cabotegravir/rilpivirine

ka-boe-teg-ra-vir/ril-pi-vir-een

Trade Name(s): (Cabenuva)

Do not confuse cabotegravir with cabozantinib, dolutegravir, elvitegravir, or raltegravir; or rilpivirine with etravirine.

• PHARMACOTHERAPEUTIC: Integrase strand transfer inhibitor (INSTI), non-nucleoside reverse transcriptase inhibitor (NNRTI). CLINICAL: Antiretroviral agent (anti-HIV).

Treatment of HIV-1 infection in adults and adolescents 12 yrs of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in pts who are virologically suppressed (HIV-1 RNA less than 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.

Contraindications: Hypersensitivity to cabotegravir or rilpivirine. Concomitant use of carBAMazepine, oxcarbazepine, PHENobarbital, phenytoin; rifabutin, rifAMPin, rifapentine; dexAMETHasone, St. John's wort. Cautions: Hepatic/renal impairment, psychiatric disorders (e.g., depression, psychosis, suicidal ideation). Concomitant use of other antiretrovirals is not recommended.

Cabotegravir inhibits HIV integrase by blocking strand transfer of retroviral DNA integration (essential for HIV replication cycle). Rilpivirine blocks noncompetitive HIV-1 reverse transcriptase (does not inhibit DNA polymerases). Therapeutic Effect: Interferes with HIV replication, slowing progression of HIV infection.

Widely distributed. Cabotegravir metabolized by enzymatic activity via glucuronidation. Rilpivirine metabolized in liver. Protein binding: 99% (or greater). Peak plasma concentration: (cabotegravir): 7 days; (rilpivirine): 3–4 days. Cabotegravir excreted in feces (59%), urine (27%). Rilpivirine excreted in feces (85%), urine (6%). Half-life: (cabotegravir): 5.6–11.5 wks; (rilpivirine): 13–28 wks. Cabotegravir and rilpivirine can remain in systemic circulation for up to 12 mos after discontinuation.

Pregnancy/Lactation: Unknown if distributed in breast milk. Breastfeeding not recommended due to risk of postnatal HIV transmission. Children: Safety and efficacy not established in pts younger than 12 yrs or weighing less than 35 kg. Elderly: Safety and efficacy not established.

DRUG: Strong CYP3A4 inducers (e.g., carBAMazepine, phenytoin, rifAMPin)may decrease concentration/effect; use contraindicated. DexAMETHasone (more than 1 dose) may decrease concentration/effect of rilpivirine. Macrolide antibiotics (e.g., azithromycin, clarithromycin) may increase concentration/effect of rilpivirine; may increase risk of torsade de pointes. HERBAL: St. John's wort may decrease concentration/effect. FOOD: None known. LAB VALUES: May increase serum ALT, AST, bilirubin, creatine phosphokinase, lipase.

Injection Suspension, Long-Acting (Co-Packaged Kit): cabotegravir 400 mg/2 mL (200 mg/mL) with rilpivirine 600 mg/2 mL (300 mg/mL), cabotegravir 600mg/3 mL (200 mg/mL) with rilpivirine 900 mg/3 mL (300 mg/mL).

Intramuscular

Note: Initiate treatment on the last day of current antiretroviral therapy (with or without an oral lead-in of cabotegravir and rilpivirine according to manufacturer guidelines). Cabotegravir and rilpivirine must be given at the same appointment by a healthcare professional. May give up to 7 days before or after scheduled injections. If a dose is missed, see manufacturer guidelines for recommendations.

Preparation · Remove vials from refrigerator and allow suspension to warm to room temperature (approx. 15 min). · Visually inspect for particulate matter or discoloration (brown tinted glass may impair inspection). Cabotegravir suspension should appear white to light pink. Rilpivirine suspension should appear white to off-white. · Shake vials well until suspension is uniform. Small air bubbles may be present. · Transfer suspension into supplied syringes (see manufacturer guidelines).

Administration · Insert each needle intramuscularly into separate gluteal sites at least 2 cm apart or on opposite sides and inject suspension(s). Do not give IV or SQ. · Do not inject into areas of active skin disease or injury such as sunburns, skin rashes, inflammation, skin infections, or active psoriasis.

Storage · Refrigerate vials in original carton until time of use. Do not freeze. · Vials warmed to room temperature may remain in carton for up to 6 hrs. Do not return to refrigerator. · Suspension-filled syringes may be stored at room temperature for up to 2 hrs. Do not refrigerate.

Note: For gluteal IM administration only.

