailability of oral levetiracetam compare to IV?

Answer 5

oral reliably high, so there is no need for dose modification when switching between oral and IV administration

Question 6

What patient and carer advice should be provided to those taking levetiracetam?

Answer 6

1) do not stop treatment abruptly, as this can cause rebound seizures
2) Drowsiness and headache, are infrequent and mild
3) Driving is prohibited unless seizure-free for 12 months, and for 6 months after changing or stopping treatment

Question 7

Outline the most common adverse reactions of lamotrigine

Answer 7

1) Headache, drowsiness, irritability, blurred vision, dizziness and gastrointestinal symptoms.
2) A few develop a skin rash within the first 8 weeks of starting, this is usually mild, but requires urgent review and possibly discontinuation of the drug

Question 8

Serious skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity syndrome can occur with the use of lamotrigine. what increases the risk of these reactions occurring? (4)

Answer 8

1) More common in patients with history of allergy or rash from other antiepileptic drugs
2) Concomitant use of valproate
3) Initial lamotrigine dosing higher than recommended,
4) More rapid dose escalation than recommended

Question 9

what patient and carer advice should be provided to those prescribed lamotrigine?

Answer 9

1) Skin reactions: report any hypersensitivity reactions
2) Blood disorders: symptoms and signs suggestive of bone-marrow failure, such as anaemia, bruising, sore throat, ulcers, fever or infection

Question 10

who should lamotrigine be used in caution with?

Answer 10

1) Avoid in those with history of hypersensitivity to other antiepileptic drugs, due to the risk of cross-reactivity.
2) Hepatic impairment : Halve dose in moderate, Quater in severe as it is metabolised in the liver

Question 11

Can lamotrigine be used in pregnancy?

Answer 11

1) No evidence that lamotrigine exposure increases the overall risk of congenital malformations, so it is a reasonable choice in women of child-bearing age
2) In pregnancy, plasma-drug concentration used to guide dosage adjustment

Question 12

Lamotrigine has many interactions arising from its metabolism by glucuronidation in the liver. outline some of the important interactions

Answer 12

1) Drugs that induce glucuronidation include carbamazepine, phenytoin, oestrogens, rifampicin and protease inhibitors. These can cause the lamotrigine concentration to fall, potentially leading to treatment failure.
2) Glucuronidation is inhibited by valproate, causing the lamotrigine concentration to rise, increasing the risk of toxicity

Question 13

What side effects can co-administration of lamotrigine and valporate cause?

Answer 13

Severe hypersensitivity reactions are more common when lamotrigine is co-administered with valproate

Question 14

1) The dose of lamotrigine is titrated slowly every 14 days. When should dose titration be repeated if restarting the drug after an interval?
2) If lamotrigine is to be withdrawn, how many weeks should this be done over?

Answer 14

1) Dose titration should be repeated if restarting after interval of more than 5 days
2) Avoid abrupt withdrawal- taper off dose over 2 weeks or longer

Question 15

What types of seizures is valporate first-line in?

Answer 15

1) Generalised tonic–clonic seizures
2) Absence seizures
3) Focal seizures
4) Myoclonic seizures

Question 16

what are the important adverse effects caused by valporate?

Answer 16

1) Common dose-related adverse events are GI upset e.g. nausea, gastric irritation and diarrhoea
2) Neurological and psychiatric effects e.g. tremor, ataxia and behavioural disturbances
3) Thrombocytopenia
4) Transient increase in liver enzymes
5) Hypersensitivity reactions include hair loss, with subsequent regrowth being curlier than original hair.
6) severe liver injury, pancreatitis, bone marrow failure and antiepileptic hypersensitivity syndrome

Question 17

what side-effects in particular are life threatening in those taking valporate, that would lead to withdrawal of treatment ?

