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Cabotegravir and rilpivirine: Drug information

Cabotegravir and rilpivirine: Drug information
(For additional information see "Cabotegravir and rilpivirine: Patient drug information" and see "Cabotegravir and rilpivirine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Cabenuva
Brand Names: Canada
  • Cabenuva
Pharmacologic Category
  • Antiretroviral, Integrase Inhibitor (Anti-HIV);
  • Antiretroviral, Reverse Transcriptase Inhibitor, Non-nucleoside (Anti-HIV)
Dosing: Adult
HIV-1 infection, treatment

HIV-1 infection, treatment: Note: May initiate with cabotegravir and rilpivirine oral lead-in prior to initiation of cabotegravir and rilpivirine injections to assess tolerability, or may proceed directly to injections without oral lead-in. Initiate injections on the final day of current antiretroviral therapy or oral lead-in, if used.

Monthly injection dosing:

Initiation injections: IM: Cabotegravir 600 mg and rilpivirine 900 mg once; begin continuation injections in 1 month.

Continuation injections: IM: Beginning 1 month after initiation injections, cabotegravir 400 mg and rilpivirine 600 mg once monthly; may be given up to 7 days before or after the date of the scheduled monthly injections.

Every-2-month injection dosing:

Initiation injections: IM: Cabotegravir 600 mg and rilpivirine 900 mg once monthly for 2 doses; begin continuation injections 2 months after the second dose (month 4). Note: Second initiation injections may be administered up to 7 days before or after the date the individual is scheduled to receive the injections.

Continuation injections: IM: Beginning 2 months after the last initiation injections, cabotegravir 600 mg and rilpivirine 900 mg once every 2 months; may be given up to 7 days before or after the date of the scheduled every-2-month injections.

Switching injection schedules:

Switching from monthly to every-2-month injection dosing: IM: Administer cabotegravir 600 mg and rilpivirine 900 mg 1 month after the last monthly continuation injections, and then cabotegravir 600 mg and rilpivirine 900 mg every 2 months thereafter.

Switching from every-2-month to monthly injection dosing: IM: Administer cabotegravir 400 mg and rilpivirine 600 mg 2 months after the last every-2-month continuation injections, and then cabotegravir 400 mg and rilpivirine 600 mg monthly thereafter.

Missed doses:

Planned missed injections:

Monthly injection dosing: If a patient plans to miss a scheduled monthly injection visit by >7 days, administer oral therapy for up to 2 months to replace missed injection visits. The first dose of oral therapy should be administered 1 month (+/- 7 days) after the last injections and continued until the day the injection dosing is restarted.

Every-2-month injection dosing: If a patient plans to miss a scheduled monthly injection visit by >7 days, administer oral therapy to replace 1 missed injection visit. The first dose of oral therapy should be administered ~2 months after the last injections and continued until the day the injection dosing is restarted.

Unplanned missed injections:

If monthly injections are missed or delayed by >7 days and oral therapy has not been administered in the interim, clinically reassess patient to determine appropriateness of resumption of injection dosing. If injection dosing will be continued, administer as follows:

Monthly injection dosing:

≤2 months since last injection: Continue with cabotegravir 400 mg and rilpivirine 600 mg IM monthly injections.

>2 months since last injection: Reinitiate with cabotegravir 600 mg and rilpivirine 900 mg IM injections, then continue to follow the cabotegravir 400 mg and rilpivirine 600 mg IM monthly injection dosing schedule.

Every-2-month injection dosing:

Second injections missed:

≤2 months since first injection: Administer cabotegravir 600 mg and rilpivirine 900 mg IM injections as soon as possible, then continue to follow the every-2-month injection dosing schedule.

>2 months since first injection: Reinitiate with cabotegravir 600 mg and rilpivirine 900 mg IM once, followed by cabotegravir 600 mg and rilpivirine 900 mg IM 1 month later. Then, continue to follow the every-2-month injection dosing schedule.

