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Hep C Discussion Forum -> Knowledge/Info Section -> About DAA Absorption
Post Info TOPIC: About DAA Absorption
Canuck


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RE: About DAA Absorption
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Further to the original link (first posted below) ... "About DAA Absorption" (acid/alklaine balance, baking soda use, etc.) ...

If you read the monographs for many of the DAA's, you will find similarities in them (whether it is Harvoni, Epclusa, Vosevi or Mav) in that various "acid  reducers" PPI's can be contraindicated for their potential negative interaction with DAA's, while you are on the DAA's. H2 antagonists and many other things that affect/reduce acid (increase your gastic ph) have to be taken into careful consideration so as not to intefere with the DAA absorption - whether it be a simple as taking the DAA as recommended with a meal, or, not taking baking soda water dosing while you are on DAA's, all has to be taken into careful consideration. 

The Mav monograph (like Vosevi) directs you to take the dose with a meal for good reason. Starting off with the right acid/alkaline environment for the drugs to be able to be liberated and absorbed. That's my take on it anyway. 

The link/post below was just trying to highlight how important it is to discuss with your doc all the other things you will be wanting to consume, before you start DAA's, that's all ...

 

Here are a couple more tidbits, "Catie" is a well known group who wish to advise folk to consider what things may affect DAA absorption ...

Excerpted from Catie:

When Harvoni is taken with the following medications it could potentially cause significant drug interactions:

·         antacids or buffered medications

·         medication to treat indigestion, heartburn or ulcers, such as nizatidine (Axid), famotidine (Pepcid AC, Peptic Guard), ranitidine (Zantac), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Losec) and pantoprazole (Pantoloc)

·          

 

Talk to your nurse, doctor and pharmacist if you are taking any of these medicines. One way to manage drug interactions is to make sure that your doctor and pharmacist know about everything you are taking, including prescription drugs, over-the-counter drugs, street drugs, herbal medications, supplements or anything else. If you have more than one doctor or pharmacist, it is possible for drug interactions to get missed. If more than one doctor is writing prescriptions for you, let each one know about everything you are taking. If possible, use the same pharmacy for all your prescriptions.

 

Harvoni monograph excerpt:

Acid Reducing Agents: Antacids (eg, aluminum and magnesium hydroxide)

H2-receptor antagonists: (eg, famotidine)

Proton-pump inhibitors: (eg, omeprazole)

Effect on Concentration - reduces ledipasvir

Ledipasvir solubility decreases as pH increases.

Drugs that increase gastric pH are expected to decrease concentration of ledipasvir.

 

It is recommended to separate antacid and HARVONI administration by 4 hours. H2-receptor antagonists may be administered simultaneously with or 12 hours apart from HARVONI at a dose that does not exceed doses comparable to famotidine 40 mg twice daily. Proton-pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with HARVONI. Proton-pump inhibitors should not be taken before HARVONI.

 

In the "About DAA Absorption" link below, info from MAV was used, to highlight the importance of taking a (mod to high fat) meal with MAV dosings, and what effect the food has, when taken with the MAV dose. How you will absorb the dose of MAV (in the company of a meal and the right acid/alkaline condition that that meal sets up). That's my take on it anyway. C.



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 64 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)
Canuck


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Things can interfere with absorption of DAA's. As rare as this occurrence may be, it is possible to absorb and accumulate too much, or, to not absorb enough of a DAA - so always read the monograph that comes with your DAA, and take your DAA as directed. In this below, I only concentrate mostly on how lowered acid conditions might affect absorption in some DAA's:

 

 

Baking soda (sodium bicarbonate) is highly alkaline, just a little may "buffer" or neutralize acid. Thus it is found in some "antacids" that people take for what they may think is a stomache acid indigestion problem. For some people with stomache complaints, some forms of chronic reflux, or an ulcer or gastritis, sometimes their problem actually becomes not too much acid, but, (in some cases) in order to resolve their problem, when gastric healing is not occurring, they may have to address having too little acid. So oral dosings, high in alkaline (like baking soda) may really not help resolve some people's problems in the long term. It helps to know what (exactly) your gastric problem is, what your "state" is, and how best to approach and remedy it, before you start treating it. You may need less acid, or, it could be you may not have enough acid.

A ph of 7 is neutral, a low ph (below 7) is acid, a high ph (over 7) is alkaline.

