Isentress HD (and Isentress)
raltegravir RAL (INSTI)
Standard DoseIsentress HD: Two 600 mg film-coated tablets once daily, with or without food, for individuals new to HIV therapy (treatment-naïve) or who are virologically suppressed (have undetectable viral load) on an initial regimen containing raltegravir.
Isentress: One 400 mg film-coated tablet twice daily, with or without food, for people with HIV treatment experience or individuals who are new to HIV therapy.
Must be taken in combination with another antiretroviral(s) from a different drug class.
Isentress HD is for adults and children weighing at least 88 pounds (40 kg). Isentress is for adults and children weighing at least 4 pounds (2 kg). Both Isentress HD and Isentress can be taken with or without food.
Isentress (but not Isentress HD) pediatric formulations are available as an oral suspension. Isentress dosing is based on weight for children less than 55 pounds; see package insert for dosing and mixing instructions. Do not substitute oral suspension for film-coated tablets.
Take missed dose as soon as possible, unless it’s closer to the time of your next dose. Do not double up on your next dose.
- See package insert for more complete information on potential side effects and interactions.
ManufacturerMerck and Co.
AWPIsentress HD and Isentress not available on formulary used
Potential Side Effects and Toxicity
In general, raltegravir is very well tolerated with infrequent side effects. Those reported in up to 3–4% of study participants include insomnia, nausea, headache and fatigue. The side effect profile in children is comparable to adults. INSTIs have been associated with weight gain.
Isentress may cause elevated levels of creatine phosphokinase (CPK, a muscle enzyme). Inform your provider or pharmacist if you have a history of rhabdomyolysis, myopathy, or increased creatine phosphokinase, or if you also take medications that may contribute to these conditions such as statins, fenofibrate, or gemfibrozil. INSTIs have been associated with adverse neuropsychiatric effects (such as depression, sleep disturbances and dizziness) in some retrospective cohort studies and case series. The DHHS guidelines recommend closely monitoring people with pre-existing psychiatric conditions on an INSTI. Chewable tablets contain phenylalanine, which can be harmful to people with phenylketonuria.
Potential Drug Interactions
It is important to take Isentress HD and Isentress only with other HIV drugs recommended by your provider because they and similar drugs are contained in other HIV medications: Biktarvy, Genvoya, Stribild, Tivicay, Triumeq, Dovato, Cabenuva, and Juluca. Isentress HD cannot be used with rifampin, but Isentress can; increase Isentress to 800 mg twice daily when using rifampin. Remember to decrease the raltegravir back to its original dose when you finish taking rifampin. There are no data on dosing of the chewable tablets with rifampin. There is no need to increase the raltegravir dose with rifabutin. With both Isentress HD and Isentress, avoid Gaviscon and other antacids containing aluminum or magnesium. Calcium-containing antacids such as Tums (calcium carbonate) can be used with Isentress, but not Isentress HD. Other acid reducers (such as Pepcid, Zantac, Prilosec, and Prevacid) are okay to use. Raltegravir is not recommended with carbamazepine or phenobarbital. Raltegravir can be used with Harvoni, Zepatier, or Epclusa. Unlike Isentress, Isentress HD cannot be used with Intelence or boosted Aptivus. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions not listed here.
Isentress HD was approved in 2017. While the original formulation, Isentress, was well tolerated and highly effective, its twice-daily dose was seen by some as a relative inconvenience. According to DHHS HIV treatment guidelines, raltegravir was downgraded from a preferred component of an initial regimen in most individuals to a component of a regimen in only certain clinical situations due to the higher pill burden as well as the relatively lower genetic barrier against the development of resistance compared to second generation INSTIs. Raltegravir-based regimens may be preferred for people with high cardiovascular risk. Raltegravir is a preferred drug for PEP (post-exposure prophylaxis—preventing HIV acquisition after a potential exposure) along with dolutegravir. Isentress is one of the preferred INSTI medications in HIV treatment guidelines for pregnancy, 400 mg twice a day in combination with 2 NRTIs. In pediatric HIV guidelines, Isentress was downgraded in 2017 from “preferred” to an “alternative” part of an initial regimen for children ages 6–12, but the powder formulation remains a preferred initial regimen for newborn and infant treatment and PEP following birth.
Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; go to apregistry.com.
Dr. Melanie Thompson:
Raltegravir, the oldest INSTI, is no longer recommended for initial therapy (other than in pregnancy) by DHHS or IAS-USA guidelines panels because newer INSTIs are less susceptible to viral resistance and can be given once daily in most situations. The HD formulation allows two pills to be taken once daily, but it is not available as an STR. In pregnancy, raltegravir must be given at 400 mg twice daily. When given with rifampin for tuberculosis, the dose of raltegravir is 800 mg twice daily.
Activist Joey Wynn:
About 16 years ago Isentress came onto the scene as the first INSTI. It is currently prescribed for initial therapy in certain situations, but not for the majority of folks just starting treatment. Pregnancy is the biggest reason for use of this older but easy to take treatment.