valproate

Question 1

monitoring requirements

Answer 1

LFTs before and during first 6 moths esp in pt most at risk
FBC and ensure no undue potential of bleeding before starting and before surgery

Question 2

T or F - pt on valproate need to have their LFTs checked before starting, and then every 6 months

Answer 2

false
before starting and then during first 6 months esp in pt most at risk

Question 3

do you need to do therapeutic drug monitoring

Answer 3

Plasma-valproate concentrations are not a useful index of efficacy, therefore routine monitoring is unhelpful.

Question 4

treatment cessation

Answer 4

Avoid abrupt withdrawal; if treatment with valproate is stopped, reduce the dose gradually over at least 4 weeks.

Question 5

suspected pregnancy - what to do

Answer 5

Female patients or their carers should be advised to immediately contact their GP for an urgent referral to a specialist in case of suspected pregnancy.
The MHRA advises that patients should not stop taking valproate without first discussing it with a specialist.

Question 6

pt and carer advice - blood or hepatic disorders

Answer 6

Patients or their carers should be told how to recognise signs and symptoms of blood or liver disorders and advised to seek immediate medical attention if symptoms develop.

Question 7

pt and carer advice - pancreatitis

Answer 7

Patients or their carers should be told how to recognise signs and symptoms of pancreatitis and advised to seek immediate medical attention if symptoms such as abdominal pain, nausea, or vomiting develop.

Question 8

SE - discontinue treatment if the following occur

Answer 8

Hepatic dysfunction:

Withdraw treatment immediately if persistent vomiting and abdominal pain, anorexia, jaundice, oedema, malaise, drowsiness, or loss of seizure control.

Pancreatitis:

Discontinue treatment if symptoms of pancreatitis develop.

Question 9

conception and contraception

Answer 9

all women and girls of childbearing potential being treated with valproate medicines must be supported on a Pregnancy Prevention Programme—pregnancy should be excluded before treatment initiation.

Highly effective contraception must be used during treatment i.e. at least 1, preferably highly effective user-independent contraceptive method (such as an intra-uterine device or implant), or 2 complementary forms including a barrier method

Question 10

conception and contraception - men

Answer 10

MHRA advises that male patients taking valproate medicines should be informed of the risk of infertility, and of data showing testicular toxicity in animal studies.

Question 11

CI in known or suspected mitochondrial disorders - why

Answer 11

higher rate of acute liver failure and liver-related deaths

Question 12

teratogenicity - what can I cause

Answer 12

Valproate is highly teratogenic and evidence supports that use in pregnancy leads to neurodevelopmental disorders (approx. 30–40% risk) and congenital malformations (approx. 10% risk).

Question 13

full pack dispensing needed. however exceptions can be made on individual pt basis, provided a risk assessment is carried out on the need to dispense repackaged valproate medicines (e.g. in a monitored dosage system. in this case what do you do instead

Answer 13

must supply PIL

Question 14

latest advice about prescribing valproate

Answer 14

• do not start in new patients (MALE OR FEMALE) under 55 unless 2 specialists have independently considered and documented that there is no other effective or tolerated treatment, or there are compelling reasons why the reproductive risks do not apply
• at next annual specialist review, F or CBP need to be reviews using revised valproate Risk Acknowledgement Form which includes the need for second specialist signature if they are to be continued on treatment
• subsequent annual reviews with one specialist

Question 15

pregnancy - migraine prophylaxis (Unlicensed) and bipolar disorder

Answer 15

MHRA advises that valproate medicines must not be used.

Question 16

pregnancy - epilepsy

Answer 16

MHRA advises valproate must not be used unless two specialists independently consider and document that there is no other effective or tolerated treatment
If valproate is to be used, the lowest effective dose should be prescribed in divided doses to be taken throughout the day; modified-release preparations may be preferable to avoid high peak plasma-valproate concentrations. There is no dose threshold considered to be without any risk, however, the risk of birth defects and neurodevelopmental disorders is greater at higher doses.

Question 17

Monitoring in pregnancy

Answer 17

Specialist prenatal monitoring should be instigated when valproate has been taken in pregnancy.

Question 18

BF

Answer 18

Present in milk—risk of haematological disorders in breast-fed newborns and infants.

Question 19

use in HI

Answer 19

avoid

Question 20

interactions with ….toxic drugs.

Answer 20

hepatotoxic e.g. statins, tetracyclines, azoles, amiodarone

Question 21

does it interact with antidepressants?

Answer 21

ADs lower seizure threshold
also increased risk hyponatraemia

Question 22

does it interact with NSAIDS and diuretics?

Answer 22

increased risk hyponatraemia

Question 23

SV + topiramate interaction

Answer 23

topiramate increases risk of toxicity when given with valproate, monitor

Question 24

avoid this abx with valproate
(Hint used for UTIs, not 1st line)

Answer 24

pivmecillinam
V increases risk of adverse effects when given with P
avoid

Question 25

unlicensed use

Answer 25

migraine prophylaxis