Introduction

Antiretroviral; human immunodeficiency virus type-1 (HIV-1) integrase strand transfer inhibitor (INSTI).

Uses for Cabotegravir (Systemic)

Treatment of HIV Infection

Cabotegravir sodium oral tablets (Vocabria) are used in combination with rilpivirine for short-term treatment of HIV-1 infection in adults and adolescents ≥12 years of age who weigh ≥35 kg and who are virologically suppressed (HIV-1 RNA<50 copies/mL) on a stable antiretroviral regimen, have no history of treatment failure, and have no known or suspected resistance to cabotegravir or rilpivirine.

Used with rilpivirine for oral lead-in dosing to assess tolerability prior to administration of a parenteral regimen of cabotegravir and rilpivirine extended-release injectable suspensions; also may be used with rilpivirine for oral therapy in patients who will miss planned doses of cabotegravir/rilpivirine injections.

Therapeutic options for treatment and prevention of HIV infection and recommendations concerning use of antiretrovirals are continuously evolving. Most appropriate antiretroviral regimen cannot be defined for every clinical scenario; select regimen based on antiretroviral potency, potential rate of resistance development, known toxicities, potential for pharmacokinetic interactions, and patient's virologic, immunologic, and clinical characteristics.

The Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents does not recommend use of cabotegravir/rilpivirine as initial therapy for patients with HIV because of the lack of data supporting efficacy in antiretroviral therapy-naïve patients. Viral suppression should first be attained on a recommended regimen.

The HHS Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV states that data on use of cabotegravir plus rilpivirine in adolescents are currently limited to safety, pharmacokinetics, and acceptability; data not yet available on use in adolescents with adherence concerns.

Pre-exposure Prophylaxis for Prevention of HIV-1 Infection

Cabotegravir extended-release injectable suspension (Apretude) is used in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection.

Cabotegravir sodium oral tablets (Vocabria) are used for at-risk adults and adolescents weighing at least 35 kg for short-term PrEP to reduce the risk of sexually acquired HIV-1 infection. The drug is used orally to determine tolerability prior to administration of parenteral cabotegravir and in patients who will miss planned doses of cabotegravir injection.

Experts recommend cabotegravir extended-release injection for PrEP in adults and adolescents weighing ≥35 kg at risk of acquiring HIV. Use of oral cabotegravir is optional for a 4-week lead-in prior to initiation of the injections. Cabotegravir injections may be especially appropriate for patients with significant renal disease, those who have had difficulty with adherence to oral PrEP therapy, and for those who prefer injections every 2 months to an oral PrEP dosing schedule.

Cabotegravir (Systemic) Dosage and Administration

General

Pretreatment Screening

• Review concomitant medications and consider potential for drug interactions.

• A negative HIV-1 test should be confirmed immediately prior to initiation of cabotegravir for HIV-1 PrEP.

Patient Monitoring

• Perform screening for HIV-1 infection prior to each IM injection for HIV-1 PrEP. Negative results from an antigen/antibody-specific test should be confirmed using an RNA-specific assay.

• Periodically monitor liver function tests (i.e., AST, ALT).

• Monitor for drug interactions and adverse effects that may result from interactions.

• Assess patient adherence to the prescribed therapy during scheduled dosing visits for PrEP.

Administration

Cabotegravir sodium (Vocabria) is administered orally as tablets. Cabotegravir extended-release injectable suspension (Apretude) is administered by IM injection.

Oral Administration

Cabotegravir sodium (Vocabria) is administered orally once daily in combination with rilpivirine (Edurant). Take at the same time each day with food.

Oral lead-in dosing to assess the tolerability of cabotegravir may be used for approximately 1 month (>28 days) prior to the initiation of cabotegravir extended-release injectable suspension (Apretude) or the combined regimen of cabotegravir and rilpivirine extended-release injectable suspension (Cabenuva).

