Hello everyone I have taken my first dose of my medicine last night……long way to go but hoping my four week tests will come back undetected

You would be better off doing Sof+Dac+Riba

Disclaimer: This is outside the published guidelines but what I might do if forced to choose.

We can see experts suggest 12 weeks Riba is enough and that makes sense based on the half life.

We know things get better on treatment.

So if doing 12 weeks Riba I would consider doing the last, rather than the first 12 weeks with Riba, particularly in the difficult situation of someone F4 with low platelets.

Psychologically it would probably be easier to add Riba as an insurance having first felt the benefits of 2 strong DAA, expecially for those who have done it tough on PEG/Riba.

The side effects people got on PEG/Riba may have been more PEG and less Riba than we thought. I have a good dozen patients who are relapses telling me it’s much easier than they expected and their numbers look good.

Then again I just took one patient off Riba because after 18 weeks he was getting sick both on the numbers and in spirit. He’s feeling much better now and we are getting some blood cells back.

For something to qualify as a generic it must show similar pharmacokinetic properties (in English similar blood levels at different points of time after taking it). You will find all the nitty gritty here:

http://www.australianprescriber.com/magazine/26/4/85/7

The Form I vs Form II argument is probably irrelevant to clinical results but it remains a fact that Form I was what was used in the Phase 3 trials everyone reads and Form II is what is used in the commercial product.

It is unlikely to make a significant difference. A 50 kg person is getting 150% of the dose an average 75 kg person gets in mg/kg terms. A 150 kg person is getting only 50% in mg/kg terms. Provided the therapeutic window is wide enough dose adjustment is not required and a one size fits all dose is fine.

That said my eyes nearly fell out of my head when I saw that Gilead had changed from using what was tested to something that was not tested in the same way (Phase 3) but rather in the same way a generic is declared bio-identical.

With the exception of Havoni, for which there is trial data from ION-1 for n=1952 people (enough to make the margin of error roughly +/- 2%) pretty much all the other HCV trials have been so small that the margin of error is +/- 5% (n=384) or +/- 10% (n=96). See the trials and the discussion of margin of error here:

http://fixhepc.com/getting-treated/major-clinical-trials.html

As a result claims of superior clinical performance lack the raw statistical horsepower delivered by a large n to prove that. It’s simply a marketing smokescreen.

Even Gilead has adjusted the goals. The commercial Sofosbuvir is NOT the medication used in the Phase 3 trials where Form I crystals of Sofosbuvir were used. In the commercial product it is the Form II crystal (also known as Form 6) that is used. Forms 2-5 are all hygroscopic and un-useable. Form II is more stable but less soluble than form I. In other words the Sofosbuvir on sale is actually a GENERIC of the original Phase 3 trial medication that proved it up.

See page 12 of the TGA submission and the AUC data showing that Form II is not as well absorbed as Form I (it’s good enough to be considered the same for generic purposes, but it is less) and that also confirms Form I was used in the Phase 3 trials.

Sadly, approving funding for only one drug doesn’t make it any cheaper for Government because the number of people requiring treatment is the same. Government pays a fixed price for a cure no matter what drug is used.

I would have to disagree with this. New Zealand uses precisely this strategy. Their policy is that we need 1 or 2 good treatments for this problem, not every treatment from every manufacturer.

This translates into a reverse auction where manufacturers are invited to submit their best prices to get and keep the Government subsidy.

New Zealand’s prices prove beyond any doubt that hard negotiation encourages Big Pharma to sharpen their pencils.

We pay 8 times more than New Zealand for the 73 common drugs – I am not making this up….

http://www.australianprescriber.com/magazine/37/5/150/1

The population of New Zealand is similar to that of Sydney. By rights we should be able to negotiate better volume discounts.

The cost savings to the PBS on this have been estimated to be more than $1 billion a year.

I think the best thing to do is follow the guidelines and either do Sof+Led or Sof+Dac.

The theoretical problem with Sof+Led+Dac is this:

Have you ever tried to walk through a door at the same time as another person – neither of you fit but alone you do.

Drugs work like a key in a lock so it’s entirely possible that 2 drugs can “fight each other” and make the combination WORSE than either drug alone.

If you must take a PPI and have Dac then do Sof+Dac.