Cabenuva

Last updated on RxList: 7/22/2021
Cabenuva Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Cabenuva?

Cabenuva (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) is a 2-drug co-packaged product of a human immunodeficiency virus type-1 (HIV-1) integrase strand transfer inhibitor (INSTI) and an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI), indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.

What Are Side Effects of Cabenuva?

Side effects of Cabenuva include:

  • fever,
  • fatigue,
  • headache,
  • musculoskeletal pain,
  • nausea,
  • sleep disorders,
  • dizziness, and
  • rash

Dosage for Cabenuva

The recommended dosing schedule: Initiate injections of Cabenuva (600 mg of cabotegravir and 900 mg of rilpivirine) on the last day of oral lead-in and continue with injections of Cabenuva (400 mg of cabotegravir and 600 mg of rilpivirine) every month thereafter.

Cabenuva In Children

The safety and efficacy of Cabenuva have not been established in pediatric patients.

What Drugs, Substances, or Supplements Interact with Cabenuva?

Cabenuva may interact with other medicines such as:

  • other antiretroviral medications for the treatment of HIV-1 infection,
  • drugs that induce uridine diphosphate glucuronosyltransferase (UGT)1A1 or cytochrome P450 (CYP)3A4,
  • drugs with a known risk of Torsade de Pointes,
  • anticonvulsants,
  • antimycobacterials,
  • systemic glucocorticoids,
  • St John's wort,
  • macrolide or ketolide antibiotics, and
  • narcotic analgesics

Tell your doctor all medications and supplements you use.

Cabenuva During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Cabenuva; it is unknown how it would affect a fetus. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Cabenuva during pregnancy. It is unknown if the components of Cabenuva are present in breast milk, affect milk production, or have effects on the breastfed infant. Breastfeeding is not recommended due to the potential for HIV-1 transmission.

Additional Information

Our Cabenuva (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension), Co-Packaged for Intramuscular Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Cabenuva Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; fever, tiredness, body aches, not feeling well; sores or blisters in your mouth; red or puffy eyes; difficult breathing; swelling of your face, lips, tongue, or throat.

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

Your cabotegravir and rilpivirine injections may be permanently discontinued if you have an allergic reaction.

Some side effects may occur within a few minutes after an injection. Tell your caregiver if you feel anxious, warm, light-headed, sweaty, or have stomach pain, or numbness in your mouth.

Call your doctor at once if you have:

  • unusual changes in mood or behavior;
  • suicidal thoughts or actions; or
  • liver problems--loss of appetite, nausea, vomiting, stomach pain (upper right side), itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

  • pain, redness, swelling, itching, bruising, warmth, or a hard lump where an injection was given;
  • fever;
  • nausea;
  • pain in your bones, joints or muscles;
  • feeling tired, sleep problems;
  • headache, dizziness; or
  • rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Cabenuva (Cabotegravir; Rilpivirine Extended-release Injectable Suspension)

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Cabenuva Professional Information

SIDE EFFECTS

The following adverse reactions are described below and in other sections of the labeling:

  • Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]
  • Post-injection reactions [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Depressive disorders [see WARNINGS AND PRECAUTIONS]

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.

The safety assessment of CABENUVA is based on the analysis of pooled 48-week data from 1,182 virologically suppressed subjects with HIV-1 infection in 2 international, multicenter, open-label pivotal trials, FLAIR and ATLAS [see Clinical Studies]. 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.

Adverse reactions were reported following exposure to CABENUVA extended-release injectable suspensions (median time exposure: 54 weeks) and data from VOCABRIA (cabotegravir) tablets and EDURANT (rilpivirine) tablets administered in combination as oral lead-in therapy (median time exposure: 5.3 weeks). 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 for other adverse reactions associated with oral rilpivirine.

The most common adverse reactions regardless of severity reported in greater than or equal to 2% of adult subjects in the pooled analyses from FLAIR and ATLAS are presented in Table 3. Selected laboratory abnormalities are included in Table 4.

Overall, 4% of subjects in the group receiving CABENUVA and 2% of subjects in the control group discontinued due to adverse events. Non-injection-site-related adverse events leading to discontinuation and occurring in more than 1 subject were headache, diarrhea, hepatitis A, and acute hepatitis B (all with an incidence less than 1%).