Consider oral therapy with cabotegravir tablets for patients planning to miss a monthly or every-2-month scheduled injection of cabotegravir extended-release injectable suspension (Apretude) or cabotegravir and rilpivirine extended-release injectable suspension (Cabenuva) by more than 7 days. For patients missing a monthly scheduled injection by more than 7 days, daily oral cabotegravir in combination with oral rilpivirine should be initiated approximately 1 month (+/- 7 days) after the last IM injection and continued until the day that IM extended-release injection is restarted. Oral replacement therapy with cabotegravir and rilpivirine may be continued for up to 2 months to replace missed monthly IM extended-release injections. For patients missing an every 2 month scheduled injection by more than 7 days, daily oral therapy with cabotegravir and rilpivirine should be initiated approximately 2 months after the last IM injection and continued until the day the IM extended-release injection is restarted.

Parenteral Administration

Administer cabotegravir extended-release suspension by gluteal IM injection.

Injection therapy may be initiated with oral cabotegravir prior to beginning IM injections, or the patient may proceed directly to cabotegravir injections without an oral lead-in.

If stored in the refrigerator, bring the vial to room temperature prior to administration (not to exceed 30°C). Once the suspension has been drawn into the syringe, administer the injection as soon as possible. The suspension may remain in the syringe for up to 2 hours, but filled syringes should not be placed in the refrigerator. If the drug remains in the syringe for more than 2 hours, discard.

If an oral lead-in is used, administer initiation injections on the last day of oral lead-in or within 3 days thereafter. The recommended initiation injection doses is a single IM injection given 1 month apart for 2 consecutive months. The second IM injection may be given up to 7 days before or after the date the patient is scheduled to receive the injections.

After the 2 initiation injection doses given consecutively 1 month apart, continue IM injections every 2 months. Injections may be given up to 7 days before or after the date the patient is scheduled to receive the injections.

Dosage

Available orally as cabotegravir sodium; dosage expressed in terms of cabotegravir.

Pediatric Patients

Treatment of HIV Infection

Oral

Lead-in Dosing to Assess Tolerability: Patients ≥12 years of age who weigh ≥35 kg are recommended to take oral cabotegravir 30 mg in combination with oral rilpivirine 25 mg daily for approximately 1 month (at least 28 days).

Oral Dosing to Replace Planned Missed Injections (Monthly Schedule): If a patient plans to miss a monthly scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, administer oral cabotegravir 30 mg with oral rilpivirine 25 mg daily for up to 2 months to replace missed injection visits. For oral therapy durations greater than 2 months, an alternative oral regimen is recommended.

Oral Dosing to Replace Planned Missed Injections (2 Month Schedule): If a patient plans to miss a scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, administer oral cabotegravir 30 mg with oral rilpivirine 25 mg daily for up to 2 months to replace 1 missed scheduled every 2 month injection.

Refer to the Vocabria prescribing information for further information related to the dosing of oral cabotegravir in this setting.

Pre-exposure Prophylaxis (PrEP) for Prevention of HIV-1 Infection

Oral

Lead-in Dosing to Assess Tolerability: In at risk adolescents who weigh ≥35 kg, administer oral cabotegravir 30 mg daily for approximately 1 month (at least 28 days). Following oral lead-in, start initiation injection of cabotegravir extended-release injectable suspension on the last day of oral lead-in or within 3 days.

Dosing to Replace Planned Missed Injections (2-month schedule): If an at risk adolescent who weighs ≥35 kg plans to miss a scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, take one oral cabotegravir 30 mg daily to replace the every 2 month injection.

IM

Initiation and Continuation Injections: Initially, for at risk adolescents weighing at least 35 kg, administer a single 600 mg injection given 1 month apart for 2 consecutive months on the last day or within 3 days of an oral lead-in (if used) and then continue with the injections every 2 months thereafter.

Unplanned Missed Injections: If a scheduled injection visit is missed or delayed by more than 7 days and oral dosing has not been taken in the interim, clinically reassess the individual to determine if resumption of injection dosing remains appropriate. If the injection dosing schedule will be continued, see the following dosing recommendations in Table 1.

