Dosage & administration
| ABC = abacavir, DTG = dolutegravir, 3TC = lamivudine. | ||
Pediatric Population Body Weight | Number of Tablets (once daily) | Recommended Daily Dose |
TRIUMEQ PD Tablets (6 kg to <25 kg) | ||
6 kg to <10 kg | 3 | 180 mg ABC, 15 mg DTG, and 90 mg 3TC |
10 kg to <14 kg | 4 | 240 mg ABC, 20 mg DTG, and 120 mg 3TC |
14 kg to <20 kg | 5 | 300 mg ABC, 25 mg DTG, and 150 mg 3TC |
20 kg to <25 kg | 6 | 360 mg ABC, 30 mg DTG, and 180 mg 3TC |
TRIUMEQ Tablets (≥25 kg) | ||
≥25 kg | 1 | 600 mg ABC, 50 mg DTG, and 300 mg 3TC |
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Triumeq prescribing information
Hypersensitivity reactions have been reported with the use of abacavir or dolutegravir, components of TRIUMEQ and TRIUMEQ PD.
Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing regimens. See full prescribing information for ZIAGEN (abacavir).
Abacavir hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment
Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir:
• All patients should be screened for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD or reinitiation of therapy with TRIUMEQ or TRIUMEQ PD, unless patients have a previously documented HLA‑B*5701 allele assessment.• TRIUMEQ and TRIUMEQ PD are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‑B*5701‑positive patients.• Before starting TRIUMEQ or TRIUMEQ PD, review medical history for prior exposure to any abacavir-containing product. NEVER restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA‑B*5701 status.• To reduce the risk of a life‑threatening hypersensitivity reaction, regardless of HLA‑B*5701 status, discontinue TRIUMEQ or TRIUMEQ PD immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications). Clinical status, including liver chemistries, should be monitored and appropriate therapy initiated.• If a hypersensitivity reaction cannot be ruled out, do not restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing products because more severe symptoms, which may include life-threatening hypotension and death, can occur within hours.• Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.• If a hypersensitivity reaction is ruled out, patients may restart TRIUMEQ or TRIUMEQ PD. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of TRIUMEQ or TRIUMEQ PD, or any other abacavir-containing product, is recommended only if medical care can be readily accessed.• A Medication Guide and Warning Card that provide information about recognition of abacavir hypersensitivity reactions should be dispensed with each new prescription and refill.
Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in <1% of subjects receiving TIVICAY in Phase 3 clinical trials. Discontinue TRIUMEQ or TRIUMEQ PD and other suspect agents 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 or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping treatment with TRIUMEQ or TRIUMEQ PD or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction.
Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.
TRIUMEQ and TRIUMEQ PD are contraindicated in patients:
• who have the HLA-B*5701 allele[see Warnings and Precautions ].• with prior hypersensitivity reaction to abacavir, dolutegravir[see Warnings and Precautions ], or lamivudine.• receiving dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events with concomitant use of dolutegravir[see Drug Interactions ].• with moderate or severe hepatic impairment[see Use in Specific Populations ].
• Presence of HLA-B*5701 allele.• Prior hypersensitivity reaction to abacavir, dolutegravir, or lamivudine.• Coadministration with dofetilide.• Moderate or severe hepatic impairment.
Hypersensitivity reactions have been reported with the use of abacavir or dolutegravir, components of TRIUMEQ and TRIUMEQ PD.
Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing regimens. See full prescribing information for ZIAGEN (abacavir).
Abacavir hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment
Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir:
• All patients should be screened for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD or reinitiation of therapy with TRIUMEQ or TRIUMEQ PD, unless patients have a previously documented HLA‑B*5701 allele assessment.• TRIUMEQ and TRIUMEQ PD are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‑B*5701‑positive patients.• Before starting TRIUMEQ or TRIUMEQ PD, review medical history for prior exposure to any abacavir-containing product. NEVER restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA‑B*5701 status.• To reduce the risk of a life‑threatening hypersensitivity reaction, regardless of HLA‑B*5701 status, discontinue TRIUMEQ or TRIUMEQ PD immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications). Clinical status, including liver chemistries, should be monitored and appropriate therapy initiated.• If a hypersensitivity reaction cannot be ruled out, do not restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing products because more severe symptoms, which may include life-threatening hypotension and death, can occur within hours.• Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.• If a hypersensitivity reaction is ruled out, patients may restart TRIUMEQ or TRIUMEQ PD. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of TRIUMEQ or TRIUMEQ PD, or any other abacavir-containing product, is recommended only if medical care can be readily accessed.• A Medication Guide and Warning Card that provide information about recognition of abacavir hypersensitivity reactions should be dispensed with each new prescription and refill.
Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in <1% of subjects receiving TIVICAY in Phase 3 clinical trials. Discontinue TRIUMEQ or TRIUMEQ PD and other suspect agents 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 or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping treatment with TRIUMEQ or TRIUMEQ PD or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction.
Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.
TRIUMEQ and TRIUMEQ PD are contraindicated in patients:
• who have the HLA-B*5701 allele[see Warnings and Precautions ].• with prior hypersensitivity reaction to abacavir, dolutegravir[see Warnings and Precautions ], or lamivudine.• receiving dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events with concomitant use of dolutegravir[see Drug Interactions ].• with moderate or severe hepatic impairment[see Use in Specific Populations ].
• Presence of HLA-B*5701 allele.• Prior hypersensitivity reaction to abacavir, dolutegravir, or lamivudine.• Coadministration with dofetilide.• Moderate or severe hepatic impairment.
