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VOCABRIA is a brand name for Cabotegravir, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Verbatim from this product's HC label. Tap a section to expand.
). VOCABRIA, cabotegravir sodium and CABENUVA, cabotegravir ER Suspension and rilpivirine ER Suspension Page 19 of 72 Protected B / Protégé B Reproductive Health: Female and Male Potential • Fertility There are no data on the effects of cabotegravir and/or rilpivirine on human male or female fertility.
Animal studies indicate no effects of cabotegravir or rilpivirine on male or female fertility. Cabotegravir when administered orally to male and female rats at exposure (AUC) greater than 20 times the exposure at the Maximum Recommended Human Dose (MRHD) of 30 mg dosed orally or 400 mg IM injection did not cause adverse effects on male or female reproductive organs or spermatogenesis, and no functional effects on mating or fertility were observed.
In rats, there were no effects on mating or fertility with rilpivirine at exposures >28 times the exposure at the MRHD of 25 mg orally once daily or 600 mg IM injection monthly. • Reproduction Antiretroviral Pregnancy Registry (APR): To monitor maternal-fetal outcomes of pregnant women with HIV exposed to VOCABRIA, CABENUVA and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established.
1 Pregnancy VOCABRIA and CABENUVA have not been studied in pregnant women. There are insufficient human data on the use of CABENUVA during pregnancy to adequately assess a 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 CABENUVA during pregnancy, NTDs were reported with dolutegravir, another integrase inhibitor.
VOCABRIA and CABENUVA should not be used in pregnant women unless the potential benefits outweigh the potential risks to the fetus. Cabotegravir Reproductive toxicity studies in pregnant rats showed that cabotegravir crosses the placenta and can be detected in fetal tissue.
Cabotegravir was not teratogenic when studied in pregnant rats and rabbits but in rats caused decreased fetal weight, a delay in the onset of parturition and increased stillbirths and neonatal deaths at exposures higher than for therapeutic doses.
The relevancy to human pregnancy is unknown. 66 times the exposure at the MRHD of 30 mg. In rats, alterations in fetal growth (decreased body weights) were observed at exposures that were 28 times the exposure at the MRHD. VOCABRIA, cabotegravir sodium and CABENUVA, cabotegravir ER Suspension and rilpivirine ER Suspension Page 20 of 72 Protected B / Protégé B In the rat pre- and post-natal studies at exposures 28 times the exposures at the MRHD of 30 mg oral or 400 mg IM dose, cabotegravir was associated with delayed onset of parturition, and increased number of stillbirths and neonatal mortalities immediately after birth.
In a cross-fostering study, similar incidences of stillbirths and early postnatal deaths were observed when rat pups born to cabotegravir- treated mothers were nursed from birth by control mothers. There was no effect on neonatal survival of control pups nursed from birth by cabotegravir-treated mothers.
). Promptly evaluate patients with depressive VOCABRIA, cabotegravir sodium and CABENUVA, cabotegravir ER Suspension and rilpivirine ER Suspension Page 17 of 72 Protected B / Protégé B symptoms to assess whether the symptoms are related to CABENUVA and to determine whether the risks of continued therapy outweigh the benefits.
Hepatoxicity Cases of hepatotoxicity, presenting as serum transaminase elevations, have been reported in patients receiving cabotegravir with or without known pre-existing hepatic disease or other identifiable risk factors (see 8 ADVERSE REACTIONS).
Hepatic adverse events have been reported in patients receiving oral rilpivirine-containing regimens. Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations.
A few cases of hepatoxicity have been reported in adult patients receiving oral rilpivirine-containing regimens who had no pre-existing hepatic disease or other identifiable risk factors. Monitoring of liver chemistries is recommended, and treatment with VOCABRIA and CABENUVA should be discontinued if hepatotoxicity is suspected (see 7 WARNINGS AND PRECAUTIONS, Long-Acting Properties of CABENUVA and Risk of Resistance Due to Treatment Discontinuation).
Long-Acting Properties of CABENUVA Residual concentrations of cabotegravir and rilpivirine injections may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Consider the long-acting characteristics of cabotegravir and rilpivirine injections if CABENUVA is discontinued (see 7 WARNINGS AND PRECAUTIONS;
, and 14 CLINICAL TRIALS). • Since VOCABRIA is indicated in combination with EDURANT, as a complete regimen, the product monograph for EDURANT should be consulted. • VOCABRIA may be used in combination with EDURANT as an oral lead-in prior to the initiation of CABENUVA to assess tolerability to cabotegravir (see Table 1 and Table 3).
• Alternatively, the health care provider and patient may proceed directly to injection therapy with CABENUVA (see Table 2 and Table 4, for monthly and every 2 month dosing recommendations, respectively). • Prior to starting CABENUVA, healthcare professionals should carefully select patients who agree to the required injection dosing schedule and counsel patients about the importance of adherence to scheduled dosing visits to help maintain viral suppression, reduce the risk of viral rebound and potential development of resistance with missed doses (see 7 WARNINGS AND PRECAUTIONS).