Third or subsequent injections missed:

≤3 months since last injection: Administer cabotegravir 600 mg and rilpivirine 900 mg IM injections as soon as possible, then continue with every-2-month injection dosing schedule.

>3 months since last injection: Reinitiate with cabotegravir 600 mg and rilpivirine 900 mg IM once, followed by cabotegravir 600 mg and rilpivirine 900 mg IM 1 month later. Then, continue to follow the every-2-month injection dosing schedule.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl 15 to <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Patients on dialysis: There are no dosage adjustments provided in the manufacturer's labeling; because of high protein binding, dialysis is not expected to alter cabotegravir exposure.

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Pediatric

(For additional information see "Cabotegravir and rilpivirine: Pediatric drug information")

HIV-1 infection, treatment

HIV-1 infection, treatment: Note: Prior to initiating injection therapy, oral lead-in therapy to assess tolerability is an option, but is not required. In Cabenuva product, the cabotegravir and rilpivirine are provided in separate vials and should be administered at the same visit.

Children ≥12 years and Adolescents, weighing ≥35 kg: Extended-release injections:

Monthly injection dosing:

Initiation injections: IM: Cabotegravir 600 mg and rilpivirine 900 mg once; initiate injections on the final day of oral lead-in therapy (if used) or of previous antiretroviral regimen. Continuation injections should begin 1 month after initial dose.

Continuation injections: IM: Cabotegravir 400 mg and rilpivirine 600 mg once monthly starting 1 month after initiation injections; may be given up to 7 days before or after the date of the scheduled monthly injections.

Every-2-month injection dosing:

Initiation injections: IM: Cabotegravir 600 mg and rilpivirine 900 mg once monthly for 2 doses; initiate injections on the final day of oral lead-in therapy (if used) or of previous antiretroviral regimen. The second dose of initiation injections may be administered up to 7 days before or after the date the individual is scheduled to receive the injections. Note: Continuation injections should begin 2 months after the second dose (month 4).

Continuation injections: IM: Cabotegravir 600 mg and rilpivirine 900 mg once every 2 months, starting 2 months after the second set of initiation injections (month 4). Continuation doses may be given up to 7 days before or after the date of the scheduled every-2-month injections.

Switching injection schedules:

Switching from monthly to every-2-month injection dosing: IM: Administer cabotegravir 600 mg and rilpivirine 900 mg 1 month after the last monthly continuation injections, and then begin cabotegravir 600 mg and rilpivirine 900 mg once every 2 months thereafter.

Switching from every-2-month to monthly injection dosing: IM: Administer cabotegravir 400 mg and rilpivirine 600 mg 2 months after the last every-2-month continuation injections, and then cabotegravir 400 mg and rilpivirine 600 mg once monthly thereafter.

Dosing adjustment for therapy interruption :

Planned: For a planned missed injection, cabotegravir and rilpivirine oral therapy should be used (see oral dosing in Cabotegravir monograph and Rilpivirine monograph).

Unplanned (missed or delayed by >7 days) without any oral bridging therapy: Reassess individual to determine if injection therapy is appropriate given importance of adherence. If decision is to continue, recommended action depends on dosing frequency, duration of therapy (ie, injection number), and time since the previous injection; see table.

Dosing After Unplanned Missed Injection

Usual Dosing Frequency

Dose Missed

Time Since Previous Dose

Recommendation

Monthly

Any

≤2 months

Continue with cabotegravir 400 mg and rilpivirine 600 mg IM monthly injections (administer as soon as possible).

>2 months

Reinitiate with cabotegravir 600 mg and rilpivirine 900 mg IM injections once, then continue to follow a cabotegravir 400 mg and rilpivirine 600 mg IM monthly injection dosing schedule.

Every-2-months

Second dose

≤2 months

Continue with cabotegravir 600 mg and rilpivirine 900 mg IM injections every 2 months (administer as soon as possible).

>2 months

Reinitiate with cabotegravir 600 mg and rilpivirine 900 mg IM once, followed by cabotegravir 600 mg and rilpivirine 900 mg IM 1 month later. Then, continue to follow the every-2-month injection dosing schedule.