Hypersensitivity reactions have been reported with the use of abacavir or dolutegravir, components of TRIUMEQ and TRIUMEQ PD.
Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing regimens. See full prescribing information for ZIAGEN (abacavir).
Abacavir hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment
Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir:
• All patients should be screened for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD or reinitiation of therapy with TRIUMEQ or TRIUMEQ PD, unless patients have a previously documented HLA‑B*5701 allele assessment.• TRIUMEQ and TRIUMEQ PD are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‑B*5701‑positive patients.• Before starting TRIUMEQ or TRIUMEQ PD, review medical history for prior exposure to any abacavir-containing product. NEVER restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA‑B*5701 status.• To reduce the risk of a life‑threatening hypersensitivity reaction, regardless of HLA‑B*5701 status, discontinue TRIUMEQ or TRIUMEQ PD immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications). Clinical status, including liver chemistries, should be monitored and appropriate therapy initiated.• If a hypersensitivity reaction cannot be ruled out, do not restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing products because more severe symptoms, which may include life-threatening hypotension and death, can occur within hours.• Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.• If a hypersensitivity reaction is ruled out, patients may restart TRIUMEQ or TRIUMEQ PD. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of TRIUMEQ or TRIUMEQ PD, or any other abacavir-containing product, is recommended only if medical care can be readily accessed.• A Medication Guide and Warning Card that provide information about recognition of abacavir hypersensitivity reactions should be dispensed with each new prescription and refill.
Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in <1% of subjects receiving TIVICAY in Phase 3 clinical trials. Discontinue TRIUMEQ or TRIUMEQ PD and other suspect agents 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 or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping treatment with TRIUMEQ or TRIUMEQ PD or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction.
Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.
Hypersensitivity reactions have been reported with the use of abacavir or dolutegravir, components of TRIUMEQ and TRIUMEQ PD.
Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing regimens. See full prescribing information for ZIAGEN (abacavir).
Abacavir hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment
Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir:
• All patients should be screened for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD or reinitiation of therapy with TRIUMEQ or TRIUMEQ PD, unless patients have a previously documented HLA‑B*5701 allele assessment.• TRIUMEQ and TRIUMEQ PD are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‑B*5701‑positive patients.• Before starting TRIUMEQ or TRIUMEQ PD, review medical history for prior exposure to any abacavir-containing product. NEVER restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA‑B*5701 status.• To reduce the risk of a life‑threatening hypersensitivity reaction, regardless of HLA‑B*5701 status, discontinue TRIUMEQ or TRIUMEQ PD immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications). Clinical status, including liver chemistries, should be monitored and appropriate therapy initiated.• If a hypersensitivity reaction cannot be ruled out, do not restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing products because more severe symptoms, which may include life-threatening hypotension and death, can occur within hours.• Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.• If a hypersensitivity reaction is ruled out, patients may restart TRIUMEQ or TRIUMEQ PD. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of TRIUMEQ or TRIUMEQ PD, or any other abacavir-containing product, is recommended only if medical care can be readily accessed.• A Medication Guide and Warning Card that provide information about recognition of abacavir hypersensitivity reactions should be dispensed with each new prescription and refill.
Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in <1% of subjects receiving TIVICAY in Phase 3 clinical trials. Discontinue TRIUMEQ or TRIUMEQ PD and other suspect agents 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 or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping treatment with TRIUMEQ or TRIUMEQ PD or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction.
Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating TRIUMEQ or TRIUMEQ PD.
Safety and efficacy of lamivudine have not been established for treatment of chronic HBV in subjects dually infected with HIV-1 and HBV. Emergence of HBV variants associated with resistance to lamivudine has been reported in HIV‑1−infected subjects who have received lamivudine‑containing antiretroviral regimens in the presence of concurrent infection with HBV. If a decision is made to administer TRIUMEQ or TRIUMEQ PD to 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 products containing lamivudine, and may occur with discontinuation of TRIUMEQ or TRIUMEQ PD. Patients who are co-infected with HIV-1 and HBV who discontinue TRIUMEQ or TRIUMEQ PD should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with TRIUMEQ or TRIUMEQ PD. If appropriate, initiation of anti-HBV therapy may be warranted, especially in patients with advanced liver disease or cirrhosis since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.
TRIUMEQ and TRIUMEQ PD are indicated for the treatment of HIV-1 infection in adults and in pediatric patients aged at least 3 months and weighing at least 6 kg.
TRIUMEQ and TRIUMEQ PD alone are not recommended in patients with resistance‑associated integrase substitutions or clinically suspected integrase strand transfer inhibitor (INSTI) resistance because the dose of dolutegravir in TRIUMEQ and TRIUMEQ PD is insufficient in these subpopulations. See full prescribing information for TIVICAY (dolutegravir).
• Before initiating TRIUMEQ or TRIUMEQ PD, screen for the HLA‑B*5701 allele because TRIUMEQ and TRIUMEQ PD contain abacavir. ().2.1 Screening for HLA−B*5701 Allele prior to Initiating TRIUMEQScreen for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD
[see Boxed Warning, Warnings and Precautions ].• Prior to or when initiating TRIUMEQ or TRIUMEQ PD, test patients for HBV infection. ()2.1 Screening for HLA−B*5701 Allele prior to Initiating TRIUMEQScreen for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD
[see Boxed Warning, Warnings and Precautions ].• TRIUMEQ and TRIUMEQ PD may be taken with or without food. (,2.4 Recommended Dosage in AdultsTRIUMEQ is a fixed-dose combination product containing 600 mg of abacavir, 50 mg of dolutegravir, and 300 mg of lamivudine. The recommended dosage regimen of TRIUMEQ in adults is one tablet once daily orally with or without food. Do not use TRIUMEQ PD in adults.
