Cabotegravir-Rilpivirine

Cabotegravir-Rilpivirine is a combination medication used for the treatment of  HIV-1 infection.

• Cabotegravir-Rilpivirine is available under the following different brand names: Cabenuva

Common side effects of Cabotegravir-Rilpivirine include:

• pain, tenderness, hardened mass or lump, swelling, redness, itching, bruising, and warmth at the injection site
• fever
• tiredness
• headache
• muscle or bone pain
• nausea
• sleep problems
• dizziness
• rash

Serious side effects of Cabotegravir-Rilpivirine include:

• hives,
• fever,
• tiredness, 
• body aches, 
• not feeling well
• muscle or joint aches
• trouble breathing
• blisters or sores in the mouth
• blisters
• redness or swelling of the eyes
• swelling of the mouth, face, lips, or tongue
• stomach cramps
• sweating
• numbness of the mouth
• feeling anxious
• feeling warm
• feeling lightheaded 
• blood pressure changes
• skin rash
• swollen glands
• muscle aches
• severe weakness
• unusual bruising
• yellowing of the skin or eyes
• unusual changes in mood or behavior;
• suicidal thoughts or actions; or
• liver problems--loss of appetite, nausea, vomiting, stomach pain (upper right side), itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Rare side effects of Cabotegravir-Rilpivirine include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injection, IM suspension 400 mg/600 mg kit

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

Injection, IM suspension 600 mg/900 mg kit

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

HIV Infection

Adult dosage

• Optional oral lead-in dosing
  • May use oral lead-in for approximately 1 month (at least 28 days) before initiating to assess tolerability of cabotegravir and rilpivirine for monthly- or every-2-month dosage regimens
  • Cabotegravir (Vocabria) 30 mg plus rilpivirine (Edurant) 25 mg once a day for approximately 1 month (at least 28 days) to ensure medications are well tolerated
• Once-monthly regimen
  • Administer each drug as 2 separate Intramuscular injections
• One-time initiating injection
  • Initiate on the last day of current ART therapy or oral lead-in (if used)
  • Cabotegravir 600 mg (3 mL) Intramuscular PLUS
• Rilpivirine 900 mg (3 mL) Intramuscular
  • Continuation injections every month
  • Administer once monthly after initial injections
• Cabotegravir 400 mg (2 mL) Intramuscular every Month PLUS
• Rilpivirine 600 mg (2 mL) Intramuscular every Month
• Give up to 7 days before or after scheduled monthly injections
• Every 2-month regimen
  • Administer each drug as 2 separate Intramuscular injections
• Initiating injections
  • Initiate on the last day of current ART therapy or oral lead-in (if used)
  • Cabotegravir 600 mg (3 mL) Intramuscular every month twice PLUS
  • Rilpivirine 900 mg (3 mL) Intramuscular every Month twice
  • Give up to 7 days before or after the scheduled second initiation injections
• Continuation injections every 2 months
  • Initiate at Month 3, and then every 2 months after that
  • Cabotegravir 600 mg (3 mL) Intramuscular every 2 months PLUS
  • Rilpivirine 900 mg (3 mL) Intramuscular every 2 months
  • Give up to 7 days before or after scheduled injections

