cabotegravir/rilpivirine (Rx)

Brand and Other Names:Cabenuva
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

Cabotegravir and rilpivirine are copackaged as 2 separate IM injections

Each dosing kit also contains 2 syringes, 2 syringe labels, 2 vial adapters, and 2 needles for IM injection (23-gauge, 1.5-inch)

Vial stoppers are not made with natural rubber latex

injection, IM suspension 400mg/600mg kit

  • Cabotegravir: 400mg/2mL
  • Rilpivirine: 600mg/2mL

injection, IM suspension 600mg/900mg kit

  • Cabotegravir: 600mg/3mL
  • Rilpivirine: 900mg/3mL

HIV Infection

Indicated as a complete regimen for treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace a current stable antiretroviral therapy (ART) regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine

Oral lead-in dosing

  • Administer oral lead-in dosing prior to administration of Cabenuva to help identify patients who may be at risk of a hypersensitivity reaction
  • Before starting once monthly IM injections of cabotegravir and rilpivirine, use daily oral regimen of cabotegravir (Vocabria) 30 mg plus rilpivirine (Edurant) 25 mg for at least 1 month to ensure medications are well tolerated

IM dosing

  • Administer each drug as 2 separate IM injections
  • One-time initiating injection
    • Administer at month 2 (on last day of oral lead-in dosing)
    • Cabotegravir 600 mg (3 mL) IM once PLUS
    • Rilpivirine 900 mg (3 mL) IM once
  • Once-monthly continuation injections
    • Administer at month 3 and once monthly thereafter
    • Cabotegravir 400 mg (2 mL) IM once PLUS
    • Rilpivirine 600 mg (2 mL) IM once

Dosage Modifications

Renal impairment

  • Mild-to-moderate (CrCl 30 to <90 mL/min): No dosage adjustment required
  • Severe (CrCl <15 mL/min) or ESRD: Increased monitoring recommended
  • ESRD not on dialysis: Pharmacokinetic effects of each drug are unknown
  • Dialysis: Cabotegravir and rilpivirine are >99% protein bound; dialysis is not expected to alter systemic exposure

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Pharmacokinetic effects are unknown

Dosing Considerations

Patient selection

  • Must be administered by a healthcare professional
  • Before initiating, carefully select patients who agree to required monthly IM injection dosing schedule
  • Educate patients regarding importance of adherence to scheduled dosing visits to maintain viral suppression and reduce risk of viral rebound and potential development of resistance with missed doses

Safety and efficacy not established

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Interactions

Interaction Checker

and cabotegravir/rilpivirine

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            Contraindicated (31)

            • apalutamide

              apalutamide will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • carbamazepine

              carbamazepine decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of carbamazepine with NNRTIs may result in a loss of virologic response and possible resistance to the NNRTI.

              carbamazepine will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • cigarette smoking

              cigarette smoking will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • dexamethasone

              dexamethasone decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

            • desogestrel

              desogestrel will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • dexlansoprazole

              dexlansoprazole decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Contraindicated. Concurrent use may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels.

            • efavirenz

              efavirenz decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be used in combination with NNRTIs.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              rilpivirine, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

            • esomeprazole

              esomeprazole decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Contraindicated. Concurrent use may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels.

            • etravirine

              etravirine decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be used in combination with NNRTIs.

            • fosphenytoin

              fosphenytoin decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

            • lamotrigine

              lamotrigine will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • lansoprazole

              lansoprazole decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Contraindicated. Concurrent use may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels.

            • nevirapine

              nevirapine decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be used in combination with NNRTIs.

            • nicotine gum

              nicotine gum will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • nicotine inhaled

              nicotine inhaled will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • nicotine intranasal

              nicotine intranasal will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • nicotine lozenge

              nicotine lozenge will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • nicotine transdermal

              nicotine transdermal will decrease the level or effect of cabotegravir by increasing elimination. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • omeprazole

              omeprazole decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Contraindicated. Concurrent use may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels.

            • oxcarbazepine

              oxcarbazepine decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

            • pantoprazole

              pantoprazole decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Contraindicated. Concurrent use may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels.

            • phenobarbital

              phenobarbital will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

              phenobarbital decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

            • phenytoin

              phenytoin will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

              phenytoin decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

            • primidone

              primidone will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • rabeprazole

              rabeprazole decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Contraindicated. Concurrent use may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels.