)2.5 Recommended Dosage and Administration Instructions for Pediatric Patients Weighing at Least 6 kgThe dosage and dosage form recommended for pediatric patients varies by weight as shown in Table 1below.
Table 1. Recommended Dosage of TRIUMEQ Tablets and TRIUMEQ PD Tablets for Oral Suspension in Pediatric Patients aTRIUMEQ is a fixed-dose combination product containing 600 mg of abacavir, 50 mg of dolutegravir, and 300 mg of lamivudine. bTRIUMEQ PD is a fixed-dose combination product containing 60 mg of abacavir, 5 mg of dolutegravir, and 30 mg of lamivudine. Body WeightTRIUMEQ TabletsaTRIUMEQ PDbNumber of TabletsTotal Daily Dose6 kg to <10 kgNot recommended
3 tablets once daily
180 mg abacavir, 15 mg dolutegravir, and 90 mg lamivudine once daily
10 kg to <14 kgNot recommended
4 tablets once daily
240 mg abacavir, 20 mg dolutegravir, and 120 mg lamivudine once daily
14 kg to <20 kgNot recommended
5 tablets once daily
300 mg abacavir, 25 mg dolutegravir, and 150 mg lamivudine once daily
20 kg to <25 kgNot recommended
6 tablets once daily
360 mg abacavir, 30 mg dolutegravir, and 180 mg lamivudine once daily
≥25 kg1 tablet once daily
Not recommended
600 mg of abacavir, 50 mg of dolutegravir, and 300 mg of lamivudine
Administer
TRIUMEQ PDtablets for oral suspension with or without food. Instruct patients (or instruct caregivers) to fullydisperse the tablets for oral suspension in 20 mL of drinking water(if using 4, 5, or 6 tablets for oral suspension)or 15 mL(if using 3 tablets for oral suspension) in the supplied cup; swirl the suspension so that no lumps remain. After full dispersion, administer the oral suspension within 30 minutes of mixing[see Instructions for Use]. Do not swallow the tablets for oral suspension whole, and do not chew, cut, or crush the tablets.For children unable to use the supplied cup, an appropriate-sized syringe may be used to administer the oral suspension.
Administer TRIUMEQ tablet with or without food. Do not chew, cut, or crush the tablet.
• Adults: One tablet of TRIUMEQ daily. ()2.4 Recommended Dosage in AdultsTRIUMEQ is a fixed-dose combination product containing 600 mg of abacavir, 50 mg of dolutegravir, and 300 mg of lamivudine. The recommended dosage regimen of TRIUMEQ in adults is one tablet once daily orally with or without food. Do not use TRIUMEQ PD in adults.
| ABC = abacavir, DTG = dolutegravir, 3TC = lamivudine. | ||
Pediatric Population Body Weight | Number of Tablets (once daily) | Recommended Daily Dose |
TRIUMEQ PD Tablets (6 kg to <25 kg) | ||
6 kg to <10 kg | 3 | 180 mg ABC, 15 mg DTG, and 90 mg 3TC |
10 kg to <14 kg | 4 | 240 mg ABC, 20 mg DTG, and 120 mg 3TC |
14 kg to <20 kg | 5 | 300 mg ABC, 25 mg DTG, and 150 mg 3TC |
20 kg to <25 kg | 6 | 360 mg ABC, 30 mg DTG, and 180 mg 3TC |
TRIUMEQ Tablets (≥25 kg) | ||
≥25 kg | 1 | 600 mg ABC, 50 mg DTG, and 300 mg 3TC |
• Do not substitute TRIUMEQ and TRIUMEQ PD on a milligram-per-milligram basis. ()2.3 Overview of TRIUMEQ Dosage FormsTRIUMEQ is available in two dosage forms.
Do not substitute TRIUMEQ tablets and TRIUMEQ PD tablets for oral suspension on a milligram-per-milligram basis due to differing pharmacokinetic profiles for the dolutegravir component[see Warnings and Precautions,Clinical Pharmacology ].• TRIUMEQ tablets: 600 mg of abacavir, 50 mg of dolutegravir, and 300 mg of lamivudine. TRIUMEQ is recommended in adults and pediatric patients weighing at least 25 kg[see Dosage and Administration ].• TRIUMEQ PD tablets for oral suspension: 60 mg of abacavir, 5 mg of dolutegravir, and 30 mg of lamivudine. TRIUMEQ PD is recommended in pediatric patients weighing 6 kg to less than 25 kg[see Dosage and Administration ].• Because TRIUMEQ PD is a fixed-dose tablet and the dosage of individual components cannot be adjusted, it may lead to a suboptimal dosing for patients weighing ≥25 kg. TRIUMEQ PD is not recommended in patients weighing 25 kg or more[see Dosage and Administration ].
• If dosing with certain UGT1A or CYP3A inducers, then the recommended dolutegravir dosage regimen should be adjusted. Seefor complete dosing recommendations. (Table 2. Dosing Recommendations for TRIUMEQ and TRIUMEQ PD with Coadministered Medications Coadministered DrugDosing RecommendationEfavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin
In adults and in pediatric patients
weighing at least 25 kg, the recommended dolutegravir dosage regimen is 50 mg twice daily. Thus, an additional TIVICAY 50-mg tablet, separated by 12 hours from TRIUMEQ, should be taken.In pediatric patients
weighing 6 kg to <25 kg, an additional weight-based dose of dolutegravir should be given separated by 12 hours from TRIUMEQ PD.• 6 to <10 kg: administer an additional 15-mg dose of dolutegravir (3 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 10 to <14 kg: administer an additional 20-mg dose of dolutegravir (4 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 14 to <20 kg: administer an additional 25-mg dose of dolutegravir (5 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 20 to <25 kg: administer an additional 30-mg dose of dolutegravir (6 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.