Third dose and after

≤3 months

Continue with cabotegravir 600 mg and rilpivirine 900 mg IM injections every 2 months (administer as soon as possible).

>3 months

Reinitiate with cabotegravir 600 mg and rilpivirine 900 mg IM once, followed by cabotegravir 600 mg and rilpivirine 900 mg IM 1 month later. Then, continue to follow the every-2-month injection dosing schedule.

Dosing: Kidney Impairment: Pediatric

Children ≥12 years and Adolescents, weighing ≥35 kg:

Mild to moderate kidney impairment: No dosage adjustment necessary.

Severe kidney impairment: There are no dosage adjustments provided in the manufacturer's labeling; increase monitoring for adverse effects.

Dialysis: There are no dosage adjustments provided in the manufacturer's labeling; because of high protein binding, dialysis is not expected to alter cabotegravir or rilpivirine exposure.

Dosing: Hepatic Impairment: Pediatric

Children ≥12 years and Adolescents, weighing ≥35 kg:

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Extended Release, Intramuscular [preservative free]:

Cabenuva: Cabotegravir 400 mg and rilpivirine 600 mg per 2 mL (4 mL); Cabotegravir 600 mg and rilpivirine 900 mg per 3 mL (6 mL) [contains polyethylene glycol (macrogol)]

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Extended Release, Intramuscular:

Generic: Cabotegravir 400 mg and rilpivirine 600 mg per 2 mL (2 mL); Cabotegravir 600 mg and rilpivirine 900 mg per 3 mL (3 mL)

Administration: Adult

IM: Note: Injections must be administered by a health care professional.

For gluteal IM administration only; do not administer by any other route. A complete dose requires 2 injections: 1 cabotegravir injection and 1 rilpivirine injection. Administer each injection at a separate gluteal injection site (on opposite sides or ≥2 cm apart) during the same visit; the ventrogluteal site is recommended. A dorsogluteal approach is acceptable if preferred by health care professional. Consider the BMI of the patient to ensure needle length is sufficient to reach the gluteus muscle; longer needles (not supplied) may be required in patients with BMI >30 kg/m2 to ensure injections are administered IM. Prior to administration, remove from refrigeration and wait ≥15 minutes for injection to come to room temperature; vials may remain in carton at room temperature for ≤6 hours. Shake each vial vigorously to ensure uniform suspension prior to drawing into syringes. Once drawn into syringes, administer as soon as possible; suspensions may remain in syringes for ≤2 hours.

Administration: Pediatric

Parenteral: IM: Note: Injections must be administered by a health care professional.

For gluteal IM administration only; do not administer by any other route. A complete dose requires 2 injections: 1 cabotegravir injection and 1 rilpivirine injection. Prior to administration, remove from refrigeration and wait ≥15 minutes for injection to come to room temperature; vials may remain in carton at room temperature for ≤6 hours. Shake each vial vigorously to ensure uniform suspension prior to drawing into syringes. Once drawn into syringes, administer as soon as possible; suspensions may remain in syringes for ≤2 hours. Administer each injection at a separate gluteal injection site (on opposite sides or ≥2 cm apart) during the same visit. The ventrogluteal site is recommended, although a dorsogluteal approach is acceptable if preferred by health care professional. Consider the BMI of the patient to ensure needle length is sufficient to reach the gluteus muscle; for patients with a higher BMI (eg, >30 kg/m2), longer needles (not supplied) may be required to ensure injections are administered IM.

Missed doses: See "Dosing: Pediatric."

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection in adults and adolescents ≥12 years of age weighing ≥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.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Also see individual agents.