            • rifabutin

              rifabutin will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response. Note: Rifabutin can be coadministered with cabotegravir PO; however, it is contraindicated with Cabenuva (cabotegravir; rilpivirine) extended-release injectable suspensions.

            • rifampin

              rifampin decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

              rifampin will increase the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            • rifapentine

              rifapentine decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

            • testosterone

              testosterone will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

            Serious - Use Alternative (44)

            • abacavir

              abacavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • artemether

              artemether and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

            • atazanavir

              atazanavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • bedaquiline

              bedaquiline and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

            • bictegravir

              bictegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • ceritinib

              ceritinib and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

            • darunavir

              darunavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • delavirdine

              delavirdine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • desflurane

              desflurane and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

            • didanosine

              didanosine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • dofetilide

              dofetilide increases toxicity of rilpivirine by QTc interval. Avoid or Use Alternate Drug.

            • dolutegravir

              dolutegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • doravirine

              doravirine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • efavirenz

              efavirenz, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • elvitegravir

              elvitegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • emtricitabine

              emtricitabine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • enfuvirtide

              enfuvirtide, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • etravirine

              etravirine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • fexinidazole

              fexinidazole and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

            • fosamprenavir

              fosamprenavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • fostemsavir

              fostemsavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • hydroxychloroquine sulfate

              hydroxychloroquine sulfate and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

            • ibalizumab

              ibalizumab, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • indinavir

              indinavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • lamivudine

              lamivudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • lefamulin

              lefamulin and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

            • macimorelin

              macimorelin and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

            • maraviroc

              maraviroc, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • mobocertinib

              mobocertinib and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

            • nelfinavir

              nelfinavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • nevirapine

              nevirapine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir will increase the level or effect of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of Viekira Pak with rilpivirine once daily is not recommended due to potential for QT interval prolongation with higher concentrations of rilpivirine

            • raltegravir

              raltegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • ribociclib

              ribociclib increases toxicity of rilpivirine by QTc interval. Avoid or Use Alternate Drug.

            • rifabutin

              rifabutin decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministered, increase rilpivirine dose to 50 mg PO once daily; when rifabutin coadministration is stopped, decrease rilpivirine dose to 25 mg once daily.

            • ritonavir

              ritonavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • saquinavir

              saquinavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • stavudine

              stavudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • tenofovir DF

              tenofovir DF, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • tipranavir

              tipranavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • umeclidinium bromide/vilanterol inhaled

              rilpivirine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • vilanterol/fluticasone furoate inhaled

              rilpivirine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • zidovudine

              zidovudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            Monitor Closely (80)

            • albuterol

              albuterol and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • alfuzosin

              rilpivirine and alfuzosin both increase QTc interval. Use Caution/Monitor.

              alfuzosin and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • aluminum hydroxide

              aluminum hydroxide decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should be given at least 2 hr before or at least 4 hr after rilpivirine. For the combination product dolutegravir/rilpivirine, antacids should be given at least 4 hr before or at least 6 hr afterwards.

              aluminum hydroxide will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.

            • aluminum hydroxide/magnesium carbonate

              aluminum hydroxide/magnesium carbonate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.

            • amiodarone

              rilpivirine increases toxicity of amiodarone by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • aluminum hydroxide/magnesium trisilicate

              aluminum hydroxide/magnesium trisilicate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.

            • amitriptyline

              rilpivirine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • amoxapine

              rilpivirine increases toxicity of amoxapine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • apomorphine

              rilpivirine increases toxicity of apomorphine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • arformoterol

              arformoterol and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

              aripiprazole and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • arsenic trioxide

              rilpivirine increases toxicity of arsenic trioxide by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • artemether/lumefantrine

              rilpivirine increases toxicity of artemether/lumefantrine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.

            • asenapine

              rilpivirine increases toxicity of asenapine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should be given at least 2 hr before or at least 4 hr after rilpivirine. For the combination product dolutegravir/rilpivirine, antacids should be given at least 4 hr before or at least 6 hr afterwards.

              aspirin/citric acid/sodium bicarbonate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.

            • atazanavir

              atazanavir increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Rilpivirine is not expected to affect the plasma concentrations of co-administered protease inhibitors. .

            • calcium carbonate

              calcium carbonate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.