)2.6 Dosage Recommendation with Certain Concomitant MedicationsThe dolutegravir dose in TRIUMEQ (50 mg) and TRIUMEQ PD (5 mg) is insufficient when coadministered with medications listed in Table 2that may decrease dolutegravir concentrations; the following dolutegravir dosage regimen is recommended.
Table 2. Dosing Recommendations for TRIUMEQ and TRIUMEQ PD with Coadministered Medications Coadministered DrugDosing RecommendationEfavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin
In adults and in pediatric patients
weighing at least 25 kg, the recommended dolutegravir dosage regimen is 50 mg twice daily. Thus, an additional TIVICAY 50-mg tablet, separated by 12 hours from TRIUMEQ, should be taken.In pediatric patients
weighing 6 kg to <25 kg, an additional weight-based dose of dolutegravir should be given separated by 12 hours from TRIUMEQ PD.• 6 to <10 kg: administer an additional 15-mg dose of dolutegravir (3 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 10 to <14 kg: administer an additional 20-mg dose of dolutegravir (4 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 14 to <20 kg: administer an additional 25-mg dose of dolutegravir (5 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 20 to <25 kg: administer an additional 30-mg dose of dolutegravir (6 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.
• Because TRIUMEQ and TRIUMEQ PD are fixed-dose tablets and cannot be dose adjusted, TRIUMEQ and TRIUMEQ PD are not recommended in patients with creatinine clearance <30 mL/min and pediatric patients with a similar degree of renal impairment based on age-appropriate assessment of renal function, or patients with hepatic impairment. (,2.7 Not Recommended Due to Lack of Dosage AdjustmentBecause TRIUMEQ and TRIUMEQ PD are fixed-dose tablets and cannot be dose adjusted, TRIUMEQ and TRIUMEQ PD are not recommended in:
• patients with creatinine clearance <30 mL/min and pediatric patients with a similar degree of renal impairment based on age-appropriate renal function assessment. There are no data available on the use of lamivudine, a component of TRIUMEQ and TRIUMEQ PD, in pediatric patients with renal impairment[see Use in Specific Populations ].• patients with mild hepatic impairment. TRIUMEQ and TRIUMEQ PD are contraindicated in patients with moderate or severe hepatic impairment[see Contraindications , Use in Specific Populations ].
)4 CONTRAINDICATIONSTRIUMEQ and TRIUMEQ PD are contraindicated in patients:
• who have the HLA-B*5701 allele[see Warnings and Precautions ].• with prior hypersensitivity reaction to abacavir, dolutegravir[see Warnings and Precautions ], or lamivudine.• receiving dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events with concomitant use of dolutegravir[see Drug Interactions ].• with moderate or severe hepatic impairment[see Use in Specific Populations ].
• Presence of HLA-B*5701 allele.• Prior hypersensitivity reaction to abacavir, dolutegravir, or lamivudine.• Coadministration with dofetilide.• Moderate or severe hepatic impairment.
TRIUMEQ tablets are purple, biconvex, oval, and debossed with “572 Trı” on one side. Each film-coated tablet contains 600 mg of abacavir (as abacavir sulfate), 50 mg of dolutegravir (as dolutegravir sodium), and 300 mg of lamivudine
TRIUMEQ and TRIUMEQ PD contain an INSTI (dolutegravir) and 2 nucleoside analogues (abacavir and lamivudine) with inhibitory activity against HIV.
Each film-coated tablet of TRIUMEQ, for oral use, contains 600 mg of abacavir (present as 702 mg of abacavir sulfate), 50 mg of dolutegravir (present as 52.6 mg of dolutegravir sodium), and 300 mg of lamivudine. The inactive ingredients of TRIUMEQ tablets include D-mannitol, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate. The tablet film‑coating contains the inactive ingredients iron oxide black, iron oxide red, macrogol/PEG, polyvinyl alcohol–part hydrolyzed, talc, and titanium oxide.
Each film-coated tablet of TRIUMEQ PD for oral suspension contains 60 mg of abacavir (present as 70.2 mg of abacavir sulfate), 5 mg of dolutegravir (present as 5.26 mg of dolutegravir sodium), and 30 mg of lamivudine. The inactive ingredients of TRIUMEQ PD tablets include acesulfame potassium, crospovidone, mannitol, microcrystalline cellulose, povidone K29/32, silicified microcrystalline cellulose, sodium starch glycolate, sodium stearyl fumarate, strawberry cream flavor and sucralose. The tablet film-coating contains the inactive ingredients: ferric oxide yellow, macrogol/PEG, polyvinyl alcohol-part hydrolyzed, talc and titanium dioxide.
The chemical name of abacavir sulfate is
Abacavir sulfate is a white to off-white solid and is soluble in water.
The chemical name of dolutegravir sodium is sodium (4
Dolutegravir sodium is a white to light yellow powder and is slightly soluble in water.
The chemical name of lamivudine is (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one. Lamivudine is the (‑)enantiomer of a dideoxy analogue of cytidine. Lamivudine has also been referred to as (‑)2′,3′-dideoxy, 3′-thiacytidine. It has a molecular formula of C8H11N3O3S and a molecular weight of 229.3 g/mol. It has the following structural formula:
Lamivudine is a white to off-white crystalline solid and is soluble in water.
