Cutting Imbruvica dosage

[Survivor1951]

With a two month supply of 420 mg Imbruvica on hand, my dose has been cut in half due to side effects. Is it advisable to cut the available tablets in half?

[cllady01 Former Volunteer]

Survivor, according to the Imbruvica site:

imbruvica.com/home, you should not cut, break, or crush the pills/tablets.

There may be others here who have had your experience and they may have an answer as to what to do with unused/unopened bottles.

[AmericanRonin]

I personally don’t think it would be such a big deal to cut the tablets in half, but I know some will disagree and think this is reckless because of the time-release coating that is on the tablets. I wonder, however, if there is some type of coating you could manually paint onto the ends of the cut tablets. I can understand if a DYI approach might be financially necessary if your insurance company won’t pony up the smaller tablets for you, and you currently have possession of over $20,000 worth of tablets. As with everything, onsult your physician.

[MsLockYourPosts Passed Volunteer in reply to AmericanRonin]

I would not consider cutting your tablets without consulting your doctor and the speciality pharmacist. We can all guess about ways to deal with this, but none of us have the training necessary to give you a safe answer.

[Dom57]

You need to get in touch with the pharmacy where they came from. They gave me a phone number for the a place in Texas that run an exchange program for the manufacturer. New pills and no cost in 48 hours.

[cajunjeff]

First let me say I agree with those who suggest you consult with your doctor and that you exchange your tablets for the smaller capsules.

With that said, here is my rant on the tablets. I believe the 420 tablets were created because some people on their own, and some under doctors orders, were taking one or two of their three 140 capsules instead of three daily. When people started taking lower doses, J&J (Jannsen) lost money.

So they switched from capsules to tablets and then outrageously started charging the same for 420, 280 and 140 tablets.

I believe the whole "don't cut your tablets up" warning has little to do with safety and efficacy and all to do with money.

j&J has since been called out on this. I was complaining about it from day one because it seemed a transparent money grab.

washingtonpost.com/news/won...

[AussieNeil Partner Administrator in reply to cajunjeff]

You are quite correct about the drug company being called out by CLL specialists on their decision to sell varying doses of Ibrutinib at the same price. The company had to reverse their ill considered decision. Incidentally this event provides strong evidence that CLL specialists are not part of some "Big Pharma" conspiracy. They prescribe Ibrutinib and other CLL treatments because of solid evidence that the drugs work very well against CLL - not because they are in cahoots with drug companies.

However, I can't agree with your comment about the "don't cut your tablets up" warning. Ibrutinib has an enteric coating. Breaking that coating is going to adversely change the way the drug is absorbed with potential impacts on how well the drug maintains controls of CLL and side effect severity.

Neil

[cajunjeff in reply to AussieNeil]

Yes, I could have worded my response better. I did start out with "consult with your doctor" because I would not advise anyone to divide a drug when the label says not to.

It is my suspicion that the tablet was purposely designed in such a way to make it hard to divide into two or three doses, hence the coating you describe. I assume the active ingredient in the tablet is no different than the active ingredient in the capsules I used to get.

And while I agree people shouldn't divide the tablet for the reasons you suggest, its even money to me a good part of the warning is scare tactics and that if I cut a tablet exactly in half, I would still get half of the enteric coating you describe and it would work just fine. I easily concede I could be wrong on this, I lack the scientific training to know for sure. I wouldn't advise anyone to divide the drug, but I still think its probably okay.

I do have the training and information to know the shenanigans jannsen has pulled with other drugs to increase their profits, a story for another day perhaps. Its why I have had a healthy cynicism from the day I got the news they switched to tablets. I am all for big pharma being richly rewarded for the risk they take, but I know firsthand how they can manipulate data, push drugs off label, employ ghostwriters and bankrupt Medicaid programs when greed takes over.

PS I came back to do this edit because "they" is a bit broad and I do not mean to imply that all pharma companies are bad or that all people that work with them are motivated by greed. There are good companies with good people and there are even good people working in bad companies. But we know from history, lawsuit discovery and fda investigations that a lot of shenanigans go on with some pharma companies chasing profit.

[AussieNeil Partner Administrator in reply to cajunjeff]

Sorry, but again I must disagree that after breaking an enteric coated tablet "it would work just fine." From Wikipedia with my emphasis "An enteric coating is a polymer barrier applied on oral medication that prevents its dissolution or disintegration in the gastric environment.[1] This helps by either protecting drugs from the acidity of the stomach, the stomach from the detrimental effects of the drug, or to release the drug after the stomach (usually in the upper tract of the intestine)." en.wikipedia.org/wiki/Enter...

When you break an enteric coated tablet, you end up with the cleaved surface without that protective barrier against an highly acidic gastric environment with a pH of less than 2 where a pH of 7 is neutral. (If you take your Ibrutinib on an empty stomach, the gastric pH can get down to 1 - 1.5pH. Janssen report that Ibrutinib is slightly more soluble at a lower pH. Ibrutinib was designed with an enteric coating - I would hope to minimise side effects and maximise absorption, not to maximise profits. The FDA approval was based on the effectiveness and side effect profile in the enteric protected form, whether by capsule or tablet. We just don't know to what extent removing some of the enteric coating impacts the drug's effectiveness and side effect profile. We could well be reducing the effective dose by more than 50% and worsening the side effects - working against the very reason we cut the tablet! Having said the above, I wouldn't be surprised if Janssen are making leverage of the enteric coating to maintain sales, but I hope that ethically they do have valid health reasons for their warning - or why add to the manufacturing cost by adding an enteric coating?

