Pill Splitting Ezetimibe and Bempedoic Acid to Save Money, Lower Side-effect risk

[PBJ]

This is good news. I am taking ezetimibe and tadalafil and would rather avoid finasteride.

[Virilius]

Remember that ezetimibe has not proven itself to avoid BPH in humans, though tadalafil is a good addition. In any case, the primary treatment for BPH remains the potent tamsulosin+finasteride/dutasteride combo. Especially the 5ar inhibitors have shown promise for reducing the incidence of prostate cancer.

[DrFraser]

Yet another benefit of ezetimibe … however, decreased liver cancer!
https://www.ausdoc.com.au/news/non-statin-cholesterol-meds-may-cut-risk-for-liver-cancer-study/

[shc]

Do any of you have results to report?

Btw, I am surprised to not see this in the thread so far, but you may want to note that the half-life of Bempedoic acid is about 15-21 hours. This makes me feel that every-other-day should be perfectly fine.

Half-life of ezetimibe is about 22 hours.

[DeStrider]

Here are my results:

Saúde Cardiovascular

FYI, here’s my results before and after taking BA (140 mg) + Ezetemibe (10 mg) + Atorvastatin (5 mg) You can see LDL went from 122 to 48 and ApoB went from 102 to 48. [image] [image]

[adssx]

@Virilius

In any case, the primary treatment for BPH remains the potent tamsulosin+finasteride/dutasteride combo.

I would avoid tamsulosin at all costs: Terazosin / doxazosin / alfuzosin may protect against dementia with Lewy bodies - #19 by adssx

[hitch]

Bempadoic Acid is absorbed in the small intestine. Does that mean pill splitting will not work?

[RapAdmin]

Bempadoic acid pill splitting doesn’t make sense because, unlike Zetia / Ezetimibe, Bempadoic acid has a very linear dose response relationship (with Ezetimibe you can take 25% of the dose and get 75%+ of the benefits). Pill Splitting Ezetimibe and Bempadoic Acid to Save Money, Lower Side-effect risk - #7 by AnUser

[hitch]

I should have explained that this is for my wife @ 120lbs. She is just starting and has a sensitive stomach (e.g. can’t handle metformin). So I’d like to start on a low dose and see how it goes…

[SilentWatcher]

Here are ingredients of NEXLIZET tablet:

Each film-coated tablet of NEXLIZET contains 180 mg of bempedoic acid and 10 mg of
ezetimibe, and the following inactive ingredients: colloidal silicon dioxide, hydroxy propyl
cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone K30,
sodium lauryl sulfate, sodium starch glycolate. The film coating comprises of FD&C Blue
#1/Brilliant Blue FCF Aluminum Lake, FD&C Blue #2/Indigo Carmine Aluminum Lake,
glyceryl monocaprylocaprate, partially hydrolyzed polyvinyl alcohol, sodium lauryl sulfate, talc,
and titanium dioxide. (link to HIGHLIGHTS OF PRESCRIBING INFORMATION)

Based on the ingredients listed, there is no clear indication that NEXLIZET tablets have an enteric coating. The excipients and film coating ingredients are typical for maintaining tablet stability and ensuring proper absorption but do not suggest acid resistance or delayed release for protection from stomach acid.

For me, it’s a kind of indication that it can be split. I’ve been taking NEXLIZET (split) for two months – the results of my lab test will come on Friday (please remind me if I forget to post the results here!).

[hitch]

Great explanation. I’m hoping you get good results on Friday!

[SilentWatcher]

@RapAdmin

Bempadoic acid pill splitting doesn’t make sense because, unlike Zetia / Ezetimibe, Bempadoic acid has a very linear dose response relationship (with Ezetimibe you can take 25% of the dose and get 75%+ of the benefits).

Let me slightly disagree. Let’s take a look at two studies:

Efficacy and Safety of a Novel Dual Modulator of Adenosine Triphosphate-Citrate Lyase and Adenosine Monophosphate-Activated Protein Kinase in Patients With Hypercholesterolemia: Results of a Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial):

ETC-1002 (->bempedoic acid) 40, 80, and 120 mg lowered least-squares mean ± SE LDL-C levels by 17.9 ± 2.2%, 25.0 ± 2.1%, and 26.6 ± 2.2%, respectively, versus a reduction of 2.1 ± 2.2% with placebo (all, p < 0.0001)

Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance)

whereas ETC-1002 (->bempedoic acid) monotherapy with 120 mg or 180 mg reduced LDL-C by 27% (P = .0008 vs EZE) and 30% (P < .0001 vs EZE), respectively

→ If I am sampling image based on those two important studies:

Doubling the dose (monotherapy, without considering effect from EZE) from 90 mg to 180 mg should theoretically increase the reduction in LDL by only 20% (to clarify for everyone: i am not referring to a further 20% decrease in LDL levels, but rather an additional differential decrease of 20%). Given the potential risk of BA in acetyl-CoA in liver pathway, considering 90 mg seems perfectly reasonable for my individual case.