Adults

Treatment of HIV Infection

Oral

Lead-in Dosing to Assess Tolerability: Administer oral cabotegravir 30 mg in combination with oral rilpivirine 25 mg once daily for approximately 1 month (at least 28 days).

Oral Dosing to Replace Planned Missed Injections (Monthly Schedule): If a patient plans to miss a monthly scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, administer oral cabotegravir 30 mg with oral rilpivirine 25 mg daily for up to 2 months to replace missed injection visits. For oral therapy durations greater than 2 months, an alternative oral regimen is recommended.

Oral Dosing to Replace Planned Missed Injections (2 Month Schedule): If a patient plans to miss a scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, take oral cabotegravir 30 mg with oral rilpivirine 25 mg daily for up to 2 months to replace 1 missed schedule every 2 month injection. Refer to the Vocabria prescribing information for further information related to the dosing of oral cabotegravir in this setting.

Pre-exposure Prophylaxis (PrEP) for Prevention of HIV-1 Infection

Oral

Lead-in Dosing to Assess Tolerability: The recommended dose of cabotegravir for the prevention of HIV infection is cabotegravir 30 mg daily for approximately 1 month (at least 28 days). Following oral lead-in, start initiation injection of cabotegravir extended-release injectable suspension on the last day of oral lead-in or within 3 days.

Dosing to Replace Planned Missed Injections (2-month schedule): If a patient plans to miss a scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, take oral cabotegravir 30 mg for up to 2 months to replace 1 missed scheduled every 2 month injection.

IM

Initiation and continuation injections:Initially administer a single 600-mg injection given 1 month apart for 2 consecutive months on the last day or within 3 days of an oral lead-in (if used) and then continue with the injections every 2 months thereafter.

Unplanned missed injections: If a scheduled injection visit is missed or delayed by more than 7 days and oral dosing has not been taken in the interim, clinically reassess the individual to determine if resumption of injection dosing remains appropriate. If the injection dosing schedule will be continued, see the dosing recommendations in Table 1.

Prescribing Limits

Special Populations

Hepatic Impairment

No dosage adjustment necessary in patients with mild or moderate hepatic impairment (Child-Pugh A or B) based on clinical studies with oral cabotegravir. The effect of severe hepatic impairment (Child-Pugh C) on pharmacokinetics is unknown.

Renal Impairment

No dosage adjustment of oral cabotegravir is necessary for patients with mild to moderate (Cl_cr 30 to <90 mL/minute) or severe renal impairment (Cl_cr <30 mL/minute). The effect of end-stage renal disease (Cl_cr <15 mL/minute) on the pharmacokinetics of oral cabotegravir is unknown.

Based on studies with oral cabotegravir, no dosage adjustment of cabotegravir extended-release injection is necessary for individuals with mild (Cl_cr 60 to <90 mL/minute) or moderate (Cl_cr 30 to <60 mL/minute) renal impairment. In individuals with severe renal impairment (Cl_cr 15 to <30 mL/minute) or end-stage renal disease (Cl_cr <15 mL/minute), increased monitoring for adverse effects is recommended.

Geriatric Use

Use caution when administering to geriatric patients.

Contraindications

• Previous hypersensitivity reaction to cabotegravir.

• Coadministration with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, or rifapentine; significant decreases in cabotegravir plasma concentrations may occur due to uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1 enzyme induction, which may result in loss of virologic response.

• For HIV-1 pre-exposure prophylaxis: Unknown or positive HIV-1 status.

Warnings/Precautions

Warnings

Potential Risk of Resistance with Cabotegravir for PrEP in Undiagnosed HIV-1 Infection

Potential risk of developing resistance if an individual acquires HIV-1 either before or while receiving or following discontinuation of cabotegravir extended-release injection. (See Boxed Warning.)

Test patients for HIV-1 infection prior to initiating oral or parenteral cabotegravir and with each subsequent injection of the drug, using a test approved or cleared by FDA for the diagnosis of acute or primary HIV-1 infection. Do not initiate cabotegravir extended-release injection for HIV-1 PrEP unless negative infection status is confirmed. Individuals who become infected with HIV-1 while receiving cabotegravir extended-release injection for PrEP must transition to a complete HIV-1 treatment regimen.

