Usual Adult Dose for HIV Infection

MONTHLY DOSING:

• Initiation Injections:
• Cabotegravir: 600 mg IM once as a single dose
• Rilpivirine: 900 mg IM once as a single dose
• Continuation Injections (1 month after initiation injections):
• Cabotegravir: 400 mg IM once a month
• Rilpivirine: 600 mg IM once a month

EVERY-2-MONTH DOSING:

• Initiation Injections:
• Cabotegravir: 600 mg IM once a month for 2 doses
• Rilpivirine: 900 mg IM once a month for 2 doses
• Continuation Injections (2 months after second initiation injections):
• Cabotegravir: 600 mg IM every 2 months
• Rilpivirine: 900 mg IM every 2 months

Comments:

• Therapy may be started with oral cabotegravir and oral rilpivirine before the IM injections (to assess tolerability of cabotegravir and rilpivirine) OR the health care provider and patient may decide to proceed directly to injection without an oral lead-in.
• If oral lead-in is used, the recommended oral dosage is a cabotegravir 30-mg tablet plus a rilpivirine 25-mg tablet once a day (with a meal); oral lead-in should be used for about 1 month (at least 28 days), followed by IM initiation injections of this product.
• This product can be injected monthly or every 2 months; health care providers should discuss the 2 dosing options with the patient before starting therapy and decide which injection dosing frequency is most appropriate for the patient.
• Initiation injections should be started on the last day of current antiretroviral therapy or oral lead-in, if used.
• Continuation injections should be started 1 month after the initiation injections for monthly dosing or 2 months after the 2 initiation injections (given consecutively 1 month apart) for every-2-month dosing.
• Cabotegravir and rilpivirine injections (initiation and continuation) should be administered at separate gluteal injection sites (on opposite sides or at least 2 cm apart) during the same visit.
• Patients may be given this product up to 7 days before or after the date of the scheduled injection dosing visit.

Use: As a complete regimen, for the treatment of HIV-1 infection to replace the current antiretroviral regimen in patients who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known/suspected resistance to either cabotegravir or rilpivirine

Usual Pediatric Dose for HIV Infection

12 years or older weighing at least 35 kg:
MONTHLY DOSING:

• Initiation Injections:
• Cabotegravir: 600 mg IM once as a single dose
• Rilpivirine: 900 mg IM once as a single dose
• Continuation Injections (1 month after initiation injections):
• Cabotegravir: 400 mg IM once a month
• Rilpivirine: 600 mg IM once a month

EVERY-2-MONTH DOSING:

• Initiation Injections:
• Cabotegravir: 600 mg IM once a month for 2 doses
• Rilpivirine: 900 mg IM once a month for 2 doses
• Continuation Injections (2 months after second initiation injections):
• Cabotegravir: 600 mg IM every 2 months
• Rilpivirine: 900 mg IM every 2 months

Comments:

• Therapy may be started with oral cabotegravir and oral rilpivirine before the IM injections (to assess tolerability of cabotegravir and rilpivirine) OR the health care provider and patient may decide to proceed directly to injection without an oral lead-in.
• If oral lead-in is used, the recommended oral dosage is a cabotegravir 30-mg tablet plus a rilpivirine 25-mg tablet once a day (with a meal); oral lead-in should be used for about 1 month (at least 28 days), followed by IM initiation injections of this product.
• This product can be injected monthly or every 2 months; health care providers should discuss the 2 dosing options with the patient before starting therapy and decide which injection dosing frequency is most appropriate for the patient.
• Initiation injections should be started on the last day of current antiretroviral therapy or oral lead-in, if used.
• Continuation injections should be started 1 month after the initiation injections for monthly dosing or 2 months after the 2 initiation injections (given consecutively 1 month apart) for every-2-month dosing.
• Cabotegravir and rilpivirine injections (initiation and continuation) should be administered at separate gluteal injection sites (on opposite sides or at least 2 cm apart) during the same visit.
• Patients may be given this product up to 7 days before or after the date of the scheduled injection dosing visit.