Any public company that doesn't operate in a way to maximise long term profitability will suffer in a competitive marketplace. Unfortunately the "right price" for any product is what the market will bear. We don't like that fact as unwilling consumers of products that can set a high price, but we'd be pleased with the return on our share investments if we were company shareholders. That said, I expect that some companies can leverage their ethical status to offset the impact of lower profits on their share price - but that's where we rely on investors to accept a lower return for investing in companies with a greater ethical focus. In reality, we need to rely on governments for setting and enforcing what our communities want in the way of acceptable business practices.

There's been a very interesting concurrent discussion on Ibrutinib cost here:

healthunlocked.com/cllsuppo....

Neil

[cajunjeff in reply to AussieNeil]

I guess we can agree to disagree on this. I took ibrutinib for several months in capsules before they switched to tablets and did just fine without the enteric coating. The Washington Post article I linked to quoted medical doctors who suspected the pill change was profit motivated. Jansen's response said nothing about enteric coating.

Once again, I am no doctor or scientist. I could be wrong. But I am not the only one who thinks the change was profit motivated though, from the wiki article:

"Janssen Pharmaceutica and Pharmacyclics introduced a new single dose table formulation with a flat pricing structure in the first half of 2018 and discontinue the capsule formulation. This caused an outcry as it was perceived to triple in the cost of the drug to the average patient.[19] Patients receiving the FDA approved and recommended doses would have seen either no price change or a price decrease with the tablet pricing structure.

Janssen Pharmaceutica and Pharmacyclics have since reversed the decision to discontinue the capsule formulation with the drug currently available in both capsule and tablet forms.[20]"

en.wikipedia.org/wiki/Ibrut...

Its also possible the coating provides some protection you reference, but that it still works reasonably well without it, it did for me.

All that said, hopefully I have been clear in each post that I do not advocate people cutting up tablets for the reasons you state. Even if what you write is true, splitting the tablets still might not be that big a deal. I took ibrutinib fro months without a coating and noticed zero change when they switched, other than I was taking one tablet instead of three capsules.

[AussieNeil Partner Administrator in reply to cajunjeff]

Did you open the enteric capsule?

Note the relevant Ibrutinib patent information: patents.google.com/patent/W...

"It is presently disclosed that when ibrutinib is administered intraduodenally versus via the gastrointestinal tract in rats, the oral bioavailability of ibrutinib unexpectedly increased from 21 % to 100% as determined by AUC. This unexpected increase in oral bioavailability of ibrutinib can translate into a number of desirable practical benefits. The increase in oral bioavailability should enable administration of ibrutinib at a significantly lower therapeutically effective dose than is currently being used. The lower variability associated with this greater bioavailability should lead to a more reliable therapeutic response as well as more predictable drug absorption. And avoidance of exposure of Ibtrutinib to the stomach and/or use of lower therapeutically effective dose of ibrutinib can reduce or altogether eliminate potential adverse side effects of this drug such as diahrrea, nausea or emesis, and dizziness." (My emphasis).

[Jonquiljo in reply to AussieNeil]

Ibrutinib is insoluble at pH > 3.0. That's why PPI drugs are not recommended to use during treatment. I remember reading an article from Janssen that showed that the pharmacokinetics of the IB were altered when pH was raised, but it really had no effect on the overall bio-availability. This is why some people still take PPI's when taking IB and it works fine. (I've got to find that article!)

I think the pharmacokinetics were altered so that the effective dose was altered by a very small percentage.

Either way I WOULD NOT recommend that anyone alter an IB tablet without the expressed consent of their physician! If there is a "give back" plan - then it should be tried.

P.S.: Acalabrutinib has the same issue - insoluble over pH of 3. My guess is that bio-availability is the same.

Also: I found the link for Ibrutinib ... fda.gov/downloads/Drugs/New...

It was published in Blood -- bloodjournal.org/content/12...

[sandybeaches in reply to cajunjeff]

Many drugs are made with an enteric coating on tablets or capsules to either prevent the drug from damage of stomach acid, to prevent damage to the stomach wall from the drug itself or to prevent the drug from being absorbed too quickly into the blood stream thereby causing, at times, dangerous side effects, depending on the drug. It is not a money grab by the pharmaceutical manufacturer, but a safety consideration for the patient! It is part of the formula that is presented, tested and approved by health boards.

For anyone else considering cutting tablets in half or opening capsules, whatever the drug, please be aware that you may be putting yourself in harms way unless the pharmacist has given instruction that the medication can be cut or opened.

Sandy Beaches

[may04cll]

Wow ! what dialogue

[MsLockYourPosts Passed Volunteer]

During my years and years of treating the zoo of animals that end up with me, in addition to consulting with my mother's doctor's when she was alive, and my own pharmacist, who won't hand you a drug he knows is new without a consult, I have always been told to not try to divide capsules or split pills unless told to do so.

I was once only able to get one med for a dog in double the strength needed. No one had the tablets I needed. That pill came in capsule form. No problem, I thought. I'd just sprinkle half of the contents on her food each morning. Both the vet and the pharmacist advised me that I could divide the contents into two capsules, and I was given empty capsules to do that (what a pain!), but advised me to not give it to her any other way until the tablets with the right dose came in.

I do agree with most that the move to one price fits all Imbruvica pills was a moneymaking venture, and J&j got called on the carpet for it, which means one can now go to smaller doses with a lower price again. It was a totally unethical move in my opinion.

But, I totally agree with Neil that one should not play around with instructions that could affect the effect of any drug. We all make decisions for ourselves that may go against advice given at times, but I think that it is irresponsible to advise anyone else to go against what their doctor or pharmacist has told them. To question - yes, if you believe there are other options, but not to go against someone's medical advisors.