TRIUMEQ PD tablets for oral suspension are yellow, capsule-shaped, strawberry cream flavored, biconvex, film-coated tablets debossed with “SV WTU” on one side. Each film-coated tablet contains 60 mg of abacavir (as abacavir sulfate), 5 mg of dolutegravir (as dolutegravir sodium), and 30 mg of lamivudine
TRIUMEQ and TRIUMEQ PD contain an INSTI (dolutegravir) and 2 nucleoside analogues (abacavir and lamivudine) with inhibitory activity against HIV.
Each film-coated tablet of TRIUMEQ, for oral use, contains 600 mg of abacavir (present as 702 mg of abacavir sulfate), 50 mg of dolutegravir (present as 52.6 mg of dolutegravir sodium), and 300 mg of lamivudine. The inactive ingredients of TRIUMEQ tablets include D-mannitol, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate. The tablet film‑coating contains the inactive ingredients iron oxide black, iron oxide red, macrogol/PEG, polyvinyl alcohol–part hydrolyzed, talc, and titanium oxide.
Each film-coated tablet of TRIUMEQ PD for oral suspension contains 60 mg of abacavir (present as 70.2 mg of abacavir sulfate), 5 mg of dolutegravir (present as 5.26 mg of dolutegravir sodium), and 30 mg of lamivudine. The inactive ingredients of TRIUMEQ PD tablets include acesulfame potassium, crospovidone, mannitol, microcrystalline cellulose, povidone K29/32, silicified microcrystalline cellulose, sodium starch glycolate, sodium stearyl fumarate, strawberry cream flavor and sucralose. The tablet film-coating contains the inactive ingredients: ferric oxide yellow, macrogol/PEG, polyvinyl alcohol-part hydrolyzed, talc and titanium dioxide.
The chemical name of abacavir sulfate is
Abacavir sulfate is a white to off-white solid and is soluble in water.
The chemical name of dolutegravir sodium is sodium (4
Dolutegravir sodium is a white to light yellow powder and is slightly soluble in water.
The chemical name of lamivudine is (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one. Lamivudine is the (‑)enantiomer of a dideoxy analogue of cytidine. Lamivudine has also been referred to as (‑)2′,3′-dideoxy, 3′-thiacytidine. It has a molecular formula of C8H11N3O3S and a molecular weight of 229.3 g/mol. It has the following structural formula:
Lamivudine is a white to off-white crystalline solid and is soluble in water.
• Pediatrics: Not recommended for patients aged <3 months or weighing <6 kg. ()8.4 Pediatric UseThe clinical data supporting use of TRIUMEQ and TRIUMEQ PD in pediatric patients with HIV-1 infection aged at least 3 months old weighing at least 6 kg is derived from the following previously conducted pediatric trials using TRIUMEQ and TRIUMEQ PD or the individual components:
• The safety, pharmacokinetics, and antiviral activity (efficacy) of TRIUMEQ and TRIUMEQ PD were established through an open-label, multicenter clinical trial (IMPAACT 2019), in which HIV-1–infected, treatment-naïve, or treatment-experienced, pediatric subjects younger than 12 years and weighing at least 6 kg to less than 40 kg were treated with TRIUMEQ or TRIUMEQ PD[see Adverse Reactions , Clinical Pharmacology , Clinical Studies].• The safety and efficacy of once-daily abacavir and lamivudine were established with a randomized, multicenter trial (ARROW [COL105677]) in HIV-1–infected, treatment-naive subjects aged 3 months to 17 years with a first-line regimen containing abacavir and lamivudine, using either the combination of EPIVIR and ZIAGEN or EPZICOM[see Adverse Reactions , Clinical Studies ].• The safety, pharmacokinetics, and antiviral activity (efficacy) of TIVICAY and TIVICAY PD were established through an ongoing, open-label, multicenter, dose-finding clinical trial (IMPAACT P1093), in which HIV-1–infected, treatment-naive or treatment-experienced, INSTI-naive, pediatric and adolescent subjects aged 4 weeks to <18 years and weighing at least 3 kg were treated with TIVICAY or TIVICAY PD plus optimized background therapy[see Adverse Reactions , Clinical Pharmacology , Clinical Studies ].• Additional pharmacokinetics data were evaluated in 2 pharmacokinetic substudies in ODYSSEY, an ongoing open-label, randomized, non-inferiority trial to evaluate the safety, efficacy, and pharmacokinetic parameters of TIVICAY or TIVICAY PD plus two nucleoside reverse transcriptase inhibitors (NRTIs) (mainly abacavir and lamivudine) compared with standard of care in HIV-1–infected pediatric subjects younger than 18 years[see Clinical Pharmacology ].
Overall, the safety, and efficacy profile of TRIUMEQ and TRIUMEQ PD in pediatric patients is comparable to that observed in adults. There are no data available on the use of lamivudine in pediatric patients with renal impairment
[see Dosage and Administration , Warnings and Precautions , Adverse Reactions , Use in Specific Populations , Clinical Pharmacology , Clinical Studies ].The safety and effectiveness of TRIUMEQ PD have not been established in pediatric patients aged less than 3 months or weighing less than 6 kg.