            • atomoxetine

              atomoxetine and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • azithromycin

              rilpivirine increases toxicity of azithromycin by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • calcium acetate

              calcium acetate decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should given at least 2 hr before or at least 4 hr after rilpivirine.

            • calcium carbonate

              calcium carbonate decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should be given at least 2 hr before or at least 4 hr after rilpivirine. For the combination product dolutegravir/rilpivirine, antacids should be given at least 4 hr before or at least 6 hr afterwards.

            • calcium chloride

              calcium chloride decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should given at least 2 hr before or at least 4 hr after rilpivirine.

            • calcium citrate

              calcium citrate decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should given at least 2 hr before or at least 4 hr after rilpivirine.

            • calcium gluconate

              calcium gluconate decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should given at least 2 hr before or at least 4 hr after rilpivirine.

            • calcium/vitamin D

              calcium/vitamin D will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer polyvalent cation products at least 2 hr before or 4 hr after taking oral cabotegravir.

              calcium/vitamin D decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should given at least 2 hr before or at least 4 hr after rilpivirine.

            • chlorpromazine

              rilpivirine increases toxicity of chlorpromazine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • magaldrate

              magaldrate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.

            • cimetidine

              cimetidine will decrease the level or effect of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Concurrent use, may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels. Administer H2 antagonists at least 12 hours before or at least 4 hours after rilpivirine.

            • ciprofloxacin

              rilpivirine increases toxicity of ciprofloxacin by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • citalopram

              rilpivirine increases toxicity of citalopram by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • clarithromycin

              clarithromycin increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Where possible, alternatives such as azithromycin should be considered.

              rilpivirine increases toxicity of clarithromycin by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • clomipramine

              rilpivirine increases toxicity of clomipramine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • clozapine

              clozapine and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • conivaptan

              conivaptan increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • cyclobenzaprine

              rilpivirine increases toxicity of cyclobenzaprine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • dasatinib

              rilpivirine increases toxicity of dasatinib by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • degarelix

              rilpivirine increases toxicity of degarelix by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • desipramine

              rilpivirine increases toxicity of desipramine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • deutetrabenazine

              deutetrabenazine and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • didanosine

              didanosine, rilpivirine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Applies to didanosine chewable tablets and powder for oral solution; administer 2 hr before or several hours after didanosine oral solution or chewable tablet administration; no dose adjustment is required when rilpivirine is coadministered with didanosine. Didanosine is to be administered on an empty stomach and at least two hours before or at least four hours after rilpivirine (which should be administered with a meal).

            • disopyramide

              rilpivirine increases toxicity of disopyramide by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • dofetilide

              rilpivirine increases toxicity of dofetilide by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • dolasetron

              rilpivirine increases toxicity of dolasetron by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • dronedarone

              rilpivirine increases toxicity of dronedarone by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • droperidol

              rilpivirine increases toxicity of droperidol by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • erythromycin base

              erythromycin base increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Where possible, alternatives such as azithromycin should be considered.

              rilpivirine increases toxicity of erythromycin base by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Where possible, alternatives such as azithromycin should be considered.

              rilpivirine increases toxicity of erythromycin ethylsuccinate by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • erythromycin lactobionate

              erythromycin lactobionate increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Where possible, alternatives such as azithromycin should be considered.

              rilpivirine increases toxicity of erythromycin lactobionate by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • erythromycin stearate

              erythromycin stearate increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Where possible, alternatives such as azithromycin should be considered.

              rilpivirine increases toxicity of erythromycin stearate by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • escitalopram

              rilpivirine increases toxicity of escitalopram by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

              escitalopram increases toxicity of rilpivirine by QTc interval. Use Caution/Monitor.

            • famotidine

              famotidine will decrease the level or effect of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Concurrent use, may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels. Administer H2 antagonists at least 12 hours before or at least 4 hours after rilpivirine.

            • flecainide

              rilpivirine increases toxicity of flecainide by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • fluconazole

              fluconazole increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No rilpivirine dose adjustment is required. Clinically monitor for breakthrough fungal infections when azole antifungals are co-administered with rilpivirine.

              rilpivirine increases toxicity of fluconazole by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • fluoxetine

              rilpivirine increases toxicity of fluoxetine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • fosamprenavir

              fosamprenavir increases effects of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Rilpivirine is not expected to affect the plasma concentrations of co-administered protease inhibitors. .

