Important Safety Information for Dovato (50mg dolutegravir/300mg lamivudine) Tablets
INDICATION
Dovato is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Dovato.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating Dovato. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If Dovato is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.
Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of Dovato. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.
Contraindications
- Do not use Dovato in patients with previous hypersensitivity reaction to dolutegravir or lamivudine
- Do not use Dovato in patients receiving dofetilide
Warnings and precautions
Hypersensitivity Reactions:
- Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
- Discontinue Dovato immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated
Hepatotoxicity:
- Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors
- 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 with use of Dovato. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
- Monitoring for hepatotoxicity is recommended
Embryo Fetal Toxicity:
- Assess the risks and benefits of Dovato and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects
- Pregnancy testing is recommended before initiation of Dovato. Individuals of childbearing potential should be counselled on the consistent use of effective contraception
Lactic Acidosis and Severe Hepatomegaly with Steatosis:
Fatal cases have been reported with the use of nucleoside analogues, including lamivudine. Discontinue Dovato if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of Dovato and other drugs may occur (see Contraindications and Drug interactions).
Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of Dovato.
Adverse reactions
The most common adverse reactions (incidence ≥2%, all grades) with Dovato were headache (3%), nausea (2%), diarrhoea (2%), insomnia (2%), fatigue (2%), and anxiety (2%).
Drug interactions
- Consult full Prescribing Information for Dovato for more information on potentially significant drug interactions
- Dovato is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
- Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir
- Administer Dovato 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, Dovato and supplements containing calcium or iron can be taken with food
Use in specific populations
- Pregnancy: There are insufficient human data on the use of Dovato during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Advise individuals of childbearing potential of the potential risk of neural tube defects. Assess the risks and benefits of Dovato and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester
- Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
- Females and Males of Reproductive Potential: Pregnancy testing is recommended before initiation of Dovato. Counsel individuals of childbearing potential taking Dovato on the consistent use of effective contraception
- Renal Impairment: Dovato is not recommended for patients with creatinine clearance <30 mL/min. Patients with a sustained creatinine clearance between 30 and 49 mL/min should be monitored for hematologic toxicities, which may require a dosage adjustment of lamivudine as an individual component
- Hepatic Impairment: Dovato is not recommended in patients with severe hepatic impairment (Child-Pugh Score C)
For more information, please see US prescribing information.
Important Safety Information for Cabenuva (cabotegravir 200mg/mL; rilpivirine 300mg/mL) extended-release injectable suspensions (marketed as Vocabria/Rekambys outside the US)
Cabenuva is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and adolescents who are 12 years of age or older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than <50 copies per /mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.
CONTRAINDICATIONS
- Do not use Cabenuva in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine
- Do not use Cabenuva in patients receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (>1 dose), and St John’s wort
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions:
- Hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported during postmarketing experience with rilpivirine-containing regimens. 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
- Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with Cabenuva
- Discontinue Cabenuva immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated.
Post-Injection Reactions:
- Serious post-injection reactions (reported in less than 1% of subjects) were reported within minutes after the injection of rilpivirine, including dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., back and chest). These events may have been associated with inadvertent (partial) intravenous administration and began to resolve within a few minutes after the injection
- Carefully follow the Instructions for Use when preparing and administering Cabenuva. The suspensions should be injected slowly via intramuscular injection and avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated
Hepatotoxicity:
- Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors
- Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations
- Monitoring of liver chemistries is recommended and treatment with Cabenuva should be discontinued if hepatotoxicity is suspected
Depressive Disorders:
- Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation or attempt) have been reported with Cabenuva or the individual products
- Promptly evaluate patients with depressive symptoms
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:
- The concomitant use of Cabenuva and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions)
- Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval
- Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes
Long-Acting Properties and Potential Associated Risks with Cabenuva:
- Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly or every-2-month injection dosing schedule because non-adherence could lead to loss of virologic response and development of resistance
- To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injection doses of Cabenuva when dosed monthly and no later than 2 months after the final injections of Cabenuva when dosed every 2 months. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible
ADVERSE REACTIONS
- The most common adverse reactions (incidence ≥2%, all grades) with Cabenuva were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash
- The safety of CABENUVA in adolescents is expected to be similar to adults
DRUG INTERACTIONS
- Refer to the applicable full Prescribing Information for important drug interactions with Cabenuva, VOCABRIA, or EDURANT
- Because Cabenuva is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
- Drugs that are strong inducers of UGT1A1 or 1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine
- Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes
USE IN SPECIFIC POPULATIONS
- Pregnancy: There are insufficient human data on the use of Cabenuva during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Discuss the benefit-risk of using Cabenuva during pregnancy and conception and consider that cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of Cabenuva. An Antiretroviral Pregnancy Registry has been established
- Lactation: The CDC recommends that HIV 1−infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Breastfeeding is also not recommended due to the potential for developing viral resistance in HIV-positive infants, adverse reactions in a breastfed infant, and detectable cabotegravir and rilpivirine concentrations in systemic circulation for up to 12 months or longer after discontinuing injections of Cabenuva
For more information please see US Prescribing Information.
Important Safety Information for Rukobia (fostemsavir), 600 mg extended-release tablets
INDICATIONS AND USAGE
- RUKOBIA, a human immunodeficiency virus type 1 (HIV-1) gp120-directed attachment inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.
CONTRAINDICATIONS
- Do not use in patients with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA.
- Do not use RUKOBIA in patients receiving strong cytochrome P450 (CYP)3A inducers, including but not limited to enzalutamide, carbamazepine, phenytoin, rifampin, mitotane, and St John’s wort (Hypericum perforatum).
WARNINGS AND PRECAUTIONS
- Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of RUKOBIA.
- QTc Prolongation with Higher than Recommended Dosages: RUKOBIA at 2,400 mg twice daily has been shown to significantly prolong the QTc interval of the electrocardiogram. Use RUKOBIA with caution in patients with a history of QTc interval prolongation or in patients with relevant pre-existing cardiac disease or who are taking drugs with a known risk of Torsade de Pointes. Elderly patients may be more susceptible to drug-induced QT interval prolongation.
Elevations in Hepatic Transaminases in Patients with Hepatitis B or C Virus Co-infection:
- Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C co-infection.
- Diligence should be applied in initiating or maintaining effective hepatitis B therapy when starting RUKOBIA in patients co-infected with hepatitis B.
Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of RUKOBIA and other drugs may occur (see Contraindications and Drug Interactions).
ADVERSE REACTIONS
- The most common adverse reaction (all grades, randomized cohort) observed in ≥5% of subjects was nausea (10%).
- 81% of adverse reactions reported with RUKOBIA were mild or moderate in severity.
DRUG INTERACTIONS
- See the full Prescribing Information for RUKOBIA for a complete list of significant drug interactions.
- Temsavir may increase plasma concentrations of grazoprevir and voxilaprevir. Use an alternative hepatitis C virus regimen if possible.
- Use the lowest possible starting dose for statins and monitor for statin-associated adverse events.
- Patients receiving RUKOBIA should not take doses of estrogen-based therapies, including oral contraceptives, that contain more than 30 mcg/day of ethinyl estradiol. Caution is advised particularly in patients with additional risk factors for thromboembolic events.
USE IN SPECIFIC POPULATIONS
- Pregnancy: There are insufficient human data on the use of RUKOBIA during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established.
- Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance, and adverse reactions in a breastfed infant.
For more information please see US Prescribing Information.
