EPILEPSY: SODIUM VALPROATE

Question 1

Category

Answer 1

Category 2

Maintained on a specific brand based on clinical judgement (seizure frequency, treatment history etc.)

Question 2

Indication

Answer 2

• all forms of epilepsy
• migraine prophylaxis
• mania

Question 3

MoA

Answer 3

Weak inhibitor of neuronal sodium channels.
Stabilises resting membrane potential.
Reduces neuronal excitability.

Question 4

Patients under 55

male or female

Answer 4

• SV should not be initated where alternative is available
• If no alt = 2 specialists must independently document this

Question 5

Contraindications

Answer 5

• Acute porphyrias
• Personal/ family history of severe hepatic dysfunction

Question 6

Main risk

Answer 6

Highly teratogenic
1g = max in pregnancy
> = increased teratogenicity

Question 7

What type of seizures is valproate used for?

Answer 7

1st line in all types of generalised seizures.

Question 8

Sodium valproate + pregnancy

Answer 8

HIGHLY TERATOGENIC
- can lead to congenital malformations and neurodevelopmental disorders
- prescribers should NOT prescribe SV to females of childbearing potential

Contraindicated in pregnant women for BPD and only considered in epilepsy if no alternative.

Question 9

When would SV be offered to women with childbearing potential

Answer 9

• No other suitable treatment
• Likelihood of pregnancy considered
• PPP in place
• Risks + benefits

Question 10

Pregnancy Prevention Programme (PPP)

Answer 10

• ONE highly effective method of contraception (e.g. IUD or implant) or TWO complementary forms of contraception
  including a barrier method.
• Fully informed of the risks of use in pregnancy, and a signed risk acknowledgement form.
• Seen annually by specialist for review.

Question 11

PPP - Pharmacists role

Answer 11

Provide valproate patient card.
Remind pt. of risks in pregnancy/need for highly effective contraception.
Remind of need for annual specialist review
Dispense as whole pack - always give PIL
Refer/contact GP if pt.not taking highly effective contraception.

Question 12

Major side effects to look out for

2

Answer 12

1. Hepatic dysfunction
2. Pancreatitis

report signs + withdraw treatment

Question 13

Side effects

Answer 13

Hepatotoxicity
Blood disorders
Pancreatitis
Hyponatraemia
GI: D+N
Transient hair loss
Weight gain

Question 14

Hepatotoxicity

Answer 14

Discontinue if abnormally prolonged prothrombin time
Monitor LFTs
* Persistent vomiting
* Abdominal pain
* Jaundice
* Malaise
* Drowsiness

Question 15

Who is at increased risk of liver toxicity from SV?

Answer 15

• Children < 3
• Metabolic disorder
• Organic brain disease
• Severe seizures + mental retard
• Multiple AEDs

Question 16

Blood disorders

Answer 16

E.g. Leucopoenia, thrombocytopenia
Monitor - FBC
* Fever
* Sore throat
* Mouth ulcers
* Bruising or bleeding

Question 17

Pancreatitis

Answer 17

Abdominal pain
N + V

Question 18

Drugs that antagonise the anticonvulsant effect of sodium valproate

Answer 18

Quinolone
Mefloquine
SSRIs
Antipsychotics
TCA/related antidepressants

Question 19

Drugs that increase the risk of hepatoxicity with sodium valproate

Answer 19

Statins
Carbamazepine
Tetracyclines
Fluconazole/ Itraconazole
Isoniazid
Methotrexate/ Sulfasalazine

Question 20

Sodium valproate increases the concentration of what drugs?

Answer 20

Enzyme inhibitors = increases the drug concentration of other anti-epileptic drugs e.g. lamotrigine, phenobarbital

Question 21

Monitoring

Answer 21

1. plasma-valproate conc
2. LFT - before and every 6 months
3. FBC

Question 22

What if liver enzymes are raised

Answer 22

• transient
• monitor until normal
• discontinnue if abnormally long prothrombin time

Question 23

Sodium Valproate and
Vitamin D
supplementation?

Answer 23

MHRA advises
* vitamin D supplementation
* immobilized for long periods or
* inadequate sun exposure or dietary intake of calcium