Depakote and Lamictal

[bpjett]

Doctor has me on

200mg Lamictal [100mg bid]

&

750 mg Depakote [250mg tid] 

When I when to the pharmacy, they said there was a RED ALERT. I know that Depakote decreases the clearance of Lamictal, my question is by how much? Anyone know? Does the dosage of Depakote matter? Like if I went to 1000mg of Depakote would that increase my Lamictal level even more?

[morpheus]

Depakote double lamotrigine levels in plasma. Your lamotrigine dose should be cut in half.

Edited February 28, 2020 by morpheus

[Iceberg]

I don’t think it’s dose dependent (? - according to the medscape prescribing guidelines) but obviously you would need to get a medical professional to weigh in there. 

[browri]

On 2/28/2020 at 1:26 PM, bpjett said:

Doctor has me on

200mg Lamictal [100mg bid]

&

750 mg Depakote [250mg tid] 

When I when to the pharmacy, they said there was a RED ALERT. I know that Depakote decreases the clearance of Lamictal, my question is by how much?

Depakote can increase Lamictal levels. Therefore, pdocs traditionally don't dose people higher on Lamictal than 100mg (usually qhs) when the patient is also taking some sort of valproate product, whether that be valproic acid, sodium valproate, or the combination of the two divalproex sodium (Depakote). However, what isn't talked about is what Lamictal can do to Depakote's levels. And this is what can be unpredictable. Lamictal can decrease or increase the levels depending on the person. Although it seems to increase them. In turn, this would further increase Depakote levels.

This shouldn't alarm anyone at all. Pharmacokinetic interactions like this have been exploited therapeutically for quite some time. In fact, valproate+lamotrigine for bipolar disorder is generally regarded as a pretty robust combination as long as it's done slowly. However, because of the risk of SJS from Lamictal, dosing needs to be careful. If the patient is currently taking valproate, then:

Weeks 1-2: 25mg qOday (every other day)

Weeks 3-4: 25mg qd

Weeks 5-6: 50mg qd

Weeks 7+: 100mg

Generally no higher than 100mg

If the patient is already taking Lamictal at 200mg, then reduce the dose to 100mg and start Depakote ER at 250mg qhs (bedtime). Increase in increments of 250mg no more frequently than every 1 week.

On 2/28/2020 at 1:26 PM, bpjett said:

Anyone know? Does the dosage of Depakote matter? Like if I went to 1000mg of Depakote would that increase my Lamictal level even more?

It does, but your weight and height matter too. Valproate is dosed by weight. And the blood level it yields would likely be a predictor of lamotrigine clearance, but it isn't something that can be calculated or measured, per se.

[Iceberg]

I think I was one 200 mg lamictal while on Depakote. Nothing bad happened, but that doc was an idiot 

[browri]

On 3/2/2020 at 7:15 PM, Iceberg said:

I think I was one 200 mg lamictal while on Depakote. Nothing bad happened, but that doc was an idiot 

Right. You're likely part of the 99% who don't experience SJS. Thing is that the 1% risk of SJS from lamotrigine skyrockets in the presence of valproate. I said at the end of my last post that there really isn't a way to calculate or represent what valproate does to lamotrigine's clearance, but in actuality, it's easier to just look at half-lives.

Lamotrigine has a reported half life of ~29 hours. But depending on who you ask, it truly can vary across a mean range of 12-59 hours. With valproate, the half life of lamotrigine can increase to 70 hours or more in some people, particularly if you already poorly metabolized lamotrigine and were on the higher end of the mean half life (i.e. ~59 hours).