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Norvir Advisory
Recommendations to Staff by Pablo Tebas, MD,
Assistant Professor of Medicine, Washington University School of Medicine, St. Louis
August 1, 1998
Somewhere between the middle and end of August Abbott will run out of ritonavir (RIT) capsules. They
will still make the liquid, which, as you know, it is difficult to take. We
currently have 75 patients in the clinic on ritonavir, mainly in combination with saquinavir (SAQ). We will start seeing the problem
when the patients run out of drug in the next few weeks. Unless Abbott
solves the problem immediately, and even if they do, there is going to be a
shortage.
I would like to have a systematic approach to the problem in the clinic.
Here are two different situations to consider:
1. Patient is Undetectable on a RIT/SAQ Regimen (and This Was the Initial Protease Regimen)
Be very careful if RTV/SQV was a "rescue" regimen. You can not go back to the previous protease failing regimen.
The options for these patients are:
- Patients start RTV liquid formulation. The concentration of the syrup is
80 mg per ml, so the patient has to take 5 ml bid. It tastes terrible. In
fact the bad thing is the after taste. It tastes better if the patient
drinks chocolate Ensure after it. Abbott will provide chocolate Ensure to
"the patients that need it." Remind the patient that the dispenser is not
dishwasher safe, and that it should be rinsed with water after use, because
if not RTV will dissolve the plastic. This would be the safest option.
- Patients stop saquinavir (and ritonavir) and switch to an alternative
protease inhibitor: indinavir 800 tid or nelfinavir 1250 bid. Remember to
talk with the patient about dietary constraints and fluid intake
requirements (refer to the attached chart). Remember to be careful if RTV/SQV was a rescue regimen.
- Drop the ritonavir and increase the dose of saquinavir to 1200 mg tid
with food (six Fortovase capsules)
- Patient increases the dose of saquinavir to 800 tid AND adds nelfinavir
750 tid. This option increases the number of pills a lot, and may be
associated with increased diarrhea. The levels of saquinavir that you
obtain with this combination are not the one that you would get with RTV/SQV
- Patient enrolls in WashU 59. To qualify for this study patient has to be
undetectable for at least 6 months. If the patient is less than 50 copies,
the study will drop the RTV/SQV and start nevirapine 200 mg q day for a
week and then 400 q day. Monitoring will be done q 4 weeks with
ultrasensitive PCR in the ACTU. This is a very reasonable option based on
the Incas trial data, if the patient is interested. This is only doable in the
setting of a clinical trial.
- DMP-266 is not yet approved, and due to the huge number of patients in
the country affected with this supply problem I think it is going to be
very difficult to get it for a significant number of them.
2. The Patient Has a Detectable Viral Load
This is a very specific situation it is important to take whatever time is necessary and to pay a lot of attention to these patients because the possibility of changing just one
drug could be very deleterious in this situation.
In this situation you have to decide if you want to maintain your patient
on this combination or if it is time for a switch. There is not much data for responses when
RTV/SQV has failed. Theory and some anecdotal reports suggest that a
nelfinavir based regimen could work (in the reverse way that RTV/SQV works
for nelfinavir failures). Again not much data. Indinavir is pretty useless
in this situation. DDI, D4T, hydroxyurea with or without an NNRTI (NVP or
DMP266) could be a last resource option.
Of the above options for the patient with undetectable viral load, there
are four that should never be done in a patient with detectable virus:
- Do not switch just the protease (option b of the above), for obvious
reasons.
- Do not add nelfinavir. You will be killing the theoretical best drug for
ritonavir failures
- Do not increase the dose of saquinavir, unless you think the patient was
on his or her way to respond. If RTV/SQV taken properly did not work, increasing
the dose of saquinavir is not going to make it
- Do not drop RTV/SQV and add an NNRTI. This will lead to resistance very
quickly. These patients are not eligible for WashU 59.
That leaves you and the patient with the option of switching to the liquid formulation, or switching everything around.
There will be pill boxes in the clinic to show the patients the different
options as well as a bottle of liquid RTV.
Three last issues:
The new recommendations for liquid RTV are to keep the liquid at average room temperature (below 77 degrees F), and not in the refrigerator. However, this may not be practical in all situations where room temperature cannot be kept at the appropriate range. Abbott is expected to clarify this recommendation and provide information on when refrigeration may be appropriate in specific situations with no anticipated effect on the efficacy of the liquid.
It is stable for 30 days after opening (it should last around 20 days).
Consider bringing the patient back to the clinic within two weeks of the
change to be sure everything is OK.
This problem will affect 15% of our clinic population, and all of you will
see cases. Bill or I will be willing to provide advice if anybody has any
questions.
Posted 8/31/98
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