integrase strand transfer inhibitors instis
Short-term treatment of HIV-1 infection 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 (in combination with rilpivirine). To be used in one of the following situations: 1) As an oral lead-in therapy to assess the tolerability of cabotegravir prior to administration of cabotegravir/rilpivirine extended-release injection; or 2) As oral therapy for patients who will miss planned dosing with the cabotegravir/rilpivirine extended-release injection.
Inhibits HIV-1 integrase, which is required for viral replication.
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.
TIME/ACTION PROFILE (blood levels)
|PO||unknown||3 hr||24 hr|
- Concurrent use of carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, or rifapentine;
- Lactation: Breast feeding not recommended in patients with HIV.
Use Cautiously in:
- Hepatic impairment;
- End-stage renal disease (CCr <15 mL/min);
- OB: Safety not established in pregnancy;
- 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
GI: HEPATOTOXICITY, nausea
Neuro: abnormal dreams, anxiety, depression, headache, insomnia, mood disturbances
Misc: HYPERSENSITIVITY REACTIONS (including angioedema)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong UGT1A1 inducers, including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine may significantly ↓ levels and effectiveness; concurrent use contraindicated.
- Antacids containing polyvalent cations, including aluminum hydroxide, calcium carbonate, or magnesium hydroxide may ↓ absorption and effectiveness of cabotegravir; administer antacids ≥2 hr before or ≥4 hr after cabotegravir.
Oral Lead-in Dosing to Assess Tolerability of Cabotegravir
PO (Adults): 30 mg once daily (taken with rilpivirine 25 mg once daily). Continue for ≥28 days to assess tolerability prior to initiating cabotegravir/rilpivirine extended-release injection therapy. The last dose of oral cabotegravir should be taken on the same day that cabotegravir/rilpivirine extended-release injection therapy is initiated.
Oral Dosing to Replace Planned Missed Doses of Cabotegravir/Rilpivirine Extended-Release Injection
PO (Adults): If a patient plans to miss a scheduled dose of cabotegravir/rilpivirine extended-release injection by >7 days, use cabotegravir 30 mg once daily (with rilpivirine 25 mg once daily) to replace up to 2 consecutive monthly injection visits. The first dose of oral therapy should be taken approximately 1 mo after the last dose of cabotegravir/rilpivirine extended-release injection and continued until the day injection dosing is restarted.
Tablets: 30 mg
- 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.
Lab Test Considerations:
Monitor liver functions tests periodically during therapy.
- Oral lead-in is used for at least 28 days concurrently with rilpivirine to assess the tolerability of cabotegravir prior to the initiation of cabotegravir/rilpivirine. Administer last oral dose on same day injections with cabotegravir/rilpivirine are started.
- If taking to replace a missed scheduled injection of cabotegravir/rilpivirine, take first dose of oral therapy approximately 1 mo after last injection dose and continue until the day injection dosing is restarted.
- PO Administer once daily with a meal at the same time each day.
- Instruct patient to take cabotegravir as directed. Take missed doses as soon as remembered. Do not stop taking cabotegravir without consulting health care professional. Instruct patient to read Patient Information before starting cabotegravir and with each Rx refill 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), 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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