Consider alternate forms of PrEP following discontinuation for individuals at continuing risk of HIV-1 acquisition and initiate within 2 months of the final injection of cabotegravir extended-release injection.

Hypersensitivity Reactions

Serious or severe hypersensitivity reactions reported with other integrase inhibitors and could occur with cabotegravir. Remain vigilant and discontinue the drug if a hypersensitivity reaction is suspected.

Discontinue cabotegravir immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, mucosal involvement [oral blisters or lesions], conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Monitor the patient, including obtaining liver aminotransferases, and initiate appropriate therapy.

Comprehensive Management to Reduce the Risk of HIV-1 Infection When Cabotegravir is Used for HIV-1 Pre-Exposure Prophylaxis

Use cabotegravir for HIV-1 PrEP as part of a comprehensive prevention strategy including adherence to the administration schedule and safer sex practices to reduce the risk of sexually transmitted infections (STIs).

Cabotegravir is not always effective in preventing HIV-1 acquisition. The time from initiation of cabotegravir for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.

Counsel HIV-1–uninfected patients to strictly adhere to the recommended dosing and testing schedule to reduce the risk of HIV-1 acquisition and the potential development of resistance.

Long-Acting Properties and Potential Associated Risks with Cabotegravir Extended-release Injection

Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer) after receiving cabotegravir extended-release injection.

Carefully select patients who agree to the required every-2-month injection dosing schedule because non-adherence could lead to HIV-1 acquisition and development of resistance.

Consider the prolonged-release characteristics when cabotegravir extended-release injection is prescribed.

Hepatotoxicity

Hepatotoxicity reported in patients receiving cabotegravir with or without known pre-existing hepatic disease or identifiable risk factors.

Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations.

Monitor liver chemistries and discontinue treatment with cabotegravir if hepatotoxicity is suspected.

Depressive Disorders

Depressive disorders (including depressed mood, depression, mood altered, mood swings, persistent depressive disorder, suicide ideation or attempt) reported with use of cabotegravir for treatment of HIV-1 infection or HIV-1 PrEP.

Promptly evaluate patients with depressive symptoms to assess whether symptoms are related to cabotegravir and to determine whether risks of continued therapy outweigh the benefits.

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

Concomitant use of cabotegravir and other drugs may result in known or potentially significant drug interactions, some of which may lead to adverse events, loss of virologic response of cabotegravir, and possible development of viral resistance.

See manufacturer's labeling for recommendations to prevent or manage these drug interactions, including dosing recommendations. Consider potential for drug interactions prior to and during therapy; review concomitant medications during therapy.

Risks Associated with Rilpivirine Treatment

Cabotegravir is indicated for use in combination with rilpivirine. Review the prescribing information for rilpivirine prior to initiation of combination therapy with cabotegravir and rilpivirine.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Data are insufficient regarding use of oral cabotegravir or extended-release cabotegravir injection in pregnant females to inform a drug-associated risk of birth defects or miscarriage. Use cabotegravir only if expected benefit justifies potential risk to the fetus.

The Health and Human Services Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission states that data are not available regarding use of cabotegravir for the treatment of HIV-1 infection during pregnancy and, therefore the drug is not recommended as a complete treatment regimen in pregnant females or females of reproductive potential trying to conceive. The Panel recommends that pregnant individuals who present to care on this regimen should be switched to an appropriate 3-drug antiretroviral regimen recommended for use in pregnancy.

The Health and Human Services Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission states that although cabotegravir has been approved by the FDA for use in PrEP, safety data are limited regarding use of the drug during conception and breastfeeding.

Lactation

Not known whether cabotegravir is distributed into human milk; however, the drug is distributed into milk in rats.

Not known whether cabotegravir affects human milk production or the breast-fed infant. Because detectable concentrations of cabotegravir remain in systemic circulation for up to 12 months after discontinuing cabotegravir extended-release injections, it is recommended that women receiving this treatment breastfeed only if the expected benefit justifies the potential risk to the infant.