• The date of the first initiation injection becomes the target treatment date going forward. g. if the target treatment date is the 12th of the month, the injection window is the 5th to the 19th of the same month, regardless of when the injection was given the previous month).
g. due to a missed injection or use of oral bridging therapy, see Table 6), the date the injections are resumed becomes the revised target treatment date. • Cabotegravir and rilpivirine injections should be administered at separate gluteal injection sites during the same visit.
2 Recommended Dose and Dosage Adjustment Adults and pediatric patients 12 years of age and older and weighing at least 35 kg: When an oral lead-in is used, dosing for CABENUVA consists of 3 distinct phases: • An oral lead-in with VOCABRIA taken together with EDURANT, • Initiation injections of CABENUVA (3 mL), and • Continuation injections with CABENUVA (3 mL every 2 months or 2 mL every month).
CABENUVA may also be initiated directly. Refer to the recommended monthly and every 2 month dosing sections below (see Table 2 and Table 4). Oral lead-in The recommended dose of VOCABRIA is one tablet, taken together with one tablet of EDURANT (rilpivirine), orally once daily with a meal.
; 9 DRUG INTERACTIONS). 2 Pharmacodynamics). Plasma rilpivirine concentrations after rilpivirine injections are comparable to those during EDURANT therapy which do not prolong the QTc interval. 2 Pharmacodynamics). CABENUVA should be used with caution when used in combination with drugs that are known to have a risk of Torsade de Pointes.
4 Drug-Drug Interactions, Table 13 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during therapy with VOCABRIA and CABENUVA; review concomitant medications during therapy with VOCABRIA and CABENUVA.
Post-Injection Reactions In clinical trials, serious post-injection reactions were reported within minutes after the injection of rilpivirine. , back and chest). 5% of subjects and began to resolve within minutes after the injection and some of the patients received supportive care.
These events may have been associated with accidental intravenous administration during the intramuscular injection procedure. Carefully follow the Instructions for Use when preparing and administering CABENUVA. Prior to administration, the CABENUVA vials should be brought to room temperature.
The suspension should be injected slowly, and care should be taken to avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after injection. If a patient experiences a post-injection reaction, monitor and treat as clinically indicated.
Risk of Resistance Due to Treatment Discontinuation It is important to carefully select patients who agree to the required injection dosing schedule because non-adherence to injections could lead to loss of virologic response and development of resistance.
To minimize the risk of developing viral resistance, it is essential to adopt an alternative, fully suppressive antiretroviral regimen. The regimen should begin no later than 1 month after the final injection doses of CABENUVA when on a monthly injection regimen, and no later than two months after the final injection doses of CABENUVA when on an every 2-month injection regimen.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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A lower dose of cabotegravir (at exposures >10 times the exposure at the MRHD of 30 mg oral or 400 mg IM dose) was not associated with delayed parturition or neonatal mortality in rats. In rabbit and rat studies there was no effect on survival when fetuses were delivered by caesarean section.
Rilpivirine No significant toxicological effects were observed in embryo-fetal toxicity studies performed with rilpivirine in rats and rabbits at exposures ≥12 (rats) and ≥57 (rabbits) times the exposure at the MRHD of 25 mg orally once daily or 600 mg IM injection monthly dose of rilpivirine in HIV-1 infected patients.
In a rat pre and postnatal development study, no adverse effects were noted in the offspring at maternal exposures ≥51 times the exposure at the MRHD of 25 mg orally once daily or 600 mg IM injection monthly dose of rilpivirine in HIV-1 infected patients.
Oral rilpivirine in combination with a background regimen was evaluated in a clinical trial of 19 pregnant women during the second and third trimesters, and postpartum. The pharmacokinetic data demonstrate that total exposure (AUC) to rilpivirine as a part of an antiretroviral regimen was approximately 30% lower during pregnancy compared with postpartum (6-12 weeks).
Virologic response was preserved throughout the trial period. No mother to child transmission occurred in all 10 infants born to the mothers who completed the trial and for whom the HIV status was available. Rilpivirine was well tolerated during pregnancy and postpartum.
There were no new safety findings compared with the known safety profile of rilpivirine in HIV-1 infected adults. Viral load should be monitored closely if the patient receives CABENUVA during pregnancy. Cabotegravir and rilpivirine have been detected in systemic circulation for up to 12 months or longer after the last injections have been administered.
Therefore, consideration should be given to the potential for fetal exposure during pregnancy (see 7 WARNINGS AND PRECAUTIONS). 2 Breastfeeding HIV-1 infected mothers should not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.