Table 3. Adverse Reactionsa (Grades 1 to 4) Reported in at Least 2% of Subjects with HIV-1 Infection in FLAIR and ATLAS Trials (Week 48 Pooled Analyses)

Adverse ReactionsCabotegravir plus Rilpivirine
(n = 591)
Current Antiretroviral Regimen
(n = 591)
All GradesAt Least Grade 2All GradesAt Least Grade 2
Injection site reactionsb83%37%00
Pyrexiac8%2%00
Fatigued5%1%<1%<1%
Headache4%<1%<1%<1%
Musculoskeletal paine3%1%<1%0
Nausea3%<1%1%<1%
Sleep disordersf2%<1%<1%0
Dizziness2%<1%<1%0
Rash g2%<1%00
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.

Injection-Associated Adverse Reactions

Local Injection Site Reactions (ISRs)

The most frequent adverse reactions associated with the intramuscular administration of CABENUVA were ISRs. After 14,682 injections, 3,663 ISRs were reported. One percent (1%) of subjects discontinued treatment with CABENUVA because of ISRs. Most ISRs were mild (Grade 1, 75%) or moderate (Grade 2, 36%). Four percent (4%) of subjects experienced severe (Grade 3) ISRs, and no subjects experienced Grade 4 ISRs. The most commonly reported ISR was localized pain/discomfort (79%) regardless of severity or relatedness. Other manifestations of ISRs reported in more than 1% of subjects over the duration of the analysis period included nodules (14%), induration (12%), swelling (8%), erythema (4%), pruritus (4%), bruising (3%), warmth (2%), and hematoma (2%). Abscess and cellulitis at the injection site were each reported in less than 1% of subjects. The median duration of ISR events was 3 days.

Other Injection-Associated Adverse Reactions

In the ATLAS and FLAIR clinical trials, an increased incidence of pyrexia (8%) was reported by subjects receiving cabotegravir plus rilpivirine injections compared with no events among subjects receiving current antiretroviral regimen. No cases were serious or led to withdrawal and the occurrences of pyrexia may represent a response to administration of CABENUVA via intramuscular injection.

Reports of musculoskeletal pain (3%) and less frequently, sciatica, were also more common in subjects 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 less than 1% of subjects after injection with rilpivirine or cabotegravir.

Less Common Adverse Reactions

The following select adverse reactions (regardless of severity) occurred in less than 2% of subjects 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.

Skin and Hypersensitivity Reactions: Hypersensitivity reactions.

Weight Increase

At Week 48, subjects in FLAIR and ATLAS who received cabotegravir plus rilpivirine had a median weight gain of 1.5 kg; those in the current antiretroviral regimen group had a median weight gain of 1.0 kg (pooled analysis). In the FLAIR trial, the median weight gain in subjects receiving cabotegravir plus rilpivirine or a dolutegravir-containing regimen was 1.3 kg and 1.5 kg, respectively, compared with 1.8 kg and 0.3 kg in the ATLAS trial in subjects receiving either cabotegravir plus rilpivirine or a protease inhibitor-, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or integrase strand transfer inhibitor (INSTI)-containing regimen, respectively.

Laboratory Abnormalities

Selected laboratory abnormalities with a worsening grade from baseline and representing the worst-grade toxicity are presented in Table 4.

Table 4. Selected Laboratory Abnormalities (Grades 3 to 4; Week 48 Pooled Analyses) in FLAIR and ATLAS Trials

Laboratory ParameterCabotegravir plus Rilpivirine
(n = 591)
Current Antiretroviral Regimen
(n = 591)
ALT (≥5.0 x ULN)2%<1%
AST (≥5.0 x ULN)2%<1%
Total bilirubin (≥2.6 x ULN)<1%<1%
Creatine phosphokinase (≥10.0 x ULN)8%4%
Lipase (≥3.0 x ULN)5%3%
ULN = Upper limit of normal.

Changes in Total Bilirubin

Small, non-progressive increases in total bilirubin (without clinical jaundice) were observed with cabotegravir plus rilpivirine. These changes are not considered clinically relevant as they likely reflect competition between cabotegravir and unconjugated bilirubin for a common clearance pathway (UGT1A1) [see CLINICAL PHARMACOLOGY].

Serum Cortisol

In pooled Phase 3 trials of EDURANT (rilpivirine), the overall mean change from baseline in basal cortisol was -0.69 (-1.12, 0.27) micrograms/dL in the group receiving EDURANT compared with -0.02 (-0.48, 0.44) micrograms/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.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing experience in patients receiving an oral rilpivirine-containing regimen. 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.

Renal And Genitourinary Disorders

Nephrotic syndrome.

Skin And Subcutaneous Tissue Disorders

Severe skin and hypersensitivity reactions, including DRESS [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Cabenuva (Cabotegravir; Rilpivirine Extended-release Injectable Suspension)

© Cabenuva Patient Information is supplied by Cerner Multum, Inc. and Cabenuva Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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