>10%: Local: Discomfort at injection site (≤79%), induration at injection site (7% to 12%), injection site nodule (10% to 17%), injection site reaction (75% to 83%), pain at injection site (≤79%)

1% to 10%:

Dermatologic: Skin rash (2%)

Endocrine & metabolic: Weight gain (<2%)

Gastrointestinal: Abdominal pain (<2%; including upper abdominal pain), diarrhea (<2%), dyspepsia (<2%), flatulence (<2%), gastritis (<2%), increased serum lipase (2% to 5%), nausea (3%), vomiting (<2%)

Hepatic: Hepatotoxicity (<2%), increased serum alanine aminotransferase (≤2%), increased serum aspartate aminotransferase (≤2%)

Hypersensitivity: Hypersensitivity reaction (<2%; including severe hypersensitivity reaction)

Local: Bruising at injection site (≤3%), erythema at injection site (2% to 4%), hematoma at injection site (≤3%), injection site pruritus (4% to 5%), skin discoloration at injection site (≤3%), swelling at injection site (5% to 8%), warm sensation at injection site (1% to 2%)

Nervous system: Abnormal dreams (<2%), anxiety (<2%; including irritability), depression (<2%), dizziness (2%), fatigue (5%), headache (4%), sleep disorder (2%)

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (3% to 8%), musculoskeletal pain (3%)

Miscellaneous: Fever (8%)

<1%:

Cardiovascular: Syncope (including presyncope and vasovagal)

Hepatic: Increased serum bilirubin

Local: Abscess at injection site, bleeding at injection site, cellulitis at injection site, local anesthesia (injection site)

Frequency not defined:

Dermatologic: Hyperhidrosis

Hepatic: Acute hepatitis B infection, hepatitis A

Nervous system: Sciatica

Postmarketing:

Dermatologic: Severe dermatological reaction

Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms

Nervous system: Abnormality in thinking (negative thoughts), depressed mood, dysphoria, emotional lability, major depressive disorder, mood changes, suicidal ideation, suicidal tendencies

Renal: Nephrotic syndrome

Contraindications

Hypersensitivity to cabotegravir, rilpivirine, or any component of the formulation; concomitant use with uridine diphosphate-glucuronosyl transferase and/or cytochrome P450 3A enzyme inducers (antiseizure medications [eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin], antimycobacterials [eg, rifabutin, rifampin, rifapentine], systemic dexamethasone [more than a single dose], St John's wort).

Warnings/Precautions

Concerns related to adverse effects:

• Depressive disorders: Depressive disorders, including depression, depressed mood, dysphoria, major depression, mood changes, negative thoughts, suicide attempts, or suicidal ideation, have been reported. Promptly evaluate patients with depressive symptoms to assess if symptoms are related to cabotegravir and rilpivirine and determine if risks of continued treatment outweigh the benefits.

• Hepatotoxicity: Hepatoxicity has been reported in patients with or without known preexisting hepatic disease or other risk factors. Patients with underlying hepatic disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations. Monitor liver chemistries and discontinue treatment if hepatotoxicity is suspected.

• Hypersensitivity reactions: Hypersensitivity reactions have been reported postmarketing with rilpivirine, including cases of drug reaction with eosinophilia and systemic symptoms. Some skin reactions were accompanied by constitutional symptoms (eg, fever); other skin reactions were associated with organ dysfunction (eg, hepatic serum biochemistry elevations). Serious or severe hypersensitivity reactions have been reported with other integrase inhibitors. Discontinue immediately if signs or symptoms of reactions (eg, severe rash, rash with fever, malaise, fatigue, muscle/joint aches, blisters, oral blisters/lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing) occur. Monitor liver transaminases and clinical status and institute appropriate therapy as indicated. May administer oral lead-in dosing prior to initiation of cabotegravir and rilpivirine to help identify patients who may be at risk for hypersensitivity.

• Injection-related reactions: Serious postinjection reactions were reported within minutes after injection of rilpivirine, including abdominal cramping, agitation, BP changes, bronchospasm, dizziness, dyspnea, flushing, oral numbness, pain (eg, back, chest), rash/urticaria, and sweating. These events were reported in <1% of subjects, began to resolve a few minutes after injection, and may have been associated with inadvertent (partial) IV administration. Observe patients for ~10 minutes after injection. If a patient experiences a postinjection reaction, monitor and treat as clinically indicated.

