Dosing & Uses
Dosage Forms & Strengths
tablet
- 30mg (Vocabria)
injection, extended-release IM suspension
- 600mg/3mL (Apretude)
HIV Infection Treatment
Oral cabotegravir is indicated in combination with rilpivirine PO as a complete regimen for short-term treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral therapy (ART) regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine
Indication specifics
- Oral lead-in to assess tolerability of cabotegravir before administration of cabotegravir extended-release injectable IM suspension, a component of Cabenuva (cabotegravir; rilpivirine extended-release injectable suspensions)
- Oral therapy for patients who will miss planned IM injection dosing with cabotegravir
Oral lead-in dosing before Cabenuva
- 30 mg PO qDay plus rilpivirine 25 mg PO qDay for at least 28 days to assess tolerability
- Take last oral dose on the same day injections with Cabenuva are started
Oral replacement dose for planned missed Cabenuva injections
- If patient plans to miss scheduled Cabenuva (cabotegravir; rilpivirine) ER injectable suspensions by >7 days, take daily PO therapy to replace up to 2 consecutive monthly or 1 scheduled every-2-month injection visit(s)
- 30 mg PO qDay plus rilpivirine 25 mg PO qDay as replacement for up to 2 consecutive months
- Take first dose of oral therapy at approximately the same time as the planned missed injection and continue until the day injection dosing restarted
HIV Pre-exposure Prophylaxis
IM
- Indicated in at-risk adults and adolescents weighing ≥35 kg for pre-exposure prophylaxis (PrEP) to reduce risk of sexually acquired HIV-1 infection
- May be initiated with oral cabotegravir before starting IM injections or may proceed directly to injection without an oral lead-in
- If an oral lead-in is used, administer initiation injections on last day of oral lead-in or within 3 days thereafter
- Initiation injections: 600 mg IM x 2 doses 1 month apart; may administer second initiation injection up to 7 days before or after the date scheduled to receive injection, THEN
- Continuation injections: 600 mg IM q2months
PO
- Indicated in at-risk adults and adolescents weighing ≥35 kg for short-term pre-exposure prophylaxis (PrEP) to reduce risk of sexually acquired HIV-1 infection
-
Indication specifics
- Oral lead-in to assess tolerability of cabotegravir before starting ER IM injections (Apretude)
- Oral PrEP for patients who will miss planned IM injection
Oral lead-in dosing before Apretude IM
- 30 mg PO qDay for ~1 month (at least 28 days)
- Following oral lead-in, initiate cabotegravir IM on last day of oral lead-in or within 3 days
Oral replacement dose for planned missed Apretude injections
- If patient plans to miss scheduled Apretude (cabotegravir) ER injectable suspension by >7 days, take daily PO therapy to replace up to 2 consecutive monthly injection visits
- 30 mg PO qDay as replacement for up to 2 consecutive months
- Take first oral dose ~2 months after the last injection of cabotegravir IM injection
- Restart cabotegravir IM q2months on day oral dosing completes or within 3 days
Dosage Modifications
Renal impairment
-
PO
- Mild-to-severe (CrCl ≥30 to <90 mL/min): No dosage adjustment required
- ESRD (<15 mL/min): Pharmacokinetic effects are unknown
- Dialysis: Cabotegravir is >99% protein bound; dialysis is not expected to alter systemic exposure
-
IM
- Mild-to-moderate (CrCl ≥60 to <90 mL/min): No dosage adjustment required
- Severe (15 to <30 mL/min) or ESRD (<15 mL/min): Increase monitoring
- ESRD not on dialysis: Pharmacokinetic effects are unknown
- Dialysis: Cabotegravir is >99% protein bound; dialysis is not expected to alter systemic exposure
Hepatic impairment
- Mild or moderate (Child-Pugh A or B): No dosage adjustment required
- Severe (Child-Pugh C): Pharmacokinetic effects are unknown
Dosing Considerations
Individuals must have a negative HIV-1 test before initiating PrEP
Dosage Forms & Strengths
tablet
- 30mg (Vocabria)
injection, extended-release IM suspension
- 600mg/3mL (Apretude)
HIV Pre-exposure Prophylaxis
Adolescents who weigh <35 kg: Safety and efficacy not established
IM
