Loading…
Cabenuva is a brand name for Cabotegravir. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION • Refer to full prescribing information for detailed information on dosage and administration recommendations. ( 2 ) • Prior to initiating treatment with CABENUVA, oral lead-in dosing may be considered to assess the tolerability of cabotegravir and rilpivirine with the recommended dosage used for approximately 1 month.
3 ) • For gluteal intramuscular injection only. 9 ) • Recommended Monthly Dosing Schedule: Initiate injections of CABENUVA (600 mg of cabotegravir and 900 mg of rilpivirine) on the last day of current antiretroviral therapy or oral lead-in and continue with injections of CABENUVA (400 mg of cabotegravir and 600 mg of rilpivirine) every month thereafter.
4 ) • Recommended Every-2-Month Dosing Schedule: Initiate injections of CABENUVA (600 mg of cabotegravir and 900 mg of rilpivirine) on the last day of current antiretroviral therapy or oral lead-in for 2 consecutive months and continue with injections of CABENUVA every 2 months thereafter.
1 Dosage and Administration Overview • CABENUVA contains cabotegravir extended-release injectable suspension in a single-dose vial and rilpivirine extended-release injectable suspension in a single-dose vial [see Dosage Forms and Strengths ( 3 )] .
9 )] . 3 )] . 5 )] . 1 )] . 4 )] . 3 Optional Oral Lead-In Dosing to Assess Tolerability of CABENUVA in Adults and Adolescents 12 Years of Age and Older and Weighing at Least 35 kg The healthcare provider and patient may decide to use an oral lead-in with oral cabotegravir and oral rilpivirine prior to the initiation of CABENUVA to assess the tolerability of cabotegravir and rilpivirine, or the healthcare provider and patient may proceed directly to injection of CABENUVA without the use of an oral lead-in.
If oral lead-in is used, the recommended oral lead-in daily dose is one 30-mg tablet of VOCABRIA (cabotegravir) and one 25-mg tablet of EDURANT (rilpivirine) taken with a meal for approximately 1 month (at least 28 days), followed by intramuscular initiation injections of CABENUVA.
5 )] . 3 )] . The recommended initiation injection doses of CABENUVA are a single 600-mg (3-mL) intramuscular injection of cabotegravir and a single 900-mg (3-mL) intramuscular injection of rilpivirine. 9 )] . Continuation injections should be initiated a month after the initiation injections.
4 )] The most common adverse reactions (Grades 1 to 4) observed in ≥2% of participants receiving CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash.
gov/medwatch . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect rates observed in practice.
1 )] . Additional safety information from other ongoing or earlier clinical trials in the cabotegravir and rilpivirine program have been considered in assessing the overall safety profile of CABENUVA. 6 weeks in ATLAS-2M). Adverse reactions included those attributable to both the oral and injectable formulations of cabotegravir and rilpivirine administered as a combination regimen.
Refer to the prescribing information for EDURANT (rilpivirine) for other adverse reactions associated with oral rilpivirine. The most common adverse reactions regardless of severity reported in ≥2% of adult participants from FLAIR and ATLAS at Week 48 are presented in Table 5 .
Selected laboratory abnormalities are included in Table 7 . At Week 96, the overall safety profile for FLAIR was consistent with that observed at Week 48, with no new safety findings identified. In the extension phase of the FLAIR study at Week 124, the overall safety profile was consistent with that observed at Week 48 and when injection therapy with CABENUVA was initiated directly without the oral lead-in phase.
Overall, 4% of participants in the group receiving CABENUVA and 2% of participants in the control group in FLAIR and ATLAS discontinued due to adverse events. Non-injection-site-related adverse events leading to discontinuation and occurring in more than 1 participant were headache, diarrhea, hepatitis A, and acute hepatitis B (all with an incidence <1%).
5 WARNINGS AND PRECAUTIONS • Serious or severe hypersensitivity reactions have been reported with cabotegravir- and rilpivirine-containing regimens. Reactions associated with cabotegravir include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).
Reactions associated with rilpivirine-containing regimens include cases of drug reaction with eosinophilia and systemic symptoms (DRESS). Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. 1 ) • Serious post-injection reactions with rilpivirine were reported.
Monitor and treat as clinically indicated. 2 ) • Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine. Monitoring of liver chemistries is recommended. Discontinue CABENUVA if hepatotoxicity is suspected. 3 ) • Depressive disorders have been reported with CABENUVA.