Based on animal studies, it is expected that cabotegravir and rilpivirine could be present in breast milk. HIV-1-infected mothers should be instructed not to breastfeed if they are receiving VOCABRIA or CABENUVA. After the last injection has been administered, cabotegravir and rilpivirine could be present in human milk for 12 months or longer.
3 Pediatrics Pediatrics (<12 years): Safety and efficacy of VOCABRIA and CABENUVA have not been established in pediatric […]
VOCABRIA is recommended to be administered for approximately one month (at least 28 days) prior to the initiation of CABENUVA to assess tolerability of the patient to cabotegravir. The final oral doses of VOCABRIA and EDURANT should be taken on the same day injections with CABENUVA are started.
See Table 1 for recommended oral dosing schedule. If a patient plans to miss a scheduled CABENUVA injection visit by more than 7 days, VOCABRIA may be used in combination with EDURANT once daily to replace up to 2 consecutive planned missed monthly injection visits (see Table 6).
Following use of the oral lead-in, or initiating directly with CABENUVA, there are two possible dosing schedules: monthly or every 2 months. Monthly Intramuscular Injection Dosing Initiation Injections (3 mL Dosing Kit) Initiate injections on the final day of oral lead-in (see Table 1).
When starting CABENUVA directly, initiate injections on the final day of prior antiretroviral therapy (see Table 2). The recommended initial injection doses of CABENUVA are a single 3 mL (600 mg) intramuscular injection of cabotegravir and a single 3 mL (900 mg) intramuscular injection of rilpivirine.
Continuation injections should be initiated a month after the initiation injection. Continuation Injections (2mL Dosing Kit) One month following the initiation injections (see Table 1 or Table 2, as applicable), the recommended continuation injection doses of CABENUVA are a single 2 mL (400 mg) intramuscular injection of cabotegravir and a single 2 mL (600 mg) intramuscular injection of rilpivirine administered once monthly.
Patients may be given CABENUVA up to 7 days before or after the date of the scheduled injection dosing visit (see Table 6). M. M. CONTINUATION INJECTIONS Month Prior to Starting Injections* Month 1** Month 2 onwards VOCABRIA 30 mg cabotegravir tablet once daily CABENUVA 3 mL (600 mg) cabotegravir injection and 3 mL (900 mg) rilpivirine injection CABENUVA 2 mL (400 mg) cabotegravir injection and 2 mL (600 mg) rilpivirine injection EDURANT 25 mg rilpivirine tablet once daily IM = Intramuscular injection *At least 28 days **Final oral doses of VOCABRIA and EDURANT should be taken on the same day as initiation injections are started.
M. M. CONTINUATION INJECTIONS Month 1 Month 2 onwards CABENUVA 3 mL (600 mg) cabotegravir injection and 3 mL (900 mg) rilpivirine injection CABENUVA 2 mL (400 mg) cabotegravir injection and 2 mL (600 mg) rilpivirine injection Every 2-Month Intramuscular Injection Dosing Initiation Injections (3 mL Dosing Kit) Initiate injections on the final day of oral lead-in (see Table 3).
When starting CABENUVA directly, initiate injections on the final day of prior antiretroviral therapy (see Table 4). The recommended initial injection doses of CABENUVA are a single 3 mL (600 mg) intramuscular injection of cabotegravir and a single 3 mL (900 mg) intramuscular injection of rilpivirine.
One month later, a second set of 3mL initiation injections should be administered. The second set of injections may be given to patients up to 7 days before or after the date of the scheduled injection dosing visit (see Table 3 or Table 4, as applicable).
Continuation Injections (3 mL Dosing […]
If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible (see 9 DRUG INTERACTIONS). Skin and Hypersensitivity Reactions Hypersensitivity reactions have been reported in association with integrase inhibitors (INSTIs) including cabotegravir.
These reactions were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. Discontinue VOCABRIA, CABENUVA or other suspected agents, immediately should signs or symptoms of hypersensitivity reaction develop.
Severe skin and hypersensitivity reactions have been reported during post marketing experience with cabotegravir and rilpivirine-containing regimens. Reactions associated with cabotegravir include Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Reactions associated with rilpivirine-containing regimens include cases of drug reaction with eosinophilia and systemic symptoms (DRESS). While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries (see 8 ADVERSE REACTIONS).
Discontinue VOCABRIA or CABENUVA immediately if signs or symptoms of severe skin or hypersensitivity reactions develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, mucosal involvement [oral blisters or lesions], conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, or difficulty breathing).
Clinical status, including laboratory parameters with liver transaminases, should be monitored and appropriate therapy initiated. For information regarding the long-acting properties of CABENUVA, see 7 WARNINGS AND PRECAUTIONS. Administer the oral lead-in dosing prior to administration of CABENUVA to help identify patients who may be at risk of a hypersensitivity reaction (see 2 CONTRAINDICATIONS;