Answer 17

1 ) Hepatic dysfunction: Withdraw immediately if persistent vomiting and abdominal pain, anorexia, jaundice, oedema, malaise, drowsiness, or loss of seizure control.
2) Pancreatitis: Discontinue treatment if symptoms of pancreatitis develop.

Question 18

what effect can valporate have on some laboratory tests

Answer 18

False-positive urine tests for ketones

Question 19

Who should valporate be used in caution with?

Answer 19

1) Avoided in women of child-bearing age, especially during conception and in the first trimester
2) Avoided in hepatic impairment
3) Dose reduction in severe renal impairment
4) Mitochondrial disorders

Question 20

valporate is the antiepileptic drug associated with the greatest risk of fetal abnormalities. what abnormalities can occur when this drug is used during pregnancy?

Answer 20

1) Neural tube defects
2) Craniofacial
3) Cardiac and Limb abnormalities
4) Developmental delay

Question 21

Valproate inhibits hepatic enzymes, increasing plasma concentration and risk of toxicity. what are the most common interactions to be aware of?

Answer 21

1) Increases plasma concentration and risk of toxicity with lamotrigine and drugs metabolised by CYT P450 enzymes, such as warfarin.
2) Valproate is itself metabolised by CYP enzymes, so its concentration is reduced and risk of seizures may be increased by CYP inducers (e.g. carbamazepine, phenytoin) and carbapenems.
3) Adverse effects are increased by CYP inhibitors (e.g. macrolides, protease inhibitors)
4) The efficacy of antiepileptic drugs is reduced by drugs that lower the seizure threshold (e.g. antipsychotics, tramadol)

Question 22

outline the monitoring requirements for valporate (3)

Answer 22

1) Monitor liver function before therapy and during first 6 months especially in patients most at risk.
2) Measure FBC and ensure no undue potential for bleeding before starting and before surgery
3) Plasma-valproate concentrations are not a useful index of efficacy, so don’t measure

Question 23

If valporate is to be withdrawn, how should this be undertaken?

Answer 23

Avoid abrupt withdrawal; reduce the dose gradually over at least 4 weeks

Question 24

what patient and carer advice should be given to those taking valporate?

Answer 24

1) Blood or hepatic disorders: recognise signs and symptoms of blood or liver disorders
2) Pancreatitis: immediate medical attention if symptoms such as abdominal pain, nausea, or vomiting develop
3) Do not stop taking valproate without first discussing it with their doctor if you get pregnant.

Question 25

what supplementation should be considered in patients that are immobilised for long periods and taking valporate?

Answer 25

vitamin D supplementation in patients that are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium

Question 26

Liver toxicity is one of the rare side effects of valporate treatment. When is it likely to occur, how should toxicity be monitored and when should treatment be discontinued?

Answer 26

1) usually in first 6 months and usually involves use of multiple antiepileptic drugs
2) Raised liver enzymes during treatment is usually transient but monitor patient until levels back to normal- discontinue if abnormally prolonged prothrombin time

Question 27

The MHRA has advised that valporate is contraindicated in women of childbearing potential unless conditions of Pregnancy Prevention Programme are met. Outline the pharmacists role in the safe supply of valporate

Answer 27

1) Ensure valporate is dispensed in whole packs if possible
2) A warning label on the carton or via a sticker
3) discuss risk with female patients each time valproate medicines are dispensed
4) Give Patient Guide and check they have seen GP or specialist to discuss their treatment and contraception

Question 28

how often must a women of childbearing potential who is taking valporate be reviewed by their specialist and what documentation needs to be signed?

Answer 28

1) At least annually under the Pregnancy Prevention Programme.
2) specialist and patient must sign the Risk Acknowledgement Form- copies of the form must be given to the patient or carer and sent to their GP

Question 29

If valproate is to be used during pregnancy how can the risk of teratogenicity be reduced?

Answer 29

1) Lowest effective dose, in divided doses or as M/R tablets to avoid peaks in plasma-valproate levels
2) Doses >1 g daily increase risk of teratogenicity