Isentress

Common Name: raltegravir (formerly MK-0518)

Brand Name: Isentress

Class: HIV integrase inhibitor (also called integrase strand transfer inhibitor or INSTI)

Standard dose: One 400 mg film-coated tablet twice a day. Can be taken with or without food, with no food restrictions. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,074.64 / month

Manufacturer contact: Merck and Co., www.isentress.com, 1 (800) 622-4477

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, though most patients had other risk factors for cancer), low white blood cell count (neutropenia), low platelets, and elevated liver enzyme levels. May cause elevated levels of a muscle enzyme (creatine kinase) on blood tests. Contact your health care provider if you experience unexplained muscle pain, tenderness, or weakness. May cause 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; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions: 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. Use caution with rifampin, which reduces plasma concentrations of Isentress. Prilosec (omeprazole) can increase concentrations of Isentress, but no dose adjustment is recommended. There is no interaction with methadone.

Tips: This star continues to shine bright. In July, Isentress became indicated for treatment in naïve patients (those who have never been on HIV drug therapy). In December 2009, U.S. HIV guidelines added Isentress along with a Truvada backbone as a preferred regimen for treatment-naive patients. The guidelines noted drawbacks: twice-a-day dosing, lack of long-term data, and a lower barrier to drug resistance than seen with boosted PIs. Greater tolerability, however, may help overcome those issues. Also, it's only one tablet per dose, and does not have to be taken with the dreaded Norvir, the way PIs are. The lack of long-term data is due to the relative newness of Isentress. Moreover, it is from a new drug class. Still, Isentress was on the market in 2007, and there has been no word from the community about toxicity, which came about much earlier with other drugs and drug classes. Last year, Isentress did something no other HIV drug ever did: it dropped viral load to undetectable in more than a whopping 90% of treatment-experienced people, out to one full year. Undetectable viral load is more difficult to achieve in this population than in people on HIV therapy for the first time. The results were exciting, but from a small study of only 103 individuals in the French ANRS 139 TRIO trial. Isentress was taken with Prezista and Intelence, a novel, nuke-sparing combination. 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. Isentress is exciting for several reasons. This is one of the truly new drugs that advanced patients are in such desperate need of. A big plus: 48-week results show cholesterol and triglyceride blood levels have not been a problem with Isentress. Moreover, it has no drug interactions with lipid-lowering medications the way PIs do. A study of once-daily vs. twice-daily Isentress in people on HIV therapy for the first time is in advanced (Phase 3) study. Please see package insert for more complete potential side effects and interactions.

Doctor

Isentress (raltegravir) was approved (one tablet twice daily without food restrictions) for use in combination with other antiretroviral drugs in the treatment of HIV infection in 2007. It is approved for use both as part of a first combination as well as for those who are treatment-experienced. It has shown great success in both settings. Raltegravir is the first drug approved in a new class of antiretrovirals called integrase inhibitors. There was a significant impact of this drug for those whose HIV had developed resistance to other drugs, since the use of raltegravir in various combinations of two other active drugs led to re-establishing virologic suppression in nearly everyone who took it. Furthermore, the studies of this agent in starting treatment showed that it was as successful as a combination based on efavirenz -- and this is one reason why the current DHHS guidelines list the combination of Truvada and raltegravir as one of four preferred initial combinations when starting treatment. While the long-term adverse effects of raltegravir are not yet fully known, given this is among the newer drugs in the field, there are several years of experience with this drug and all of the current data clearly supports that this is very well tolerated by most, though not all, people who take it. The current focus of research for this drug is to assess how well it works when taken once daily instead of twice daily -- early reports are encouraging, but large studies are underway to be more confident about this simpler dosing schedule. -- Cal Cohen, M.D.

Activist

The first in its class, and fast becoming the fair-haired darling of new HIV drugs, Isentress has been accorded preferred status for both treatment-experienced and treatment-naive patients. This drug has been a lifesaver for many who had run out of options, and with virtually no side effects, it is fast becoming a favorite for patients who want to switch to a more tolerable regimen without the CNS, GI, or lipid problems of the more common HIV meds. The only minor drawback is the fact that it must be taken twice daily. Other integrase inhibitors in the pipeline will offer once-daily dosing, but require Norvir or another booster. -- Jeff Taylor