- Indicated in at-risk adults and adolescents who weigh ≥35 kg for pre-exposure prophylaxis (PrEP) to reduce risk of sexually acquired HIV-1 infection
- May be initiated with oral cabotegravir before starting IM injections or may proceed directly to injection without an oral lead-in
- If an oral lead-in is used, administer initiation injections on last day of oral lead-in or within 3 days thereafter
- Initiation injections: 600 mg IM x 2 doses 1 month apart; may administer second initiation injection up to 7 days before or after the date scheduled to receive injection, THEN
- Continuation injections: 600 mg IM q2months
PO
- Indicated in at-risk adults and adolescents who weigh ≥35 kg for short-term pre-exposure prophylaxis (PrEP) to reduce risk of sexually acquired HIV-1 infection
-
Indication specifics
- Oral lead-in to assess tolerability of cabotegravir before starting ER IM injections (Apretude)
- Oral PrEP for patients who will miss planned IM injection
Oral lead-in dosing before Apretude IM
- 30 mg PO qDay for ~1 month (at least 28 days)
- Following oral lead-in, initiate cabotegravir IM on last day of oral lead-in or within 3 days
Oral replacement dose for planned missed Apretude injections
- If patient plans to miss scheduled Apretude (cabotegravir) ER injectable suspension by >7 days, take daily PO therapy to replace up to 2 consecutive monthly injection visits
- 30 mg PO qDay as replacement for up to 2 consecutive months
- Take first oral dose ~2 months after the last injection of cabotegravir IM injection
- Restart cabotegravir IM q2months on day oral dosing completes or within 3 days
Dosage Modifications
Renal impairment
-
PO
- Mild-to-severe (CrCl ≥30 to <90 mL/min): No dosage adjustment required
- ESRD (<15 mL/min): Pharmacokinetic effects are unknown
- Dialysis: Cabotegravir is >99% protein bound; dialysis is not expected to alter systemic exposure
-
IM
- Mild-to-moderate (CrCl ≥60 to <90 mL/min): No dosage adjustment required
- Severe (15 to <30 mL/min) or ESRD (<15 mL/min): Increase monitoring
- ESRD not on dialysis: Pharmacokinetic effects are unknown
- Dialysis: Cabotegravir is >99% protein bound; dialysis is not expected to alter systemic exposure
Hepatic impairment
- Mild or moderate (Child-Pugh A or B): No dosage adjustment required
- Severe (Child-Pugh C): Pharmacokinetic effects are unknown
Dosing Considerations
Individuals must have a negative HIV-1 test before initiating PrEP
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (16)
- apalutamide
apalutamide will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- carbamazepine
carbamazepine will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- cigarette smoking
cigarette smoking will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- desogestrel
desogestrel will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- lamotrigine
lamotrigine will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- nicotine gum
nicotine gum will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- nicotine inhaled
nicotine inhaled will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- nicotine intranasal
nicotine intranasal will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- nicotine lozenge
nicotine lozenge will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- nicotine transdermal
nicotine transdermal will decrease the level or effect of cabotegravir by increasing elimination. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- phenobarbital
phenobarbital will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- phenytoin
phenytoin will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- primidone
primidone will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- rifabutin
rifabutin will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response. Note: Rifabutin can be coadministered with cabotegravir PO; however, it is contraindicated with Cabenuva (cabotegravir; rilpivirine) extended-release injectable suspensions.
- rifampin
rifampin will increase the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
- testosterone
testosterone will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.
