Looking for help

[[Je...]]

Hello! I am in the process of weaning my 5 year old son off of Onfi (Clobazam).  He has been on this medication for over two years to treat a rare type of pediatric epilepsy. We have attempted a wean before and he is EXTREMELY sensitive to changes in dose and suffers intense withdrawal symptoms (increased seizures and hallucinations).  I am hoping to gain knowledge and support so that I can safely wean this drug.  Thank you!

 

[[Pa...]]

Hello JessZini, Welcome to BenzoBuddies!

 

Your situation brings tears to my eye and sends chills up and down my spine, I am so very sorry for you and your son, what a horrible situation.  I can't imagine having to deal with benzo withdrawal symptoms as an innocent child, not understanding what is happening, it's hard enough on an adult. 

 

Can you tell us a bit more, what is your son's dose and what have his previous reductions been, and of course, what his Dr is suggesting.  We can help you, we seem to be the unwanted experts of this particular situation, not many understand the full impact of withdrawing from these drugs.

 

Pamster

[[Je...]]

Pamster,

 

Thank you so much for replying.  My son has been on Onfi for 2 1/2 years.  His highest dose was 7.5 mg and his current dose is 1.35 mg.  Our last wean attempt was a year ago.  We were dropping .1 mgs every two weeks and it was going well.  We attempted to drop .2 mgs and go from 1.4 mg to 1.2 mgs when we hit a wall.  He seized constantly for 24 hours and was having horrible hallucinations, screaming for me to save him from an invisible terror. We went back up to 1.4 mgs and haven't touched it since. We also attempted a wean in July 2018.  I can't recall the dose decrease when we hit a wall, but he was hospitalized because of the seizure increase and lost the ability to walk and talk. 

 

His neurologists aren't much help. We've even had a few recommend we just stop it because he's on such a low dose, which we know is a terrible idea.  We recently started a wean of .05 mgs every 10 days, at my suggestion.  We are on day 5 of the first drop from 1.4 mg to 1.35 mg.

 

Additionally, he is on a medical version of the ketogenic diet as a treatment for his epilepsy, so cannot have the liquid version because of the carb count.  We are crushing a 5 mg pill, mixing is with 5 mls of water and discarding to get the desired dose.  It's not ideal, but the best we could come up with. 

 

I am open to any and all suggestions.  The thought of seeing him suffer so greatly again is terrifying, but I know he will be so much better off without this drug.  Thank you in advance for any help you can offer. 

[[Pa...]]

Hi JessZini,

 

Thank you for filling in some details, I'm grateful you're so in tune to your son's needs and sensitive to his reactions to the reductions in dose, it's good you've slowed it down.  It's quite common to need to slow down the lower in dose one gets, we've had hundreds of members report experiencing the same thing. 

 

It sounds like his Dr's are on board with the discontinuation of the Clobazam, thank you for letting us know, we wouldn't want to go against medical advice for something so critical.  Your decision to not just stop the drug is the right one, no dose is small when it comes to these drugs.  You mention you hold each reduction for 10 days, how did you arrive at this timetable, was this from your research or symptom based? 

 

It sounds like you're using liquid titraion, I'm not experienced with this method so I've asked for some input as to the method you're using, it sounds like you've done a remarkable job thus far.  Have you noticed any new symptoms since you made the last reduction?

 

I'm sorry I've asked more questions than provided answers but we need to get the full measure of your situation, we can't have your little guy suffering any more than he already is.

 

Whatever happens, know you're not alone because we understand his pain and the helplessness you feel.

 

 

[[Li...]]

Hello, JessZini.  You are facing an unimaginably difficult situation with courage and determination.  Your son is indeed fortunate to have you as his mother and advocate.  I have one question and a suggestion for your consideration. 

 

(1) Is the following an option? Consulting with a compounding pharmacist about the possibility of preparing a compounded liquid that would be (a) keto-friendly and (b) low enough in concentration (e.g. 0.1 mg/mL) to support small, gradual reductions in dose.

 

(2) If finding and working with a qualified and experienced compounding pharmacist (e.g. one who is affiliated with a children’s hospital) is not an option, you may want to revisit the “recipe” you are using to prepare your homemade liquid. According to PubChem and DrugBank, the experimental solubility of pure clobazam in water is 188mg/L (0.188 mg/mL).

[[Je...]]

Pamster and Libertas,

 

Thank you both so much for your responses.  I'm in tears with gratitude.  It seems like I've run into nothing but dead ends as far as receiving guidance until now. 

 

Pamster- The 10 day increments come from experience with symptoms, as well as guidance from our neurologist as to how long the body takes to react to the reductions.

 

Libertas- This information is so valuable.  I'll look into a compound pharmacist to see if it's an option.  I am aware that our method is not ideal, as I'm seeing the crushed pill in the liquid and shaking it as I discard in an attempt to have it equally distributed (again, not an ideal method).  It's comforting to know that there is a backup solution if I can't find a compound pharmacist.

 

Two follow up questions:

 

Does our wean schedule sound reasonable? (lowering .05 mgs every 10 days)

 

I'm having a difficult time understanding the difference between a direct taper and a titration taper.  How would you classify our wean? Is a titration taper more fitting considering his history?

 

Again, thank you so so much for your guidance and support!

[[Pa...]]

We're happy to help JessZini.

