About to start Valcyte — pointers?

Hoosierfans

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Hey all,

In the next week or so, my doc is starting me on Valcyte. It’s not something he commonly prescribes in his practice (he’s not an ME / CFS specialist), but we agreed after getting back some high EBV IGG antibodies, and high HHV-6 IGG antibodies, that based on research we had read here and help from folks like @Learner1 , a trial of Valctye would be in order for the severe nerve / skin burning that I have (along w other symptoms).

Any tips or pointers when taking Valcyte? He is monitoring blood work every 30 days while I am on it. We were thinking of 450 mg for 4 days, up to 450 mg 2 x day and if tolerating then about another week move up to 450 mg 3 x day.
 

Pyrrhus

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Any tips or pointers when taking Valcyte? He is monitoring blood work every 30 days while I am on it. We were thinking of 450 mg for 4 days, up to 450 mg 2 x day and if tolerating then about another week move up to 450 mg 3 x day.
Is this dosing because you have kidney impairment or because your doctor is worried about immunological side effects?

Remember that the standard dosage is 450mg four times a day. (or 900mg 2x/day)
If you take a sub-optimal dosage for long enough, the virus will become resistant to the drug.
(Direct-acting antiviral drugs are the one exception to the "start low and go slow" rule.)

In my case, I saw no immunological changes except a 85% drop in my monocytes during the first 12 weeks of Valcyte. After 12 weeks, my monocyte levels bounced back up to normal levels while I continued the Valcyte. This is likely due to the fact that many of my circulating monocytes were infected with CMV. (CMV loves to hide out in monocytes.)

Best of luck.
 

Hoosierfans

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Hey @Pyrrhus, after our appointment today, he decided that he wanted to “hit it hard” and start me on 1800 mg (900 mg 2 x day) for a month and then 900 mg per day for 6 months (or longer, we will see how I respond). I thought we were going to titrate up, but he said after researching and talking to a few docs....it’s best to do exactly what you said — hit the viruses with a decent dose so they don’t become resistent.

Did the Valcyte help you?
 

Pyrrhus

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Did the Valcyte help you?
There was no effect on my ME symptoms while on Valcyte.

@Pyrrhus hm maybe i need to up my famvir then. Only on 500 atm.
Famciclovir dosing is different from Valcyte dosing, but since it's also a direct-acting antiviral, suboptimal doses may lead to resistance.

Here is what the FDA prescribing information for Famciclovir says:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf said:
Herpes labialis: (cold sores) 1500 mg as a single dose
Genital herpes: Treatment of recurrent episodes 1000 mg twice daily for 1 day
Genital herpes: Suppressive therapy 250 mg twice daily
Herpes zoster: (shingles) 500 mg every 8 hours for 7 days
Hope this helps.
 

bensmith

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Jeez ive been on it for months. Ill talk to dr levine and see what she says.

I believe she gave it to me for my ebv
 
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Hey @Pyrrhus, after our appointment today, he decided that he wanted to “hit it hard” and start me on 1800 mg (900 mg 2 x day) for a month and then 900 mg per day for 6 months (or longer, we will see how I respond). I thought we were going to titrate up, but he said after researching and talking to a few docs....it’s best to do exactly what you said — hit the viruses with a decent dose so they don’t become resistent.

Did the Valcyte help you?

Honestly you only need to take Valcyte once a day. The intracellular half-life (inside a cell) is around 24 hours.

"Intracellular ganciclovir triphosphate concentrations are at least 10-fold higher in CMV-infected cells than in noninfected cells,157 and intracellular ganciclovir triphosphate has a half-life of 24 hours or longer."
source: ganciclovir summary (valganciclovir is prodrug)

Unlike monotherapy for HIV, monotherapy for herpes viruses is much less likely to cause resistance as they are DNA viruses not RNA viruses.

I'm pretty much my old self now, I even need to take valacyclovir less and less, still make it a point to come back occasionally and help.

Give it a shot, if the side effects are too much you can just stop and move on something else or hope that time will make things better.

I took Valcyte for 4-5 months, no real side effects, just expensive. HSV1 was my problem, massive migraines and debilitating fatigue.

Valacyclovir is used for the alpha herpes viruses, HSV1, HSV2, and VZV. But when acyclovir triphosphate is incorporated into CMV it actually is better than Ganciclovir triphosphate because it results in chain termination, not just a poor substrate that continues on.
 

Pyrrhus

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Honestly you only need to take Valcyte once a day. The intracellular half-life (inside a cell) is around 24 hours.
The intracellular half-life is not what determines dosing in this case- it is the bioavailability and elimination kinetics that makes multiple doses a recommendation in order to optimize intracellular levels of the drug.

Unlike monotherapy for HIV, monotherapy for herpes viruses is much less likely to cause resistance as they are DNA viruses not RNA viruses.
Not true. Drug resistance to anti-herpesviral drugs is well documented and is quite common with long-term use. HIV is not an RNA virus, it is a retrovirus, which is neither an RNA virus nor a DNA virus under the Baltimore classification.

But when acyclovir triphosphate is incorporated into CMV it actually is better than Ganciclovir triphosphate because it results in chain termination, not just a poor substrate that continues on.
Both acyclovir and ganciclovir are chain-terminators. Acyclovir is not effective against CMV, neither in vitro nor in vivo.

