For virologically suppressed adults with HIV-1. See Full Indication.

Risks & Side Effects of CABENUVA

The information below gives an overview of the potential risks and side effects of CABENUVA as observed in ATLAS and FLAIR clinical trials, including warnings and precautions, drug-related adverse events, discontinuation rates due to adverse events, injection site reactions, and patient perception of injections.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions:

Hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported during postmarketing experience with rilpivirine-containing regimens. 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

Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with CABENUVA 

Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. Prescribe the oral lead-in prior to administration of CABENUVA to help identify patients who may be at risk of a hypersensitivity reaction

Post-Injection Reactions:

Serious post-injection reactions (reported in less than 1% of subjects) were reported within minutes after the injection of rilpivirine, including dyspnea, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure. These events may have been associated with inadvertent (partial) intravenous administration and began to resolve within a few minutes after the injection 

Carefully follow the Instructions for Use when preparing and administering CABENUVA to avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated

Hepatotoxicity:

Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors

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

Depressive Disorders:

Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation or attempt) have been reported with CABENUVA or the individual products

Promptly evaluate patients with depressive symptoms

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:

The concomitant use of CABENUVA and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions)

Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval.  CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes 

Long-Acting Properties and Potential Associated Risks with CABENUVA:

Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly injection dosing schedule because non-adherence to monthly injections or missed doses could lead to loss of virologic response and development of resistance

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 injection doses of CABENUVA. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible

Majority of adverse reactions were Grades 1-2

POOLED ANALYSIS: ADVERSE REACTIONS* (ALL GRADES) REPORTED IN ≥2% OF PATIENTS THROUGH WEEK 481,2

Pooled analysis of incidence of injection site reactions from  Week 4 to Week 48
Adverse Reactions Table

*Adverse reactions defined as “treatment-related” as assessed by the investigator.1 Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=potentially life-threatening; Grade 5=death.3 Pyrexia: includes pyrexia, feeling hot, chills, influenza-like illness, body temperature increased.1 §Fatigue: includes fatigue, malaise, asthenia.1 Musculoskeletal pain: includes musculoskeletal pain, musculoskeletal discomfort, back pain, myalgia, pain in extremity.1 Sleep disorders: includes insomnia, poor quality sleep, somnolence.1 #Rash: includes erythema, pruritis, pruritis generalized, purpura, rash-erythematous, generalized, macular.1

AE=adverse event.

  • 4% of patients experienced Grade 3 ISRs, and no patients experienced Grades 4-5 ISRs1
  • Non-injection site-related adverse reactions leading to discontinuation and occurring in >1 patient were headache, diarrhea, hepatitis A, and acute hepatitis B (all with an incidence <1%)1

Of patients discontinued CABENUVA due to adverse events1

Of patients discontinued CABENUVA due to injection site reactions1

FLAIR 96 Weeks: Safety Data

Adverse reactions were similar at Week 48 and Week 964

SAFETY OVERVIEW 4

Pooled analysis of incidence of injection site reactions from  Week 4 to Week 48
adverse

**Or DTG plus 2 NRTIs if HLA-B*5701-positive.1 ††Includes 1 subject at Week-48 data analysis who is not present at Week-96 data analysis.4  ‡‡2 pyrexia, 2 fatigue, 2 dizziness, 1 headache/nausea, 1 presyncope, 1 depressed mood, 1 pyrexia/chills, 1 chronic sinusitis/chronic tonsillitis, 1 back pain nasopharyngitis, 1 musculoskeletal pain, 1 anxiety, 1 influenza-like illness, 1 asthenia/depressed mood.4 §§1 diarrhea/abdominal pain/nasopharyngitis/eye pain, 1 insomnia, 1 abnormal dreams, 1 poor quality sleep, 1 nausea, 1 hypercholesterolemia/vitamin D decreased.4 ‖‖Grade 3=severe; Grade 4=potentially life-threatening.3

AE=adverse event; ISR=injection site reaction; SAE=serious adverse reaction.

**Or DTG plus 2 NRTIs if HLA-B*5701-positive.1 ††Includes 1 subject at Week-48 data analysis who is not present at Week-96 data analysis.4 ‡‡Grade 3=severe; Grade 4=potentially life-threatening.3 §§2 pyrexia, 2 fatigue, 2 dizziness, 1 headache/nausea, 1 presyncope, 1 depressed mood, 1 pyrexia/chills, 1 chronic sinusitis/chronic tonsillitis, 1 back pain nasopharyngitis, 1 musculoskeletal pain, 1 anxiety, 1 influenza-like illness, 1 asthenia/depressed mood.4 ‖‖1 diarrhea/abdominal pain/nasopharyngitis/eye pain, 1 insomnia, 1 abnormal dreams, 1 poor quality sleep, 1 nausea, 1 hypercholesterolemia/vitamin D decreased.4

AE=adverse event; ISR=injection site reaction; SAE=serious adverse reaction.

No new safety signals identified through Week 96

INJECTION SITE REACTIONS

88% of patients experienced at least one ISR through Week 964

  • The majority (3082/3100, 99%) of ISRs were Grades 1-2 and most (89%) resolved within ≤7 days (median duration of 3 days [interquartile range, 2 to 4])4
  • Between Week 48 and Week 96, 1 patient withdrew due to an ISR4
  • An additional 3 patients receiving CABENUVA withdrew from the study through Week 96; the primary reason for discontinuation given was "withdrew consent due to intolerability of injections"4

ADVERSE REACTIONS* (ALL GRADES, EXCLUDING LOCAL ISRs) REPORTED IN ≥3% OF PATIENTS IN EITHER ARM THROUGH WEEK 964

adverse reactions
adverse reactions

*Adverse reactions defined as “treatment-related” as assessed by the investigator.1 **Or DTG plus 2 NRTIs if HLA-B*5701-positive.1 ¶¶Between Weeks 48 and 96, discontinuations occurred due to: hepatitis A (3); acute hepatitis B (2); depression (2); and 1 each acute hepatitis C, hepatitis C, secondary syphilis, discomfort, diarrhea, vomiting, aminotransferase increased, and adenocarcinoma of colon; a participant could have more than one reason for withdrawal.

