Usual Adult Dose for HIV Infection

30 mg orally once a day

Comments:

• To be taken with rilpivirine tablets (25 mg orally once a day); the manufacturer product information for rilpivirine tablets should be consulted.
• Oral lead-in may be used to assess tolerability of cabotegravir before the initiation of cabotegravir-rilpivirine IM; oral lead-in is recommended for about 1 month (at least 28 days).
• The last oral dose should be administered on the same day injections with cabotegravir-rilpivirine IM are started.
• If a patient plans to miss a monthly scheduled injection of cabotegravir-rilpivirine IM by more than 7 days, daily oral therapy may be used for up to 2 months to replace missed injection visits.
• The first dose of oral therapy should be administered about 1 month (plus/minus 7 days) after the last injection dose of cabotegravir-rilpivirine IM and continued until the day injection dosing is restarted.
• For oral therapy with this drug and rilpivirine tablets of durations longer than 2 months, an alternative oral regimen is recommended.
• The manufacturer product information for cabotegravir-rilpivirine IM should be consulted to resume monthly injection dosing.
• If a patient plans to miss a scheduled every-2-month injection of cabotegravir-rilpivirine IM by more than 7 days, daily oral therapy may be used for up to 2 months to replace 1 missed scheduled every-2-month injection.
• The first dose of oral therapy should be administered about 2 months after the last injection dose of cabotegravir-rilpivirine IM and continued until the day injection dosing is restarted.
• For oral therapy with this drug and rilpivirine tablets of durations longer than 2 months, an alternative oral regimen is recommended.
• The manufacturer product information for cabotegravir-rilpivirine IM should be consulted to resume every-2-month injection dosing.

• Oral lead-in to assess tolerability of this drug before starting cabotegravir IM (a component of cabotegravir-rilpivirine IM)
• Oral therapy for patients who will miss planned injection dosing with cabotegravir-rilpivirine IM

Usual Adult Dose for Pre-Exposure Prophylaxis

Oral lead-in: 30 mg orally once a day for at least 28 days

IM:

• Initiation injection: 600 mg IM once a month for 2 doses
• Continuation injection (2 months after the second initiation injection): 600 mg IM every 2 months

• Patients must have a negative HIV-1 test before starting IM or oral cabotegravir for HIV-1 preexposure prophylaxis (PrEP).
• Therapy may be started with the oral tablets before the IM injection OR the patient may proceed directly to IM injection without an oral lead-in.

• Oral lead-in may be used to assess tolerability of this drug before the initiation of the IM injection; oral lead-in is recommended for about 1 month (at least 28 days).
• IM therapy should start on the last day of oral lead-in or within 3 days.
• If a patient plans to miss a monthly scheduled IM injection by more than 7 days, the oral tablets should be used once a day to replace 1 every-2-month injection visit.
• The first dose of oral therapy should be administered about 2 months after the last injection dose of the IM injection.
• The IM injection should be restarted on the day oral dosing ends or within 3 days.
• The manufacturer product information for the IM injection should be consulted regarding resumption of every-2-month injection dosing.

• If oral lead-in is used, the initiation injections should be started on the last day of oral lead-in or within 3 days thereafter.
• Continuation injections should be started 2 months after the initiation injections.
• Patients may be given the IM injection up to 7 days before or after the date of the scheduled injection dosing visit.

• IM Injection: In at-risk patients, for PrEP to reduce the risk of sexually acquired HIV-1 infection
• Oral Tablets: In at-risk patients, for short-term PrEP to reduce the risk of sexually acquired HIV-1 infection; may be used as:
• Oral lead-in to assess tolerability of this drug before starting cabotegravir IM
• Oral PrEP for patients who will miss planned injection dosing with cabotegravir IM

Usual Pediatric Dose for HIV Infection

12 years or older:

