Mar 27, 1997
Can you please introduce the new protease inhibitor Viracept(Nelfinavir)? I would like to know more about it. What is the dosage? What are some of its side effects? How does it affect CD4 cell count and viral load?
| Response from Dr. Cohen
Nelfinavir (Viracept) is the fourth protease inhibitor to be approved by the FDA. The dose is 750 mg (three 250 mg capsules) three times daily. It should be taken with food, and does not have to be taken exactly every 8 hours.
The most common side effect is loose stools (not profuse diarrhea), which can betreated with drugs like Imodium or Lomotil.
The effect of nelfinavir on CD4 count and viral load is similar to that seen with ritonavir (Norvir) and indinavir (Crixivan). Actually, the magnitude of the viral load reduction was somewhat less in the nelfinavir trials than has been seen with the other protease inhibitors, but it's hard to compare one trial to another since they're different trials conducted on different patients.
In the trials conducted to date, the best results were seen with the combination of AZT, 3TC, and nelfinavir (in those who'd not been on those drugs before). Patients taking d4T + nelfinavir didn't do quite as well, perhaps providing further evidence that two nucleosides may be better than one in combination witha protease inhibitor.
Drug interactions are similar to what is seen with indinavir. You shouldn't take either with Hismanal, Seldane, or Propulsid, for example. Rifampin and rifabutin are also a problem. Nevirapine (Viramune) lowers nelfinavir levels a bit, and so it may be necessary to increase the nelfinavir dose. Nelfinavir increases saquinavir (Invirase) levels, but not nearly as much as ritonavir does, so if the two are combined you still have to take a lot of saquinavir.
It is being said that nelfinavir resistant virus remains susceptible to ritonavir and indinavir, and therefore it makes sense to use it first. While there may be some justification for that idea, it's still a mistake to assume that there's absolutely no cross-resistance between the drugs. Cross-resistanceis especially likely to develop (with any protease inhibitor) if you keep taking it despite active viral replication and allow your virus to develop a lot of secondary mutations.
Whether nelfinavir will be an answer for people resistant to indinavir or ritonavir remains to be seen. We should know soon, since it is being widely prescribed for that purpose. I suspect it may work in some, but certainly not all such patients.
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