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Medicines Monitoring

Valproic acid and Sodium valproate monitoring

Last updated
Topics: MonitoringSodium valproateValproic acid
Using this page · Individualise medicines monitoring

This medicines monitoring page has been written using publications and expert opinion. It is designed to save clinician time, but not replace professional responsibility. When using this page you should: ensure an individualised monitoring plan is developed in partnership with the patient and take account of any locally agreed advice and guidance.

Contents

  1. Before starting
    1. Required
  3. After started or dose changed
    1. Required
  5. Ongoing once stable
    1. Required
    2. Before surgery or following spontaneous bleeding or bruising
    3. Consider
  7. Abnormal results
    1. Hepatic function
    2. Haematological effects
    3. Pancreatitis
    4. Vitamin D deficiency
  9. Notes
    1. Advice to patients
    2. Brand prescribing
    3. Conception and pregnancy
    4. Bone fractures
  11. Bibliography
  12. Update history

Before starting

Required

  • Baseline
    • Body weight or Body mass index
    • Clotting screeningincluding bleeding time and coagulation tests
    • Full blood count
    • Liver function tests
    • Age screeningsee ‘Specialist initiation only’ section.

Specialist initiation only

Valproate must not be used in women or girls of childbearing potential unless there is a Pregnancy Prevention Programme in place.

Only specialists can initiate or recommend initiation in adults and children. Valproate must not be initiated in patients (male or female) under the age of 55, unless two specialists independently review and document that there is no other effective or tolerated treatment or the risks do not apply to the individual patient.

After started or dose changed

Required

  • Periodically
    • Liver function testsduring the first 6 months

Ongoing once stable

Required

  • At 6 months, then annually
    • Full blood count
    • Liver function tests
    • Body weight or Body mass index

Before surgery or following spontaneous bleeding or bruising

  • Once
    • Clotting screeningincluding bleeding time and coagulation tests
    • Full blood count

Consider

  • Periodically
    • Plasma valproate concentration

Routine monitoring of plasma valproate concentrations is not recommended. Consider monitoring when investigating:

  • adherence
  • unexplained loss of seizure control
  • suspected toxicity
  • a pharmacokinetic interaction
  • onset of specific clinical conditions (such as organ failure, status epilepticus)

Abnormal results

Hepatic function

Raised liver enzymes are usually transient and usually occur at the beginning of therapy. Liver damage usually occurs within first 6 months of therapy with maximum risk between 2 and 12 weeks. Assess the patient clinically and monitor FBC and liver function (including prothrombin time and coagulation tests) until return to normal. Discontinue if abnormal liver function occurs.

Haematological effects

If spontaneous bruising or bleeding occurs, withhold treatment pending investigation. Discontinue if abnormally prolonged prothrombin time or blood dyscrasias.

Pancreatitis

Discontinue valproate if pancreatitis develops.

Vitamin D deficiency

Valproate is thought to affect bone mineral metabolism which may lead to vitamin D deficiency, hypocalcaemia, and hypophosphatemia in chronically treated patients with epilepsy. Consider vitamin D supplementation.

Notes

Advice to patients

Advise patients and carers to be aware of the signs of:

Blood or liver disorders

Seek immediate medical attention if symptoms develop, such as:

  • unexplained bleeding
  • bruising, purpura
  • sore throat
  • fever
  • malaise

Liver disorders

Seek immediate medical attention if symptoms develop, such as:

  • sudden onset of weakness
  • malaise
  • anorexia
  • lethargy
  • oedema
  • drowsiness
  • repeated vomiting
  • abdominal pain
  • jaundice
  • recurrence of seizures

Pancreatitis

Seek immediate medical attention if symptoms develop, such as:

  • abdominal pain
  • nausea and vomiting

Suicidal ideation and behaviours

Seek immediate medical attention if symptoms develop, such as:

  • mood changes
  • distressing or suicidal thoughts

Brand prescribing

Valproate is classified by the MHRA as a category 2 medicine. Use clinical judgement when deciding whether to switch between branded and generic products for people with epilepsy.

Conception and pregnancy

There is a significant risk of birth defects and developmental disorders in children born to women who take valproate during pregnancy. Paternal exposure to valproate around the time of conception also has a significant risk of birth defects and developmental disorders in their children.

The MHRA advice provides full information on the risks and issues of valproate use by women and girls. Safety and educational materials have also been provided by the MHRA to support the regulatory measures for valproate in men and women under 55 year of age.

Healthcare professionals can also refer to:

Bone fractures

Decreasing bone mineral density, osteopenia, osteoporosis and fractures may occur in patients on long-term therapy with valproate. Consider vitamin D supplementation for people with risk factors for these conditions who are on long-term valproate. Risk factors include:

  • immobility for long periods
  • inadequate sun exposure
  • inadequate dietary calcium intake

Bibliography

Update history

  1. Republished
  2. Full review and update to reflect current advice including regulatory information from MHRA. Additional information added for when to consider plasma valproate concentrations and management of abnormal results.
  1. Published