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.
Evidence of decreased viral replication and reduced viral load with slowed progression of HIV and its sequelae.
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.
Absorption: Well absorbed following oral administration.
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 (blood levels)
|cabotegravir IM||unknown||7 days||unknown|
|rilpivirine IM||unknown||3–4 days||unknown|
- Hypersensitivity to cabotegravir or rilpivirine;
- Concurrent use of carbamazepine, dexamethasone (more than a single dose), oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John's wort;
- OB: Not recommended for use during pregnancy;
- Lactation: Breast feeding not recommended in patients with HIV.
Use Cautiously in:
- History of depression or suicide attempt;
- Hepatic impairment;
- Severe renal impairment (CCr 15–30 mL/min) or end-stage renal disease (CCr <15 mL/min);
- Pedi: Safety and effectiveness not established in children;
- Geri: Use with caution in older adults, considering concurrent disease states, drug therapy, and age-related ↓ in hepatic and renal function.
Adverse Reactions/Side Effects
Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash
GI: HEPATOTOXICITY, ↑ lipase, nausea
Local: injection site reactions
Metabolic: ↑ weight
MS: ↑ creatine kinase, pain
Neuro: SUICIDAL THOUGHTS/BEHAVIORS, depression, dizziness, fatigue, headache, insomnia, mood disturbances, negative thoughts, somnolence
Misc: HYPERSENSITIVITY REACTIONS (including angioedema), fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- 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.
- Macrolide antibiotics, including azithromycin, clarithromycin, and erythromycin may ↑ rilpivirine levels and risk of toxicity, including QT interval prolongation; use alternative antibiotic therapy.
- QT interval prolonging drugs may ↑ risk of QT interval prolongation and torsades de pointes.
- May ↓ levels and effects of methadone.
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.
IM (Adults): 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.
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)
- Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
- 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.
- Observe patient for 10 min following injections for post-injection reactions (dyspnea, agitation, abdominal cramping, flushing, sweating, oral numbness, changes in blood pressure).
Lab Test Considerations:
Monitor liver functions tests periodically during therapy. Discontinue therapy is hepatotoxicity is suspected.
- 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. Start injections of cabotegravir/rilpivirine on last day of PO lead-in therapy.
- IM Administer cabotegravir and rilpivirine at separate gluteal (preferably ventrogluteal) injection sites (on opposite sides or 2 cm apart) during the same visit. Use needles long enough for IM injection. Allow suspensions to come to room temperature for 15 min before administration. Stable at room temperature for up to 6 hr. Shake suspensions vigorously to mix. Administer within 2 hr of drawing into syringe. Start continuation injections a month after the initiation injections.
- Instruct patient in the importance of adhering to monthly schedule of injections. Planned Missed Injections: If a 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 approximately 1 mo after the last injection dose and continued until the day injection dosing is restarted. Unplanned Missed Injections: If monthly injections are missed or delayed by >7 days and PO therapy has not been taken in the interim, health care professional will reassess patient to determine if resumption of injection dosing remains appropriate. Instruct patient to read Patient Information before starting cabotegravir/rilpivirine therapy and with each injection in case of changes.
- 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.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy and avoid breast feeding. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to cabotegravir during pregnancy. Register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
- Decrease in viral load and improvement in CD4 cell counts.
- Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
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