How to taper valproate?

From the FDA Drug Label

Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks.

To taper valproate, do not abruptly discontinue the drug. The dosage of concomitant antiepilepsy drugs can be reduced by approximately 25% every 2 weeks. However, there is no specific guidance on tapering valproate itself. 1

From the Research

Tapering Valproate

To taper valproate, the following steps can be considered:

• Gradually reduce the dosage of valproate over a period of time, as abrupt withdrawal can lead to severe side effects or seizures 2
• The rate of tapering may vary depending on the individual patient and the specific circumstances, but a common approach is to reduce the dose by 25% per week 2
• Monitor the patient closely for signs of withdrawal or increased seizure activity during the tapering process 2
• Consider using a dosing algorithm, such as the one used in a study to convert patients from valproate monotherapy to lamotrigine monotherapy, to guide the tapering process 3

Important Considerations

Some important considerations when tapering valproate include:

• The potential for increased seizure activity or status epilepticus, particularly in patients with a history of seizure disorders 4, 5
• The risk of adverse effects, such as gastrointestinal disturbances, tremor, and body weight gain, which may be exacerbated during the tapering process 4, 5
• The potential for interactions with other medications, including other antiepileptic drugs, which may affect the tapering process 4, 5

Pharmacokinetics and Pharmacodynamics

The pharmacokinetics and pharmacodynamics of valproate should be taken into account when tapering the medication, including:

• The elimination half-life of valproate, which is approximately 9-18 hours, but may be shorter in patients taking enzyme-inducing agents 4
• The protein binding of valproate, which is approximately 90%, and may affect the drug's pharmacokinetics and pharmacodynamics 4
• The potential for valproate to inhibit the metabolism of other medications, which may affect the tapering process 4, 5