Prompt evaluation is recommended for depressive symptoms. 4 ) • Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients up to 12 months or longer. It is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injections of CABENUVA when dosed monthly and no later than 2 months after the final injections when dosed every 2 months.
If virologic failure is suspected, prescribe an alternative regimen as soon as possible. 1 Hypersensitivity Reactions Serious or severe hypersensitivity reactions have been reported with cabotegravir- and rilpivirine-containing regimens.
2 )] . 2 )] . While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries. 3 ), Contraindications ( 4 )] .
Remain vigilant and discontinue CABENUVA if a hypersensitivity reaction is suspected [see Contraindications ( 4 ), Adverse Reactions ( 6 )] . Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, mucosal involvement [oral blisters or lesions], conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing).
1 )] . 3 )] : o Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin o Antimycobacterials: Rifabutin, rifampin, rifapentine o Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment) o Herbal product: St John’s wort ( Hypericum perforatum ) • Previous hypersensitivity reaction to cabotegravir or rilpivirine.
( 4 ) • Coadministration with drugs where significant decreases in cabotegravir and/or rilpivirine plasma concentrations may occur, which may result in loss of virologic response. ( 4 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Know a brand we are missing in United States of America? Suggest a brand →
Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Continuation Injections (CABENUVA 400-mg/600-mg Kit) After the initiation injections, the recommended monthly continuation injection doses of CABENUVA are a single 400-mg (2-mL) intramuscular injection of cabotegravir and a single 600-mg (2-mL) intramuscular injection of rilpivirine at each visit ( Table 1 ).
9 )] . Patients may be given CABENUVA up to 7 days before or after the date the patient is scheduled to receive monthly injections. Table 1. Recommended Dosing Schedule with Optional Oral Lead-In or Direct to Injection for Monthly Injection a The optional oral therapy should be continued until the day the first injection is administered.
b Given on the last day of current antiretroviral therapy or oral lead-in if used. 3 )] . The recommended initiation injection doses of CABENUVA are a single 600-mg (3-mL) intramuscular injection of cabotegravir and a single 900-mg (3-mL) intramuscular injection of rilpivirine 1 month apart for 2 consecutive months ( Table 2 ).
9 )] . Patients may be given CABENUVA up to 7 days before or after the date the patient is scheduled to receive the second initiation injections. Continuation Injections (CABENUVA 600-mg/900-mg Kit) After the 2 initiation doses given consecutively 1 month apart (Months 1 and 2), the recommended continuation injection doses (Month 4 onwards) of CABENUVA are a single 600-mg (3-mL) intramuscular injection of cabotegravir and a single 900-mg (3-mL) intramuscular injection of rilpivirine administered every 2 months ( Table 2 ).
9 )] . Patients may be given CABENUVA up to 7 days before or after the date the patient is scheduled to receive the injections. Table 2. Recommended Dosing Schedule with Optional Oral Lead-In or Direct to Injection for Every-2-Month Injection a The optional oral therapy should be continued until the day the first injection is administered.
b For the every-2-month injection dosing schedule in adults, Initiation Injections are injections administered at Month 1 and Month 2 and Continuation Injections are injections administered every 2 months onwards (starting Month 4).
c Given on the last day of current antiretroviral therapy or oral lead-in if used. 6 Dosing Recommendations When Switching from Monthly to Every-2-Month Intramuscular Injections Patients switching from a monthly continuation injection schedule (a single 400-mg [2-mL] gluteal intramuscular injection of cabotegravir and a single 600-mg [2-mL] intramuscular injection of rilpivirine) to an every-2-month continuation injection dosing schedule should receive a single 600-mg (3-mL) intramuscular injection of cabotegravir and a single 900-mg (3-mL) intramuscular injection of rilpivirine administered 1 month after the last monthly continuation injections and then every 2 months thereafter.
9 )] . 7 Dosing Recommendations When Switching from Every-2-Month to Monthly Intramuscular Injections Patients switching from an every-2-month continuation injection schedule (a single 600-mg [3-mL] intramuscular injection of cabotegravir and a single 900-mg [3-mL] intramuscular injection of rilpivirine) to a monthly continuation dosing schedule should receive a single 400-mg (2-mL) intramuscular injection of cabotegravir and a single 600-mg (2-mL) intramuscular injection of rilpivirine 2 months after the last every-2‑month continuation injection and then monthly thereafter.