 

I'm grateful to see you're doing a symptom based taper and as for your schedule, you're in the best position to determine that, no two tapers are alike.  You've been at this a long time and have done a remarkable job so I would suggest continuing to monitor his symptoms to guide you.

 

You are tapering your son directly from his original benzodiazepine using titration.  We made the category of direct taper because some members wish to crossover to another benzo before tapering, this would be called substitution taper, sorry for the confusion.

 

I've been tasked by Libertas to ask you how frequently you dose your son and in what amounts, also if he is showing any signs of interdose withdrawal.  She doesn't log in as often as I do and hoped you could provide this information so she could have it when she next drops in.

[[Je...]]

We dose every evening at 7:30 pm.  We lowered his dose from 1.4 mg to 1.35 mg six days ago. It's difficult to gauge withdrawal symptoms because he has a rare type of pediatric epilepsy and has seizures most nights while he sleeps.  On the fourth day of the dose drop, he had more seizures than he usually does while sleeping.  But it's tough to know if it was due to withdrawal or just the nature of his epilepsy syndrome. 

 

Our plan is to drop his dose by .05 mg every 10 days while monitoring his symptoms.

 

Thank you!

[[Li...]]

Hello, JessZini.

 

I’m so glad you found our responses helpful.

 

I just want to double-check ... are you aware that BenzoBuddies is an all-volunteer, peer support community? (I ask because many new members are not.)  As laypeople, members are not qualified (or allowed) to give medical or pharmaceutical advice.  What we can do is share our experiences and offer information/ideas/suggestions for you to consider in collaboration with appropriately qualified healthcare professionals.  I suspect I am preaching to the choir here, but given your son’s age and serious health condition, it is very important that his healthcare team is fully aware of and supportive of this taper.

 

Thank you for letting us know the dosing schedule you are using (once a day) as well as how your son is responding to the first reduction.  Have you reported the increase in nighttime seizure activity to your son’s healthcare team?  What do they recommend?

 

Re: compounding ...

 

I am delighted (and relieved) that you are willing to investigate compounding as an option.  Preparing and using homemade liquids confers risk.  At this point in time, the degree of risk is unknown. To our knowledge, no homemade liquids for any of the benzodiazepines have been tested for homogeneity, potency, or stability over time. Also, the pharmacokinetic and pharmacodynamic effects of homemade liquids are unknown because they have not been studied. 

 

If I were in your shoes, I would feel much more comfortable having an experienced compounding pharmacist prepare the liquid formulation. S/he can prepare a liquid that is both “keto compliant” and at a suitably low concentration to support small, gradual reductions in dose.

 

FYI According to an article I read last night, one of the most widely used suspending vehicles for oral compounded suspensions (OraPlus) is carbohydrate free!  You would, of course, want to verify this with a compounding pharmacist, but if it is correct, this is encouraging news.

 

Re: the wean schedule (taper rate and schedule) you are contemplating ...

 

Before we address that, let’s take a look at what we can learn from your son’s last taper.  If I am understanding you correctly, you made the following reductions every 14 days:

 

1.8 -> 1.7  = 5.56%

1.7 -> 1.6  = 5.88%

1.6 -> 1.5  =  6.25%

1.5 -> 1.4  =  6.67%

1.4 -> 1.2  =  14.29%

 

He was doing ok at a taper rate ranging from 5.56% up to 6.67% every 14 days.  When the taper rate was doubled to 14.29%, he hit a wall.  This suggests he may be able to tolerate taper rates in the range of 5 - 6%.

 

The severity of his crash coupled with the fact that it is not uncommon for people to discover they have to decrease their taper rate when they get lower in dose, supports using a lower taper rate to begin the next phase of the taper.

 

So, if I’m understanding you correctly, the taper plan is to make the following reductions every 10 days:

 

1.40 -> 1.35  = 3.5%

1.35 -> 1.30  = 3.70%

1.30 -> 1.25  = 3.85%

 

As you can see from the above, by reducing his dose by a fixed amount each time, his taper rate will increase over time.  You will want to keep a close eye on this, especially if his symptoms increase and/or the taper rate approaches 5%.

 

The alternative to reducing by a fixed amount is to reduce by a fixed percentage. For example:

 

1.40 -> 1.35000 =  3.5%

1.35 -> 1.30275 =  3.5%

 

The downside of the fixed percentage approach is that you may end up tapering at a slower rate than you might actually be able to tolerate and, consequently, the taper will take longer.

 

The bottom line? The only way to know if this taper rate and schedule are appropriate is to try it and closely monitor withdrawal symptoms.  If they increase, then either the fixed amount reduction of 0.05mg is too high and/or the number of days you are waiting between reductions is not sufficient.

 

One last point regarding how long to wait between reductions (i.e., taper schedule) ...

 

According to Tolbert and Larsen (reference below) the half‐life of clobazam after a single oral dose ranges from 36 to 42 hours; the half‐life of its major metabolite — N‐desmethylclobazam ranges — from 59 to 74 hours.  This means that clobazam has a relatively long half-life so it may take a while for withdrawal effects to emerge and then subside to a tolerable level before the next reduction.

 

Reference:

 

Tolbert D, Larsen F. A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam. J Clin Pharmacol. 2019;59(1):7–19. doi:10.1002/jcph.1313. Accessed online April 15, 2020 at:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585772/