Disease-related concerns:

• Renal impairment: Use with caution in patients with CrCl <30 mL/minute.

Concurrent drug therapy issues:

• QTc prolongation: Doses of oral rilpivirine 3 and 12 times the recommended oral dose have been associated with QTc prolongation; plasma rilpivirine concentrations after injection are comparable to those seen with the usual recommended oral doses that do not prolong the QT interval. Use caution when coadministering with a drug with a known risk of torsades de pointes.

Dosage form specific issues:

• Discontinuation of therapy: Residual concentrations of cabotegravir and rilpivirine long-acting injections may remain in the systemic circulation of patients for ≥12 months; consider this if cabotegravir and rilpivirine are discontinued.

Other warnings/precautions:

• Resistance: Carefully select patients who agree to the required injection schedule; nonadherence to injection schedule or missed doses could lead to loss of virologic response and development of resistance. In addition, to minimize risk of developing resistance upon discontinuation, a fully suppressive antiretroviral regimen must be adopted no later than 1 month after the final monthly injection or 2 months after the final every-2-month injection of cabotegravir and rilpivirine.

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antacids: May decrease the serum concentration of Rilpivirine. Management: Administer antacids at least 2 hours before or 4 hours after oral rilpivirine when used with most rilpivirine products. However, administer antacids at least 6 hours before or 4 hours after the rilpivirine/dolutegravir combination product. Risk D: Consider therapy modification

Antihepaciviral Combination Products: May increase the serum concentration of Rilpivirine. Risk X: Avoid combination

Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination

CarBAMazepine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Rilpivirine. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Rilpivirine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced rilpivirine efficacy (eg, loss of virologic response or resistance). Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Rilpivirine. Risk C: Monitor therapy

DexAMETHasone (Systemic): May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Didanosine: Rilpivirine may decrease the absorption of Didanosine. Didanosine may decrease the absorption of Rilpivirine. More specifically, simultaneous coadministration of these drugs creates a conflict between recommendations to administer with (rilpivirine) and without (didanosine) food. Management: Administer didanosine on an empty stomach at least 2 hours before or 4 hours after rilpivirine, due to the requirement that rilpivirine be administered with food. Risk D: Consider therapy modification

Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination

Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Ergonovine. Specifically, this would be most likely with delavrdine, while other Non-Nucleoside Reverse Transcriptase Inhibitors may be more likely to decrease the concentration of Ergonovine. Risk X: Avoid combination

Fosphenytoin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Rilpivirine. Management: Administer histamine H2 receptor antagonists (H2RAs) at least 12 hours before or 4 hours after oral rilpivirine. Risk D: Consider therapy modification

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Ketoconazole (Systemic): May increase the serum concentration of Rilpivirine. Rilpivirine may decrease the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy

Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Levomethadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Levomethadone. Management: Levomethadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Risk C: Monitor therapy

Macrolide Antibiotics: May increase the serum concentration of Rilpivirine. Management: Consider the use of azithromycin or another non-macrolide alternative when appropriate to avoid this potential interaction. Risk D: Consider therapy modification

Methadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the metabolism of Methadone. Management: Methadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Risk C: Monitor therapy

Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy

OXcarbazepine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

OXcarbazepine: May decrease the serum concentration of Cabotegravir. Risk X: Avoid combination

PHENobarbital: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Phenytoin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Polyvalent Cation Containing Products: May decrease the serum concentration of Cabotegravir. Management: Administer polyvalent cation containing products at least 2 hours before or 4 hours after oral cabotegravir. Risk D: Consider therapy modification

Primidone: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Reverse Transcriptase Inhibitors (Non-Nucleoside): May enhance the adverse/toxic effect of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, efavirenz and nevirapine may decrease the serum concentrations of other non-nucleoside reverse transcriptase inhibitors. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, delavirdine may increase the serum concentration of etravirine. Risk X: Avoid combination