9 )] . 2 )] . Patients who miss a scheduled injection visit should be clinically reassessed to ensure resumption of therapy remains appropriate. Refer to Table 3 for dosing recommendations after missed injections. Planned Missed Injections for Patients on the Monthly Dosing Schedule If a patient plans to miss a scheduled injection visit by more than 7 days, VOCABRIA in combination with EDURANT once daily may be used for up to 2 months to replace missed injection visits, or any other fully suppressive oral antiretroviral regimen may be used until injections are resumed.
The recommended oral daily dose is one 30-mg tablet of VOCABRIA (cabotegravir) and one 25-mg tablet of EDURANT (rilpivirine). Take VOCABRIA with EDURANT at approximately the same time each day with a meal. The first dose of oral therapy should be taken 1 month (+/-7 days) after the last injection dose of CABENUVA and continued until the day injection dosing is restarted.
Refer to Table 3 for injection dosing recommendations. For oral therapy with VOCABRIA and EDURANT of durations greater than 2 months, an alternative oral regimen is recommended. 6 )] . If injection dosing will be continued, see Table 3 for dosing recommendations.
Table 3. Injection Dosing Recommendations after Missed Injections for Patients on the Monthly Dosing Schedule a a Refer to oral dosing recommendations if a patient plans to miss a scheduled injection visit. Time since Last Injection Recommendation Less than or equal to 2 months Resume with 400-mg (2-mL) cabotegravir and 600-mg (2-mL) rilpivirine gluteal intramuscular monthly injections as soon as possible.
Greater than 2 months Re-initiate the patient with 600-mg (3-mL) cabotegravir and 900-mg (3‑mL) rilpivirine gluteal intramuscular injections then continue to follow the 400‑mg (2‑mL) cabotegravir and 600-mg (2-mL) rilpivirine gluteal intramuscular monthly injection dosing schedule.
Planned Missed Injections for Patients on the Every-2-Month Dosing Schedule If a patient plans to miss a scheduled injection visit by more than 7 days, VOCABRIA in combination with EDURANT once daily may be used for up to 2 months to replace 1 missed injection visit, or any other fully suppressive oral antiretroviral regimen may be used until injections are resumed.
The recommended oral daily dose is one 30‑mg tablet of VOCABRIA (cabotegravir) and one 25‑mg tablet of EDURANT (rilpivirine). Take VOCABRIA with EDURANT at approximately the same time each day with a meal. The first dose of oral therapy should be taken approximately 2 months after the last injection dose of CABENUVA and continued until the day injection dosing is restarted.
Refer to Table 4 for injection dosing recommendations. For oral therapy with VOCABRIA and EDURANT of durations greater than 2 months, an alternative oral regimen is recommended. 6 )] . If the every-2‑month dosing schedule will be continued, see Table 4 for dosing recommendations.
Table 4. Injection Dosing Recommendations after Missed Injections for Patients on the Every-2-Month Dosing Schedule Missed Injection Visit Time since Last Injection Recommendation Injection 2 (Month 2) Less than or equal to 2 months Resume with 600-mg (3-mL) cabotegravir and 900‑mg (3‑mL) rilpivirine intramuscular injections as soon as possible, then continue to follow the every-2-month injection dosing schedule.
Greater than 2 months Re-initiate the patient with 600-mg (3-mL) cabotegravir and 900-mg (3‑mL) rilpivirine intramuscular injections, followed by the second initiation injection dose 1 month later. Then continue to follow the every-2-month injection dosing schedule thereafter.
Injection 3 or later (Month 4 onwards) Less than or equal to 3 months Resume with 600-mg (3-mL) cabotegravir and 900‑mg (3‑mL) rilpivirine intramuscular injections as soon as possible and continue with the every‑2‑month injection dosing schedule.
Greater than 3 months Re-initiate the patient with 600-mg (3-mL) cabotegravir and 900-mg (3‑mL) rilpivirine intramuscular injections, followed by the second initiation injection dose 1 month later. Then continue with the every-2-month injection dosing schedule thereafter.
9 Administration Instructions for Injections Refer to the Instructions for Use for complete administration instructions with illustrations. Carefully follow these instructions and ensure that the vial adaptor is used correctly when preparing the suspension for injection to avoid leakage.
