cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension (CAB LA/RPV LA)
Standard DoseTwo long-acting intramuscular gluteal (butt muscle) injections once monthly. Consists of one injection of long-acting cabotegravir and one injection of long-acting rilpivirine. No food restrictions.
For adults switching from a stable HIV regimen who have undetectable viral load (less than 50 copies per mL) with no history of antiretroviral treatment failure and no drug resistance or suspected resistance to cabotegravir or rilpivirine. A month of daily oral lead-in therapy is required before injections begin, consisting of a 30 mg tablet of cabotegravir (Vocabria) and a 25 mg tablet of rilpivirine (Edurant). Oral rilpivirine must be taken with food; the injectable does not. Initiate injections on last day of oral lead-in. If up to eight weeks of treatment is missed (four injections total), restart therapy with the maintenance dose of 400 mg CAB LA plus 600 mg RPV LA. If more than eight weeks of therapy has been missed, restart treatment with the higher initial dose of 600 mg CAB LA plus 900 mg RPV LA, then continue with the lower doses thereafter. The oral medications can also be used as “bridging” if shots cannot be obtained on time. Increased monitoring is recommended when CrCl is less than 30. The effect of severe liver impairment on Cabenuva is unknown.
- See Edurant (rilpivirine); Vocabria (cabotegravir) is not available separately
- See package insert for more complete information on potential side effects and interactions.
AWP28-day oral lead-in provided at no cost
Loading dose (600 mg/900 mg): $7,128 (estimated based on WAC)
Maintenance dose (400 mg/600 mg): $4,752/month (estimated based on WAC)
Potential Side Effects and Toxicity
Oral lead-in should be used to assess for tolerability. The most common adverse reactions observed in 2% or more of people receiving Cabenuva in clinical trials were injection site reactions (83%, with 37% having at least Grade 2—moderate), pyrexia (fever), fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Serious post-injection reactions reported within minutes of administration (in less than 1% of people injected) may have been associated with inadvertent (partial) intravenous administration and began to resolve within a few minutes after injection in clinical studies: difficulty breathing (dyspnea), abdominal cramping, agitation, flushing, sweating, oral numbness, and changes in blood pressure. Instructions for injection should be followed carefully to avoid accidental intravenous administration. People given injections should be observed for approximately 10 minutes afterwards to monitor for potential reactions.
Liver toxicity (hepatotoxicity) has been reported with or without pre-existing liver disease or risk factors. People with underlying live disease or marked elevations in transaminases (a lab measure that indicates there is damage to the liver) may be at increased risk for rising transaminase level or worsening of current elevated levels. Depressive disorders (including depression, major depression, depressed moods, altered moods, mood swings, dysphoria, negative thoughts, or suicidal ideation and attempts) have been reported with Cabenuva. People experiencing depressive symptoms should be monitored.
DHHS guidelines recommend closely monitoring patients with pre-existing psychiatric conditions on an INSTI. Serious or severe hypersensitivity reactions have occurred with other INSTIs and could occur with Cabenuva. Monitor for signs of hypersensitivity, including elevated liver transaminases, and treat as needed. New data associate INSTIs with weight gain; see a different INSTI page for more information. There was a median weight gain of 3.3 pounds in Cabenuva trials.
Potential Drug Interactions
New interactions may be discovered after approval. Cabenuva is contraindicated with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (more than one dose), or the herb St. John’s wort. Clinical monitoring of methadone is recommended because it may need to be adjusted. 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 which are not listed here.
As ViiV Healthcare pointed out, Cabenuva changes HIV treatment from 365 dosing days per year to just 12. FDA approval was based on two Phase 3 studies, ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen). See data on the online version of this drug page. Residual concentrations of cabotegravir and rilpivirine may remain in the body for more than a year after discontinuation, but are not expected to affect the use of subsequent HIV drugs.
Together, they included more than 1,100 individuals from 16 countries. ATLAS and FLAIR found that Cabenuva was as effective as a three-drug regimen at helping people reach undetectable viral load. Serious adverse events occurred in 4% (24/591) of individuals taking Cabenuva, and of that group, 3% (17/591) of adverse events led to withdrawal. Results are out to one year. In the LATTE-2 study with people on first-time HIV therapy, cabotegravir plus rilpivirine administered every 4 weeks or every 8 weeks was found to be as effective as the traditional three-med (even if only as one pill) oral combination given to people in the control group of the trial. There was some virologic failure in the 8-week group vs. none in the 4-week; hence, research went forward with only 4-week dosing. This success was out to 96 weeks (nearly two years). Moreover, the majority of participants given shots in the Phase III ATLAS study (more than 96%) said they preferred the injections every month or two months to taking their previous daily HIV oral regimen, despite any side effect or injection site reaction.
Dr. Melanie Thompson:
At long last, Cabenuva was approved by FDA in January, given as two separate injections in the buttock. Thirty days of oral cabotegravir (now called Vocabria) and Edurant will be provided as a lead-in before beginning injectable medicines to ensure viral suppression along with safety and tolerability. After all, once injected, there’s no reversing the side effects. In an unusual move, IAS-USA guidelines recommended this combination in advance of FDA approval for the population outlined by FDA. As with Juluca, this regimen should not be used by people with hepatitis B, as neither of the drugs has HBV activity. ATLAS 2M used an 8-week schedule for people who had been on ATLAS, with good result. If FDA approves dosing every 8 weeks, the logistics of administration will be less taxing on patients and clinics—and less expensive! Both drugs last a very long time in the body, in some cases over a year, but the levels decline over time to the point that they won’t suppress virus, but could select for resistant virus. Adherence to dosing is therefore very important. These drugs are injected into buttock muscles, not arms. People with buttock implants were excluded from trials. Injection site reactions are common, but tend to be mild and to decrease over time. The prohibition on acid blocking agents with oral rilpivirine does not apply to the injectable form, however, there still can be drug interactions that affect the levels of these and other drugs.
Drug interactions should be looked at closely before adding new drugs while taking this regimen. Implementation will be the challenge for this duo. Dosing will require an increased number of visits for people who are now coming to clinic only every 3 to 6 months or less often. Likewise, reminders will be necessary. This is a great application for smartphone apps, but still requires clinic supervision. For missed injections, additional effort will be needed to help people get to the clinic. This may require transportation support, and visits at non-traditional hours for folks who have difficulty getting off of work. Clearly, administration costs will add to the price of the drugs, and will depend on third-party payors to cover. It is unclear how Ryan White and other public clinics will cover administration costs.
These challenges are surmountable, but in the short run it may be difficult to manage this new paradigm as clinics are struggling to manage COVID-19. The annual Wholesale Acquisition Cost for monthly dosing is quite high ($48,720 for the first year) and includes the higher price ($5,940) of the initial loading dose. If injections can be given every 8 weeks, it may lessen the price burden, and become competitive with the also overpriced drugs Biktarvy and Genvoya. (Sorry, here I am on my pricing soapbox again!) Cabenuva won’t be for everyone, but some people are eagerly awaiting the opportunity to stop taking pills, even if it means more frequent clinic visits. We need as many options as possible to help people with HIV maintain suppressed virus if we are to end the HIV pandemic.
Activist Bridgette Picou:
Cabenuva offers freedom from being tied to daily pills, more privacy about treatment, and less daily effects on the body processes. It’s not completely concern free, as the injections have to be given in a healthcare setting, and adherence to the dosing schedule is more important because of its infrequency. A lot of people seem to prefer the idea of monthly injections over daily pills.