Switching tx from sof+led to sof+dac - thoughts?

This topic has 17 replies, 10 voices, and was last updated 8 years, 9 months ago by LondonGirl.

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25 December 2015 at 4:32 pm #7287
dointime
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- Guardian Angel
@dointime
Hi all,

Ok, so I know that there have never been trials where sof+led was done for 12 weeks and then sof+dac.
I also am aware of the possibility of concurrent use of some drugs cancelling out the effect of either and maybe making the situation worse.
So if you tell me that it is stupid to even think about doing this then I can’t disagree.

However, I have read the pharmacokinetics of both led and dac and I can’t see a reason why you shouldn’t follow led with dac, even though the led will be disappearing with a half life of 47 hrs while the dac is building up. Note especially that I am not talking about concurrent use, I am talking about serial use.

There seem to be 2 issues but neither of them indicate any problem:
1.
led does not use the CYP enzymes to metabolise while dac does, so no conflict there.
2.
led may be coadministered with P-gp and/or BCRP inhibitors. dac is both of those, so no conflict there.

You may be wondering why I would even want to think about this. Well, I don’t have a good clinical reason, it is just a matter of logistics, and the price of dac came into it too. But now I am wondering.

So if you know of a valid reason why this is a bad idea I’d like to hear it please – by that I mean over and above just an unsubstantiated opinion that it is a bad idea.

Thanks
dt
25 December 2015 at 4:38 pm #7288
Paul-Jarman-facebook
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@paul-jarman-facebook
I am surprised more people havn’t considerd that question. I personally suspect Dac is a better drug than Led but can’t substantiate that claim it’s just an opinion.

cheers

Two time relapser.

SVR 4 achieved 12/16 at last
SVR 12 achieved 22/02/2017 The Bastard has been defeated

GT 3 – about 28 yrs with HCV
25 December 2015 at 4:51 pm #7290
dointime
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@dointime
Paul,

Thanks so much for your prompt and open-minded reply. I find that I am really nervous about asking this question, so go easy on me folks. I figure that if I can’t ask it here then I can’t ask it anywhere. You all have no idea how much deep doo doo I would be in if I mentioned this to my doc.

Actually, I suspect too that dac is better than led. I figure that if there’s any virus that the led did not finish off then the dac might, or even just the continuation of the sof will eventually get it. So I do have a clinical reason of sorts, but not one that I can substantiate any more than you.

It is the switchover that is worrying me, ie. the time that led is still in my plasma and dac is also coming on stream. In the unlikely event that they were to cancel each other out for a reason that I haven’t figured out, that would be most unfortunate. Maybe I should continue with the riba for a period during the switchover in case of this? Of course I would hate to do that.

dt
25 December 2015 at 4:55 pm #7291
pkhow
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- Acolyte
@pkhow
I started on Sofos+Led for 3 days then switched to Sofos+Dacl. Now at week 6 and will continue to week 12. As i have a bottle of Led was considering an extra month changing back to Sofos+Led at week 12. Not sure but I have been considering it .

Genotype1b probably since 1978.
On prior TX. Started TX 11nov15
Sofosburvir + Daclatasvir FixHepC
VL Undetected 4weeks thanks to
Dr Freeman and FixHepC
25 December 2015 at 5:07 pm #7292
dointime
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@dointime
That’s very interesting pkhow. There’s no way to tell the effect on the drugs’ efficacy during the switchover, but I would be interested to know if you had any side effects that you attribute to the switch? I suppose though that it would be hard to pinpoint the cause of a side effect at only 3 days in.

dt
25 December 2015 at 5:09 pm #7293
Gaj
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@gaj
Hi dt,

I’m wondering if one thing that you may want to take into consideration is if you are unfortunate enough to relapse. Usually the recommendation is to use a different Tx if available. Having used the two main NS5A inhibitors previously, what would then be your best option for retreatment?

G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
25 December 2015 at 5:23 pm #7294
dointime
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@dointime
Hi GAJ,

You raise a good point. I think the whole question of retreatment with the same or another NS5A is a thorny one given our current lack of knowledge about it. At this point in time I am not convinced enough about the possible success rate that I would want to do it. My liver is not bad, so I could wait if I had to for a better tx to come along for NS5A relapsers.

If I were to change my mind then there are other NS5As in the near future that could be used, meanwhile more data is coming in all the time. I guess the moral for now is – don’t relapse the first time. My hope is that adding 12 weeks sof+dac will ensure that, not sabotage it!

dt
25 December 2015 at 6:19 pm #7296
Gaj
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@gaj
Hi dt,

I assumed you meant 12wks Led followed by 12wks Dac for a total of 24wks Tx? Is that correct? You say your liver isn’t bad so is there some other reason to treat for that long? Or are you doing it to try to ensure no relapse?

If the latter is the case then I would have to wonder whether doubling up on the guidelines, with a medication change or not, was the best solution. While Sof/Led/Dac are a lot milder than previous treatments I suspect they do have some trade offs regarding their effects on our bodies as seen by the various sides people experience. I would seek expert medical advice. YMMV.