Patient-reported local injection site reactions decreased over time

Overall, 83% of patients experienced at least one ISR through Week 48.1

Self-reported ISRs could potentially underestimate the true rate of ISRs over time. ISRs may still be present but not reported during the course of the study.

POOLED ANALYSIS (SECONDARY ENDPOINT): INCIDENCE OF ISRs REPORTED BY VISIT (ALL GRADES)2,5

Pooled_Analysis_Incidence_of_ISRS_Reported_by_Patients_Over_Time
Pooled analysis of incidence of injection site reactions from  Week 4 to Week 48

My primary side effect is soreness on my right side for about two to three days. Over time, it has gotten less tender and sore.

– Jayson, clinical study participant. Compensated by ViiV Healthcare.

Patient experience is not indicative of all patient experiences or trial results.

The median duration of ISR events was 3 days (range: 1-341 days).1,2

  • 88% of events lasted between 1-7 days
  • 6% lasted 8-14 days
  • 5% lasted >14 days5

Most common local injection site reaction was pain

83

Of patients experienced at least one ISR through Week 481

POOLED ANALYSIS: PATIENTS (>1%) REPORTING ISRs THROUGH WEEK 481,2

##591 patients were used to calculate the 77% reporting localized pain, as opposed to 581 patients used to calculate the 79% listed in the Prescribing Information for CABENUVA.1,2

  • Abscess and cellulitis at the injection site were each reported in <1% of patients1
25

3663 (25%) ISRs were reported after 14,682 injections1

POOLED ANALYSIS: ISR EVENTS BY INJECTIONS GIVEN THROUGH WEEK 482,5

##591 patients were used to calculate the 77% reporting localized pain, as opposed to 581 patients used to calculate the 79% listed in the Prescribing Information for CABENUVA.1,2

  • Abscess and cellulitis at the injection site were each reported in <1% of patients1

Other injection site reactions

Other injection-associated adverse reactions included an increased incidence of pyrexia (8%)***; reports of musculoskeletal pain (3%) and less frequently, sciatica; and vasovagal or pre-syncopal reactions (<1%).1

***No cases were serious or led to withdrawal, and the occurrences of pyrexia may represent a response to administration of CABENUVA via intramuscular injection.

FLAIR 96 Weeks: ISRs

1% of patients discontinued due to ISRs through Week 96

Between Week 48 and Week 96, 1 additional patient discontinued CABENUVA due to ISRs4†††

In FLAIR, through Week 96:

  • The majority (3082/3100, 99%) of ISRs were Grade 1-24
  • Most (89%) ISR events resolved within ≤7 days (median duration of 3 days [interquartile range, 2 to 4])4
  • Patient-reported local ISRs decreased from baseline to Week 962,4
    • Self-reported ISRs could potentially underestimate the true rate of ISRs over time. ISRs may still be present but not reported during the course of the study
83

of patients experienced at least one ISR through Week 962

PATIENTS (≥5%) REPORTING ISRs THROUGH WEEK 962

left
25

3100 (25%) ISRs were reported after 12,552 injections2

ISR EVENTS (MOST FREQUENT) BY INJECTIONS GIVEN THROUGH WEEK 962,4

right

††† An additional 3 patients receiving CABENUVA withdrew from the study between Week 48 and Week 96; the primary reason for discontinuation given was “withdrew consent due to intolerability of injections.”4

87% of patients rated ISRs/pain as “totally acceptable” or “very acceptable” at Week 48

In ATLAS and FLAIR, patient perception of injections was evaluated as a secondary endpoint. Patients receiving CABENUVA were asked to respond to 21 questions included in the PIN questionnaire (scored on a scale of 1-5).2

The PIN questionnaire included 2 questions in the acceptance domain2:

  1. How acceptable was/were your local reaction(s)? 
  2. How acceptable was your pain? 

The score was calculated as the average of the 2 items within the domain. Higher scores represent a worse perception of the injection. Weeks 41 and 48 were compared to Week 5 based on the Wilcoxon signed-rank test. Average scores in Week 41 and 48 were each statistically significantly different from the average score in Week 5 (P<0.001 for each comparison).2

Clinical significance is unknown. These data collected directly from patients should not be used to infer clinical significance and should not be interpreted as a reflection of the efficacy or safety of a regimen. 

POOLED ANALYSIS: ACCEPTANCE DOMAIN2

‡‡‡Percentages may total more than 100% due to rounding.

PIN=perception of injection.

References:

  1. CABENUVA [packaged insert]. Research Triangle Park, NC: ViiV Healthcare; 2021.
  2. Data on file, ViiV Healthcare.
  3. National Institute of Allergy and Infectious Diseases. DAIDS RSC Regulatory Support Center. DAIDS Adverse Event Grading Tables. Corrected version 1.2, July 2017. Accessed January 11, 2021. https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.
  4. Orkin C, Oka S, Philibert P, et al. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV. 2021;8:e185–96.
  5. Rizzardini G, Overton ET, Orkin C, et al. Long-acting injectable cabotegravir + rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials. J Acquir Immune Defic Syndr. 2020;85(4):498-506.

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