Pediatric dosage

• Children below 12 years: Safety and efficacy not established
• Children above 12 years (weight above 35 kg): May administer with optional oral lead-in therapy (at least 28 days) or direct-to-injection
• Optional oral lead-in dosing
  • May use oral lead-in for approximately 1 month (at least 28 days) before initiating to assess tolerability of cabotegravir and rilpivirine for monthly- or every-2-month dosage regimens
  • Cabotegravir (Vocabria) 30 mg plus rilpivirine (Edurant) 25 mg once a day for approximately 1 month (at least 28 days) to ensure medications are well tolerated
• Once-monthly regimen
  • Administer each drug as 2 separate Intramuscular injections
• One-time initiating injection
  • Initiate on the last day of current ART therapy or oral lead-in (if used)
  • Cabotegravir 600 mg (3 mL) Intramuscular PLUS
  • Rilpivirine 900 mg (3 mL) Intramuscular
• Continuation injections every month
  • Administer once monthly after initial injections
  • Cabotegravir 400 mg (2 mL) Intramuscular every Month PLUS
  • Rilpivirine 600 mg (2 mL) Intramuscular every month
  • Give up to 7 days before or after scheduled monthly injections
• Every 2-month regimen
  • Administer each drug as 2 separate Intramuscular injections
• Initiating injections
  • Initiate on the last day of current ART therapy or oral lead-in (if used)
  • Cabotegravir 600 mg (3 mL) Intramuscular every month for 2 PLUS
  • Rilpivirine 900 mg (3 mL) Intramuscular every month for 2
  • Give up to 7 days before or after scheduled second initiation injections
• Continuation injections every 2 months
  • Initiate at Month 3, and then every 2 months thereafter
  • Cabotegravir 600 mg (3 mL) Intramuscular every 2 months PLUS
  • Rilpivirine 900 mg (3 mL) Intramuscular every 2 months
  • Give up to 7 days before or after scheduled injections

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Cabotegravir-Rilpivirine has severe interactions with at least 31 other drugs.
• Cabotegravir-Rilpivirine has serious interactions with at least 56 other drugs.
• Cabotegravir-Rilpivirine has moderate interactions with at least 90 other drugs.
• Cabotegravir-Rilpivirine has severe interactions with the following drugs:
  • chloroquine
  • crizotinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

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 (.g, above 1 dose of dexamethasone) and St John’s wort

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Cabotegravir-Rilpivirine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Cabotegravir-Rilpivirine?”

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 the 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, and mood swings) reported; promptly evaluate if symptoms emerge; determine whether risks of continued therapy outweigh the benefits
• To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen below 1 month after final injections when dosed monthly and below 2 months after final injections when dosed every 2 months; if virologic failure is suspected, switch to an alternative regimen as soon as possible
• 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, bronchospasm, rash/urticaria, dizziness, pain (.g, back and chest)
  • 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
• Post-injection reactions
  • Serious postinjection reactions were reported within minutes after injection of rilpivirine
  • Symptoms included dyspnea, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure
  • Symptoms began to resolve within minutes after injection, with some patients receiving supportive care
  • These events may have been associated with accidental IV administration during the Intramuscular injection procedure
  • Carefully follow Instructions for Use when preparing and administering
  • Slowly inject suspensions via IM injection, and avoid accidental IV administration
  • Observe patients briefly (Approximately 10 minutes) after the injection
  • If a post-injection reaction occurs, monitor, and treat as clinically indicated
• Drug interaction overview
  • Caution if coadministered with drugs that may cause torsade de points
  • 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 raltegravir 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 every month
  • Macrolide or ketolide antibiotics
    • Macrolides are expected to increase rilpivirine concentrations and are associated with torsade de points
    • 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 (.g, aluminum, magnesium hydroxide, calcium carbonate) may decrease cabotegravir absorption
    • Administer antacids at least 2 hours before or 4 hours after taking cabotegravir

Pregnancy and Lactation

• 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 the 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 raltegravir 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 discontinuation; therefore, consider the potential for fetal exposure during pregnancy
• Rilpivirine human data
  • Prospective reports to APR to PO rilpivirine-containing regimens during the first trimester of pregnancy (above 390 reports) and the second/third trimester of pregnancy (above 170 reports), the prevalence of birth defects was 1.3% and 1.1% following the 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 affects breastfed infants
  • CDC recommends that women in the United States should not breastfeed their infants because of the risk of the following H4
  • Postnatal HIV transmission (in HIV-negative infants)
  • Developing viral resistance (in HIV-positive infants)
  • Adverse reactions in nursing infants