Because of the risk of adverse effects in the infant and the risk of HIV transmission, HIV-infected women should not breast-feed infants. For uninfected mothers receiving oral cabotegravir for HIV-1 PrEP, assess the benefit-risk of using this medication to the infant while breastfeeding.

Pediatric Use

Safety, efficacy, and pharmacokinetics of oral and injectable cabotegravir not established in pediatric patients <12 years of age or weighing <35 kg.

Safety, efficacy, and pharmacokinetics of oral and injectable cabotegravir were evaluated in HIV-1-infected pediatric patients 12 to <18 years of age weighing ≥35 kg in an ongoing, open-label, non-comparative clinical trial.

Safety of oral cabotegravir in adolescents is expected to be similar to adults, as there is no clinically significant difference in drug exposure.

Safety and efficacy of oral cabotegravir for HIV-1 PrEP in pediatric patients ≥12 years of age weighing ≥35 kg who are at-risk of HIV-1 infection is supported by data from 2 controlled clinical trials in adults.

Geriatric Use

Clinical trials of oral and injectable cabotegravir did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger subjects. In general, exercise caution when using in geriatric patients.

Renal Impairment

No dosage adjustment of oral or injectable cabotegravir is necessary for patients with mild or moderate (Cl_cr 30 mL/minute to <90 mL/minute) renal impairment. In patients with severe renal impairment (Cl_cr <30 mL/minute), no dosage changes recommended for oral cabotegravir; however, in patients receiving injectable extended-release cabotegravir with severe renal impairment (Cl_cr 15 to <30 mL/minute) or end-stage renal disease (Cl_cr <15 mL/minute), increased monitoring for adverse effects is recommended.

The effect of end-stage renal disease ( <15 mL/minute) on pharmacokinetics of cabotegravir is unknown. Dialysis not expected to alter exposure of cabotegravir.

Hepatic Impairment

No dosage adjustment of oral or injectable cabotegravir is necessary for patients with mild or moderate hepatic impairment (Child-Pugh class A or B). The effect of severe hepatic impairment (Child-Pugh class C) on the pharmacokinetics of oral or injectable cabotegravir is unknown.

Common Adverse Effects

Most common adverse reactions reported in at least 3 HIV-infected patients receiving oral cabotegravir: fatigue, headache, diarrhea, nausea, dizziness, abnormal dreams, anxiety, insomnia, abdominal discomfort, abdominal distension, asthenia.

Most common adverse reactions (≥1%) in HIV-uninfected patients receiving oral cabotegravir: headache, diarrhea, nausea, dizziness, upper respiratory tract infection, somnolence, fatigue, abnormal dreams, abdominal pain.

Most common adverse reactions (≥1%) in patients receiving cabotegravir extended-release injection: injection site reactions, diarrhea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, upper respiratory infection.

General

Pretreatment Screening

• Review concomitant medications and consider potential for drug interactions.

• A negative HIV-1 test should be confirmed immediately prior to initiation of cabotegravir for HIV-1 PrEP.

Patient Monitoring

• Perform screening for HIV-1 infection prior to each IM injection for HIV-1 PrEP. Negative results from an antigen/antibody-specific test should be confirmed using an RNA-specific assay.

• Periodically monitor liver function tests (i.e., AST, ALT).

• Monitor for drug interactions and adverse effects that may result from interactions.

• Assess patient adherence to the prescribed therapy during scheduled dosing visits for PrEP.

Administration

Cabotegravir sodium (Vocabria) is administered orally as tablets. Cabotegravir extended-release injectable suspension (Apretude) is administered by IM injection.

Oral Administration

Cabotegravir sodium (Vocabria) is administered orally once daily in combination with rilpivirine (Edurant). Take at the same time each day with food.

Oral lead-in dosing to assess the tolerability of cabotegravir may be used for approximately 1 month (>28 days) prior to the initiation of cabotegravir extended-release injectable suspension (Apretude) or the combined regimen of cabotegravir and rilpivirine extended-release injectable suspension (Cabenuva).