• TRIUMEQ and TRIUMEQ PD are not recommended in patients with creatinine clearance less than 30 mL/min and pediatric patients with a similar degree of renal impairment based on age-appropriate assessment of renal function. ()8.6 Patients with Impaired Renal FunctionTRIUMEQ and TRIUMEQ PD are not recommended for patients with creatinine clearance <30 mL/min and pediatric patients with a similar degree of renal impairment based on age-appropriate assessment of renal function because TRIUMEQ and TRIUMEQ PD are fixed-dose combinations, and the dosage of the individual components cannot be adjusted. If a dose reduction of lamivudine, a component of TRIUMEQ and TRIUMEQ PD, is required for patients with creatinine clearance <30 mL/min and in pediatric patients with a similar degree of renal impairment based on age-appropriate assessment of renal function, then the individual components should be used
[see Clinical Pharmacology ].Patients with a creatinine clearance between 30 and 49 mL/min receiving TRIUMEQ may experience a 1.6- to 3.3-fold higher lamivudine exposure (AUC) than patients with a creatinine clearance ≥50 mL/min. There are no safety data from randomized, controlled trials comparing TRIUMEQ to the individual components in patients with a creatinine clearance between 30 and 49 mL/min who received dose-adjusted lamivudine. Additionally, there are no data available on the use of lamivudine in pediatric patients with renal impairment. In the original lamivudine registrational trials in combination with zidovudine, higher lamivudine exposures were associated with higher rates of hematologic toxicities (neutropenia and anemia), although discontinuations due to neutropenia or anemia each occurred in <1% of subjects.
Patients with a sustained creatinine clearance between 30 and 49 mL/min or pediatric patients with a similar degree of renal impairment based on an age-appropriate assessment of renal function who receive TRIUMEQ or TRIUMEQ PD should be monitored for hematologic toxicities. If new or worsening neutropenia or anemia develop, dose adjustment of lamivudine, per lamivudine prescribing information, is recommended. If lamivudine dose adjustment is indicated, TRIUMEQ or TRIUMEQ PD should be discontinued, and the individual components should be used to construct the treatment regimen.
• If a dose reduction of abacavir, a component of TRIUMEQ and TRIUMEQ PD, is required for patients with mild hepatic impairment, then the individual components should be used. ()8.7 Patients with Impaired Hepatic FunctionTRIUMEQ and TRIUMEQ PD are fixed-dose combinations, and the dosage of the individual components cannot be adjusted. If a dose reduction of abacavir, a component of TRIUMEQ and TRIUMEQ PD, is required for patients with mild hepatic impairment (Child-Pugh Score A), then the individual components should be used
[see Clinical Pharmacology ].The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate (Child-Pugh Score B) or severe (Child-Pugh Score C) hepatic impairment; therefore, TRIUMEQ and TRIUMEQ PD are contraindicated in these patients
[see Contraindications ].
TRIUMEQ and TRIUMEQ PD are contraindicated in patients:
• who have the HLA-B*5701 allele[see Warnings and Precautions (.)]5.1 Hypersensitivity ReactionsHypersensitivity reactions have been reported with the use of abacavir or dolutegravir, components of TRIUMEQ and TRIUMEQ PD.
AbacavirSerious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing regimens. See full prescribing information for ZIAGEN (abacavir).
Abacavir hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment
[see Adverse Reactions ]. Patients who carry the HLA‑B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA‑B*5701 allele have developed hypersensitivity reactions. Hypersensitivity to abacavir was reported in approximately 206 (8%) of 2,670 patients in 9 clinical trials with abacavir-containing products where HLA‑B*5701 screening was not performed. The incidence of suspected abacavir hypersensitivity reactions in clinical trials was 1% when subjects carrying the HLA-B*5701 allele were excluded. In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making.Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir:
• All patients should be screened for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD or reinitiation of therapy with TRIUMEQ or TRIUMEQ PD, unless patients have a previously documented HLA‑B*5701 allele assessment.• TRIUMEQ and TRIUMEQ PD are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‑B*5701‑positive patients.• Before starting TRIUMEQ or TRIUMEQ PD, review medical history for prior exposure to any abacavir-containing product. NEVER restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA‑B*5701 status.• To reduce the risk of a life‑threatening hypersensitivity reaction, regardless of HLA‑B*5701 status, discontinue TRIUMEQ or TRIUMEQ PD immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications). Clinical status, including liver chemistries, should be monitored and appropriate therapy initiated.• If a hypersensitivity reaction cannot be ruled out, do not restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing products because more severe symptoms, which may include life-threatening hypotension and death, can occur within hours.• Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.• If a hypersensitivity reaction is ruled out, patients may restart TRIUMEQ or TRIUMEQ PD. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of TRIUMEQ or TRIUMEQ PD, or any other abacavir-containing product, is recommended only if medical care can be readily accessed.• A Medication Guide and Warning Card that provide information about recognition of abacavir hypersensitivity reactions should be dispensed with each new prescription and refill.
DolutegravirHypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in <1% of subjects receiving TIVICAY in Phase 3 clinical trials. Discontinue TRIUMEQ or TRIUMEQ PD and other suspect agents 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 or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping treatment with TRIUMEQ or TRIUMEQ PD or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction.
Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.
• with prior hypersensitivity reaction to abacavir, dolutegravir[see Warnings and Precautions (, or lamivudine.)]5.1 Hypersensitivity ReactionsHypersensitivity reactions have been reported with the use of abacavir or dolutegravir, components of TRIUMEQ and TRIUMEQ PD.
AbacavirSerious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing regimens. See full prescribing information for ZIAGEN (abacavir).