5 )] . Cabotegravir and rilpivirine are suspensions for gluteal intramuscular injection that do not need further dilution or reconstitution. Administer each injection at separate gluteal injection sites (on opposite sides or at least 2 cm apart) during the same visit.
The ventrogluteal site is recommended. A dorsogluteal approach (upper outer quadrant) is acceptable, if preferred by the healthcare professional. Do not administer by any other route or anatomical site. Consider the body mass index (BMI) of the patient to ensure that the needle length is sufficient to reach the gluteus muscle.
Longer needle lengths (not included in the dosing kit) may be required for patients with higher BMI (example: >30 kg/m 2 ) to ensure that injections are administered intramuscularly as opposed to subcutaneously. The administration order of cabotegravir and rilpivirine injections is not important.
Before preparing the injections, remove CABENUVA from the refrigerator and wait at least 15 minutes to allow the medicines to come to room temperature. The vials may remain in the carton at room temperature for up to 6 hours; do not put back into the refrigerator.
If not used within 6 hours, the medication must be discarded. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The cabotegravir vial has a brown tint to the glass that may limit visual inspection.
Discard CABENUVA if either medicine exhibits particulate matter or discoloration. Shake each vial of CABENUVA vigorously so that the suspensions look uniform before injecting. Small air bubbles are expected and acceptable. Once the suspensions have been drawn into the respective syringes, the injections should be administered as soon as possible, but may remain in the syringes for up to 2 hours.
The filled syringes should not be placed in the refrigerator. If the medicine remains in the syringes for more than 2 hours, the filled syringes and needles must be discarded [see How Supplied/Storage and Handling ( 16 )] .
In ATLAS-2M, 2% of participants in both treatment groups discontinued due to adverse events. Non-injection-site–related adverse events leading to discontinuation and occurring in more than 1 participant in ATLAS-2M were fatigue, pyrexia, headache, presyncope, acute hepatitis B, hyperhidrosis, and abnormal dreams that occurred with an incidence of ≤1% in either treatment group.
Table 5. Adverse Reactions a (Grades 1 to 4) Reported in at Least 2% of Participants with HIV-1 Infection in FLAIR and ATLAS Trials (Week 48 Pooled Analyses) a Adverse reactions defined as “treatment-related” as assessed by the investigator.
b See Injection-Associated Adverse Reactions for additional information. c Pyrexia: includes pyrexia, feeling hot, chills, influenza-like illness, body temperature increased. d Fatigue: includes fatigue, malaise, asthenia. e Musculoskeletal pain: includes musculoskeletal pain, musculoskeletal discomfort, back pain, myalgia, pain in extremity.
f Sleep disorders: includes insomnia, poor quality sleep, somnolence. g Rash: includes erythema, pruritus, pruritus generalized, purpura, rash, rash- erythematous, generalized, macular. Adverse Reactions Cabotegravir plus Rilpivirine Once Monthly (n = 591) Current Antiretroviral Regimen (n = 591) All Grades At Least Grade 2 All Grades At Least Grade 2 Injection site reactions b 83% 37% 0 0 Pyrexia c 8% 2% 0 0 Fatigue d 5% 1% <1% <1% Headache 4% <1% <1% <1% Musculoskeletal pain e 3% 1% <1% 0 Nausea 3% <1% 1% <1% Sleep disorders f 2% <1% <1% 0 Dizziness 2% <1% <1% 0 Rash g 2% <1% 0 0 In ATLAS-2M, the type and frequency of adverse reactions reported in participants receiving CABENUVA once monthly or CABENUVA once every 2 months for 48 weeks were similar.
Differences between treatment arms were reported for the types of injection-associated adverse reactions (see Injection-Associated Adverse Reactions for additional information).
Injection-Associated Adverse Reactions:
Local Injection Site Reactions (ISRs): In the 3 Phase 3 studies, FLAIR, ATLAS, and ATLAS‑2M, the most frequent adverse reactions associated with the intramuscular administration of CABENUVA were ISRs. In the pooled analysis of FLAIR and ATLAS, 83% of participants reported any injection site reaction with the monthly dosing regimen, with 1% of participants who discontinued treatment with CABENUVA because of ISRs.
After 14,682 injections, 3,663 ISRs were reported. The severity of ISRs was generally mild (Grade 1: 75% of participants) or moderate (Grade 2: 36% of participants). Four percent (4%) of participants experienced severe (Grade 3) ISRs, and no participant experienced Grade 4 ISRs.