Use: As a complete regimen, for the treatment of HIV-1 infection to replace the current antiretroviral regimen in patients who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known/suspected resistance to either cabotegravir or rilpivirine

Renal Dose Adjustments

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): Increased monitoring for side effects recommended.

Comments:

• In patients with ESRD not on dialysis, effects on the pharmacokinetics of each component are unknown.

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:

• The effect of severe liver dysfunction on the pharmacokinetics of each component is unknown.

Dose Adjustments

Switching from monthly to every-2-month injections: Starting 1 month after the last cabotegravir 400 mg and rilpivirine 600 mg continuation injection doses, patients should receive cabotegravir 600 mg and rilpivirine 900 mg IM every 2 months.

Switching from every-2-month to monthly injections: Starting 2 months after the last cabotegravir 600 mg and rilpivirine 900 mg continuation injection doses, patients should receive cabotegravir 400 mg and rilpivirine 600 mg IM once a month.

MISSED DOSES:
Adherence to the 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 for Patients on the Monthly Dosing Schedule:

• If a patient plans to miss a scheduled injection visit by more than 7 days, oral cabotegravir plus oral rilpivirine may be used for up to 2 months to replace missed injection visits, or any other fully suppressive oral antiretroviral regimen may be used until injections are resumed.
• For oral therapy with cabotegravir and rilpivirine tablets: The recommended dosage is cabotegravir 30 mg plus rilpivirine 25 mg orally once a day; for durations longer than 2 months, an alternative oral regimen is recommended.
• The first dose of oral therapy should be administered 1 month (plus/minus 7 days) after the last injection dose of this product and continued until the day injection dosing is restarted.

Unplanned Missed Injections for Patients on the Monthly Dosing Schedule:

• If monthly injections are missed or delayed by more than 7 days and oral therapy 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 for Patients on the Monthly Dosing Schedule should be consulted.

Injection Dosing Recommendations after Missed Injections for Patients on the Monthly Dosing Schedule:

• Up to 2 months since last injection: The monthly injection dosing schedule (cabotegravir 400 mg and rilpivirine 600 mg IM once a month) should be resumed as soon as possible.
• Greater than 2 months since last injection: The patient should be reinitiated on cabotegravir 600 mg and rilpivirine 900 mg, and then should continue to follow the monthly injection dosing schedule (cabotegravir 400 mg and rilpivirine 600 mg IM once a month).

Planned Missed Injections for Patients on the Every-2-Month Dosing Schedule:

• If a patient plans to miss a scheduled injection visit by more than 7 days, oral cabotegravir plus oral rilpivirine may be used for up to 2 months to replace 1 missed injection visit, or any other fully suppressive oral antiretroviral regimen may be used until injections are resumed.
• For oral therapy with cabotegravir and rilpivirine tablets: The recommended dosage is cabotegravir 30 mg plus rilpivirine 25 mg orally once a day; for durations longer than 2 months, an alternative oral regimen is recommended.
• The first dose of oral therapy should be administered about 2 months after the last injection dose of this product and continued until the day injection dosing is restarted.

Unplanned Missed Injections for Patients on the Every-2-Month Dosing Schedule:

• If a scheduled every-2-month injection visit is missed or delayed by more than 7 days and oral therapy has not been taken in the interim, the patient should be clinically reassessed to determine if resumption of injection dosing remains appropriate.
• If the every-2-month dosing schedule will be continued, Injection Dosing Recommendations after Missed Injections for Patients on the Every-2-Month Dosing Schedule should be consulted.

