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Is timed dosing still important with new meds?
Jul 25, 2000

After three years on meds that required exact 8-hr dosing, my partner and I have been switched to new twice-daily regimens, but without specific instructions as to dosing intervals. He was on Crix/Combivir and I was on Viracept/Combivir. His new meds are Combivir and 100 mg Norvir/800 mg crix twice daily, and I was changed to Ziagen/Combivir twice daily. We both had undetectable VLs, below 50, with his CD4s in the 600+/36% range and mine at 360/22%, and our labs still look good on the new meds at three months. Our question is about dosing intervals. We are both accustomed to sticking rigidly to an 8-hour schedule, and we are worried about being a bit too loose with what we presume is basically a 12-hour schedule. Is it important to hit that twelfth hour on the nose? Or will it hurt anything to be a couple of hours under or over that mark? Thanks for your great work on this forum. It means a lot to us.

Response from Dr. Pavia

Great question(s). The trick to determining dose schedules seems to be the need to avoid low levels at the end of the dosing period (the trough level). With drugs that are cleared rapidly, like crixivan by itself, a few hours makes a big difference. The curve for norvir plus crixivan looks much better, and the levels at 12 hours stay well above the minimum to inhibit the virus. Thus, it is really a twice a day (bid) regimen rather than every 12 hours on the dot. How far off can you be? One to two hours is probably fine, especially if that makes it easier to take with meals.

The same probably applies to combivir ziagen. Twice a day, with doses 11 to 13 hours apart is certainly fine, and up to 14 hours is probably safe. However, if you are in the habit of being on a schedule, it may make it much easier to remember.

Hope that helps

Andrew T. Pavia, M.D.



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