The median duration of overall ISR events was 3 days. The most commonly reported ISR in FLAIR and ATLAS was pain/discomfort, with 79% reported in the group receiving CABENUVA. In ATLAS-2M, 75% of participants reported any injection site reaction in both the monthly and every‑2‑month dosing regimens, with <1% of participants who discontinued treatment with CABENUVA because of ISRs.
When dosing monthly, after 15,711 injections, 3,152 ISRs were reported. When dosing every 2 months, after 8,470 injections, 2,507 ISRs were reported. The severity of ISRs was generally mild (Grade 1: 70% and 71% of participants) or moderate (Grade 2: 28% and 27% of participants) in monthly and every‑2‑month dosing regimens, respectively.
Four percent (4%) of participants in the monthly group and 3% of participants in the every‑2‑month group experienced severe (Grade 3) ISRs, and no participant experienced Grade 4 ISRs. The median duration of overall ISR events was 3 days for both dosing regimens.
The most commonly reported ISR in ATLAS‑2M was pain/discomfort, with 71% and 73% reported in the monthly and every‑2‑month dosing regimens, respectively. The severity and duration of ISRs, including pain/discomfort, were similar for both dosing regimens and in participants without prior exposure to CABENUVA.
The most commonly reported ISR (Grades 1 to 3) in at least 1% of adult participants in the pooled analyses from FLAIR and ATLAS, and from ATLAS‑2M, are presented in Table 6 . The side‑by‑side tabulation is to simplify presentation; direct comparison across trials should not be made due to differing trials.
Table 6. Injection Site Reactions (Grades 1 to 3) Reported in at Least 1% of Participants in FLAIR and ATLAS (Pooled Analysis) and ATLAS-2M Trials (Week 48 Analysis) Anesthesia, abscess, cellulitis, and hemorrhage at the injection site were each reported in <1% of participants.
Injection Site Reactions FLAIR and ATLAS ATLAS-2M Cabotegravir plus Rilpivirine Once Monthly (n = 591) Cabotegravir plus Rilpivirine Once Every 2 Months (n = 522) Cabotegravir plus Rilpivirine Once Monthly (n = 523) Any injection site reaction 83% 75% 75% Pain/discomfort 79% 73% 71% Nodules 14% 10% 17% Induration 12% 8% 7% Swelling 8% 6% 5% Erythema 4% 2% 3% Pruritus 4% 5% 5% Bruising/discoloration 3% 2% 2% Warmth 2% 1% 2% Hematoma 2% <1% 3% Other Injection-Associated Adverse Reactions: In the ATLAS and FLAIR clinical trials, an increased incidence of pyrexia (8%) was reported by participants receiving cabotegravir plus rilpivirine injections compared with no events among participants receiving current antiretroviral regimen.
In ATLAS and FLAIR, no cases were serious or led to withdrawal and the occurrences of pyrexia may represent a response to administration of CABENUVA via intramuscular injection. In ATLAS-2M, 1 participant in each arm reported pyrexia that led to withdrawal.
In ATLAS and FLAIR, reports of musculoskeletal pain (3%) and less frequently, sciatica, were also more common in participants receiving cabotegravir plus rilpivirine compared with the current antiretroviral regimen and some events had a temporal association with injection.
Vasovagal or pre-syncopal reactions were reported in <1% of participants after injection with rilpivirine or cabotegravir.
Less Common Adverse Reactions:
The following select adverse reactions (regardless of severity) occurred in <2% of participants receiving cabotegravir plus rilpivirine.
Gastrointestinal Disorders:
Abdominal pain (including upper abdominal pain), gastritis, dyspepsia, vomiting, diarrhea, and flatulence.
Hepatobiliary Disorders:
Hepatotoxicity.
Investigations:
Weight increase (see below) .
Psychiatric Disorders:
Anxiety (including anxiety and irritability), depression, abnormal dreams, suicidal ideation, and suicide attempt (these events were observed primarily in participants with a pre-existing history of depression or other psychiatric illness).
Skin and Hypersensitivity Reactions:
Hypersensitivity reactions. 0 kg (pooled analysis). 3 kg, respectively, in the ATLAS trial in participants receiving either cabotegravir plus rilpivirine or a protease inhibitor-, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or integrase strand transfer inhibitor (INSTI)-containing regimen, respectively.