• At least 35 kg: 30 mg orally once a day

• To be taken with rilpivirine tablets (25 mg orally once a day); the manufacturer product information for rilpivirine tablets should be consulted.
• Oral lead-in may be used to assess tolerability of cabotegravir before the initiation of cabotegravir-rilpivirine IM; oral lead-in is recommended for about 1 month (at least 28 days).
• The last oral dose should be administered on the same day injections with cabotegravir-rilpivirine IM are started.
• If a patient plans to miss a monthly scheduled injection of cabotegravir-rilpivirine IM by more than 7 days, daily oral therapy may be used for up to 2 months to replace missed injection visits.
• The first dose of oral therapy should be administered about 1 month (plus/minus 7 days) after the last injection dose of cabotegravir-rilpivirine IM and continued until the day injection dosing is restarted.
• For oral therapy with this drug and rilpivirine tablets of durations longer than 2 months, an alternative oral regimen is recommended.
• The manufacturer product information for cabotegravir-rilpivirine IM should be consulted to resume monthly injection dosing.
• If a patient plans to miss a scheduled every-2-month injection of cabotegravir-rilpivirine IM by more than 7 days, daily oral therapy may be used for up to 2 months to replace 1 missed scheduled every-2-month injection.
• The first dose of oral therapy should be administered about 2 months after the last injection dose of cabotegravir-rilpivirine IM and continued until the day injection dosing is restarted.
• For oral therapy with this drug and rilpivirine tablets of durations longer than 2 months, an alternative oral regimen is recommended.
• The manufacturer product information for cabotegravir-rilpivirine IM should be consulted to resume every-2-month injection dosing.

• Oral lead-in to assess tolerability of this drug before starting cabotegravir IM (a component of cabotegravir-rilpivirine IM)
• Oral therapy for patients who will miss planned injection dosing with cabotegravir-rilpivirine IM

Usual Pediatric Dose for Pre-Exposure Prophylaxis

Adolescents weighing at least 35 kg:
Oral lead-in: 30 mg orally once a day for at least 28 days

IM:

• Initiation injection: 600 mg IM once a month for 2 doses
• Continuation injection (2 months after the second initiation injection): 600 mg IM every 2 months

• Patients must have a negative HIV-1 test before starting IM or oral cabotegravir for HIV-1 PrEP.
• Therapy may be started with the oral tablets before the IM injection OR the patient may proceed directly to IM injection without an oral lead-in.

• Oral lead-in may be used to assess tolerability of this drug before the initiation of the IM injection; oral lead-in is recommended for about 1 month (at least 28 days).
• IM therapy should start on the last day of oral lead-in or within 3 days.
• If a patient plans to miss a monthly scheduled IM injection by more than 7 days, the oral tablets should be used once a day to replace 1 every-2-month injection visit.
• The first dose of oral therapy should be administered about 2 months after the last injection dose of the IM injection.
• The IM injection should be restarted on the day oral dosing ends or within 3 days.
• The manufacturer product information for the IM injection should be consulted regarding resumption of every-2-month injection dosing.

• If oral lead-in is used, the initiation injections should be started on the last day of oral lead-in or within 3 days thereafter.
• Continuation injections should be started 2 months after the initiation injections.
• Patients may be given the IM injection up to 7 days before or after the date of the scheduled injection dosing visit.

• IM Injection: In at-risk patients, for PrEP to reduce the risk of sexually acquired HIV-1 infection
• Oral Tablets: In at-risk patients, for short-term PrEP to reduce the risk of sexually acquired HIV-1 infection; may be used as:
• Oral lead-in to assess tolerability of this drug before starting cabotegravir IM
• Oral PrEP for patients who will miss planned injection dosing with cabotegravir IM

Renal Dose Adjustments

IM:

• Mild to moderate renal dysfunction (CrCl 30 to less than 90 mL/min): No adjustment recommended.
• Severe renal dysfunction (CrCl 15 to less than 30 mL/min) or ESRD (CrCl less than 15 mL/min) not on dialysis: Increased monitoring for side effects recommended.

• Mild to moderate renal dysfunction (CrCl 30 to less than 90 mL/min) or severe renal dysfunction (CrCl less than 30 mL/min): No adjustment recommended.
• ESRD (CrCl less than 15 mL/min) not on dialysis: Data not available

Liver Dose Adjustments

Mild or moderate liver dysfunction (Child-Pugh A or B): No adjustment recommended.
Severe liver dysfunction (Child-Pugh C): Data not available

Comments:

• This drug has not been studied in patients with severe liver dysfunction.