[SilentWatcher]

As promised, here are results after 2 months on 90mg BA and 5mg EZE (split):

Test	Initial	Current	Change	“Normal Range”
GOT (AST)	28 U/l	54 U/l	(High)	8–48 U/l
GPT (ALT)	27 U/l	36 U/l		7–55 U/l
GGT	3 U/l	7 U/l		0–51 U/l
Uric Acid	6.2 mg/dl	5.4 mg/dl		3.4–7.0 mg/dl
Triglycerides	82 mg/dl	56 mg/dl		<150 mg/dl
Total Cholesterol	154 mg/dl	119 mg/dl		<200 mg/dl
HDL Cholesterol	39 mg/dl	40 mg/dl		≥40 mg/dl
LDL Cholesterol	98 mg/dl	66 mg/dl		<100 mg/dl
Non-HDL Cholesterol	115 mg/dl	79 mg/dl		<130 mg/dl

What does it mean:

• Lipid profile: improved —LDL and triglycerides dropped (for LDL -33%).
• Uric acid: Reduced from 6.2 to 5.4 mg/dl (->empagliflozin).
• Liver enzymes: A bit of a mixed result. GOT (AST) spiked above the normal range (54 U/l), but GPT (ALT) and GGT are still normal.
  • I suspect this could be due to heavy HIIT training on the day before and a mild cold I had three days ago, which might have temporarily raised GOT (AST).

I’ll be rechecking my liver enzymes in the coming weeks to see if they normalize.

Cardiovascular markers improved, liver enzymes slightly elevated (likely due to exercise? + cold?), and uric acid is down (empagliflozin is working).

[DeStrider]

I have noticed my liver enzymes are up as well since taking Bempedoic Acid and Ezetemibe.

[SilentWatcher]

@DeStrider, but still in healthy range <50! - it is good! In my case - AST is elevated and ALT and GGT are normal, it is less likely that liver disease is the cause of the elevation… so I should track it over time.

[RapamycinCurious]

One thing to consider is that third-world generics may not distribute the active drug evenly throughout the tablet, such that you could split the pill in half and get an 80% dose in one half and only 20% of the dose in the second half. See this 2007 paper:

https://www.researchgate.net/profile/Michael-Veronin-2/publication/6242785/figure/fig1/AS:601689027534860@1520465251291/mages-of-the-innovator-product-simvastatin-tablet-and-generic-versions-imported-from_W640.jpg

“Tablet A is the US innovator product and tablets B, C, D, and E are from Mexico, Thailand, Brazil, and India, respectively. … Bottom row, left to right: near-infrared spectroscopic images of the same tablets, revealing their internal compositions. Clumps of the active pharmaceutical ingredient are visible as bright spots. In samples B, D, and E, the active pharmaceutical ingredient particles are agglomerated and not evenly distributed.”
https://journals.sagepub.com/doi/10.1345/aph.1H680

[cl-user]

@RapamycinCurious

One thing to consider is that third-world generics may not distribute the active drug evenly throughout the tablet, such that you could split the pill in half and get an 80% dose in one half and only 20% of the dose in the second half.

If the blend is so badly mixed that to can get a 80/20% distribution by splitting a pill in half that’s basically 50% ± 30% and that would imply that the variance of the content of the full pills would be approximatively 100% ± 42% so 58 to 142% for the whole pill which looks very high to me.

I don’t know the regulations but I’m pretty sure that a 42% variation per pill is too much. Hopefully!

[RapAdmin]

@RapamycinCurious

One thing to consider is that third-world generics may not distribute the active drug evenly throughout the tablet, such that you could split the pill in half and get an 80% dose in one half and only 20% of the dose in the second half. See this 2007 paper:

I would argue (based on the information in the book by Katherine Eban; Bottle of Lies) that there is wide variability between the different Indian generic drug manufacturers. If you focus on the major vendors that also sell to the USA, you are very likely to get products that are very comparable to the US products.

She talks in the book about tiers of manufacturers, the lowest tier companies sell their products for very low prices to Africa (etc.) and those products are very inferior. Other products are manufactured for higher prices by the larger Indian Pharma and they are close to, or meet, the US FDA standards.

See list of major Indian Pharma companies here: Rapamycin etc., Purchase Price Comparison Spreadsheet, and Issues Discussion - #40 by RapAdmin

[RapamycinCurious]

@cl-user

f the blend is so badly mixed that to can get a 80/20% distribution by splitting a pill in half that’s basically 50% ± 30% and that would imply that the variance of the content of the full pills would be approximatively 100% ± 42% so 58 to 142% for the whole pill which looks very high to me.

I don’t know the regulations but I’m pretty sure that a 42% variation per pill is too much. Hopefully!

It totally would not pass muster for a drug manufactured by a branded, approved product. The point is that many people on this forum are not buying the branded, approved product, but Indian generics, not all of which are even nominally regulated by FDA.

@RapAdmin

I would argue (based on the information in the book by Katherine Eban; Bottle of Lies) that there is wide variability between the different Indian generic drug manufacturers. If you focus on the major vendors that also sell to the USA, you are very likely to get products that are very comparable to the US products.

I’m sure you’re less likely to have these troubles with manufacturers whose products are approved as generics for the USA. But the many failed inspections for the manufacturers of such products and the horror shows documented in Eban’s book even for those who are approved generics argues that this can provide only limited assurance. Not to mention the possibility of fraud when Company X’s pill is bought online from India rather than in the US from a regulated pharmacy.

[RapamycinCurious]

This website appears legit, and may suggest that splitting bempedoic acid tablets is OK. They have ezetimibe + bemp tablets listed on the ‘do not crush’ list, but don’t have either eze or bemp on their own. Since we know that eze tabs can be split (provided they’re properly dispersed, as above), I think that implies that while there is some fancy footwork involved in putting the two of them into one, either alone may be split without messing with their delivery.

Do Not Crush List - March 2023 Update | HelloPharmacist