Serious - Use Alternative (31)
- abacavir
abacavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- atazanavir
atazanavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- betibeglogene autotemcel
cabotegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
- bictegravir
bictegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- darunavir
darunavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- delavirdine
delavirdine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- didanosine
didanosine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- dolutegravir
dolutegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- doravirine
doravirine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- efavirenz
efavirenz, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- elivaldogene autotemcel
elivaldogene autotemcel, cabotegravir. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.
- elvitegravir
elvitegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- emtricitabine
emtricitabine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- enfuvirtide
enfuvirtide, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- etravirine
etravirine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- fosamprenavir
fosamprenavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- fostemsavir
fostemsavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- ibalizumab
ibalizumab, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- indinavir
indinavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- lamivudine
lamivudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- maraviroc
maraviroc, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- nelfinavir
nelfinavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- nevirapine
nevirapine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- raltegravir
raltegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- ritonavir
ritonavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- saquinavir
saquinavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- stavudine
stavudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- tenofovir DF
tenofovir DF, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- tipranavir
tipranavir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
- zidovudine
zidovudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
Monitor Closely (13)
- aluminum hydroxide
aluminum hydroxide will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.
- aluminum hydroxide/magnesium carbonate
aluminum hydroxide/magnesium carbonate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.
- aluminum hydroxide/magnesium trisilicate
aluminum hydroxide/magnesium trisilicate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.
- aspirin/citric acid/sodium bicarbonate
aspirin/citric acid/sodium bicarbonate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.
- calcium carbonate
calcium carbonate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.
- calcium/vitamin D
calcium/vitamin D will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer polyvalent cation products at least 2 hr before or 4 hr after taking oral cabotegravir.
- magaldrate
magaldrate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.
- magnesium chloride
magnesium chloride will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer polyvalent cation products at least 2 hr before or 4 hr after taking oral cabotegravir.
- magnesium citrate
magnesium citrate will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer polyvalent cation products at least 2 hr before or 4 hr after taking oral cabotegravir.
- magnesium hydroxide
magnesium hydroxide will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.
- magnesium oxide
magnesium oxide will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer antacid products at least 2 hr before or 4 hr after taking oral cabotegravir.
- ublituximab
ublituximab decreases effects of cabotegravir by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.
- zinc
zinc will decrease the level or effect of cabotegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer polyvalent cation containing products at least 2 hr before or 4 hr after oral cabotegravir.
Minor (0)
Adverse Effects
>10%
IM
- Injection site reaction (38-82%)
- Creatine phosphokinase ≥10x ULN (2-15%)
- Headache (4-12%)
1-10%
IM
- Creatinine >1.8x ULN or increased to ≥1.5x baseline (3-5%)
- Diarrhea (4%)
- Upper respiratory tract infection (4%)
- Pyrexia (≤4%)
- Fatigue (3-4%)
- Nausea (3-4%)
- Dizziness (2-4%)
- AST ≥5x ULN (≤3%)
- Lipase ≥3x ULN (≤3%)
- Sleep disorders (1-3%)
- Abdominal pain (1-2%)
- Vomiting (≤2%)
- Myalgia (≤2%)
- Rash (≤2%)
- Decreased appetite (≤2%)