I hope this clarifies.
 

heapsreal

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Valcyte can be hard to tolerate. Id be cautious of upping the dose too quickly as you can feel alot worse onit. Many dont feel well until they stopped valcyte and then noticed the improvement it gave.

This is just me and knowing what i know now, id stay on famvir 500mg twice a day and valcyte 450mg once a day and only 6 months on valcyte then stop and give time to reasses. Blood work after first month and then every 3 months. Definitely use NAC to help protect liver.

But pt and your dr need to keep reassessing how one feels on it and blood values. It can lower white cell counts, stress liver and kidneys as well as feel crappy on it.
 
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The intracellular half-life is not what determines dosing in this case- it is the bioavailability and elimination kinetics that makes multiple doses a recommendation in order to optimize intracellular levels of the drug.



Not true. Drug resistance to anti-herpesviral drugs is well documented and is quite common with long-term use. HIV is not an RNA virus, it is a retrovirus, which is neither an RNA virus nor a DNA virus under the Baltimore classification.



Both acyclovir and ganciclovir are chain-terminators. Acyclovir is not effective against CMV, neither in vitro nor in vivo.

I hope this clarifies.
Intracellular half-life is what matters, not plasma half-life. That's why AZT was originally prescribed every 4 hours and then they discovered the half-life of the active drug

"The short plasma half-life and concentrations of zidovudine do not accurately reflect the more robust intracellular concentrations of the zidovudine phosphorylated forms."
Source: Science direct zidovudine info

Immunocompetent resistance is rare, less than 1%. People with ME/CFS I would still generally consider immunocompetent but they are having a hell of a time with their metabolic system (mitochondria fracturing etc).
"In spite of the distribution of over 2.3 × 106 kg of these nucleoside analogues, the prevalence of acyclovir resistance in herpes simplex virus isolates from immunocompetent hosts has remained stable at approximately 0.3%. In immuncompromised patients, in whom the risk for developing resistance is much greater, the prevalence of resistant virus has also remained stable but at a higher level, typically 4 to 7%. "
Source: NIH ayclovir and penciclovir resistance rates

Acyclovir is a direct chain terminator, not gancicloivr or penciclovir, they are poor chain substrates.
ganciclovir triphosphate serves as a poor substrate for chain elongation - https://en.wikipedia.org/wiki/Ganciclovir. Notice it can still elongate or continue to link new nucleosides.
I know you're not supposed to source wiki but who cares :woot:

Penciclovir triphosphate acts as a competitive inhibitor of the natural substrate required for viral DNA replication, but does not irreversibly terminate DNA replication. Penciclovir sciencedirect

ACVTP competes with naturally occurring nucleoside triphosphates and is incorporated into the elongating viral DNA chain as it replicates, resulting in chain termination Acyclovir Sciencedirect


I've consumed all those drugs including several HIV drugs. Not trying to be better than you but people should know the right information.

I've experienced the worst symptoms of ME/CFS where I was laid up in a bed for days at a time and had to break every 30 minutes just so I could work for 45 mins in my house. I'm talking from a consumer who is knowledgeable.
 
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nryanh94

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Is this dosing because you have kidney impairment or because your doctor is worried about immunological side effects?

Remember that the standard dosage is 450mg four times a day. (or 900mg 2x/day)
If you take a sub-optimal dosage for long enough, the virus will become resistant to the drug.
(Direct-acting antiviral drugs are the one exception to the "start low and go slow" rule.)

In my case, I saw no immunological changes except a 85% drop in my monocytes during the first 12 weeks of Valcyte. After 12 weeks, my monocyte levels bounced back up to normal levels while I continued the Valcyte. This is likely due to the fact that many of my circulating monocytes were infected with CMV. (CMV loves to hide out in monocytes.)

Best of luck.
Hi, just curious where you found this standard dosage as I’ve been prescribed Valcyte at 450mg twice a day by an ME specialist.
I’ve searched all through the forums and all I could find was Dr. Learner’s suggestion. But even his was 450 2* a day, and if tolerated it was bumped to 3 pills a day.

(From Dr. Lerner’s ME/CFS Treatment Guide). Dr. Lerner recommends “valganciclovir (Valcyte) one 450-mg capsule daily for three days, followed by two 450-mg capsules in the morning daily. Liver function tests are studied very carefully. If there is any abnormality, one alters the dosage. Given the patient’s ability to safely tolerate two 450-mg capsules, dosing can be increased to two, 450-mg capsules in the morning and a one additional 450-mg capsule twelve hours later. Liver function tests, again, must be studied carefully and frequently.”
 

Pyrrhus

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Hi, just curious where you found this standard dosage as I’ve been prescribed Valcyte at 450mg twice a day by an ME specialist.
I’ve searched all through the forums and all I could find was Dr. Learner’s suggestion. But even his was 450 2* a day, and if tolerated it was bumped to 3 pills a day.
Here is the Montoya study:
https://pubmed.ncbi.nlm.nih.gov/17276366/

And here is the prescribing information from the U.S. FDA:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021304s012,022257s007lbl.pdf

Hope this helps.