HIV-1 Infection

IM: ADULTS, CHILDREN 12 YRS AND OLDER WEIGHING AT LEAST 35 KG: Monthly regimen: Initially, 600 mg (cabotegravir) and 900 mg (rilpivirine) once on the last day of current antiretroviral therapy, then continue with injections of 400 mg (cabotegravir) and 600 mg (rilpivirine) monthly thereafter. Every 2-mo regimen: Initially, (on the last day of current antiretroviral therapy), 600 mg (cabotegravir) and 900 mg (rilpivirine) once monthly for 2 consecutive mos, then 600 mg (cabotegravir) and 900 mg (rilpivirine) q2 mos thereafter (begin 2 mos after last initiation injection).

Dose Modification

Switching Regimen from Monthly to Every 2 mos: Give 600 mg (cabotegravir) and 900 mg (rilpivirine) once 1 mo after last maintenance dose, then continue same dose q2mos. Switching Regimen from Every 2 mos to Monthly: Give 400 mg (cabotegravir) and 600 mg (rilpivirine) once 2 mos after last maintenance dose, then continue same dose monthly.

Dosage in Renal Impairment

Mild to moderate impairment: No dose adjustment. Severe impairment: Recommend increased monitoring for adverse effects/toxic reactions. Recommend increased monitoring for adverse effects/toxic reactions. ESRD: Not specified; use caution.

Dosage in Hepatic Impairment

Mild to moderate impairment: No dose adjustment. Severe impairment: Not specified; use caution.

Frequent (83%): Injection site reactions (pain/discomfort, nodules, induration, swelling, erythema, pruritus, bruising/discoloration, warmth, hematoma). Occasional (8%–5%): Pyrexia, fatigue, malaise, asthenia. Rare (4% to less than 2%): Headache, musculoskeletal pain, myalgia, nausea, insomnia, somnolence, rash, abdominal pain, weight gain, anxiety, abnormal dreams.

Hypersensitivity reactions, including angioedema, dyspnea, hepatitis; severe rash that is accompanied by blisters, fatigue, fever, muscle and joint pain, oral lesions may occur. Serious postinjection reactions (abdominal cramping, agitation, bronchospasm, chest or back pain, dizziness, flushing, oral numbness, sweating) reported in less than 1% of pts. Hepatotoxicity may occur in pts with or without prior hepatic impairment. Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported. DRESS may present as facial swelling, eosinophilia, fever, lymphadenopathy, rash, which may involve other organ systems, such as hepatitis, hematologic abnormalities, myocarditis, nephritis. May increase risk of suicidal behavior and ideation. Other psychological disorders may include depression, dysphoria, irritability, mood swings.

• BASELINE ASSESSMENTObtain LFT, CD4+ count, viral load, HIV-1 RNA level; pregnancy test in females of reproductive potential. Pts should be carefully selected for treatment and must agree to comply with the required dosing schedule. Advise pts that noncompliance may cause drug resistance and viral rebound. Question history of hepatic/renal impairment; psychiatric disorder, suicidal ideation and behavior. Receive full medication history (including herbal products) and screen for contraindications/interactions. Concomitant use of other medications may need to be adjusted or discontinued.INTERVENTION/EVALUATIONMonitor CD4+ count, viral load, HIV-1 RNA level for treatment effectiveness. Monitor LFT for hepatic injury (bruising, jaundice, right upper abdominal pain, nausea, vomiting, weight loss). Cough, dyspnea, fever, excess band cells on CBC may indicate acute infection (WBC may be unreliable in pts with uncontrolled HIV infection). Diligently assess for suicidal ideation and behavior; new-onset or worsening of anxiety, depression, mood disorder. Consult mental health professional if mood disorder is suspected. Monitor for hypersensitive reactions, serious injection reactions, symptoms of DRESS.PATIENT/FAMILY TEACHING
• Treatment does not cure HIV infection or reduce risk of transmission. Practice safe sex with barrier methods or abstinence.
• Drug resistance or viral rebound can form if treatment is interrupted; do not miss scheduled injection appointments. · As immune system strengthens, it may respond to dormant infections hidden within the body. Report any new fever, chills, body aches, cough, night sweats, shortness of breath. · Report symptoms of drug-induced hypersensitivity syndrome (e.g., fever, swollen face/lymph nodes, skin rash/peeling/inflammation). · Seek immediate medical attention if thoughts of suicide, new-onset or worsening of anxiety, depression, or changes in mood occurs. · There is a high risk of interactions with other medications. Do not take newly prescribed medications unless approved by prescriber who originally started therapy. Do not take herbal products, esp. St John's wort. · Breastfeeding not recommended. · Report liver problems (abdominal pain, bruising, clay-colored stool, amber or dark-colored urine, yellowing of the skin or eyes), rash. · Severe allergic reactions may occur. Seek immediate medical attention if difficulty breathing, dizziness, fast heart rate, itching, hives, rash; swelling of the face, lips, or tongue occurs.