Standard DoseRukobia, approved July 2nd, is dosed as a 600 mg tablet taken twice daily with or without food. It must be taken in combination with other HIV antiretrovirals.
One 600 mg tablet twice daily without regard to food. For heavily treatment-experienced people with multidrug-resistant virus on a failing HIV regimen due to resistance, intolerance, or safety considerations. Must be taken in combination with another antiretroviral(s).
Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose.
See package insert for more complete information on potential side effects and interactions.
Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there may be are other drug interactions which are not listed here.
Entry/attachment inhibitor: GP120 attachment inhibitor
Potential Side Effects and Toxicity
At the time of approval, the most common side effect seen was nausea, in 10% of study participants. Other side effects, observed less often, were diarrhea and fatigue. An earlier safety analysis of the Phase 3 BRIGHTE study at Week 96 found that 94% of participants experienced at least one side effect during this Phase 3 study, though most were mild in severity. Moderate to severe side effects had occurred in 21% of participants and included nausea, diarrhea, headache, immune reconstitution inflammatory syndrome (IRIS), vomiting, fatigue, and weakness or lack of energy. Twelve participants had serious side effects that were related to treatment with fostemsavir, and seven percent of participants had side effects that caused them to leave the study.
Potential Drug Interactions
New interactions continue to be discovered after drug approval. Dose modification of fostemsavir is not required when co-administering with tenofovir DF, ritonavir-boosted atazanavir, ritonavir-boosted darunavir with or without etravirine, etravirine alone, ritonavir alone, or raltegravir + tenofovir DF. Dose modification is also not required when co-administering with rifabutin (with or without ritonavir). It is not recommended to co-administer with rifampin, an antimycobacterial used for tuberculosis treatment, due to significantly reduced levels of fostemsavir. Cannot be taken with (contraindicated with) enzalutamide (an androgen receptor inhibitor); the anticonvulsants carbamazepine and phenytoin; the cancer drug mitotane; or the herb St. John’s wort. Based on fostemsavir’s metabolism, a theoretical interaction likely exists with statins (drugs used to treat high cholesterol). This may require a dose reduction or adjustment of certain statins when co-administered with fostemsavir. No dose modification necessary when co-administered with methadone or buprenorphine. Fostemsavir could affect oral contraceptive concentrations, especially those containing ethinyl estradiol. If a booster is not given in the regimen with fostemsavir, it may be co-administered with a combined oral contraceptive containing norethindrone and 30 mcg or less of ethinyl estradiol.
Fostemsavir was submitted for FDA approval in December 2019 and approved July 2020. Rukobia is the first HIV drug of its type to get this far in development. It’s a gp120 attachment inhibitor. (That’s under the drug class of HIV entry inhibitors.) Watch a video of its mechanism of action at youtu.be/WnreXE-TVi8. Rukobia Fostemsavir works on the gp120 protein that lies on the surface of human immune cells. It’s a necessary part of getting the virus to enter the cell. Rukobia prevents attachment to the CD4 immune cell by binding to the CD4 receptor binding sites on gp120 on the virus. This causes the virus to accumulate in extracellular space and is subsequently removed by the body’s immune system. Very cool. Rukobia is designed to be used in HIV treatment-experienced people, who typically have fewer options for HIV treatment than those just beginning antiretroviral therapy. An option for treatment-experienced individuals is a good thing. “Even in the era of modern HAART [highly active antiretroviral therapy], antiretroviral (ARV) failure and resistance is still a problem worldwide,” wrote HIV specialist Dr. Pedro Cahn and colleagues in Current Opinion in HIV and AIDS published in July 2018. Dr. Cahn worked on fostemsavir research. Given that Rukobia does not appear to have cross-resistance to any currently approved antiretroviral as well as its activity regardless of HIV tropism makes it a welcome new drug for patients with very limited treatment options. Rukobia is active against CCR5, CXCR4, and dual-mixed virus (Selzentry is only active against CCR5). An advantage of the HIV entry inhibitors has been to help create an optimized regimen for people needing a new drug. In the Phase 3 BRIGHTE study with fostemsavir, study participants all started the trial with treatment failure on the HIV regimen they were taking at the time of entry into the trial. They were heavily treatment experienced with multidrug resistance. Unfortunately, more treatment experience tends to lead to a less likely chance of therapy success later on down the line. This is why medical providers ask HIV patients to take their meds as best they can. According to results reported in October 2018, the people in BRIGHTE who were able to add one or two other new drugs to their regimen along with the fostemsavir (called an “optimized background therapy,” or OBT), did better than those who only had fostemsavir as a new option. For the OBT group, 54% experienced undetectable viral load at one year of treatment (146 of the 272 OBT participants). For the group just adding fostemsavir, because there was nothing else available that they could add, 38% reached undetectable viral load. This was highly clinically significant for these patients. At the time of approval, 96-week results showed that 60% of the 272 OBT participants had undetectable viral load (less than 40 copies) and an average T cell increase of 205. For the group of 99 participants who only added fostemsavir, 37% had viral load less than 40 at 96 weeks, with an average T cell increase of 119. For more data, including medications added for optimized therapy, go to the FDA approval announcement at bit.ly/FDAannouncementRukobia.
Dr. Ross Slotten says:
Fostemsavir, a new agent developed by ViiV, a division of GSK, is a unique class of medication that works by preventing the envelope of HIV from attaching to its receptor on the CD4 (T helper) cell. Unlike entry inhibitors such as maraviroc (Selzentry), the tropism of the virus is unimportant. The medication is taken orally twice daily and must be combined with one or more medications to be effective. The results of a Phase III study known as the BRIGHTE trial were presented at the International AIDS Society meeting in Mexico City in July 2019. Study participants were heavily pretreated and resistant to three classes of HIV medications but were still sensitive to at least one other class of medication. After 96 weeks, 60% of participants were maximally suppressed to less than 40 copies. The most common side effects were nausea and diarrhea, which were mild. Once again, this is a niche drug, designed specifically for those individuals who have failed most other therapies. Unless it can be combined into a once-daily tablet or be given as an injectable agent monthly, yearly, or whatever, it will never be a first-line treatment for HIV infection. Resistance to fostemsavir occurs, so noncompliant people living with HIV will fail a fostemsavir-containing regimen also.
Activist Bridgette Picou says:
Fostemsavir works by binding to a specific protein called gp120 on the virus, blocking it and thereby prohibiting it from attaching to the CD4 cell. It is a prodrug as opposed to an HIV medication itself. For patients with very resistant HIV it is a fresh way to fight the virus, but is not intended for patients newly starting therapy or those who have achieved viral suppression through regular ART treatment. Since the gp120 protein is common between HIV strains, there is a high barrier to resistance.