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. |
| Molecular Weight | 405.85 Da |
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 | No adequate human data; based on animal studies, potential risk of embryo-fetal toxicity. Use only if benefit outweighs risk. |
| 2nd trimester | No adequate human data; animal studies show no teratogenicity but potential for maternal toxicity. Caution advised. |
| 3rd trimester | No adequate human data; animal studies show no adverse fetal effects at therapeutic doses. Consider risk-benefit. |
Clinical note
Comprehensive clinical and safety monograph for VOCABRIA (VOCABRIA).
| Placental transfer | Extensive placental transfer observed in animal studies; human data limited but likely crosses due to low molecular weight. |
| Breastfeeding | Cabotegravir is excreted in human milk. Data limited; potential for viral resistance in infants if HIV exposure occurs. Breastfeeding not recommended in HIV-positive women in developed settings. |
■ 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 |
Hypersensitivity to cabotegravir or any excipientsConcomitant use with drugs that induce UGT1A1 (e.g., rifampin, carbamazepine) due to subtherapeutic levels
| 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. |
| Food/Dietary | No food interactions are known for Vocabria. The oral tablet can be taken with or without food. Alcohol may exacerbate CNS effects (e.g., dizziness) but no direct pharmacokinetic interaction. |
Loading safety data…
| Lactation Rating | L4 (possibly hazardous) |
| 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. |
| 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. |
| Clinical Pearls | Vocabria (cabotegravir) is an integrase strand transfer inhibitor (INSTI) used for HIV-1 pre-exposure prophylaxis (PrEP). Administer as an intramuscular gluteal injection; do not inject subcutaneously or intravenously. The oral lead-in (30 mg daily for approximately 1 month) is recommended to assess tolerability before starting the long-acting injectable. Missed doses require rescheduling within 7 days; if >7 days, restart the oral lead-in. Monitor for hypersensitivity reactions (including hepatitis), depressive disorders, and hepatotoxicity. Cabotegravir may cause small increases in serum creatinine due to inhibition of tubular secretion; monitor renal function. Concomitant use with strong UGT1A1 inducers (e.g., rifampin, carbamazepine) is contraindicated as they reduce cabotegravir concentrations. |
| Patient Advice | Vocabria is an injection given every 2 months to prevent HIV infection; it must not be used if you already have HIV. · You must be HIV-negative before starting and during treatment; get tested regularly. · An oral tablet must be taken for about 1 month before starting injections to check for side effects. · Missing injection appointments can reduce effectiveness; if you miss a dose by more than 7 days, you may need to restart oral tablets. · Do not take this drug if you are taking certain medications like rifampin, carbamazepine, or St. John's wort; inform your doctor of all medications. · Common side effects include injection site reactions, headache, and mild nausea; serious side effects include allergic reactions (rash, fever, liver problems) and depression. · If you experience signs of HIV infection (fever, night sweats, swollen glands), contact your doctor immediately. · Vocabria does not prevent other sexually transmitted infections; use condoms. |