Abacavir hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment
[see Adverse Reactions ]. Patients who carry the HLA‑B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA‑B*5701 allele have developed hypersensitivity reactions. Hypersensitivity to abacavir was reported in approximately 206 (8%) of 2,670 patients in 9 clinical trials with abacavir-containing products where HLA‑B*5701 screening was not performed. The incidence of suspected abacavir hypersensitivity reactions in clinical trials was 1% when subjects carrying the HLA-B*5701 allele were excluded. In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making.Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir:
• All patients should be screened for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD or reinitiation of therapy with TRIUMEQ or TRIUMEQ PD, unless patients have a previously documented HLA‑B*5701 allele assessment.• TRIUMEQ and TRIUMEQ PD are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‑B*5701‑positive patients.• Before starting TRIUMEQ or TRIUMEQ PD, review medical history for prior exposure to any abacavir-containing product. NEVER restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA‑B*5701 status.• To reduce the risk of a life‑threatening hypersensitivity reaction, regardless of HLA‑B*5701 status, discontinue TRIUMEQ or TRIUMEQ PD immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications). Clinical status, including liver chemistries, should be monitored and appropriate therapy initiated.• If a hypersensitivity reaction cannot be ruled out, do not restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing products because more severe symptoms, which may include life-threatening hypotension and death, can occur within hours.• Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.• If a hypersensitivity reaction is ruled out, patients may restart TRIUMEQ or TRIUMEQ PD. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of TRIUMEQ or TRIUMEQ PD, or any other abacavir-containing product, is recommended only if medical care can be readily accessed.• A Medication Guide and Warning Card that provide information about recognition of abacavir hypersensitivity reactions should be dispensed with each new prescription and refill.
DolutegravirHypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in <1% of subjects receiving TIVICAY in Phase 3 clinical trials. Discontinue TRIUMEQ or TRIUMEQ PD and other suspect agents 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 or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing). Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated. Delay in stopping treatment with TRIUMEQ or TRIUMEQ PD or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction.
Clinically, it is not possible to determine whether a hypersensitivity reaction with TRIUMEQ or TRIUMEQ PD would be caused by abacavir or dolutegravir. Therefore, never restart TRIUMEQ or TRIUMEQ PD or any other abacavir- or dolutegravir-containing product in patients who have stopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.
• receiving dofetilide due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events with concomitant use of dolutegravir[see Drug Interactions (.)]7 DRUG INTERACTIONSCoadministration of TRIUMEQ or TRIUMEQ PD with other drugs can alter the concentration of other drugs and other drugs may alter the concentrations of TRIUMEQ or TRIUMEQ PD. The potential drug-drug interactions must be considered prior to and during therapy.
7.1 Effect of Dolutegravir on the Pharmacokinetics of Other AgentsIn vitro, dolutegravir inhibited the renal organic cation transporters (OCT)2 (IC50= 1.93 microM) and multidrug and toxin extrusion transporter (MATE)1 (IC50= 6.34 microM). In vivo, dolutegravir inhibits tubular secretion of creatinine by inhibiting OCT2 and potentially MATE1. Dolutegravir may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 (dofetilide, dalfampridine, and metformin)
[see Contraindications , Drug Interactions ].In vitro, dolutegravir inhibited the basolateral renal transporters, organic anion transporter (OAT) 1 (IC50= 2.12 microM) and OAT3 (IC50= 1.97 microM). However, in vivo, dolutegravir did not alter the plasma concentrations of tenofovir or para-amino hippurate, substrates of OAT1 and OAT3.
In vitro, dolutegravir did not inhibit (IC50>50 microM) the following: cytochrome P450 (CYP)1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A, uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1, UGT2B7, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt export pump (BSEP), organic anion transporter polypeptide (OATP)1B1, OATP1B3, OCT1, or multidrug resistance protein (MRP)2, or MRP4. In vitro, dolutegravir did not induce CYP1A2, CYP2B6, CYP3A4. Based on these data and the results of drug interaction trials, dolutegravir is not expected to affect the pharmacokinetics of drugs that are substrates of these enzymes or transporters.
In drug interaction trials, dolutegravir did not have a clinically relevant effect on the pharmacokinetics of the following drugs: tenofovir, methadone, midazolam, rilpivirine, and oral contraceptives containing norgestimate and ethinyl estradiol. Using cross-study comparisons to historical pharmacokinetic data for each interacting drug, dolutegravir did not appear to affect the pharmacokinetics of the following drugs: atazanavir, darunavir, efavirenz, etravirine, fosamprenavir, lopinavir, ritonavir, and boceprevir.
7.2 Effect of Other Agents on the Pharmacokinetics of DolutegravirDolutegravir is metabolized by UGT1A1 with some contribution from CYP3A. Dolutegravir is also a substrate of UGT1A3, UGT1A9, BCRP, and P-gp in vitro. Drugs that induce those enzymes and transporters may decrease dolutegravir plasma concentrations and reduce the therapeutic effect of dolutegravir.
Coadministration of dolutegravir and other drugs that inhibit these enzymes may increase dolutegravir plasma concentrations.
Etravirine significantly reduced plasma concentrations of dolutegravir, but the effect of etravirine was mitigated by coadministration of lopinavir/ritonavir or darunavir/ritonavir and is expected to be mitigated by atazanavir/ritonavir
[see Drug Interactions , Clinical Pharmacology ].In vitro, dolutegravir was not a substrate of OATP1B1 or OATP1B3.
Darunavir/ritonavir, lopinavir/ritonavir, rilpivirine, tenofovir, boceprevir, prednisone, rifabutin, and omeprazole had no clinically significant effect on the pharmacokinetics of dolutegravir.
7.3 Established and Other Potentially Significant Drug InteractionsThere were no drug-drug interaction trials conducted with the abacavir, dolutegravir, and lamivudine fixed-dose combination tablets.