Dose Adjustments

MISSED DOSES (HIV-1 PrEP):
Adherence to injection dosing schedule is strongly recommended; patients who miss a scheduled injection visit should be clinically reassessed to ensure resumption of therapy remains appropriate.

Planned Missed Injections:

• If a patient plans to miss a scheduled every-2-month continuation injection visit by more than 7 days, the oral tablets should be used daily (30 mg orally once a day) for up to 2 months to replace 1 missed scheduled every-2-month injection; an alternative oral regimen is recommended for oral PrEP durations exceeding 2 months.
• The first dose of oral PrEP should be administered about 2 months after the last dose of the IM injection.
• Injection dosing should be restarted on the day oral dosing ends or within 3 days; thereafter, as recommended below (Injection Dosing Recommendations after Missed Injections).

• If a scheduled injection visit is missed/delayed by more than 7 days and oral dosing has not been taken in the interim, the patient should be clinically reassessed to determine if resumption of injection dosing remains appropriate.
• If injection dosing will be continued, Injection Dosing Recommendations after Missed Injections should be consulted.

• If second injection is missed and time since first injection is:
• Up to 2 months: 600 mg IM as soon as possible and then should continue with the every-2-month injection dosing schedule
• Greater than 2 months: 600 mg IM once a month for 2 doses and then should continue with the every-2-month injection dosing schedule
• If third or subsequent injection is missed and time since prior injection is:
• Up to 3 months: 600 mg IM as soon as possible and then should continue with the every-2-month injection dosing schedule
• Greater than 3 months: 600 mg IM once a month for 2 doses and then should continue with the every-2-month injection dosing schedule

Precautions

US BOXED WARNING (IM INJECTION):

• DRUG RESISTANCE RISK WITH HIV-1 PREEXPOSURE PROPHYLAXIS USE IN UNDIAGNOSED EARLY HIV-1 INFECTION: Patients must be tested for HIV-1 infection before starting this drug (IM injection or oral tablets), and with each subsequent injection of the IM formulation, using a test approved/cleared by the US FDA for diagnosis of acute/primary HIV-1 infection; drug-resistant HIV-1 variants identified with use of the IM injection by patients with undiagnosed HIV-1 infection. The IM injection should not be started for HIV-1 PrEP unless negative infection status is confirmed; patients who become infected with HIV-1 while receiving this drug for PrEP must switch to a complete HIV-1 treatment regimen.

• Previous hypersensitivity reaction to the active component
• Coadministration with drugs that significantly decrease cabotegravir plasma levels due to UGT1A1 enzyme induction (which may lead to loss of virologic response), including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine
• HIV-1 Treatment: Contraindications to rilpivirine
• HIV-1 PrEP: Unknown or positive HIV-1 status

Dialysis

Data not available

Comments:

• This drug is highly bound to plasma proteins; significant removal via dialysis is unlikely.

Other Comments

Administration advice:
HIV-1 TREATMENT:

• Oral Tablets:
• Consult the manufacturer product information for cabotegravir-rilpivirine IM before starting this drug to ensure treatment with cabotegravir-rilpivirine IM is appropriate.
• Administer this drug with oral rilpivirine at about the same time each day with a meal.

• Test patients for HIV-1 infection before starting this drug (IM injection or oral tablets), and with each subsequent injection of the IM formulation, using a test approved/cleared by the US FDA for diagnosis of acute/primary HIV-1 infection; if an antigen/antibody-specific test is used and results are negative, confirm those negative results using an RNA-specific assay, even if results of the RNA-assay are available after administration of this drug.
• Oral Tablets:
• Consult the manufacturer product information for the IM injection before starting this drug to ensure use of the IM injection is appropriate.
• IM Injection:
• For gluteal IM use only; do not administer by any other route or anatomical site.
• Injections must be administered by a health care provider; consult the Instructions for Use for complete administration instructions.
• The ventrogluteal site is recommended for injection; a dorsogluteal approach (upper outer quadrant) is acceptable, if preferred by health care professional.
• Consider patient's BMI to ensure the needle length is sufficient to reach the gluteus muscle; may need longer needle lengths (not included in dosing kit) for patients with higher BMI (e.g., greater than 30 kg/m2) to ensure injections are administered IM and not subcutaneously

