Pronunciation:
ka-boe-teg-ra-vir/ril-pi-vir-een
Trade Name(s)
Ther. Class.
Pharm. Class.
integrase strand transfer inhibitors instis
non nucleoside reverse transcriptase inhibitors
Management of 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.
Cabotegravir: Inhibits HIV-1 integrase, which is required for viral replication Rilpivirine: Inhibits HIV-replication by noncompetitively inhibiting HIV reverse transcriptase.
Therapeutic Effect(s):
Evidence of decreased viral replication and reduced viral load with slowed progression of HIV and its sequelae.
Cabotegravir
Absorption: Increased with high-fat meals.
Distribution: Distributed to extravascular tissues.
Protein Binding: >99%.
Metabolism and Excretion: Primarily metabolized by the uridine diphosphate glucuronosyltransferase (UGT) 1A1 enzyme system, with some involvement of UGT1A9. Primarily excreted in feces as unchanged drug (47%), with 27% excreted in urine as metabolites.
Half-life: 41 hr.
Rilpivirine
Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: 99.7%.
Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A isoenzyme; 25% excreted in feces unchanged, <1% excreted unchanged in urine.
Half-life: 50 hr
TIME/ACTION PROFILE (plasma concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
cabotegravir IM | unknown | 7 days | unknown |
rilpivirine IM | unknown | 3–4 days | unknown |
Contraindicated in:
Use Cautiously in:
CV: QT interval prolongation
Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash
GI: ↑ lipase, HEPATOTOXICITY, nausea
Local: injection site reactions
Metabolic: ↑ weight
MS: ↑ creatine kinase, pain
Neuro: depression, dizziness, fatigue, headache, insomnia, mood disturbances, negative thoughts, somnolence, SUICIDAL THOUGHTS/BEHAVIORS
Misc: fever, HYPERSENSITIVITY REACTIONS (including angioedema)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
Strong UGT1A1 inducers or CYP3A inducers, including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, or rifapentine may significantly ↓ cabotegravir and rilpivirine levels and effectiveness; concurrent use contraindicated.
Use of more than a single dose of dexamethasone may significantly ↓ rilpivirine levels and effectiveness; concurrent use contraindicated.
Drug-Natural Products:
St. John's wort may significantly ↓ rilpivirine levels and effectiveness; concurrent use contraindicated.
Lead-in therapy with oral cabotegravir and oral rilpivirine must be used for at least 28 days to assess tolerability to both cabotegravir and rilpivirine prior to initiating cabotegravir/rilpivirine extended-release injection therapy.
Monthly Dosing
IM (Adults and Children ≥12 yr and ≥35 kg): Initiation injections: Cabotegravir 600 mg as single injection and rilpivirine 900 mg as single injection, both administered on the final day of lead-in therapy with oral cabotegravir and oral rilpivirine. Continuation injections: Cabotegravir 400-mg injection and rilpvirine 600-mg injection once monthly (administer both injections during same visit). Start continuation injections 1 mo following initiation injections. Monthly injections may be given within 7 days of originally scheduled date of injection. Switching to every 2-mo injection dosing: Administer cabotegravir 600-mg injection and rilpivirine 900-mg injection one mo after the last monthly continuation injection and then every 2 mo thereafter. Planned missed injections: If patient plans to miss a scheduled injection visit by >7 days, give oral cabotegravir 30 mg once daily and oral rilpivirine 25 mg once daily initiated at the same time as missed injection of cabotegravir/rilpivirine and then continued until day the cabotegravir/rilpivirine extended-release injection is restarted (oral replacement therapy can be continued for up to 2 mo). If time since last injection ≤2 mo, resume injection with cabotegravir 400-mg injection and rilpivirine 600-mg injection once monthly. If time since last injection >2 mo, resume injection with initiation injection of cabotegravir 600-mg single injection and rilpivirine 900-mg single injection followed in 1 mo by continuation injections of cabotegravir 400-mg injection and rilpivirine 600-mg injection once monthly (start continuation injections 1 mo following initiation injections). Unplanned missed injections: If monthly injections are missed or delayed by >7 days and oral cabotegravir and oral rilpivirine therapy have not been taken in the interim, reassess patient to determine if resumption of injection dosing remains appropriate.
