Meds, Mind, Body & Benefits > Questions About Treatment & Side Effects

Missed 5 Doses - AND FREAKING OUT

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I will be so appreciative for any information someone can give me.

I have been on a regimen (my first) of Reyataz, Truvada and Norvir since May 13. First time I have ever been on meds, and I've experienced no side effects whatsoever, except for a bit of fatigue.  I take a number of other drugs, plus some vitamins, and thus the total number of pills I swallow in the mornings is 10.

Last Wednesday, I was preparing to go away for a few days, and I laid out my regimen in one of those daily pill boxes. But today I discovered that I failed to include the Norvir! I have been amazingly diligent about taking these meds, every morning at exactly the same time. But because the Norvir was in the refrigerator, I somehow neglected to include them. The net effect is that I went 5 days without the Norvir, and I am totally freaking out. I'm scared to death that this is going to destroy the efficacy of this regimen, which, as I said, has been very easy on me. I feel like such an utter fool, screwing up my very first regimen, and frankly, I feel like I must be the first person in the world to make such a stupid mistake.

I've read whatever I could find about missed doses, and it basically says to take it when you remember, but don't double up (in my case, QUINTUPLE up!) on missed doses. So I believe I know what to do going forward, but obviously I'm terribly worried that I've totally screwed this up.

Does anyone have any ideas about whether this is likely to be the case?

Incidentally, I am obviously a newbie, but I have already learned so much from this site and these forums. Thanks for any help you might be able to give me.

Missing doses is a problem, but a one time event like this is not going to matter too much. If you missed ALL your doses, that would be a problem. The key to resistance is that the virus is replicating somewhere and can come up with the variability required to obtain resistance. If you go on and off meds, the virus can go through bursts of replication that can bring about the resistant strain. As you were on other drugs, the virus replication was probably still low and the problem decreased in magnitude. I wouldn't suggest you do it again, but a one time event is not going to significantly decrease how effective the drug is.


Tim Horn:

As confusing as my explanation may be, there's some interesting science that's potentially on your side. 

The reason why Norvir is used in combination with Reyataz and Truvada is because the tenofovir in Truvada can lower levels of Reyataz in the bloodstream.  To counter this, Norvir is added to boost Reyataz levels, so that the amount of Reyataz in the bloodstream remains within the therapeutic range. 

Simply put, Norvir inhibits an enzyme (called cytochrome P450 3A4) in the body responsible for metabolizing Reyataz.  By blocking this enzyme, Reyataz levels become elevated in the bloodstream.  Not only can this help increase the effectiveness of Reyataz, but it can also help offset the negative interaction between tenofovir and Reyataz.  This is why Norvir MUST be combined with Reyataz if Reyataz is combined with Truvada (or Viread). 

The combination of Norvir and Reyataz calls for one 100mg Norvir capsule plus two 150mg Reyataz capsules once a day.  But you're telling us that you haven't taken your Norvir for five days, which suggests that your Reyataz levels have likely fallen in the absence of Norvir "boosting."   This would certainly be the case if Norvir has a "reversible" affect on the P450 3A4 enzyme -- that is, the effect of Norvir dwindles if it is not taken consistently. 

But here's where the good news comes in: Norvir may actually have an IRREVERSIBLE effect on this enzyme, meaning that it may have a lasting inhibitory effect on P450 3A4, long after the Norvir is discontinued.  In other words, the Norvir you (temporarily) stopped taking five days ago may still have a lingering effect on the Reyataz you continued to take, helping to keep the Reyataz levels within the necessary range.

Here's an abstract of one study to consider:

I will say that this is very preliminary science... and in no way suggests that people should consider taking less Norvir if they're on a Norvir-boosted regimen.  But it may be a saving grace for you, during this unexpected interruption. 

Some experts might argue that ALL medications should be stopped at the same time in situations such as this. And, of course, it's ALWAYS best to get in touch with your doctor IMMEDIATELY if you find yourself in a situation such as this, to get his or her advice or to see if there's some way to secure an emergency supply of medication. 

Oh... and one other thing... do your Norvir capsules really need to be refrigerated?  If they're used within two months of picking them up from your pharmacist (and kept below 77-degrees fahrenheit), there's no need for them to be kept in the fridge.  This, I'm sure, will make them much less likely to be forgotten. 

Tim Horn

Thanks Tim for posting the abstract, I have been hunting for it...

Tenofovir (Viread) reduces levels of unboosted atazanavir (Reyataz) - AUC* by 25% and Cmin** by 40% - and this is significant.

When tenofovir is in the same combination, the recommendation is to boost 300mg atazanavir with 100mg ritonavir. Atazanavir concentrations are then well above the levels achieved with the 400mg unboosted dose. Tenofovir levels are also increased, but this don't seem to lead to increased tenofovir side effects.

Here is a report of the 'Dear Dr' letter issued about using tenofovir (Viread) with atazanavir (Reyataz) - 'Important new pharmacokinetic data for atazanavir sulfate (Reyataz™) in combination with tenofovir disoproxil fumarate (Viread®)'

- matt "never take Norvir on Saturdays (this is true)" the newt

* AUC = Area under the curve: is a measure of drug concentration over time, AUCs are used as a guide for dosing interval and to compare different drugs' availability in the body.

** Cmin:  the lowest level of drug in the blood  at the end of a dosing interval (ie before this begins to increase from the next dose).

...putting science aside, to answer the existential question, you are very, very, very unlikey to have screwed up your drug combination by not taking the Norvir for 5 days. 

Not getting caught out is something of an art, and for a flake like me mean squirrelling 1-5 doe stashes around the world (well, my world): work drawer, gym bag, work bag, 3 friends' houses, my ex's house, in winter every coat I use.  Without the Norvir though, cos I reckon if I am caugh out I can always take this when I get home a few hours later:)

- matt "viral load undetectable (for now)" the newt

Now playing - Elgar's 2nd Symphony


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