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Test Positive Aware Network
Isentress (Raltegravir, RAL, Formerly MK-0518)
January/February 2008
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Brand Name: Isentress
Common Name: raltegravir (RAL, formerly MK-0518)
Class: Integrase inhibitor
Standard Dose: One 400 mg film-coated tablet twice a day, with or without food. Take missed dose as soon as possible, but do not double up on your next dose.
AWP: $1,012.50 / month.
Manufacturer contact: Merck and Co.,
www.Isentress.com, 1 (800) 622–4477
AIDSInfo: 1 (800) HIV–0440 (448–0440), www.aidsinfo.nih.gov
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| Potential side effects and toxicity: |
Very tolerable, but most common were diarrhea, nausea, headache, and fever. Less common were abdominal pain, vomiting, fatigue, weakness, dizziness, and lipodystrophy. Other observations with unclear relationship to Isentress include cancer (new and recurrent). Most patients had other risk factors for cancer, low white count (neutropenia), low platelets, and elevated liver tests. Elevated levels of a muscle enzyme (creatine kinase) on blood tests. Contact your healthcare provider if you experience unexplained muscle pain, tenderness, or weakness. Hypersensitivity (allergic reaction), anemia, neutropenia, and gastritis. Increases in ALT, AST, and total bilirubin, all signs of liver toxicity, seen in around 8% of people taking Isentress. Increases were more likely in people also infected with hepatitis B or C. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; report symptoms of illness, such as shingles and TB, to health care provider.
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| Potential drug interactions: |
Isentress is not expected to affect the drug concentrations of other PIs, non-nukes, methadone, cholesterol medications, antifungals, proton pump inhibitors (like Prilosec), oral contraceptives, and erectile-dysfunction drugs. It did have an effect on the concentrations of Epivir and Viread. Rifampin reduces the concentrations of Isentress; caution should be used when coadministering. Aptivus/Norvir can also decrease the concentrations of Isentress but no clinically significant interaction was observed from the clinical studies in patients receiving both drugs. Dose adjustment is not required. Reyataz and Reyataz/Norvir increase blood levels of Isentress, but no dose adjustment is recommended. Caution advised in people taking medications that can cause muscle problems. Caution with rifampin, which reduces plasma concentrations of Isentress.
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| Tips: |
According to treatment advocates, Isentress is a rising star. The data is in accord with the advocate view that advanced patients are having dramatic results and almost no side effects. Many people on long-time therapy became undetectable for the first time. One doctor reported that patients at his clinic could not believe they had received Isentress instead of placebo during studies. Some HIV specialists are now switching patients off Fuzeon and on to Isentress. There are hopes of Isentress replacing a boosted PI. Isentress is exciting for several reasons. This is one of the truly new drugs that advanced patients are in so desperate need of. Isentress doesn't have to be boosted with the dreaded Norvir like so many other new HIV drugs, has had no major interactions with other HIV drugs, and can be taken with or without food. A big plus: cholesterol and triglyceride blood levels have not been a problem with Isentress, out to 48 weeks results. It's shown good potency in early (two weeks) results in both people on therapy for the first time and those who were heavily treatment-experienced, compared to the gold-standard Sustiva plus optimized background. The idea of such early and amazing potency -- never seen with an HIV drug before -- is exciting. An amazing number of people reached undetectable viral load in durable results: at 48 weeks, 64 to 71% of people on Isentress (depending on the dose used in study) had less than 400 viral load; 46 to 64% of them had less than 50. The majority of people with treatment failure, however, were those who had no other active drug to add along with Isentress. With so many new and newer HIV drugs on the market now (Prezista, Selzentry, Aptivus, Intelence, Fuzeon) that problem should be less common. The rate of side effects was similar to the study group taking placebo (both the placebo group and the Isentress group used an optimized background -- the best drug combination they could take). In data presented to the FDA for approval, the people taking raltegravir had more than twice the decrease in viral load than seen in the placebo (dummy pill) group (-1.85 vs. -0.84 log). This drug did its best when used with Fuzeon. It was not, however, tested with other newer drugs now available in the pharmacy. In vitro (test tube) cross-resistance has been observed to other integrase inhibitors under development, which could limit this class in the future. More research is needed in this area. Please see package insert for more complete potential side effects and interactions.
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| Doctor |
| After the virus enters the cell, its RNA gets turned into DNA by reverse transcriptase. The viral DNA then enters the nucleus and gets inserted ("integrated") into human DNA. Integrase inhibitors block the step. The development of these drugs has been slow and painful, but they're finally here, and the first one out of the gate looks like a winner. Patients with extensive drug resistance in the BENCHMRK trials did extremely well if they took Isentress with at least one fully active drug. In fact, the results were at least as good as what we expect in patients starting therapy for the first time with no resistance. There's also a smaller trial comparing Isentress with Sustiva (in combination with Viread and Epivir) as first-line therapy, and both drugs looked great. Isentress drove the viral load down faster than Sustiva, though that may not make any difference in the long-term. Isentress is very well tolerated. Side effects in clinical trials have generally been "the same as placebo," and you can't do much better than that. Of course, with just one year's worth of data, it's too soon to declare it free of toxicity, but the early data are encouraging. We'll sort out the uses of Isentress with time, but if you've got resistant virus and need to put together a new regimen, using Isentress is a no-brainer. The more challenging question is what to combine it with to prevent resistance. Resistance to integrase inhibitors can occur rapidly if they're not combined with other active drugs. I'm hoping we'll use this drug wisely, so we don't see an epidemic of integrase inhibitor resistance a year from now. -- Joel Gallant, M.D. |
| Activist |
In very advanced patients, Isentress, like Selzentry, showed little or no evidence of any added toxicity. Unlike Selzentry, people don't seem to have many lingering doubts about Isentress. Its availability has been met with a level of enthusiasm not seen for any drug in many years. This is backed up by initial sales in the marketplace, which have taken off like a rocket and have even carried some other new drugs, such as Prezista, along with it. -- Martin Delaney
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This article was provided by Test Positive Aware Network. It is a part of the publication Positively Aware.
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