Injection Dosing Recommendations after Missed Injections for Patients on the Every-2-Month Dosing Schedule:

• Missed injection visit for injection 2 (Month 2):
• Up to 2 months since last injection: Cabotegravir 600 mg and rilpivirine 900 mg injection doses should be resumed as soon as possible, and then should continue to follow with the every-2-month injection dosing schedule.
• Greater than 2 months since last injection: The patient should be reinitiated on cabotegravir 600 mg and rilpivirine 900 mg injection doses (once a month for 2 doses), and then should continue to follow the every-2-month injection dosing schedule thereafter.
• Missed injection visit for injection 3 or later (Month 4 onwards):
• Up to 3 months since last injection: Cabotegravir 600 mg and rilpivirine 900 mg injection doses should be resumed as soon as possible, and then should continue with the every-2-month injection dosing schedule.
• Greater than 3 months since last injection: The patient should be reinitiated on cabotegravir 600 mg and rilpivirine 900 mg injection doses (once a month for 2 doses), and then should continue with the every-2-month injection dosing schedule thereafter.

Precautions

CONTRAINDICATIONS:

• Previous hypersensitivity reaction to either active component
• Coadministration with drugs that significantly decrease cabotegravir and/or rilpivirine plasma levels due to UGT1A1 and/or CYP450 3A enzyme induction (which may lead to loss of virologic response), including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (more than a single-dose therapy), St. John's wort

Safety and efficacy have not been established in pediatric patients younger than 12 years or weighing less than 35 kg.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Comments:

• Each component of this product is highly bound to plasma proteins; significant removal via dialysis is unlikely.

Other Comments

Administration advice:

• 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.
• A complete dose requires 2 injections: 1 injection of cabotegravir and 1 injection of rilpivirine.
• Administer cabotegravir and rilpivirine injections at separate gluteal injection sites (on opposite sides or at least 2 cm apart) during the same visit; while the ventrogluteal site is recommended, 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
• The order of administration of cabotegravir and rilpivirine injections is not important.
• Observe patients for about 10 minutes after the injection.
• Adherence to injection dosing schedule strongly recommended.
• Clinically reassess patients who miss a scheduled injection visit to ensure resumption of therapy remains appropriate.

Storage requirements:

• Unopened vials: Store in refrigerator at 2C to 8C (36F to 46F) in original carton until ready to use; do not freeze.
• Before preparing the injections for administration, remove vials from refrigerator and allow to equilibrate to room temperature (not to exceed 25C [77F]) for at least 15 minutes.
• Vials may remain in carton at room temperature for up to 6 hours; do not return to the refrigerator. If the vials are not used within 6 hours, they must be discarded.
• Filled syringes: Once the suspensions have been drawn into the respective syringes, the injections should be administered as soon as possible, but may remain in the syringe for up to 2 hours.
• Do not place the filled syringes in the refrigerator.
• If 2 hours are exceeded, the filled syringes and needles must be discarded.

Reconstitution/preparation techniques:

• This suspensions should not be mixed with any other product or diluent; no further dilution or reconstitution is needed.
• Each vial should be shaken vigorously, so the suspensions look uniform before injecting; small air bubbles are expected and acceptable.
• The manufacturer product information (Instructions for Use) should be consulted.

General:

• This product contains cabotegravir extended-release injectable suspension in a single-dose vial and rilpivirine extended-release injectable suspension in a single-dose vial.
• Before starting this product, health care providers should carefully select patients who agree to the required monthly or every-2-month injection dosing schedule and counsel patients about the importance of keeping scheduled dosing visits (to help maintain viral suppression and reduce risk of viral rebound and potential development of resistance with missed doses).
• This product should not be used in patients with known/suspected resistance to cabotegravir or rilpivirine.

Monitoring:

• Hepatic: Liver chemistries

Patient advice:

• 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 medical evaluation at once if depressive symptoms develop.
• Continued medication adherence and scheduled visits are important to help maintain viral suppression and to reduce risk of loss of virologic response and development of resistance.
• Contact health care provider if you plan to miss a scheduled injection visit; if treatment with this product is stopped, you will need to take other medicines to treat your HIV-1 infection.