• Injection: Store at 2C to 25C (36F to 77F) in original carton until ready to use; exposure up to 30C (86F) permitted; do not freeze.
• Tablets: Store below 30C (86F).

• This drug should not be mixed with any other product or diluent.
• If the pack was stored in the refrigerator, the vial should be brought to room temperature (not to exceed 30C [86F]) before administration; no heating methods besides warmth of hands should be used.
• The vial should be shaken vigorously, so the suspension looks uniform before injecting; small air bubbles are expected and acceptable.
• Once the suspension has been drawn into the syringe, the injection should be administered as soon as possible, but may remain in the syringe for up to 2 hours (not in the refrigerator); if 2 hours are exceeded, the filled syringe and needle must be discarded.
• The manufacturer product information (Instructions for Use) should be consulted.

• Before starting the oral tablets, health care professionals should be aware that use of cabotegravir-rilpivirine IM with rifabutin is contraindicated.
• This drug should not be used in patients with known/suspected resistance to cabotegravir or rilpivirine.
• The manufacturer product information for rilpivirine tablets should be consulted.

• Before starting the IM injection, health care providers should carefully select patients who agree to the required injection dosing and testing schedule.
• Before starting this drug, patients should be counseled about the importance of adherence to scheduled dosing visits.
• The health care provider and patient may decide to use an oral lead-in with the oral tablets before starting the IM injection to assess tolerability of this drug OR the health care provider and patient may proceed directly to IM injection of this drug without using an oral lead-in.
• No safety and efficacy data are available for use of the IM injection with an oral lead-in; however, in HIV-1 treatment clinical trials, data show that an oral lead-in is not needed to ensure adequate plasma drug exposure upon starting injections and safety and efficacy results of cabotegravir-rilpivirine IM were similar when administered with and without oral lead-in.

• Hepatic: Liver chemistries
• Infections/Infestations: For HIV-1 when used for PrEP (before each injection and upon diagnosis of any other sexually transmitted infections [STIs])

• Read the US FDA-approved patient labeling (Patient Information).
• Contact health care provider at once if rash develops; stop this drug immediately and seek medical care if rash develops with fever, generally ill feeling, extreme tiredness, muscle/joint aches, blisters, oral blisters/lesions, eye inflammation, facial swelling, swelling of the eyes/lips/tongue/mouth, difficulty breathing, and/or signs/symptoms of liver problems (e.g., yellowing of the skin/whites of the eyes, dark/tea-colored urine, pale-colored stools/bowel movements, nausea, vomiting, loss of appetite, pain/aching/sensitivity on the right side below the ribs).
• Seek prompt medical evaluation if depressive symptoms develop.

• It is important to take this drug on a regular dosing schedule with a meal at the same time as oral rilpivirine; avoid missing doses as this can lead to development of resistance. If a dose is missed, take it as soon as you remember.

• Use this drug as part of an overall HIV-1 infection prevention strategy, including adherence to administration schedule and safer sex practices (including condoms) to reduce risk of STIs.
• Adherence to scheduled dosing visits is important to help reduce risk of acquiring HIV-1 infection and development of resistance.
• Resistance to this drug may occur if HIV-1 is acquired before or during therapy or after stopping this drug; it is important to be clinically reassessed for risk of HIV-1 acquisition and tested frequently to confirm HIV-1 negative status.
• If HIV-1 infection is confirmed, contact health care professional since HIV-1 treatment must be started.
• Consider alternative forms of PrEP after stopping this drug if at continued risk of acquiring HIV-1; start within 2 months of the last injection of this drug.
• Discontinue the IM injection if hepatotoxicity is confirmed.