G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
25 December 2015 at 8:02 pm #7300
dointime
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@dointime
Yes 24 weeks is correct. I am doing it for the reason you say, ie. to hopefully ensure no relapse. I know it is an extra burden on the body that may not be necessary but I will monitor that and stop if I get into trouble. All the trials of these meds had 24 week arms and did not throw up safety issues which prohibited the 24 week duration being recommended for some people. Of course none of the trials included a switch of NS5A med in the middle, so that is an unknown. Somehow I don’t think I am going to find any more expert advice on it out there than I am going to find right here.

dt
25 December 2015 at 8:02 pm #7301
Enkel
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@enkel
I have the feeling that sof/dac is the best pill ever will exist. After the trials of generic anyone who is informed will use a generic sof/dac combo which is better than every other combo.

Male, Fibro F1. Geno 1b. ALT 67 before treatment Viral load 5 million. My huge viral load replicates in my nervous system as I suffer anxiety.
Started Twinvir 12/12/15.
Two weeks
ALT 17 at 2 weeks
Viral Load UND at 2 weeks
ALT 13.5 at 7 weeks EOT
ALT 10.5 at 15 weeks EOT
ALT 13 at 27 weeks EOT, VL UND, Cured
29 December 2015 at 11:19 am #7482
Archer
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- Recovery Champion
@archer
It might help people to think about this if your signature with more information was available.
29 December 2015 at 11:30 am #7484
Dr James
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@fixhepc
I am starting to get a bit nervous about whether my treatment is going to do the job after 12 weeks. There has been a lot of conversation about treating for longer and changing the medications to ensure no relapse. I take Sof/Led and have five weeks to go. Should I be worried that I am not taking the medication for long enough? May be worrying over nothing of course…I can be a worry wart at times

YMMV
29 December 2015 at 11:53 am #7485
Chapel
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@chapel
I support Archer’s view that we should all put our basic treatment info as a signature in our profiles so we can comment on particular cases. Admittedly writing a signature is a bit unwieldy, but this will get you started: click on your name at the top of the page, then sign in again as demanded, enter signature details, then sign in again if prompted (I think it is twice?).
Now everyone will know your genotype, previous treatment etc without having to go back into old posts.

M, 57, Live in Wellington,NZ.
Genotype 1a diagnosed in 2013.
Treating for the first time since October 31 with Buyers Club Sof/Led. Thanks so much guys. Minimal side effects apart from sore throat at the start..
Viral load 5.4m when treatment started, Undetected at 4 weeks, 8 weeks, End of Treatment and 12-weeks post EOT. Yay!
29 December 2015 at 12:35 pm #7486
LondonGirl
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@londongirl
This is indeed very helpful

GT1a Dec14 F2/8.7 VL 900000-2.5M
Jan16 Hepcivir-L MonkMed/Redemption
Baseline: VL 913575 Alt 76 Platelets low
Wk2 VL1157 Alt 23
DET Wk 8 VL 32 Alt19 ‘In the slow lane’
June16 Fibro 5.7 F0/1 LIF 1.5
Wk 11 VL<12 Alt 13 Det/Unq
Extending tx 12 wks Mylan Sofo/Dac MonkMed
Wk 14 VL <12 Det/Unq
Wk 16 VL UNDETECTED
Wk 22 + 4 Wks Sunprevir FixHepC
Wk 24 UNDETECTED Alt 13
Wk 12 post tx SVR12 Wk 26 SVR24
Thank-you Tim, Dr Debasis @ MonkMed & Dr Freeman @ Fix HepC
29 December 2015 at 3:10 pm #7489
LondonGirl
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@londongirl
Hi Lynn , It’s not for me to say as I am no Dr., but as a personal opinion with a Fibro of 0 & LFTs normal, from what I’ve read, 12 weeks should do you just fine. Most Drs at NHS England are offering only 8 weeks in this situation, although 12 weeks is recommended. I take it you are treatment naive? Keep the faith

GT1a Dec14 F2/8.7 VL 900000-2.5M
Jan16 Hepcivir-L MonkMed/Redemption
Baseline: VL 913575 Alt 76 Platelets low
Wk2 VL1157 Alt 23
DET Wk 8 VL 32 Alt19 ‘In the slow lane’
June16 Fibro 5.7 F0/1 LIF 1.5
Wk 11 VL<12 Alt 13 Det/Unq
Extending tx 12 wks Mylan Sofo/Dac MonkMed
Wk 14 VL <12 Det/Unq
Wk 16 VL UNDETECTED
Wk 22 + 4 Wks Sunprevir FixHepC
Wk 24 UNDETECTED Alt 13
Wk 12 post tx SVR12 Wk 26 SVR24
Thank-you Tim, Dr Debasis @ MonkMed & Dr Freeman @ Fix HepC
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