- Somnolence (≤2%)
- ALT ≥5x ULN (≤2%)
- Flatulence (≤1%)
- Back pain (≤1%)
<1%
PO
- Headache
- Nausea
- Abnormal dreams
- Anxiety
- Insomnia
IM
- Hepatobiliary disorders: Hepatotoxicity
- Investigations: Weight increase
- Psychiatric disorders: Depression
Frequency Not Defined
Hypersensitivity reactions (including angioedema and urticaria)
Hepatotoxicity
Depressive disorders
Warnings
Black Box Warning
PrEP
- Test individuals for HIV-1 infection before initiating IM or oral cabotegravir for PrEP, and with each subsequent IM injection
- Drug-resistant HIV-1 variants identified with use of cabotegravir IM for PrEP by individuals with undiagnosed HIV-1 infection
- Do not initiate for HIV-1 PrEP unless negative infection status confirmed
- Individuals who become infected with HIV-1 while receiving cabotegravir for PrEP must transition to a complete HIV-1 treatment regimen
Contraindications
Previous hypersensitivity to cabotegravir
Coadministration with UGT1A1 inducers such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, and rifapentine, owing to possible loss of virologic response
HIV-1 treatment: Before initiating cabotegravir PO, note that use of Cabenuva ER injectable suspensions with rifabutin is contraindicated
HIV-1 PrEP: Unknown or positive HIV-1 status
Cautions
Hepatotoxicity reported in patients with or without known preexisting hepatic disease or known risk factors; monitoring of liver chemistries recommended; discontinue treatment if hepatotoxicity suspected
Depressive disorders (including depressed mood, depression, mood altered, mood swings) reported; promptly evaluate if symptoms emerge; determine whether risks of continued therapy outweigh benefits
Owing to use in combination with rilpivirine, consider contraindications, cautions, and drug interactions associated with rilpivirine
Hypersensitivity
- Serious or severe hypersensitivity reactions reported with other integrase inhibitors
- Discontinue 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 clinical status, including liver transaminases, and initiate appropriate therapy as warranted
Drug interaction overview
-
Other antiretroviral medications for HIV-1 infection
- Cabotegravir plus rilpivirine is a complete ART regimen
- Coadministration with other ARTs is not recommended
-
UGT1A1 or UGT1A9 inducers
- Contraindicated
- Primarily metabolized by UGT1A1 with some contribution from UGT1A9
- Strong UGT1A1 or 1A9 inducers are expected to decrease cabotegravir plasma concentrations and may result in loss of virologic response
-
Polyvalent cation-containing products
- Modify dosage schedule
- Coadministration with antacids containing polyvalent cations (eg, aluminum, magnesium hydroxide, calcium carbonate) may decrease cabotegravir absorption
- Administer antacids at least 2 hr before or 4 hr after taking cabotegravir
Pregnancy & Lactation
Pregnancy
Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263; rate of miscarriage is not reported in the APR; the background risk for major birth defects and miscarriage for the indicated population is unknown
Data are insufficient regarding use during pregnancy to adequately assess drug-associated risk of birth defects and miscarriage
While there are insufficient human data to assess the risk of neural tube defects (NTDs) with exposure to cabotegravir during pregnancy, NTDs were associated with dolutegravir, another integrase inhibitor
Data from a birth outcome surveillance study in Botswana showed that dolutegravir, another integrase inhibitor, was associated with increased risk of NTDs when administered at time of conception and in early pregnancy; data from clinical trials are insufficient to address this risk with cabotegravir
Healthcare providers should discuss benefit-risk of using drug with individuals of childbearing potential or during pregnancy
Clinical considerations
- Cabotegravir detected in systemic circulation for up to 12 months or longer after discontinuing IM injections; therefore, consider potential for fetal exposure during pregnancy
Lactation
Unknown if present in human breast milk, affects human milk production, or effects on breastfed infants
Because of potential for HIV-1 transmission (in HIV-1–negative infants), developing viral resistance (in HIV-1–positive infants), and adverse reactions in a breastfed infant similar to those seen in adults, instruct HIV-1–infected mothers not to breastfeed if they are receiving drug for the treatment of HIV-1 infection
Due to detectable cabotegravir concentrations in systemic circulation for up to 12 months or longer after discontinuing IM injections, females should breastfeed only if the expected benefit justifies the potential risk to infant