Every 2-Month Dosing
IM (Adults and Children ≥12 yr and ≥35 kg): Initiation injections: Cabotegravir 600-mg injection and rilpivirine 900-mg injection once monthly for 2 consecutive mo, with the first set of injections being administered on the final day of lead-in therapy with oral cabotegravir and oral rilpivirine. Second initiation injection may be given within 7 days of originally scheduled date of injection. Continuation injections: Cabotegravir 600-mg injection and rilpvirine 900-mg injection every 2 mo (administer both injections during same visit). Start continuation injections 2 mo following second initiation injection. Every 2-mo injections may be given within 7 days of originally scheduled date of injection. Switching to monthly injection dosing: Administer cabotegravir 400-mg injection and rilpivirine 600-mg injection 2 mo after the last monthly continuation injection and then once monthly thereafter. Planned missed injections: If patient plans to miss a scheduled injection visit by >7 days, give oral cabotegravir 30 mg once daily and oral rilpivirine 25 mg once daily initiated at the same time as missed injection of cabotegravir/rilpivirine and then continued until day the cabotegravir/rilpivirine extended-release injection is restarted (oral replacement therapy can be continued for up to 2 mo). If time since second initiation injection ≤2 mo, resume initiation injection with cabotegravir 600-mg injection and rilpivirine 900-mg injection, followed by continuation injections every 2 mo (starting 2 mo following second initiation injection). If time since second initiation injection >2 mo, restart the two initiation injections (see above) given once monthly for 2 consecutive months, followed by the continuation injections (see above) given every 2 mo. If patient misses a continuation injection by ≤3 mo, resume injection with cabotegravir 600-mg injection and rilpivirine 900-mg injection every 2 mo. If time since last injection >3 mo, restart the two initiation injections (see above) given once monthly for 2 consecutive mo followed by the continuation injections (see above) given every 2 mo. Unplanned missed injections: If monthly injections are missed or delayed by >7 days and oral cabotegravir and oral rilpivirine therapy have not been taken in the interim, reassess patient to determine if resumption of injection dosing remains appropriate.
Extended-release suspension for injection: 400-mg/600-mg kit (200 mg/mL vial of cabotegravir and 300 mg/mL vial of rilpivirine), 600-mg/900-mg kit (200 mg/mL vial of cabotegravir and 300 mg/mL vial of rilpivirine)
Monitor for anxiety, depression (especially in patients with a history of psychiatric illness), suicidal ideation, and paranoia during therapy.
Monitor for signs and symptoms of hypersensitivity reactions (severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing) during therapy. Discontinue cabotegravir immediately if reactions occur.
Lab Test Considerations:
Monitor liver functions tests periodically during therapy. Discontinue therapy is hepatotoxicity is suspected.
Advise patient to notify health care professional if signs and symptoms of allergic reaction (fever, generally ill feeling, tiredness, muscle or joint aches, trouble breathing, blisters or sores in mouth, blisters, redness or swelling of eyes, swelling of mouth, face, lips, or tongue), post-injection reactions (trouble breathing, stomach cramps, sweating, numbness of mouth, feeling anxious, feeling warm, feeling lightheaded or faint, blood pressure changes), liver problems (yellow skin or white part of eyes, dark or "tea-colored" urine, light-colored stools, nausea or vomiting, loss of appetite, pain, aching, or tenderness on the right side of stomach area, itching) or depression (feeling sad or hopeless, feeling anxious or restless, have thoughts of hurting yourself (suicide) or have tried to hurt yourself) occur.