CABENUVA

Cabenuva Generic Name & Formulations

Legal Class

General Description

Cabotegravir ext-rel (200mg/mL), rilpivirine ext-rel (300mg/mL); 400mg/600mg, 600mg/900mg; per co-packaged kit; susp for IM inj.

Pharmacological Class

HIV-1 integrase strand transfer inhibitor (INSTI) + non-nucleoside reverse transcriptase inhibitor.

How Supplied

Kit—1 (1 vial of cabotegravir + 1 vial of rilpivirine) w. supplies

Manufacturer

ViiV Healthcare

Generic Availability

Mechanism of Action

Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. Rilpivirine inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase. It does not inhibit the human cellular DNA polymerases α, β and γ.

Cabenuva Indications

Indications

As a complete regimen for HIV-1 infection to replace the current antiretroviral regimen in patients 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.

Cabenuva Dosage and Administration

Adult

Must be administered by a healthcare provider. Give each IM inj at separate gluteal inj sites (on opposite sides or 2cm apart) during same visit; preferably ventrogluteal site. Do not administer by any other route or anatomical site. ≥12yrs (≥35kg): Prior to initiation, may consider giving oral lead-in dosing (with Vocabria and Edurant) for approx. 1 month (≥28 days) to assess tolerability or may proceed directly to Cabenuva inj without use of an oral lead-in. Select appropriate inj dosing option. Monthly dosing: initiate single injections of 600mg/900mg (on the last day of current antiretroviral therapy or oral lead-in, if used), then continue single injections of 400mg/600mg once monthly onwards. Or, every 2-month dosing: initiate single injections of 600mg/900mg (on the last day of current antiretroviral therapy or oral lead-in, if used) consecutively 1 month apart for 2 months (Months 1 and 2), and then continue every 2 months onwards (starting at Month 4). Both regimens: may give injections up to 7 days before or after the scheduled date to receive monthly or every 2-month injections. Switching from monthly to every 2-month injections, every 2-month to monthly injections, missed injections: see full labeling.

Children

<12yrs or <35kg: not established.

Cabenuva Contraindications

Contraindications

Concomitant carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (more than 1 dose), St. John's wort.

Cabenuva Boxed Warnings

Not Applicable

Cabenuva Warnings/Precautions

Warnings/Precautions

Discontinue immediately if hypersensitivity reactions develop. Monitor for post-inj reactions; treat appropriately if occur. Underlying liver disease or marked elevation in transaminases. Monitor liver function; discontinue if hepatotoxicity is suspected. Promptly evaluate if depressive symptoms occur. Long-acting properties: residual drug concentrations may remain ≥12months. Switch to an alternative regimen if virologic failure is suspected. Severe hepatic impairment. Severe renal impairment or ESRD: monitor. Elderly. Pregnancy: monitor. Nursing mothers: not recommended.

Cabenuva Pharmacokinetics

Absorption

Time to maximum plasma concentration (median): 7 days (cabotegravir); 3–4 days (rilpivirine).

Distribution

Plasma protein bound: >99.8% (cabotegravir); 99.7% (rilpivirine). Blood-to-plasma ratio: 0.52 (cabotegravir); 0.7 (rilpivirine). CSF-to-plasma concentration ratio (median): 0.003 (cabotegravir); 0.01 (rilpivirine).

Metabolism

Cabotegravir: UGT1A1, UGT1A9 (minor); rilpivirine: CYP3A.

Elimination

Cabotegravir: fecal (59%), renal (27%); rilpivirine: fecal (85%), renal (6%). Half-life: 5.6–11.5 weeks (cabotegravir); 13–28 weeks (rilpivirine).

Cabenuva Interactions

Interactions

See Contraindications. Concomitant other antiretroviral drugs: not recommended. Cabotegravir: antagonized by strong UGT1A1 or 1A9 inducers. Rilpivirine: antagonized by CYP3A inducers or may be potentiated by CYP3A inhibitors. Concomitant drugs with a known risk for torsade de pointes (eg, azithromycin, clarithromycin, erythromycin); caution; consider alternatives. Concomitant methadone; monitor; may need dose adjustment.

Cabenuva Adverse Reactions

Adverse Reactions

Inj site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, rash; hepatotoxicity, depressive disorders.

Cabenuva Clinical Trials

See Literature

Cabenuva Note