integrase strand transfer inhibitors instis
- PO 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 (Cabenuva); or 2) As oral therapy for patients who will miss planned dosing with the cabotegravir/rilpivirine extended-release injection (Cabenuva).
- PO IM Pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk individuals. 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 extended-release injection (Apretude); or 2) As oral PrEP for patients who will miss planned dosing with the cabotegravir extended-release injection (Apretude).
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.
- Reduction in risk of sexually acquired HIV infection in at-risk individuals.
Absorption: Increased with high-fat meals after oral administration.
Distribution: Widely 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: PO: 41 hr; IM: 5.6–11.5 wk.
TIME/ACTION PROFILE (plasma concentrations)
|PO||unknown||3 hr||24 hr|
|IM||unknown||7 days||2 mo|
- Concurrent use of carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, or rifapentine;
- Unknown or positive HIV-1 status (for HIV-1 PrEP only)
- Lactation: Breastfeeding not recommended in patients with HIV.
Use Cautiously in:
- Severe hepatic impairment;
- End-stage renal disease (CCr <15 mL/min);
- Severe renal impairment (CCr 15–<30 mL/min) (injection only)
- OB: Safety not established in pregnancy;
- Pedi: Safety and effectiveness not established in children <12 yr;
- 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: diarrhea, HEPATOTOXICITY, nausea
Local: injection site reactions
MS: ↑ creatine kinase (injection)
Neuro: abnormal dreams, anxiety, depression, dizziness, fatigue, headache, insomnia, mood disturbances
Misc: fever, HYPERSENSITIVITY REACTIONS (including angioedema)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- 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.
- May ↓ methadone levels and effectiveness.
Oral Lead-in Dosing to Assess Tolerability of Cabotegravir
PO (Adults and Children ≥12 yr and ≥35 kg): 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 (Cabenuva) therapy. The last dose of oral cabotegravir should be taken on the same day that cabotegravir/rilpivirine extended-release injection (Cabenuva) therapy is initiated.
Oral Dosing to Replace Planned Missed Doses of Cabotegravir/Rilpivirine Extended-Release Injection (Cabenuva)
PO (Adults and Children ≥12 yr and ≥35 kg): To replace planned missed cabotegravir/rilpivirine extended-release injections (Cabenuva) for patients on monthly dosing schedule (if patient plans to miss scheduled monthly injection by >7 days): 30 mg once daily (with 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 (Cabenuva) is restarted (oral replacement therapy can be continued for up to 2 mo). To replace planned missed cabotegravir/rilpivirine extended-release injections (Cabenuva) for patients on every 2-month dosing schedule (if patient plans to miss scheduled every 2-month injection by >7 days): 30 mg once daily (with rilpivirine 25 mg once daily) initiated the same time as missed injection of cabotegravir/rilpivirine and then continued until day the cabotegravir/rilpivirine extended-release injection (Cabenuva) is restarted (oral replacement therapy can be continued for up to 2 mo).
HIV-1 Pre-exposure ProphylaxisMay initiate with cabotegravir oral lead-in therapy (to assess tolerability of cabotegravir) prior to cabotegravir IM injections or may precede directly to cabotegravir IM injections without oral lead-in.
Oral Lead-in Therapy
PO (Adults and Children ≥12 yr and ≥35 kg): 30 mg once daily. Continue for ≥28 days to assess tolerability prior to initiating IM therapy (see Initiation Injection Therapy section below).
IM (Adults and Children ≥12 yr and ≥35 kg): With oral lead-in therapy: 600 mg once monthly for 2 consecutive mo (second initiation injection may be administered up to 7 days before or after the date the individual is scheduled to receive the injection), then proceed with Continuation Injections. First initiation injection should be given on the last day of oral cabotegravir lead-in therapy or within 3 days of the last dose of oral cabotegravir lead-in therapy (see Oral Lead-in Therapy section above to assess tolerability of cabotegravir). Without oral lead-in therapy: 600 mg once monthly for 2 consecutive mo (second initiation injection may be administered up to 7 days before or after the date the individual is scheduled to receive the injection), then proceed with Continuation Injections.
IM (Adults and Children ≥12 yr and ≥35 kg): 600 mg every 2 mo starting 2 mo after the last initiation injection (injection may be administered up to 7 days before or after the date the individual is scheduled to receive the injection).
Missed Doses of Injection
PO (Adults and Children ≥12 yr and ≥35 kg): Planned missed injections: If a patient plans to miss a scheduled every 2-mo dose of cabotegravir extended-release injection (Apretude) by >7 days, use cabotegravir 30 mg once daily to replace one every 2-mo injection. The first dose of oral therapy should be taken approximately 2 mo after the last dose of cabotegravir extended-release injection (Apretude) and continued until the day that injection dosing is restarted or within 3 days of injection dosing being restarted. For oral PrEP durations >2 months, use an alternative oral regimen for PrEP. Unplanned missed injections: If a scheduled injection visit is missed or delayed by >7 days and oral dosing has not been taken in the interim, clinically reassess to determine if injection therapy remains appropriate.
Tablets (Vocabria): 30 mg
Extended-release suspension for injection (Apretude): 200 mg/mL
- 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.
- IM Apretude : Before starting Apretude for HIV-1 PrEP, ask seronegative individuals about recent (in past month) potential exposure events (condomless sex or condom breaking during sex with a partner of unknown HIV-1 status or unknown viremic status, a recent sexually transmitted infection [STI]), and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (fever, fatigue, myalgia, skin rash). If recent (<1 mo) exposures to HIV-1 are suspected or symptoms consistent with acute HIV-1 infection are present, use an FDA-approved test as an aid in diagnosis of acute or primary HIV-1 infection. When using Apretude for HIV-1 PrEP, test for HIV-1 before each injection and upon diagnosis of any other STIs. If an individual has confirmed HIV-1 infection, then individual must be transitioned to a complete HIV-1 treatment regimen. Apretude may be initiated with oral cabotegravir prior to intramuscular injections or patient may proceed directly to injection of Apretude without an oral lead-in.
- Prior to starting Apretude , carefully select individuals who agree to the required injection dosing and testing schedule and counsel individuals about the importance of adherence to scheduled dosing visits to help reduce the risk of acquiring HIV-1 infection and development of resistance.
- Bring to room temperature prior to administration. Administer undiluted in the ventrogluteal or dorsogluteal site; do not administer by any other route or anatomical site. Consider the body mass index (BMI) of the individual to ensure that the needle length is sufficient to reach the gluteus muscle. Longer needle lengths may be required for individuals with higher BMI (>30 kg/m2 ) to ensure injection is administered IM and not subcut. Solution is white to light pink; do not administer solutions that are discolored or contain particulate matter. Do not freeze. Do not mix with any other product or diluent. Administer dose as soon as possible; may remain in the syringe for up to 2 hr.
- 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.
- Apretude is not always effective in preventing HIV-1. Encourage consistent and correct condom use; knowledge of partner(s)' HIV-1 status, including viral suppression status; regular testing for STIs that can facilitate HIV-1 transmission.
- 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 breastfeeding. Cabotegravir is detected in systemic circulation for ≥12 mo after discontinuing Apretude. 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 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.