            • foscarnet

              rilpivirine increases toxicity of foscarnet by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • fostemsavir

              rilpivirine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • gemifloxacin

              rilpivirine increases toxicity of gemifloxacin by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • haloperidol

              rilpivirine increases toxicity of haloperidol by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • ibuprofen/famotidine

              ibuprofen/famotidine, rilpivirine. increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Combination of rilpivirine and H2-receptor antagonists should be used with caution as coadministration may cause significant decreases in rilpivirine plasma concentrations (increase in gastric pH). Administer famotidine at least 12 hours before or at least 4 hours after rilpivirine.

            • ibutilide

              ibutilide increases toxicity of rilpivirine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.

              rilpivirine increases toxicity of ibutilide by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • iloperidone

              rilpivirine increases toxicity of iloperidone by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • indapamide

              rilpivirine increases toxicity of indapamide by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • indinavir

              indinavir increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoniazid

              isoniazid increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isradipine

              rilpivirine increases toxicity of isradipine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • itraconazole

              itraconazole increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No rilpivirine dose adjustment is required. Clinically monitor for breakthrough fungal infections when azole antifungals are co-administered with rilpivirine.

            • ketoconazole

              ketoconazole increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No rilpivirine dose adjustment is required. Clinically monitor for breakthrough fungal infections when azole antifungals are co-administered with rilpivirine.

            • lapatinib

              rilpivirine increases toxicity of lapatinib by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • levofloxacin

              rilpivirine increases toxicity of levofloxacin by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • lopinavir

              lopinavir increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dose adjustment is required during concurrent use.

              rilpivirine increases toxicity of lopinavir by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.

            • lumefantrine

              rilpivirine increases toxicity of lumefantrine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.

            • magnesium chloride

              magnesium chloride will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer polyvalent cation products at least 2 hr before or 4 hr after taking oral cabotegravir.

              magnesium chloride decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should given at least 2 hr before or at least 4 hr after rilpivirine.

            • magnesium citrate

              magnesium citrate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer polyvalent cation products at least 2 hr before or 4 hr after taking oral cabotegravir.

            • magnesium gluconate

              magnesium gluconate decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should given at least 2 hr before or at least 4 hr after rilpivirine.

            • magnesium hydroxide

              magnesium hydroxide will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.

            • magnesium oxide

              magnesium oxide will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.

              magnesium oxide decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should be given at least 2 hr before or at least 4 hr after rilpivirine. For the combination product dolutegravir/rilpivirine, antacids should be given at least 4 hr before or at least 6 hr afterwards.

            • magnesium sulfate

              magnesium sulfate decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Coadministration of antacids with rilpivirine may cause significant decreases in rilpivirine plasma concentrations because of increased gastric pH. If antacids must be administered, they should given at least 2 hr before or at least 4 hr after rilpivirine.

            • zinc

              zinc will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer polyvalent cation containing products at least 2 hr before or 4 hr after oral cabotegravir.

            Minor (2)

            • chloroquine

              chloroquine increases toxicity of rilpivirine by QTc interval. Minor/Significance Unknown.

            • crizotinib

              crizotinib and rilpivirine both increase QTc interval. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Injection site reactions, all grades (83%)

            Injection site reactions, ≥Grade 2 (37%)

            1-10%

            All grades

            • Pyrexia (8%)
            • Fatigue (5%)
            • Headache (4%)
            • Musculoskeletal pain (3%)
            • Nausea (3%)
            • Sleep disorders (2%)
            • Dizziness (2%)
            • Rash (2%)

            Grade ≥2

            • Pyrexia (2%)
            • Fatigue (1%)
            • Musculoskeletal pain (1%)

            Grade 3 or 4 laboratory parameters

            • Creatine phosphokinase ≥10 x ULN (8%)
            • Lipase ≥3 x ULN (5%)
            • ALT/AST ≥5 x ULN (2%)

            <2%

            • Gastrointestinal disorders: Abdominal pain (including upper abdominal pain), gastritis, dyspepsia, vomiting, diarrhea, and flatulence
            • Hepatobiliary disorders: Hepatotoxicity
            • Investigations: Weight increase
            • Psychiatric disorders: Anxiety (including anxiety and irritability), depression, abnormal dreams
            • Skin and hypersensitivity reactions: Hypersensitivity reactions

