question-icon

Are there any negative interactions between Phenytoin and Divalproex?

default
Posted on Thu, 12 Mar 2015
Question: I need answers about meds prescribed for someone with schizophrenia.
The prescription is:
Morning
175mg of clozapine, 100mg of phenytoin sodium (controls seizures)
Bedtime
225mg of clozapine, 100mg of phenytoin sodium, 1250mg of divalproex sodium (controls seizures, mania), 2 mg lorazepam (sedative to address insomnia)
My questions are:
1. Why more clozapine just before bed (225mg compared to 175mg in the morning) when the lorazepam is knocking him out?
2. Why two types of seizure meds at night and one type during the day?
3. Are there any negative interactions between phenytoin and divalproex?
4. Why much more seizure meds at night?
He's only had seizures during the day and they were very rare.
5. Might the clozapine dosage be contributing to his seizures?
doctor
Answered by Dr. Seikhoo Bishnoi (14 minutes later)
Brief Answer:
Clozapine is known to lower down seizure threshold

Detailed Answer:
Hello thanks for asking from HCM for your health related queries

I have read your query and understand your problem. Coming directly to your doubts-

1) Clozapine is a second generation antipsychotic drug and the drug has sedation as side effects. Commonly this is utilised to achieve sedation. Though the patient has been already prescribed Lorazepam but still high dose in evening hours ensures good sleep, while high doses in day time may result in drowsiness which can be distressing. Secondly Clozapine is known to lower seizure threshold. In day time a lot of things may stimulate seizures so high doses are usually avoided and this may be the second reason patient been advised to take more doses in evening.

2) As patient is on Clozapine which lowers seizure threshold so this could be the reason that he has been prescribed two seizure medicines. The doses are more in night time because these medicines are known to cause sedation and drowsiness and with night time doses individual would not feel that effect. The reason for two medicines could also be the recurrence of seizures, but ultimately it depends upon clinician's choice.

3) If phenytoin and valproate are used together then in various studies Valproate is found to have synergistic effects on actions of phenytoin. There are no significant negative interactions between these drugs.

4) More medicines at night because to prevent day time sedation because these medicines are known to cause significant sedation.

5) Clozapine is known to induce seizures in some susceptible patients. So the drug should be used judiciously in high risk patients.

Thanks, hope this helps you. Please ask again for more doubts.
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
default
Follow up: Dr. Seikhoo Bishnoi (10 hours later)
With metabolism lower at night, less stimulants at night, and Lorazepam at night why would he need a higher dose of clozapine at night and an additional seizure drug at night?

He has no history of seizures at night.
doctor
Answered by Dr. Seikhoo Bishnoi (3 hours later)
Brief Answer:
Clozapine reduces seizure threshold

Detailed Answer:
Hello thanks for asking a follow up

The drugs of seizure have long actions and they are prescribed to provide effective seizure discharge control over 24 hours. As Clozapine is known to cause significant sedation so it is advised to be taken in evening hours. The drug is also known to reduce seizure threshold so high doses can reduce seizure threshold in evening and to protect from that probably additional seizure drug has been added in night times.

Lorazepam can help in seizure to some extent and its higher doses would be required to achieve sedation which is given by clozapine. So this is the reason that other drugs apart from Lorazepam are advised in evening because they also cause sedation.

Thanks
Above answer was peer-reviewed by : Dr. Chakravarthy Mazumdar
doctor
Answered by
Dr.
Dr. Seikhoo Bishnoi

Psychiatrist

Practicing since :2007

Answered : 5187 Questions

premium_optimized

The User accepted the expert's answer

Share on
Are there any negative interactions between Phenytoin and Divalproex?

Brief Answer: Clozapine is known to lower down seizure threshold Detailed Answer: Hello thanks for asking from HCM for your health related queries I have read your query and understand your problem. Coming directly to your doubts- 1) Clozapine is a second generation antipsychotic drug and the drug has sedation as side effects. Commonly this is utilised to achieve sedation. Though the patient has been already prescribed Lorazepam but still high dose in evening hours ensures good sleep, while high doses in day time may result in drowsiness which can be distressing. Secondly Clozapine is known to lower seizure threshold. In day time a lot of things may stimulate seizures so high doses are usually avoided and this may be the second reason patient been advised to take more doses in evening. 2) As patient is on Clozapine which lowers seizure threshold so this could be the reason that he has been prescribed two seizure medicines. The doses are more in night time because these medicines are known to cause sedation and drowsiness and with night time doses individual would not feel that effect. The reason for two medicines could also be the recurrence of seizures, but ultimately it depends upon clinician's choice. 3) If phenytoin and valproate are used together then in various studies Valproate is found to have synergistic effects on actions of phenytoin. There are no significant negative interactions between these drugs. 4) More medicines at night because to prevent day time sedation because these medicines are known to cause significant sedation. 5) Clozapine is known to induce seizures in some susceptible patients. So the drug should be used judiciously in high risk patients. Thanks, hope this helps you. Please ask again for more doubts.