Restarting Lamictal after skipping for a few days; when do you start over at 25 mg?

[SpongeBob DoctorPants]

A patient of mine reportedly stopped taking her medications 3 days ago, one of which was Lamictal 100 mg nightly. In residency I was taught that if a patient skips their Lamictal dose for 3 consecutive days, you need to start back over at 25 mg per day upon resuming, to minimize the risk of SJS. I don't know if that was just my attending's opinion at that time, or if there is anything evidence-based behind it. Anyone know what the risk would be with resuming 100 mg right away, or rapidly titrating the dose back up? Or would it be best to do the 25 mg for 2 weeks, then 50 for 2 weeks, etc.?

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[wolfvgang22]

Well, based on what patients around here admit to doing all the time, stopping 150mg daily for two or three weeks and then randomly restarting at 150mg daily whenever they feel like it seems to be low risk for SJS. We tell them not to do that and why when we start lamotrigine, but you know how patients can be.

I always start over with a new titration, given the chance. If they cause their SJS despite our warnings, that's on them, I already documented I told them not to be cavalier with this medication, and I'm likely to stop prescribing lamotrigine for such patients. Given the opportunity, I'm going to follow protocol.

 

[whopper]

There's no clinical data from studies as far as I know showing how long the duration should be when we should tell patients to restart Lamotrigine by going back to the starting dosages.

From my own clinical experience if patients forgot to take a high dosage by just a handful of days there never was a problem.

From my educated guess I suspect the period where risk of SJS goes up from not taking it would likely be at least a few weeks based on the mechanism likely being involved with the immune system. Serum Ig half life is about 3 weeks, but this is based on conjecture that's not based on empirical data.

 

[hamstergang]

The incidence of SJS with Lamictal without a slow titration is very small, so any one doctor's individual experience won't be powered well enough to detect the difference between when to restart at 25mg and when to restart at whatever dose the patient was at.

So when in doubt, I'd look at what semi-formal guidelines may exist. UpToDate says to start at the beginning if missed for more than 5 half-lives, and to start low and still gradually get back to where you were if missed for fewer than 5 half-lives.

 

[Animal Mother]

I was also taught 3 days in residency, but half of what residents are taught is folklore, so it’s good to get in the habit of looking things up on your own.

GlaxoSmithKline product sheet recommends restarting it after 5 half-lives. Average half-life is about 26 hours, so roughly 5 days.

I would use the half-life to get a rough idea where they might be when deciding what dose to restart at for <5d.

 

[TexasPhysician]

No board will give me approval to test when the risk significantly elevates to cause SJS.

The real issue to consider is liability. Lamictal has been shown to cause SJS with quick titrations. No way I’m taking any chances in a court room. Greater than 2 days off Lamictal and I’m restarting it. I document such and always warn of restarting it upon initial consent.

 

[DisorderedDoc417]

Our policy in residency is also 3 days or greater and we retitrate.

 

[Crayola227]

If 5 days is sorta the outside based on the math of 1/2 lives, then 3 days just sorta jives with me as a moderate point for the tip between restart vs resume. Pushing it to closer to 5, the outside, won't sound as good in court. Not that anything bad ever sounds good in court, but 3 > 5.

 

[Crayola227]

I had a patient do a restart themselves after probably like 5 days. They were covered in rash. They continued taking it, and they were OK. But I would not have wanted to be responsible for any of that at all.

 

[whopper]

UpToDate says to start at the beginning if missed for more than 5 half-lives, and to start low and still gradually get back to where you were if missed for fewer than 5 half-lives.

Finally! Some source giving a guideline. It was in Uptodate but what was the original source?

 

[Animal Mother]

Finally! Some source giving a guideline. It was in Uptodate but what was the original source?

As I mentioned earlier, the product monograph perhaps? Theyre compiled by the drug company and approved by the FDA.

 

[Crayola227]

I don't claim there's data to my next thoughts. But it wouldn't be terribly difficult to come up with the pharmacokinetics to look at what the predicted AUC is at a dose, and what it is going backward on the titration schedule to what the dose would be there, and it's AUC, and then use the half-lives to calculate when one would drop below that. Although, it raises a concern because I read somewhere that abrupt cessation of lamotrigine can also be dangerous. So you might think you could figure out where someone is at after however many days, and restart at that lower dose (but not the very start at 25 mg) and then work upward. I get that this is a thought experiment and likely not as straightforward to do.

This sounds to me like an interesting conversation to have with a knowledgeable pharmacist.