valproate Flashcards
monitoring requirements
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
T or F - pt on valproate need to have their LFTs checked before starting, and then every 6 months
false
before starting and then during first 6 months esp in pt most at risk
do you need to do therapeutic drug monitoring
Plasma-valproate concentrations are not a useful index of efficacy, therefore routine monitoring is unhelpful.
treatment cessation
Avoid abrupt withdrawal; if treatment with valproate is stopped, reduce the dose gradually over at least 4 weeks.
suspected pregnancy - what to do
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.
pt and carer advice - blood or hepatic disorders
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.
pt and carer advice - pancreatitis
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.
SE - discontinue treatment if the following occur
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.
conception and contraception
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
conception and contraception - men
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.
CI in known or suspected mitochondrial disorders - why
higher rate of acute liver failure and liver-related deaths
teratogenicity - what can I cause
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).
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
must supply PIL
latest advice about prescribing valproate
- 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
pregnancy - migraine prophylaxis (Unlicensed) and bipolar disorder
MHRA advises that valproate medicines must not be used.
pregnancy - epilepsy
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.
Monitoring in pregnancy
Specialist prenatal monitoring should be instigated when valproate has been taken in pregnancy.
BF
Present in milk—risk of haematological disorders in breast-fed newborns and infants.
use in HI
avoid
interactions with ….toxic drugs.
hepatotoxic e.g. statins, tetracyclines, azoles, amiodarone
does it interact with antidepressants?
ADs lower seizure threshold
also increased risk hyponatraemia
does it interact with NSAIDS and diuretics?
increased risk hyponatraemia
SV + topiramate interaction
topiramate increases risk of toxicity when given with valproate, monitor
avoid this abx with valproate
(Hint used for UTIs, not 1st line)
pivmecillinam
V increases risk of adverse effects when given with P
avoid
unlicensed use
migraine prophylaxis
name the abx that SV interacts with & should be avoided
valporate increases risk of adverse effects when given with pivmecillinam, avoid
what electrolyte disturbance can it cause
hyponatraemia
You see a patient who has come back to you because their UTI symptoms are still present after finishing 3 day course of nitrofurantoin. You are aware that 2nd line options include nitro (if not used 1st line), fosfomycin, pivmecillinam or amoxicillin (only if susceptible due to high rate of resistance). This is the patients current drug history: citalopram 10mg OD, lansoprazole 30mg OD, depakote 500mg GR tabs, colecalciferol 800mg caps. Which abx is unsuitable and why?
Do not give pivmecillinam because when valporate is given with it, there is increased risk of adverse effects. Avoid
Should you consider vitamin D supplementation
Yes in people immobilised for long periods of time or inadequate sun exposure or dietary intake of calcium
patient has raised liver enzymes during valproate treatmemt. what should you do
raised liver enzymes during treatment usually transient
however reassess pt clinically and liver function (including prothrombin) needs to be monitored until normal
discontinue if abnormally prolonged prothrombin