Consider oral therapy with cabotegravir tablets for patients planning to miss a monthly or every-2-month scheduled injection of cabotegravir extended-release injectable suspension (Apretude) or cabotegravir and rilpivirine extended-release injectable suspension (Cabenuva) by more than 7 days. For patients missing a monthly scheduled injection by more than 7 days, daily oral cabotegravir in combination with oral rilpivirine should be initiated approximately 1 month (+/- 7 days) after the last IM injection and continued until the day that IM extended-release injection is restarted. Oral replacement therapy with cabotegravir and rilpivirine may be continued for up to 2 months to replace missed monthly IM extended-release injections. For patients missing an every 2 month scheduled injection by more than 7 days, daily oral therapy with cabotegravir and rilpivirine should be initiated approximately 2 months after the last IM injection and continued until the day the IM extended-release injection is restarted.

Parenteral Administration

Administer cabotegravir extended-release suspension by gluteal IM injection.

Injection therapy may be initiated with oral cabotegravir prior to beginning IM injections, or the patient may proceed directly to cabotegravir injections without an oral lead-in.

If stored in the refrigerator, bring the vial to room temperature prior to administration (not to exceed 30°C). Once the suspension has been drawn into the syringe, administer the injection as soon as possible. The suspension may remain in the syringe for up to 2 hours, but filled syringes should not be placed in the refrigerator. If the drug remains in the syringe for more than 2 hours, discard.

If an oral lead-in is used, administer initiation injections on the last day of oral lead-in or within 3 days thereafter. The recommended initiation injection doses is a single IM injection given 1 month apart for 2 consecutive months. The second IM injection may be given up to 7 days before or after the date the patient is scheduled to receive the injections.

After the 2 initiation injection doses given consecutively 1 month apart, continue IM injections every 2 months. Injections may be given up to 7 days before or after the date the patient is scheduled to receive the injections.

Dosage

Available orally as cabotegravir sodium; dosage expressed in terms of cabotegravir.

Pediatric Patients

Treatment of HIV Infection

Oral

Lead-in Dosing to Assess Tolerability: Patients ≥12 years of age who weigh ≥35 kg are recommended to take oral cabotegravir 30 mg in combination with oral rilpivirine 25 mg daily for approximately 1 month (at least 28 days).

Oral Dosing to Replace Planned Missed Injections (Monthly Schedule): If a patient plans to miss a monthly scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, administer oral cabotegravir 30 mg with oral rilpivirine 25 mg daily for up to 2 months to replace missed injection visits. For oral therapy durations greater than 2 months, an alternative oral regimen is recommended.

Oral Dosing to Replace Planned Missed Injections (2 Month Schedule): If a patient plans to miss a scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, administer oral cabotegravir 30 mg with oral rilpivirine 25 mg daily for up to 2 months to replace 1 missed scheduled every 2 month injection.

Refer to the Vocabria prescribing information for further information related to the dosing of oral cabotegravir in this setting.

Pre-exposure Prophylaxis (PrEP) for Prevention of HIV-1 Infection

Oral

Lead-in Dosing to Assess Tolerability: In at risk adolescents who weigh ≥35 kg, administer oral cabotegravir 30 mg daily for approximately 1 month (at least 28 days). Following oral lead-in, start initiation injection of cabotegravir extended-release injectable suspension on the last day of oral lead-in or within 3 days.

Dosing to Replace Planned Missed Injections (2-month schedule): If an at risk adolescent who weighs ≥35 kg plans to miss a scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, take one oral cabotegravir 30 mg daily to replace the every 2 month injection.

IM

Initiation and Continuation Injections: Initially, for at risk adolescents weighing at least 35 kg, administer a single 600 mg injection given 1 month apart for 2 consecutive months on the last day or within 3 days of an oral lead-in (if used) and then continue with the injections every 2 months thereafter.

Unplanned Missed Injections: If a scheduled injection visit is missed or delayed by more than 7 days and oral dosing has not been taken in the interim, clinically reassess the individual to determine if resumption of injection dosing remains appropriate. If the injection dosing schedule will be continued, see the following dosing recommendations in Table 1.

