Standard DoseOne 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 to the time of your next dose. Do not double up on your next dose. Tablet should be swallowed whole; do not chew, crush, or split tablets.
- See package insert for more complete information on potential side effects and interactions.
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. Use with caution in patients who have a history of QTc prolongation (a heart problem). Liver problems can occur, but are very rare. The risk may be greater for people with a history of hepatitis B or C, but may occur in patients without a history of liver disease.
Potential Drug Interactions
Note: new interactions may continue to be discovered after a drug’s approval. Dose modification of fostemsavir is not required when co-administering with atazanavir/ritonavir, cobicistat, darunavir/cobicistat, darunavir/ritonavir with and without etravirine, etravirine, maraviroc, raltegravir, ritonavir, or tenofovir DF. Dose modification is also not required when co-administering with buprenorphine/naloxone, famotidine, methadone, norethindrone, or 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. Fostemsavir increases concentrations of statins (medications used to treat cholesterol). Use the lowest possible starting dose for statins and monitor for statin-associated adverse effects. Rukobia should be used with caution when taken with other medications with a known risk for torsades de pointes or QT prolongation (these abnormal heart rhythms can make the heart stop). 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. It cannot be taken by trans women on estrogen hormone therapy due to the significantly increased risk for a blood clot.
May increase levels of the hepatitis C virus (HCV) drugs grazoprevir and voxilaprevir; however, the magnitude of increase in exposure is currently unknown. Increased levels of grazoprevir may increase the risk of liver enzymes. Use an alternative HCV regimen if possible. 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 other drug interactions which are not listed here.
Rukobia is a gp120 attachment inhibitor. A member of the drug class of HIV entry inhibitors, Rukobia works on the gp120 envelope protein that lies on the surface of the virus. It’s a necessary part of getting the virus to enter the cell. Rukobia prevents attachment to the CD4 immune cell by blocking gp120 from binding to the CD4 receptor binding sites. This causes the virus to accumulate in extracellular space and is subsequently removed by the body’s immune system. Very cool. Watch a video of its mechanism of action at youtu.be/WnreXE-TVi8. Rukobia is designed to be used in highly 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, it is 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). 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 patients with HIV to take their meds exactly as prescribed. 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 individuals with HIV-2, commonly found in some other countries, Rukobia would not be recommended as HIV-2 is inherently resistant to it. For more data, including medications added for optimized therapy, go to the FDA approval announcement at fda.gov/news-events/press-announcements/fda-approves-new-hiv-treatment-patients-limited-treatment-options.
Dr. Melanie Thompson:
After many years in development, Rukobia, the first attachment inhibitor, was approved last year for people with multidrug resistant virus and limited options. It is taken twice daily, has few side effects, and does not require food for absorption. It is metabolized in the body into temsavir, the active component.
The BRIGHTE study allowed use of Trogarzo along with fostemsavir and other drugs, so there are some scant data about the combination (along with other drugs), indicating that the combination is safe and can be effective.
Some drugs decrease temsavir levels and can impact Rukobia’s activity against HIV, and therefore should not be taken together. These include some seizure medications; enzalutamide (Xtandi), an anti-androgen taken by some transgender women; the tuberculosis drug rifampin; and the herbal supplement St. John’s wort.
As is always the case with heavily resistant virus, the more active drugs in the regimen, the more effective and durable Rukobia will be.
Activist Bridgette Picou:
Fostemsavir is intended for heavily treatment-experienced people who have multidrug resistance (treatment failure) to multiple medications. Rukobia is a prodrug. This means the drug is metabolized by the body into the active compound. It binds to a protein on the virus itself, gp120, preventing it from entering the cell. The protein is found across multiple virus strains. This may help more patients achieve viral suppression than with regular therapy. It also has a high barrier to drug resistance.