            <1%

            Grade ≥2

            • Total bilirubin ≥2.6 x ULN
            • Headache
            • Nausea
            • Sleep disorders
            • Dizziness
            • Rash

            Postmarketing Reports

            Renal and genitourinary disorders: Nephrotic syndrome

            Skin and subcutaneous tissue disorders: Severe skin and hypersensitivity reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS)

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            Warnings

            Contraindications

            Documented hypersensitivity

            UGT1A1 or CYP3A inducers

            • Coadministration with UGT1A1 inducers and/or CYP3A inducers may significantly decrease cabotegravir and/or rilpivirine plasma concentrations owing to possible loss of virologic response
            • Examples of UGT1A1 inducers include carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine
            • Examples of CYP3A inducers include systemic glucocorticoids (eg, >1 dose of dexamethasone) and St John’s wort

            Cautions

            Serious postinjection reactions were reported within minutes after injection of rilpivirine, including dyspnea, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure; symptoms began to resolve within a few minutes after injection; these events may have been associated with inadvertent (partial) IV administration; observe patient for 10 minutes after injection

            Hepatotoxicity reported in patients with or without known preexisting hepatic disease or known risk factors; monitoring of liver chemistries recommended; discontinue treatment if hepatotoxicity suspected

            Depressive disorders (including depressed mood, depression, mood altered, mood swings) reported; promptly evaluate if symptoms emerge; determine whether risks of continued therapy outweigh benefits

            Hypersensitivity

            • Serious or severe hypersensitivity reactions reported with other integrase inhibitors
            • Discontinue 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)
            • Postmarketing experience with rilpivirine-containing regimens has included drug reaction with eosinophilia and systemic symptoms (DRESS)
            • Monitor clinical status, including liver transaminases, and initiate appropriate therapy as warranted

            Drug interaction overview

            • Other antiretroviral medications for HIV-1 infection
              • Cabotegravir plus rilpivirine is a complete ART regimen
              • Coadministration with other ARTs is not recommended
              • Residual concentrations of IM cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer); these residual concentrations are not expected to affect the exposures of ARTs initiated after discontinuation of cabotegravir and rilpivirine
            • UGT1A1 or UGT1A9 inducers
              • Contraindicated
              • Cabotegravir is primarily metabolized by UGT1A1 with some contribution from UGT1A9
              • Strong UGT1A1 or 1A9 inducers are expected to decrease cabotegravir plasma concentrations and may result in loss of virologic response
            • CYP3A inducers
              • Contraindicated
              • Rilpivirine is primarily metabolized by CYP3A
              • Strong CYP3A inducers are contraindicated with rilpivirine owing to concern for decreased rilpivirine plasma concentrations and potential loss of virologic response
            • QT-prolonging drugs or strong CYP3A inhibitors
              • Caution if coadministered with drugs that prolong QT interval or drugs that may raise rilpivirine systemic exposure
              • QT prolongation may occur with rilpivirine peak plasma concentrations 4.4-fold and 11.6-fold higher than those observed with rilpivirine 600 IM qMonth
            • Macrolide or ketolide antibiotics
              • Macrolides are expected to increase rilpivirine concentrations and are associated with torsade de pointes
              • When possible, consider azithromycin, which increases rilpivirine concentrations less than other macrolides
            • Polyvalent cation-containing products
              • Modify dosage schedule
              • Coadministration with antacids containing polyvalent cations (eg, aluminum, magnesium hydroxide, calcium carbonate) may decrease cabotegravir absorption
              • Administer antacids at least 2 hr before or 4 hr after taking cabotegravir
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            Pregnancy & Lactation

            Pregnancy

            Encourage patients to register for the Antiretroviral Pregnancy Registry (APR) by calling 1-800-258-4263

            Data are insufficient regarding use during pregnancy to adequately assess drug-associated risk of birth defects and miscarriage

            While there are insufficient human data to assess the risk of neural tube defects (NTDs) with exposure to cabotegravir during pregnancy, NTDs were associated with dolutegravir, another integrase inhibitor

            Cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing; therefore, consider potential for fetal exposure during pregnancy

            Rilpivirine human data

            • Prospective reports to APR to PO rilpivirine-containing regimens during the first trimester of pregnancy (>390 reports) and during second/third trimester of pregnancy (>170 reports), the prevalence of birth defects was 1.3% and 1.1% following first and second/third trimester exposures, respectively, compared with the background birth defect rate of 2.7% in the US reference population

