Cabotegravir and rilpivirine (co-packaged)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]
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Overview
Cabotegravir and rilpivirine (co-packaged) is an HIV-1 integrase strand transfer inhibitor (INSTI), and rilpivirine, an HIV-1 non‑nucleoside reverse transcriptase inhibitor that is FDA approved 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 antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.. Common adverse reactions include injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- 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 antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.
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.
- CABENUVA must be administered by a healthcare provider by gluteal intramuscular injection.
- CABENUVA may be initiated with oral cabotegravir and oral rilpivirine prior to the intramuscular injections or the patient may proceed directly to injection of CABENUVA without an oral lead-in.
- CABENUVA can be injected monthly or every 2 months.
- Healthcare providers should discuss these 2 dosing options with the patient prior to starting CABENUVA and decide which injection dosing frequency would be the most appropriate option for the patient.
- Kit of single-dose vials of 400 mg/2 mL (200 mg/mL) of cabotegravir extended-release injectable suspension and 600 mg/2 mL (300 mg/mL) of rilpivirine extended-release injectable suspension.
- Kit of single-dose vials of 600 mg/3 mL (200 mg/mL) of cabotegravir extended-release injectable suspension and 900 mg/3 mL (300 mg/mL) of rilpivirine extended-release injectable suspension.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cabotegravir and rilpivirine (co-packaged) in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cabotegravir and rilpivirine (co-packaged) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
The safety and effectiveness of CABENUVA have been established in adolescents aged 12 to younger than 18 years and weighing at least 35 kg.
- Kit of single-dose vials of 400 mg/2 mL (200 mg/mL) of cabotegravir extended-release injectable suspension and 600 mg/2 mL (300 mg/mL) of rilpivirine extended-release injectable suspension.
- Kit of single-dose vials of 600 mg/3 mL (200 mg/mL) of cabotegravir extended-release injectable suspension and 900 mg/3 mL (300 mg/mL) of rilpivirine extended-release injectable suspension.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cabotegravir and rilpivirine (co-packaged) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cabotegravir and rilpivirine (co-packaged) in pediatric patients.
Contraindications
CABENUVA is contraindicated in patients:
- with previous hypersensitivity reaction to cabotegravir or rilpivirine
- receiving the following coadministered drugs for which significant decreases in cabotegravir and/or rilpivirine plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase (UGT)1A1 and/or cytochrome P450 (CYP)3A enzyme induction, which may result in loss of virologic response:
- Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin
- Antimycobacterials: Rifabutin, rifampin, rifapentine
- Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment)
- Herbal product: St John’s wort (Hypericum perforatum)
Warnings
Hypersensitivity Reactions
- 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).
- 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. Administration of cabotegravir and rilpivirine oral lead-in dosing was used in clinical studies to help identify patients who may be at risk of a hypersensitivity reaction.
- Remain vigilant and discontinue CABENUVA if a hypersensitivity reaction is suspected
- 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). Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. For information regarding the long-acting properties of CABENUVA.
- Administer oral lead-in dosing prior to administration of CABENUVA to help identify patients who may be at risk of a hypersensitivity reaction .
Post-Injection Reactions
- In clinical trials, serious post-injection reactions were reported within minutes after the injection of rilpivirine. These events included symptoms such as dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., 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. These events may have been associated with accidental intravenous administration during the intramuscular injection procedure
- Carefully follow the Instructions for Use when preparing and administering CABENUVA. The suspensions should be injected slowly via intramuscular injection, and care should be taken to avoid accidental intravenous administration.
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- Observe patients briefly (approximately 10 minutes) after the injection. If a patient experiences a post-injection reaction, 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. For information regarding the long-acting properties of CABENUVA.
Depressive Disorders
- Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation, suicide attempt) have been reported with CABENUVA or the individual drug products.
- 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.
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, some of which may lead to adverse events, loss of virologic response of CABENUVA, and possible development of viral resistance.
- Rilpivirine 75-mg and 300-mg once-daily oral doses (3 and 12 times, respectively, the recommended oral dosage) in healthy adults prolonged the QTc interval with mean steady-state Cmax values 4.4- and 11.6-fold, respectively, higher than Cmax values associated with the recommended 600-mg monthly dose of rilpivirine extended-release injectable suspension and 4.1- and 10.7-fold, respectively, higher than Cmax values associated with the recommended 900-mg every-2-month dose of rilpivirine extended release injectable suspension.
- CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes.
See TABLE 8 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during therapy with, and after discontinuation of, CABENUVA; review concomitant medications during therapy with CABENUVA.
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). It is important to carefully select patients who agree to the required monthly or every-2-month injection dosing schedule because non-adherence to monthly or every-2-month 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 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.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Cabotegravir and rilpivirine (co-packaged) in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cabotegravir and rilpivirine (co-packaged) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Cabotegravir and rilpivirine (co-packaged) during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Cabotegravir and rilpivirine (co-packaged) in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Cabotegravir and rilpivirine (co-packaged) in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Cabotegravir and rilpivirine (co-packaged) in geriatric settings.
Gender
There is no FDA guidance on the use of Cabotegravir and rilpivirine (co-packaged) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Cabotegravir and rilpivirine (co-packaged) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Cabotegravir and rilpivirine (co-packaged) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Cabotegravir and rilpivirine (co-packaged) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Cabotegravir and rilpivirine (co-packaged) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Cabotegravir and rilpivirine (co-packaged) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Administration in the drug label.
Monitoring
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Cabotegravir and rilpivirine (co-packaged) and IV administrations.
Overdosage
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Mechanism of Action in the drug label.
Structure
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Structure in the drug label.
Pharmacodynamics
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Clinical Studies in the drug label.
How Supplied
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) How Supplied in the drug label.
Storage
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Cabotegravir and rilpivirine (co-packaged) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
CABENUVA
Look-Alike Drug Names
There is limited information regarding Cabotegravir and rilpivirine (co-packaged) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.