 

People also take oral doses of (alkaline) baking soda solution for other reasons - perhaps trying to "de-acidify" themselves for various reasons. It is important to discuss, thoroughly, with your doc (for his advice) anything you think you might be needing or wanting to take during anti-viral treatment, before you start taking your anti-virals.

 

... Acid-reducing agents and proton-pump inhibitors (PPIs) increase gastric pH  (increases alkalinity)  and can alter the bioavailability of antiviral drugs ...

 

·    Excerpt from 2015 Hepatology Journal - Review Article - Travis B. Dick, Lance S. Lindberg, Debra D. Ramirez, Michael R. Charlton 

G  Guide to drug-drug interactions with direct-acting antiviral agents for the treatment of hepatitis C viral infection

 ... Acid Suppressants

The solubility of ledipasvir decreases as pH increases; therefore, ledipasvir is particularly dependent upon acidic environments for absorption (Table 7).[7] Coadministration with proton-pump inhibitors (PPIs) is not recommended, and avoiding anti-acids within 4 hours of ledipasvir administration is important. The package label for ledipasvir states that concomitant administration with omeprazole 20 mg daily is safe. When omeprazole is coadministered with ledipasvir, concentrations of ledipasvir are not significantly decreased when given at the same time. However, when omeprazole is administered 2 hours prior to ledipasvir administration, concentrations of ledipasvir are reduced by approximately 50% to concentrations where viral resistance may become a concern.[7]

No published data are available for ledipasvir administration in those chronically taking a PPI or omeprazole doses greater than 20 mg daily. The half-life for the restoration of acid secretion is 24 hours for those taking omeprazole and 46 hours for pantoprazole.[20] Therefore, the duration of acid suppression in those on chronic PPIs may decrease the likelihood of ledipasvir absorption and increase the risk of viral resistance. Alternatively, famotidine was successfully given with ledipasvir in clinical trials, up to 20 mg by mouth twice daily.[21] We advocate famotidine use over PPIs and encourage administration of ledipasvir with an acidic juice to increase the likelihood of absorption. The same pH dependence is expected for Gilead's next-generation NS5A inhibitor, GS-5816 (VEL). Importantly, other DAAs for HCV, including NS5A, NS5B, and protease inhibitors, are not dependent upon pH for drug absorption ...

______________________________________________________________________________

Always ask first, when you are on any anti-viral, what you can or cannot take additionally, even seemingly benign over the counter things, vitamins, supplements, a non-ordinary diet, or things that some people may consider natural remedies, including drinking baking soda water.

There are now many newer articles and info available (about what can affect anti-viral drug absorption) than what is found above. This above (although it does speak to things current about some DAA's), is old, as seen by the reference to the NS5A  "VEL" (in Gilead's Epclusa and Vosevi) which, at the time of this article writing, was not even referred to by "name", it was still sporting it's "number" (GS-5816) then!

Keep in mind though, through extensive trials (for all these DAA's), they strive to come up with the very best dosages to be abundantly effective under perhaps not always the most ideal or possibly slightly differing absorption circumstances, and if the DAA's are taken (as directed) they should be effective enough to cure almost everyone. It is important to take every dose, as directed. If they say to take it with food - do so. If they suggest you avoid certain things, do so.

For instance, (below), are excerpts about the absorption of glec/pib, currently found within Mavyret's monograph.

 

From Mavyret Monograph - Re: Aborption ...

                                                                   Glec                      Pib

Absorption Tmax (h) a -                                 5.0                       5.0

 Effect of meal (relative to fasting) b -           ^83-163%          ^ 40-53%

 

a. Median Tmax following single doses of glecaprevir and pibrentasvir in healthy subjects.

b. Mean systemic exposures with moderate to high fat meals ...

 

My understanding of the (above) part of the monograph:

* Maximum absorption (reaching the highest peak of the drugs in your bloodstream) probably occurs at hour 5 after dose ingestion.

* Glec/pib dosings should occur with food - better absorption of the drugs are seen when taken with food (moderate to high fat meals).

 

As per the monograph - take your dose of glec/pib at the same time, everyday, with food. Never forget to take a dose. If you ever do forget a dose, and you realize this within 18 hours of when you should have taken it, in that case, take the forgotten dose right away - then, take your next regularly scheduled dose, on time, as per usual. If you have forgotten your dose for more than 18 hours, contact the emergency numbers your doc or pharmacy will have provided to you, for their advice.



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 64 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)
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