For uninfected mothers receiving the drug for HIV-1 PrEP, assess the benefit-risk of the drug to the infant while breastfeeding
CDC recommends that females in the United States should not breastfeed their infants because of risk of the following
- Postnatal HIV transmission (in HIV-negative infants)
- Developing viral resistance (in HIV-positive infants)
- Adverse reactions in nursing infants
Animal data
- Cabotegravir detected in plasma of nursing pups on lactation day 10 in rat prenatal and postnatal development study
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibits HIV integrase by binding to the integrase-active site and blocking the strand transfer step of retroviral DNA integration, which is essential for the HIV replication cycle
Absorption
PO
- Peak plasma time: 3 hr
- Peak plasma concentration: 8 mcg/mL
- AUC: 145 mcg⋅h/mL
IM
Peak plasma time: 7 days
-
Aged ≥18 yr
- Peak plasma concentration: 8 mcg/mL (initiation); 4 mcg/mL (continuation)
- AUC: 1,591 mcg⋅hr/mL (initiation); 3,764 mcg⋅hr/mL (continuation)
-
Aged 12 to <18 yr (predicted pharmacokinetics)
- Peak plasma concentration: 11.2 mcg/mL (initiation); 7.23 mcg/mL (continuation)
- AUC: 2,123 mcg⋅hr/mL (initiation); 4,871 mcg⋅hr/mL (continuation)
Distribution
Protein bound: >99.8%
Metabolism
Metabolized by UGT1A1 (major) and UGT1A9 (minor)
Elimination
Half-life: 41 hr (PO); 5.6-11.5 weeks (IM)
Excretion: Urine 27%; feces 59% (47% unchanged)
Administration
Oral Administration
Take on regular dosing schedule with a meal at the same time as rilpivirine
Missed dose: Take as soon as remembered
Do not stop taking the drug or run out of cabotegravir, owing risk for viral resistance
IM Preparation
If pack stored in refrigerator, bring to room temperature before administration (not to exceed 30ºC [86ºF])
Inspect visually for particulate matter and discoloration before administration; vial has brown tint to glass that may limit visual inspection; discard vial if particulate matter or discoloration observed
Shake vial vigorously so suspension looks uniform before injecting; small air bubbles are expected and acceptable
Once suspension drawn into syringe, administer as soon as possible, but may remain in the syringe for up to 2 hr
Do not place filled syringe in refrigerator; discard if not administered within 2 hr
Do not mix with any other product or diluent
Consider individual’s BMI to ensure needle length is sufficient to reach gluteus muscle
Longer needle lengths (not included in dosing kit) may be required with higher BM (eg, >30 kg/m2) to ensure injection is administered IM as opposed to SC
IM Administration
Administer as single IM injection in gluteal muscle by health care provider every 2 months
May administer injection up to 7 days before or after the date scheduled to receive injection
Injection site
- Ventrogluteal site recommended
- Dorsogluteal approach (upper outer quadrant) acceptable, if preferred by healthcare professional
- Do not administer by any other route or anatomical site
Missed dose
-
Planned missed injection
- ≥7 days: Daily oral cabotegravir for up to 2 consecutive months to replace 1 missed scheduled 600-mg every 2-month injection
- Take first dose of oral PrEP ~2 months after last 600-mg IM
- Restart injection on day oral dosing completes or within 3 days
- For oral PrEP durations >2 months, an alternative oral regimen is recommended
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Unplanned missed injections
- If a scheduled injection visit is missed or delayed by >7 days and oral dosing has not been taken in the interim, clinically reassess individual to determine if resumption of injection dosing remains appropriate
-
Injection dosing recommendations after second missed injection
- Time since first injection ≤2 months: 600 mg IM as soon as possible, then continue with q2month schedule
- Time since first injection >2 months: Restart with 600 mg IM, followed by second 600-mg initiation injection 1 month later, then continue with q2month schedule thereafter
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Injection dosing recommendations after third or subsequent missed injection
- Time since last injection ≤3 months: 600 mg IM as soon as possible, then continue with q2month schedule
- Time since last injection >3 months: Restart with 600 mg IM, followed by second 600-mg initiation injection 1 month later, then continue with q2month schedule thereafter
Storage
Tablets: Store below 30ºC (86ºF)
Unopened IM suspension
- Store at 2-25ºC (36-77ºF) in original carton until ready to use
- Exposure up to 30ºC permitted; do not freeze
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