Rifabutin: May decrease the serum concentration of Rilpivirine. Management: Increase rilpivirine dose to 50 mg/day during rifabutin treatment. Use of rifabutin with emtricitabine/rilpivirine/tenofovir alafenamide product is not recommended. Use with IV cabotegravir/rilpivirine is contraindicated. Risk D: Consider therapy modification

Rifabutin: May decrease the serum concentration of Cabotegravir. Additionally, rifabutin may decrease rilpivirine concentrations, a drug often coadministered with IV cabotegravir. Management: Do not use long-acting injectable cabotegravir (Cabenuva) with rifabutin. Cabotegravir dose adjustments required if extended-release suspension (Apretude) is coadministered with rifabutin. No interaction expected with cabotegravir tablets. Risk D: Consider therapy modification

RifAMPin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Rifapentine: May decrease the serum concentration of Cabotegravir. Risk X: Avoid combination

Rifapentine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Saquinavir: Rilpivirine may enhance the arrhythmogenic effect of Saquinavir. Saquinavir may increase the serum concentration of Rilpivirine. Risk X: Avoid combination

St John's Wort: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

UGT1A1 Inducers: May decrease the serum concentration of Cabotegravir. Risk X: Avoid combination

Reproductive Considerations

The Health and Human Services perinatal HIV guidelines note data are insufficient to recommend injectable cabotegravir in combination with rilpivirine for patients with HIV infection who are not yet pregnant but are trying to conceive. The long half-life of the injection should be considered in patients planning to conceive (HHS [perinatal] 2021).

Refer to individual monographs for additional information.

Pregnancy Considerations

The Health and Human Services perinatal HIV guidelines do not recommend injectable cabotegravir in combination with rilpivirine for pregnant patients with HIV infection who are antiretroviral-naive, who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen); data are insufficient to recommend use in patients who become pregnant during therapy. Patients who become pregnant on the long-acting IM formulation should be changed to an oral regimen within 4 weeks of the last injection. Pregnant patients who present with this combination as a 2-drug regimen should be changed to a preferred or alternative oral 3-drug regimen (HHS [perinatal] 2021).

Refer to individual monographs for additional information.

Breastfeeding Considerations

It is not known if cabotegravir or rilpivirine are present in breast milk.

Refer to individual monographs for additional information.

Monitoring Parameters

Liver chemistries; signs/symptoms of hypersensitivity and/or skin reactions; injection-related reactions; mood changes.

Mechanism of Action

Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration.

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor; activity is mediated by noncompetitive inhibition of HIV-1 reverse transcriptase.

Pharmacokinetics

Note: Pharmacokinetics in pediatric patients ≥12 years of age weighing ≥35 kg are similar to in adults.

Distribution: CSF:plasma concentration ratio: Cabotegravir: Range: 0.002 to 0.004; Rilpivirine: Range: Not quantifiable to 0.02.

Protein binding: Cabotegravir: >99.8%; Rilpivirine: 99.7%.

Metabolism: Cabotegravir: UGT1A1, UGT1A9 (minor); Rilpivirine: CYP3A.

Half-life elimination: Cabotegravir: 5.6 to 11.5 weeks; Rilpivirine: 13 to 28 weeks.

Time to peak: Cabotegravir: 7 days; Rilpivirine: 3 to 4 days.

Excretion:

Cabotegravir: Urine: 27% (0% as unchanged drug); Feces: 59% (47% as unchanged drug).

Rilpivirine: Urine: 6% (<1% as unchanged drug); Feces: 85% (26% as unchanged drug).

Brand Names: International
  • Cabenuva (AU)


For country code abbreviations (show table)
  1. Cabenuva (cabotegravir and rilpivirine) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; April 2022.
  2. US Department of Health and Human Services (HHS) Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. https://clinicalinfo.hiv.gov/en/guidelines/pediatric-opportunistic-infection/whats-new. Updated January 22, 2022. Accessed May 11, 2022.
  3. US Department of Health and Human Services (HHS) Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Perinatal_GL.pdf. Updated December 30, 2021. Accessed January 3, 2022.
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