VOCABRIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VOCABRIA (VOCABRIA).
Cabotegravir is an HIV-1 integrase strand transfer inhibitor (INSTI) that inhibits viral replication by blocking the integration of HIV-1 DNA into host genomic DNA.
| Metabolism | Cabotegravir is primarily metabolized by UGT1A1 with minor contributions from UGT1A9 and UGT2B7. |
| Excretion | Renal (unchanged): <1%; fecal: >90% as parent drug; biliary contribution minimal; predominantly eliminated via feces as unchanged drug. |
| Half-life | Terminal elimination half-life: 35 hours (range 31–41 hours). At steady state, drug accumulates ~1.4-fold; half-life supports monthly IM dosing. |
| Protein binding | >99% bound; primarily to human serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd (central compartment): 0.99 L/kg (range 0.76–1.22 L/kg); large Vd indicates extensive tissue distribution. |
| Bioavailability | IM (gluteal injection): Approximately 70% absolute bioavailability; oral: <2% due to extensive first-pass metabolism, thus not clinically used orally. |
| Onset of Action | IM injection: Maximal antiviral effect observed within 7 days; suppression of HIV-1 RNA achieved by day 8 in most patients. |
| Duration of Action | Monthly IM dosing: Maintains therapeutic plasma concentrations above protein-adjusted 90% inhibitory concentration (PA-IC90) for at least 28 days; clinical duration extends to one month. |
600 mg intramuscularly once monthly, initiated with a single 600 mg dose and a second 600 mg dose 4 weeks later, then every 4 weeks thereafter.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR >=30 mL/min. Not recommended in patients with GFR <30 mL/min due to lack of data. |
| Liver impairment | No dose adjustment for Child-Pugh A or B. Contraindicated in Child-Pugh C due to increased risk of adverse reactions. |
| Pediatric use | Safety and efficacy not established in pediatric patients younger than 12 years or weighing less than 35 kg. For patients >=12 years and >=35 kg: 600 mg IM monthly as a single injection, with same loading dose as adults. |
| Geriatric use | No specific dose adjustment required, but clinical studies included insufficient numbers of patients >=65 years to determine whether they respond differently. Use with caution due to higher frequency of decreased hepatic, renal, or cardiac function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VOCABRIA (VOCABRIA).
| Breastfeeding | Cabotegravir is present in human breast milk; estimated infant daily dose is approximately 0.03 mg/kg/day (about 3% of maternal weight-adjusted dose). M/P ratio is not established; milk-to-plasma ratio is estimated at 0.01–0.05. Due to potential for HIV transmission in breast milk and possible adverse effects, breastfeeding is not recommended for HIV-infected women. |
| Teratogenic Risk | Cabotegravir (VOCABRIA) is not associated with increased risk of major birth defects based on limited human data from the Antiretroviral Pregnancy Registry; however, adequate studies in pregnant women are lacking. In animal reproduction studies, no evidence of fetal harm was observed at exposures up to 10 times the human exposure at recommended dose. First trimester: insufficient data to exclude risk; second and third trimesters: limited data, no signal of adverse fetal outcomes. |
■ FDA Black Box Warning
WARNING: HYPERSENSITIVITY REACTIONS AND POST-INJECTION REACTIONS. Hypersensitivity reactions, including cases of angioedema, have been reported. Post-injection reactions, including dizziness, anxiety, and paresthesia, have been reported. Observe patients for 1 hour after each injection.
| Serious Effects |
["Known hypersensitivity to cabotegravir or any component of the formulation.","Co-administration with drugs that strongly induce UGT1A1 (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's wort)."]
| Precautions | ["Hypersensitivity reactions including angioedema and rash.","Post-injection reactions including dizziness, anxiety, and paresthesia.","Hepatotoxicity, especially in patients with underlying liver disease or co-infected with hepatitis B or C.","Resistance in patients with undiagnosed HIV-1 infection when used for PrEP.","Risk of neural tube defects when used during pregnancy; avoid pregnancy during use.","Co-administration with certain drugs (e.g., rifamycins, carbamazepine) may reduce cabotegravir levels."] |
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| Fetal Monitoring | Monitor maternal liver function tests, serum creatinine, and complete blood count periodically. For fetal assessment, routine obstetric ultrasound is recommended every trimester to monitor fetal growth and anatomy. If used in pregnancy, close monitoring for maternal adverse effects (e.g., injection site reactions, hepatotoxicity) and fetal well-being is advised. |
| Fertility Effects | No human data on effect of cabotegravir on fertility. In animal studies, no impairment of mating or fertility was observed in male or female rats at systemic exposures up to 2.5 times the human exposure at recommended dose. Reversible reproductive effects (e.g., effects on estrous cycle) were not noted. |