            Lactation

            Unknown if present in human breast milk, affects human milk production, or effects on breastfed infants

            CDC recommends that women in the United States should not breastfeed their infants because of risk of the following H4

            Postnatal HIV transmission (in HIV-negative infants)

            Developing viral resistance (in HIV-positive infants)

            Adverse reactions in nursing infants

            Animal data

            • Animal lactation studies have not been conducted; however, cabotegravir and rilpivirine were detected in plasma of nursing pups on lactation days 10 and 7 respectively in rat prenatal and postnatal development study

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Cabotegravir: HIV-1 integrase strand transfer inhibitor (INSTI); cabotegravir, an analog of dolutegravir, prevents viral DNA integration into the host genome and inhibits HIV replication

            Rilpivirine: Non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1; inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase

            Absorption

            Peak plasma time

            • Cabotegravir: 7 days
            • Rilpivirine: 3-4 days

            Peak plasma concentration

            • Cabotegravir, monthly IM: 4.2 mcg/mL
            • Rilpivirine, monthly IM: 116 ng/mL

            AUC

            • Cabotegravir, monthly IM: 2,415 mcg⋅h/mL
            • Rilpivirine, monthly IM: 65,603 ng⋅h/mL

            Distribution

            Protein bound: >99%

            Metabolism

            Cabotegravir: Metabolized by UGT1A1 (major) and UGT1A9 (minor)

            Rilpivirine: Metabolized primarily by CYP3A

            Elimination

            Half-life

            • Cabotegravir: 5.6-11.5 weeks
            • Rilpivirine: 13-28 weeks

            Excretion

            • Cabotegravir: Urine 27%; feces 59%
            • Rilpivirine: Urine 6%; feces 85%
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            Administration

            IM Preparation

            Remove from refrigerator and wait at least 15 minutes to allow vials to come to room temperature; not to exceed 25ºC (77ºF)

            Vials may remain in the carton at room temperature for up to 6 hr; discard if not used within 6 hr

            Inspect visually for particulate matter and discoloration before administration; cabotegravir vial has a brown tint to the glass which may limit visual inspection

            Shake each vial vigorously until suspensions look uniform before injecting; small air bubbles are expected and acceptable

            Do not mix with any other product or diluent

            Once cabotegravir and rilpivirine suspensions have been drawn into their separate syringes, administer as soon as possible; suspension may remain in syringes for up to 2 hr; discard if 2 hr exceeded

            IM Administration

            Suspension are for gluteal intramuscular injections

            No further dilution or reconstitution needed

            Ventrogluteal site recommended; administer each injection at separate gluteal injection sites (on opposite sides or 2 cm apart) during the same visit

            Do not administer by any other route or anatomical site

            Consider patient’s BMI to ensure 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 (eg, >30 kg/m2) to ensure that injections are administered IM as opposed to SC

            Administration order of cabotegravir and rilpivirine injections is not important

            Monitor patient for 10 minutes after injection to observe for injection related adverse effects

            Missed injections

            • Adherence to monthly injection dosing schedule is strongly recommended to avoid viral resistance
            • Reassess patients to ensure resumption of therapy remains appropriate
            • Planned missed IM injections
              • Plans to miss scheduled injection visit by >7 days: Take daily PO therapy to replace up to 2 consecutive monthly injection visits
              • Take first dose of PO therapy ~1 month after the last injection and continue until the day injection dosing restarted
            • Unplanned missed IM injections
              • If monthly injections are missed or delayed by >7 days and PO therapy has not been taken in the interim, clinically reassess patient to determine if resumption of injection dosing remains appropriate
              • If injection dosing will be continued, see below for resuming IM injection dosing
            • Resume IM injection dosing
              • Time since last injection ≤2 months: Resume cabotegravir 400 mg and rilpivirine 600 mg IM
              • Time since last injection >2 months: Reinitiate with cabotegravir 600 mg and rilpivirine 900 mg IM once, then continue to follow with cabotegravir 400 mg and rilpivirine 600 mg IM qMonth

            Storage

            Refrigerate at 2-8ºC (36-46ºF) in original carton until ready to use

            Do not freeze

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            Images

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            Patient Handout

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.