Rescriptor (delavirdine, DLV) received FDA approval in April 1997, becoming the second non-nucleoside reverse transcriptase inhibitor (NNRTI) available. Mixed results from clinical trials and a difficult dosing schedule (two pills three times a day) combine to make it one of the least-prescribed antiretrovirals.
Rescriptor certainly didn't wow the FDA Advisory Panel that reviewed it back in 1996. The vote was a tie -- four for approval and four against -- due to the drug's lackluster performance in the trials that were submitted for review. At that time, trials were still being designed that added one new drug to a failing regimen, inevitably leading to unimpressive results. One trial (0017) comparing Rescriptor plus Videx (ddI) to Videx alone was stopped early when the number of deaths was nearly equal in both groups. Another trial, ACTG 261, showed a trend toward better CD4 increases in people taking Rescriptor with Videx and Retrovir (AZT) compared to those taking only Videx and Retrovir, but no viral load results were reported at the hearing.
Faced with a non-recommendation from its advisory panel, the FDA decided to wait for the viral load results from ACTG 261. When those results showed that viral loads went down slightly more in people taking the three-drug combination than in people taking only two drugs, the FDA granted approval. (Follow-up results found that there was no real difference between the groups, however.)
Later trials have also questioned Rescriptor's staying power. In a study of 373 people who had taken few or no antiretrovirals (Study 0021 Part II), 82% of those taking Rescriptor with Retrovir and Epivir (3TC) had viral loads below 400 after three months, but only 45% were below 400 after a year on the combination. Similarly, 345 people in another trial (13C) had poor results -- after a year, only 29% of people taking Rescriptor with two nucleoside analogs had viral loads below 400.
So the picture seems clear -- poor efficacy combined with difficult dosing make Rescriptor a drug to be avoided, right? Well, as always with HIV, nothing is simple. Rescriptor may not be strong enough with nucleoside analogs, but the situation changes with protease inhibitors. In ACTG 370, 63 people who were taking Epivir either switched to Rescriptor or stayed on Epivir. Everyone also added the protease inhibitor Crixivan (indinavir) and Retrovir. After a year, 83% of those who switched to Rescriptor had viral loads below 200 compared to only 48% of those who stayed on Epivir. This may be due to the fact that Rescriptor raises blood levels of Crixivan. While that may be a good thing, it can also increase the risk of Crixivan side effects such as kidney stones.
Now that there are a number of drugs available to fight HIV, Rescriptor's ability to boost Crixivan levels isn't as needed as it once was, especially since it has to be taken three times a day. Viramune (nevirapine) and Sustiva (efavirenz), the other available NNRTIs, have proven their effectiveness when combined with two nucleosides, so most people don't want to risk starting treatment with Rescriptor since resistance to one NNRTI usually means resistance to all three. While most HIV treatment guidelines recommend the other NNRTIs as a part of preferred first regimens, none put Rescriptor in the "preferred" category, and the drug has never even been approved for sale in Europe.
As with the other NNRTIs, Rescriptor's most common side effect is rash, which occurred in about 35% of people in clinical trials. In most people, it went away within two weeks while still on the drug, but the rash was severe in 4% of people in the trials. There have been two reported cases of Stevens-Johnson syndrome, which is a severe allergic reaction.
Another challenge for Rescriptor is the long list of drugs that cannot be taken with it, including certain antihistamines, antiarrhythmics, calcium channel blockers, sedatives, cholesterol-lowering drugs, and many more. Because the list is so long, it's probably best to check the package insert that comes with the drug and talk with your healthcare provider about any other medications you're taking. As with all of the NNRTIs and protease inhibitors, St. John's wort (hypericum) should be avoided, since it may lower the levels of these drugs. Rescriptor may increase levels of Viagra (sildenafil), so the dose of Viagra may need to be lowered.
Viramune and Agenerase (amprenavir) lower levels of Rescriptor, but Rescriptor raises levels of Crixivan, Viracept (nelfinavir), Norvir (ritonavir), and Fortovase (soft-gel saquinavir). Taking Rescriptor at the same time as Videx buffered tablets lowers levels of both drugs -- they should be taken at least one hour apart. Rescriptor should also be taken at least one hour apart from antacids.
When to Consider It
Rescriptor is usually not recommended as part of a first regimen since the risk of developing resistance is significant and usually leads to cross-resistance to the other NNRTIs. People who need to boost the level of a protease inhibitor (PI) and don't want to use Norvir may find it useful, however. Rescriptor can still be used to boost PI levels in the bloodstream even if your HIV is resistant to Rescriptor.
Rescriptor is classified as an FDA pregnancy category C drug. Controlled studies of pregnant women haven't been conducted. Of ten infants known to have been exposed to Rescriptor in the womb, nine had no birth defects and one, born prematurely, had a heart defect that wasn't unusual and resolved after birth. Rescriptor shouldn't be used during pregnancy unless the potential benefit outweighs the potential risk to the mother and fetus.
1,200 mg a day, taken at a dose of 400 mg three times a day. Each dose usually consists of two 200-mg tablets. Rescriptor is also available in 100-mg tablets, which can be dissolved in water (the 200-mg tablets will not dissolve). The dissolved form was tried in children, but most of them switched to tablets. Rescriptor can be taken with or without food. It has not been approved for pediatric use.
FDA Approval: 1997
Manufacturer: Agouron Pharmaceuticals (subsidiary of Pfizer)
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