CABOTEGRAVIR INJ,SUSP,SA
Clinical Criteria Summary
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Patient Eligibility & Inclusion Criteria
- • Prescribed by or in collaboration with a provider experienced or trained in PrEP administration (designated facility providers)
- • Substantial risk of HIV acquisition: sex without condoms, recent or frequent sexually transmitted infections (STIs), sexual relationship with an HIV-infected partner, injection drug abuse with equipment sharing
- • Must also meet at least one additional criterion:
- Intolerance to Truvada or Descovy
- CrCl <60 mL/min or multiple risk factors for significant renal dysfunction
- Patient-specific factors impacting adherence to daily oral PrEP (cognitive difficulties, gastrointestinal dysfunction, unstable housing, stigma, or fear of discovery)
- Very high-risk for HIV acquisition (MSM engaging in frequent condom-less receptive anal intercourse, repeated STIs, or high-risk sexual activity with partners known/likely to be HIV-infected)
Exclusion Criteria
- • Significant noncompliance with follow-up appointments unless barriers to compliance have been significantly addressed by the provider
- • Drug interactions that preclude administration of CAB (UGT1A1 inducers, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifamycin derivatives, St. John’s Wort)
Dosing & Administration Criteria
- • Dosing: 600mg IM monthly for 2 months, then every 2 months
- • Administration site: Gluteal muscle (absorption from other sites can be unpredictable)
Pre-Administration & Monitoring Criteria
- • HIV must be excluded prior to administration of CAB
- • Clinical recommendations for monitoring should be consulted
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Indication & Patient Population
- Indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents.
- Recommended for individuals reporting sexual behaviors placing them at substantial ongoing risk of HIV acquisition, and persons who inject drugs (PWID) with injection practices placing them at ongoing risk.
- Particularly beneficial for patients unable to adhere to oral daily dosing due to cognitive dysfunction impacting adherence, unstable housing or homelessness, gastrointestinal dysfunction impairing absorption, previous medication non-adherence despite regular clinic visit adherence, mental illness or substance abuse impacting compliance, or concerns about stigma/discovery of PrEP use by family or friends.
- May be considered on a case-by-case basis for those at highest risk of HIV infection (e.g., frequent condom-less or unprotected sexual encounters with partners known/at high risk for HIV, frequent needle/equipment sharing with IDU).
Dosing & Administration Requirements
- Dosage form: 600mg extended-release injectable suspension for intramuscular (IM) administration.
- Dosing schedule: 600mg IM repeated 4 weeks later, then every 8 weeks. Can be administered up to 7 days before or after the due date.
- Oral lead-in (30mg daily by mouth for 28 days) is OPTIONAL; if used, injection should start on the last day of oral therapy or within 3 days thereafter.
- Injectable must be administered by a healthcare professional.
- If a scheduled dose is missed by >7 days, clinical reassessment is required to ensure resumption remains appropriate; dosing schedule may need adjustment (e.g., restarting with 2 monthly doses prior to resuming every-2-month schedule).
- Oral cabotegravir (30mg daily for up to 2 months) can be used to replace one scheduled every-2-month injection if a patient is known/scheduled to miss an injection.
Testing & Monitoring Requirements
- A negative HIV-1 test MUST be completed and confirmed negative prior to initiating therapy AND with each subsequent injection (at least every 2 months).
- Testing should be repeated upon diagnosis of other STIs.
- For patients with recent high-risk behaviors, evaluate for clinical symptoms compatible with acute HIV infection; if present, use an FDA-cleared/approved test for acute HIV diagnosis.
- Patients must agree to required injection dosing and testing schedules; adherence counseling and support are required.
Contraindications & Warnings/Precautions
- Contraindicated in patients with unknown or positive HIV status.
- Contraindicated with previous hypersensitivity to cabotegravir.
- Contraindicated with co-administration of moderate-strong inducers of UGT1A1 due to potential loss of efficacy from decreased plasma concentrations.
- Boxed Warning: Risk of drug resistance if used as PrEP in undiagnosed HIV infection; monotherapy in undiagnosed HIV-1 may result in INSTI resistance. Patients found HIV-positive must immediately transition to a full antiretroviral regimen.
- Long-acting properties: Residual concentrations may remain for up to 12 months or longer. If discontinued, alternative PrEP should be considered for those remaining at high risk beginning within 2 months of the last injection; additional oral PrEP should be started within 4 weeks after the last dose in those continuing to engage in high-risk behaviors. Patients must reliably attend clinic visits.
- Hepatotoxicity: Clinical and lab monitoring should be considered; discontinue if suspected.
- Depressive disorders: Reported (including depression, suicide ideation/attempt).
- Hypersensitivity reactions: Oral lead-in may help identify risk prior to long-acting injection.
Special Populations & Organ Function Considerations
- Renal insufficiency: No dosage adjustment for mild/moderate impairment. Increased monitoring recommended for severe impairment (CrCl 15-29 mL/min) or ESRD (CrCl <15 mL/min). Dialysis not expected to alter exposures. Particularly beneficial for patients with CrCl <30 mL/min or multiple risk factors for nephrotoxicity.
- Hepatic insufficiency: No dose adjustment for mild-moderate impairment (CTP A or B). Impact of severe impairment unknown.
- Pregnancy: Insufficient data; neural tube defects associated with other INSTIs. Animal studies showed delayed parturition, increased stillbirths/neonatal deaths at >28x RHD. Pregnancy registry exists. Consider prolonged concentrations in women of childbearing potential.
- Lactation: Unknown if present in human milk. Recommended to breastfeed only if benefits outweigh risks given potential persistence >12 months. Present in rat milk.
- Geriatric: No dose adjustment required; very limited data in patients ≥65 years.
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Indications & Target Populations
- HIV preexposure prophylaxis (PrEP) for men who have sex with men (MSM), transgender women (TGW), cisgender men, and cisgender women at risk for HIV sexual acquisition.
- Patients at very high risk of transmission (e.g., frequent condom-less sexual encounters, partners with uncontrolled HIV infection).
Renal & Skeletal Considerations
- Alternative to oral PrEP for patients with renal dysfunction.
- Unlikely to impact renal function or bone mineral density.
- Appropriate alternative for patients with osteoporosis or osteopenia.
Adherence & Behavioral Factors
- Beneficial for patients unable to adhere to daily oral dosing due to unstable housing, stigma, cognitive difficulties, uncontrolled mental illness, or substance use disorders.
- Requires patient agreement to comply with a strict every-2-month injection and testing schedule.
- Long half-life may pose a risk if therapy is abruptly discontinued while continuing high-risk behaviors (subtherapeutic concentrations may persist for up to 1 year, increasing resistance risk).
Contraindications & Drug Interactions
- Should not be used in patients receiving strong CYP inducers.
- Indicated for patients with contraindications or intolerance to tenofovir or emtricitabine.
Monitoring & Testing Requirements
- HIV must be excluded at baseline and at least every 2 months while on therapy.
- Adherence counseling and support required; patients educated on side effects, particularly during the first month of therapy.
- Additional monitoring (e.g., sexually transmitted infections, serum lipids, weight) per CDC/USPSTF guidelines.
Administration & Prescribing Requirements
- Long-acting intramuscular injection formulation.
- Oral lead-in is optional but may be used to assess early tolerance prior to long-lasting injection; oral CAB must be procured from Theracom.
- Prior authorization (PA-F) on the VA National Formulary (VANF).
- Must be prescribed by Infectious Diseases, HIV, or other PrEP providers with training/experience in managing HIV PrEP patients.