0 kg.
Laboratory Abnormalities:
Selected laboratory abnormalities with a worsening grade from baseline and representing the worst-grade toxicity are presented in Table 7 . The side-by-side tabulation is to simplify presentation; direct comparison across trials should not be made due to differing trials.
Table 7. Selected Laboratory Abnormalities (Grades 3 to 4, Week 48) in FLAIR and ATLAS (Pooled Analyses) and ATLAS-2M Trials ALT = Alanine Aminotransferase, ULN = Upper limit of normal, AST = Aspartate Transaminase. 0 x ULN) 5% 3% 3% 2% Changes in Total Bilirubin: Small, non-progressive increases in total bilirubin (without clinical jaundice) were observed with cabotegravir plus rilpivirine.
3 )]. 44) mcg/dL in the control group. Abnormal responses to ACTH stimulation tests were also higher in the group receiving EDURANT. The clinical significance of the higher abnormal rate of ACTH stimulation tests in the group receiving EDURANT is not known.
Refer to the prescribing information for EDURANT for additional information. 2 )] . In cohort 1, 55 virologically suppressed adolescents with HIV-1 received background antiretroviral therapy in addition to either oral cabotegravir (n = 30) followed by injectable cabotegravir (n = 29), or oral rilpivirine (n = 25) followed by injectable rilpivirine (n = 23).
Adverse reactions were reported in 38% of adolescents receiving either cabotegravir or rilpivirine. Thirty-three percent of participants reported at least 1 ISR. All ISRs were Grade 1 or Grade 2. Two participants had Grade 3 adverse reactions of hypersensitivity (n = 1, oral rilpivirine) and insomnia (n = 1, injectable cabotegravir).
The Grade 3 adverse reaction of drug hypersensitivity led to discontinuation of rilpivirine during oral lead-in. The adverse reactions reported by more than one participant (regardless of severity) were injection site pain (n = 18), headache (n = 2), hypersensitivity (n = 2), insomnia (n = 2), and nausea (n = 2).
In cohort 2, 144 virologically suppressed adolescents with HIV-1 received oral cabotegravir plus oral rilpivirine followed by injectable cabotegravir plus injectable rilpivirine. Adverse reactions were reported in 35% of adolescents receiving cabotegravir plus rilpivirine.
Thirty-four percent of participants reported at least 1 ISR. The majority of these participants experienced Grade 1 or Grade 2 ISRs. Two participants had Grade 3 ISRs consisting of injection site abscess (n = 2) and injection site pain in one of these two participants (symptoms resolved in both participants).
All non-ISR adverse reactions were ≤ Grade 2. Non-injection-site associated adverse reactions reported by more than one participant (regardless of severity) were headache (n = 3), nausea (n = 2), rash (n = 2) and rash pruritic (n = 2).
2 Postmarketing Experience The following adverse reactions have been identified during postmarketing experience in patients receiving cabotegravir- or oral-rilpivirine-containing regimens. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
1 )] . Renal and Genitourinary Disorders Nephrotic syndrome. 1 )] .
Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. 6 )] . 3 ), Contraindications ( 4 )] . 2 Post-Injection Reactions In clinical trials, serious post-injection reactions were reported within minutes after the injection of rilpivirine.
, back and chest). These events were reported in <1% of participants and began to resolve within minutes after the injection, with some patients receiving supportive care. 1 )] . Carefully follow the Instructions for Use when preparing and administering CABENUVA.
9 )] . Observe patients briefly (approximately 10 minutes) after the injection. If a patient experiences a post-injection reaction, monitor and treat as clinically indicated. 1 )] . Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations.
Monitoring of liver chemistries is recommended and treatment with CABENUVA should be discontinued if hepatotoxicity is suspected. 6 )] . 1 )] . Promptly evaluate patients with depressive symptoms to assess whether the symptoms are related to CABENUVA and to determine whether the risks of continued therapy outweigh the benefits.
4 )] . 2 )] . 4 )] . See Table 8 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. 4 )] . 6 Long-Acting Properties and Potential Associated Risks with CABENUVA Residual concentrations of both cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer).
4 )] . To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injections of CABENUVA when dosed monthly and no later than 2 months after the final injections of CABENUVA when dosed every 2 months.
If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible.