Cabotegravir & Vitamin B3 (Niacin®) [class:green]

Cabotegravir is primarily metabolized by UGT1A1 with a minor UGT1A9 component.³³¹¹ 

For HIV PrEP (cabotegravir), dosing consists of:

1) Optional oral lead-in dose (at least 28 days). Cabotegravir 30 mg once daily.   The final oral dose of cabotegravir should be taken on the same day as the injection is started.Continuation Injections

2)  Initiation injections (two separate 3 mL injections).  Initiate injections on the final day of oral lead-in (if using).  Administer 3 mL (600 mg) cabotegravir via IM injection at a gluteal site, given 1 month apart for 2 consecutive months.  Individuals may be given the second cabotegravir initiation injection up to 7 days before or after the date the individual is scheduled to receive the injection.

3)  Maintenance injections.  After the 2 initiation injection doses given consecutively 1 month apart, administer cabotegravir 600-mg (3-mL) via IM injection every 2 months. Individuals may be given the next cabotegravir injection up to 7 days before or after the date the individual is scheduled to receive the injection.

For maintenance treatment of HIV (cabotegravir/rilpivirine):

1)  Every 2-month IM dosing (3 mL dosing kit):

    a)  optional oral lead-in dose (at least 28 days). Cabotegravir 30 mg once daily taken with rilpivirine 25 mg once daily; rilpivirine must be taken with a meal.   The final oral doses of cabotegravir and rilpivirine should be taken on the same day as injections are started.

    b)  Initiation injections (Month 1 and Month 2).  Initiate injections on the final day of oral lead-in (if using), or on final day of prior antiretroviral therapy.  Administer 3 mL (600 mg) cabotegravir and 3 mL (900 mg) rilpivirine via IM injection at separate gluteal sites at the same visit.  One month later, administer a second set of 3 mL initiation injections.

   c)  Continuation injections (Month 4 and every 2 months onwards).  Administer 3 mL (600 mg) cabotegravir and 3 mL (900 mg) rilpivirine via IM injection at separate gluteal sites at the same visit.  Patients may be given injections up to 7 days before or after the date of the scheduled q2monthly 3 mL injection dosing visit.

2) Every 1-month IM dosing (3 mL dosing kit for initiation, 2 mL dosing kit for continuation).

    a)  optional oral lead-in dose (at least 28 days). Cabotegravir 30 mg once daily taken with rilpivirine 25 mg once daily; rilpivirine must be taken with a meal.   The final oral doses of cabotegravir and rilpivirine should be taken on the same day as injections are started.

    b)  Initiation injections (Month 1).  Initiate injections on the final day of oral lead-in (if using), or on final day of prior antiretroviral therapy.  Administer 3 mL (600 mg) cabotegravir and 3 mL (900 mg) rilpivirine via IM injection at separate gluteal sites at the same visit.  

   c)  Continuation injections (Month 2 and every month onwards).  One month following initiation injections, administer 2 mL (400 mg) cabotegravir and 2 mL (600 mg) rilpivirine via IM injection at separate gluteal sites at the same visit.  Patients may be given injections up to 7 days before or after the date of the scheduled monthly 2 mL injection dosing visit.

Missed doses:

a)  oral cabotegravir tablet:  take as soon as the patient remembers if it is more than 12 hours until the next dose.  If the next dose is due within 12 hours, skip the missed dose and resume usual dosing schedule.

b)  every 2 month injections:  if less than or equal to 2 months since last injection, resume with 3 mL dosing as soon as possible.  If it has been more than 2 months since the last injection, reinitiate the patient on 3 mL injections for 2 months, and then continue every other month dosing.  If the patient was on oral therapy, resume injections on the same day as the last day of oral therapy.

c)  monthly injections:  if less than or equal to 2 months since last injection, resume with 2 mL dosing as soon as possible.  If it has been more than 2 months since the last injection, reinitiate the patient on 3 mL injections and then continue monthly 2 mL injections of cabotegravir and rilpivirine.  If the patient was on oral therapy, resume injections on the same day as the last day of oral therapy.

Oral bridging (planned missed injections):

For planned missed injections (oral bridging):  take first oral dose starting at the time of the planned missed injection date.  Oral cabotegravir and rilpivrine, or any fully suppressive oral antiretroviral regimen may be used.  Oral therapy can be used for a duration of two months.  Resume injections on the last day of oral therapy dosing.

Multiple dose pharmacokinetics of cabotegravir 30 mg orally once daily:  Cmax 8.1 ug/mL, AUC 146 ug.h/mL, and Ctrough 4.7 ug/mL.³³¹¹

Following monthly IM injections of cabotegravir 400 mg suspension:  Cmax 4.2 ug/mL, AUC 2461.h/mL, and Ctrough 2.9 ug/mL.  Cabotegravir has been detected in plasma up to 52 weeks or longer after administration of a single injection.  Pharmacokinetic steady-state is achieved by 44 weeks.  Plasma cabotegravir exposure increases in proportion or slightly less than in proportion to dose following single and repeat IM injection of doses ranging from 100 to 800 mg.³³¹¹ 

Cabotegravir is present in the female and male genital tract. Median cervical and vaginal tissue:plasma ratios ranged from 0.16 to 0.28 and median rectal tissue:plasma ratios were ≤0.08 following a single 400mg IM injection at 4, 8, and 12 weeks after dosing.³³¹¹

Cabotegravir is present in CSF. In HIV-1 infected patients receiving cabotegravir long-acting injectable suspension plus rilpivirine long-acting injectable suspension in combination, the median cabotegravir CSF-to-plasma concentration ratio (n=16) was 0.304% to 0.344% (range:
0.218% to 0.449%) and higher than corresponding median unbound cabotegravir concentrations in plasma 1 week following a steady-state cabotegravir injection or rilpivirine injection given monthly or every 2 months.³³¹¹

Following a single injection of CAB LA 600mg and RPV LA 900mg to the vastus lateralis (lateral thigh) in 14 healthy adults without HIV: Cmax 3.38 ug/mL, Tmax 1 week, AUC 3832 h*ug/mL.  Concentration at week 4 and 8 were 2.56 ug/mL (15-fold) and 0.88 ug/mL (5.3-fold) above protein-adjusted IC90 for CAB.³⁶³⁵  

Cabotegravir plasma exposure was generally found to be comparable between monthly subcutaneous (SC) anterior abdominal and intramuscular gluteal (IM) injection in a study of 93 participants with >3 years of experience with IM injections of cabotegravir+rilpivirine.  The 90% confidence interval of the geometric LSM ratios of Cmax and Ctau of the 3 SC monthly injections were all within 0.8-1.25 bioequivalence limits of the IM gluteal injection immediately prior to the first SC injection.  Pain (48%), nodules (34%), and erythema (26%) were the most commonly reported SC-related injection site reactions, with a median duration of 10 days.  At week 12, 84/93 (90%) participants maintained HIV VL <50 copies/mL copies/mL³⁷²³