Adults

Treatment of HIV Infection

Oral

Lead-in Dosing to Assess Tolerability: Administer oral cabotegravir 30 mg in combination with oral rilpivirine 25 mg once daily for approximately 1 month (at least 28 days).

Oral Dosing to Replace Planned Missed Injections (Monthly Schedule): If a patient plans to miss a monthly scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, administer oral cabotegravir 30 mg with oral rilpivirine 25 mg daily for up to 2 months to replace missed injection visits. For oral therapy durations greater than 2 months, an alternative oral regimen is recommended.

Oral Dosing to Replace Planned Missed Injections (2 Month Schedule): If a patient plans to miss a scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, take oral cabotegravir 30 mg with oral rilpivirine 25 mg daily for up to 2 months to replace 1 missed schedule every 2 month injection. Refer to the Vocabria prescribing information for further information related to the dosing of oral cabotegravir in this setting.

Pre-exposure Prophylaxis (PrEP) for Prevention of HIV-1 Infection

Oral

Lead-in Dosing to Assess Tolerability: The recommended dose of cabotegravir for the prevention of HIV infection is cabotegravir 30 mg daily for approximately 1 month (at least 28 days). Following oral lead-in, start initiation injection of cabotegravir extended-release injectable suspension on the last day of oral lead-in or within 3 days.

Dosing to Replace Planned Missed Injections (2-month schedule): If a patient plans to miss a scheduled dose of cabotegravir and rilpivirine extended-release injectable suspensions by more than 7 days, take oral cabotegravir 30 mg for up to 2 months to replace 1 missed scheduled every 2 month injection.

IM

Initiation and continuation injections:Initially administer a single 600-mg injection given 1 month apart for 2 consecutive months on the last day or within 3 days of an oral lead-in (if used) and then continue with the injections every 2 months thereafter.

Unplanned missed injections: If a scheduled injection visit is missed or delayed by more than 7 days and oral dosing has not been taken in the interim, clinically reassess the individual to determine if resumption of injection dosing remains appropriate. If the injection dosing schedule will be continued, see the dosing recommendations in Table 1.

Prescribing Limits

Special Populations

Hepatic Impairment

No dosage adjustment necessary in patients with mild or moderate hepatic impairment (Child-Pugh A or B) based on clinical studies with oral cabotegravir. The effect of severe hepatic impairment (Child-Pugh C) on pharmacokinetics is unknown.

Renal Impairment

No dosage adjustment of oral cabotegravir is necessary for patients with mild to moderate (Cl_cr 30 to <90 mL/minute) or severe renal impairment (Cl_cr <30 mL/minute). The effect of end-stage renal disease (Cl_cr <15 mL/minute) on the pharmacokinetics of oral cabotegravir is unknown.

Based on studies with oral cabotegravir, no dosage adjustment of cabotegravir extended-release injection is necessary for individuals with mild (Cl_cr 60 to <90 mL/minute) or moderate (Cl_cr 30 to <60 mL/minute) renal impairment. In individuals with severe renal impairment (Cl_cr 15 to <30 mL/minute) or end-stage renal disease (Cl_cr <15 mL/minute), increased monitoring for adverse effects is recommended.

Geriatric Use

Use caution when administering to geriatric patients.

Primarily metabolized by uridine diphosphate-glucuronosyltransferase (UGT) 1A1 with some contribution from UGT1A9. Strong inducers of UGT1A1 or UGT1A9 are expected to decrease cabotegravir plasma concentrations and may result in loss of efficacy; therefore, coadministration of cabotegravir with these drugs is contraindicated.

Cabotegravir in combination with rilpivirine is a recommended complete regimen for the treatment of HIV-1 infection; coadministration of cabotegravir with other antiretroviral medications for PrEP is not recommended.

Residual concentrations of cabotegravir extended-release injection may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer); however, these residual concentrations are not expected to affect the exposures of antiretroviral drugs that are initiated after discontinuation.

Specific Drugs