Information regarding potential drug interactions with the individual components of TRIUMEQ and TRIUMEQ PD are provided below. These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy.
[See Contraindications , Clinical Pharmacology .]Table 6. Established and Other Potentially Significant Drug Interactions for Dolutegravir: Alterations in Dose May Be Recommended Based on Drug Interaction Trials or Predicted Interactions a See Clinical Pharmacology Table 8or Table 10for magnitude of interaction.Concomitant Drug Class:Drug NameEffect on ConcentrationClinical CommentHIV-1 Antiviral AgentsNon-nucleoside reverse transcriptase inhibitor:Etravirinea
↓Dolutegravir
Use of TRIUMEQ or TRIUMEQ PD with etravirine without coadministration of atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir is not recommended.
Non-nucleoside reverse transcriptase inhibitor:Efavirenza
↓Dolutegravir
In adults and in pediatric patients
weighing at least 25 kg, adjust dolutegravir dose to 50 mg twice daily. An additional 50-mg dose of TIVICAY should be taken, separated by 12 hours from TRIUMEQ.In pediatric patients
weighing 6 to <25 kg, an additional weight-based dose of dolutegravir should be given separated by 12 hours from TRIUMEQ PD.• 6 to <10 kg: administer an additional 15-mg dose of dolutegravir (3 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 10 to <14 kg: administer an additional 20-mg dose of dolutegravir (4 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 14 to <20 kg: administer an additional 25-mg dose of dolutegravir (5 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 20 to <25 kg: administer an additional 30-mg dose of dolutegravir (6 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.
Non-nucleoside reverse transcriptase inhibitor:Nevirapine
↓Dolutegravir
Avoid coadministration with TRIUMEQ or TRIUMEQ PD because there are insufficient data to make dosing recommendations.
Protease inhibitor:Fosamprenavir/ritonavira
Tipranavir/ritonavira↓Dolutegravir
In adults and in pediatric patients
weighing at least 25 kg, adjust dolutegravir dose to 50 mg twice daily. An additional TIVICAY 50-mg dose should be taken, separated by 12 hours from TRIUMEQ.In pediatric patients
weighing 10 to <25 kg, an additional weight-based dose of dolutegravir should be given separated by 12 hours from TRIUMEQ PD.• 6 to <10 kg: administer an additional 15-mg dose of dolutegravir (3 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 10 to <14 kg: administer an additional 20-mg dose of dolutegravir (4 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 14 to <20 kg: administer an additional 25-mg dose of dolutegravir (5 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 20 to <25 kg: administer an additional 30-mg dose of dolutegravir (6 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.
Other AgentsAntiarrhythmic:Dofetilide
↑Dofetilide
Coadministration is contraindicated with TRIUMEQ and TRIUMEQ PD
[see Contraindications ].Potassium channel blocker:Dalfampridine
↑Dalfampridine
Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking dalfampridine concurrently with TRIUMEQ or TRIUMEQ PD should be considered against the risk of seizures in these patients.
Carbamazepinea
↓Dolutegravir
In adults and in pediatric patients
weighing at least 25 kg, adjust dolutegravir dose to 50 mg twice daily. An additional TIVICAY 50-mg dose should be taken, separated by 12 hours from TRIUMEQ.In pediatric patients
weighing 6 to <25 kg, an additional weight-based dose of dolutegravir should be given separated by 12 hours from TRIUMEQ PD.• 6 to <10 kg: administer an additional 15-mg dose of dolutegravir (3 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 10 to <14 kg: administer an additional 20-mg dose of dolutegravir (4 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 14 to <20 kg: administer an additional 25-mg dose of dolutegravir (5 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 20 to <25 kg: administer an additional 30-mg dose of dolutegravir (6 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.
Oxcarbazepine
Phenytoin
Phenobarbital
St. John’s wort (Hypericum perforatum)↓Dolutegravir
Avoid coadministration with TRIUMEQ or TRIUMEQ PD because there are insufficient data to make dosing recommendations.
Medications containing polyvalent cations(e.g., Mg or Al):Cation-containing antacidsaor laxatives
Sucralfate
Buffered medications
↓Dolutegravir
Administer TRIUMEQ or TRIUMEQ PD 2 hours before or 6 hours after taking medications containing polyvalent cations.
Oral calcium and iron supplements, including multivitamins containing calcium or irona↓Dolutegravir
When taken with food, TRIUMEQ or TRIUMEQ PD and supplements or multivitamins containing calcium or iron can be taken at the same time. Under fasting conditions, TRIUMEQ or TRIUMEQ PD should be taken 2 hours before or 6 hours after taking supplements containing calcium or iron.
Metformina
↑Metformin
Refer to the prescribing information for metformin for assessing the benefit and risk of concomitant use of TRIUMEQ or TRIUMEQ PD and metformin.
Rifampina
↓Dolutegravir
In adults and in pediatric patients
weighing at least 25 kg, adjust dolutegravir dose to 50 mg twice daily. An additional 50-mg dose of TIVICAY should be taken, separated by 12 hours from TRIUMEQ.In pediatric patients
weighing 6 to <25 kg, an additional weight-based dose of dolutegravir should be given separated by 12 hours from TRIUMEQ PD.• 6 to <10 kg: administer an additional 15-mg dose of dolutegravir (3 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 10 to <14 kg: administer an additional 20-mg dose of dolutegravir (4 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 14 to <20 kg: administer an additional 25-mg dose of dolutegravir (5 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.• 20 to <25 kg: administer an additional 30-mg dose of dolutegravir (6 TIVICAY PD tablets for oral suspension), 12 hours after TRIUMEQ PD.
MethadoneAbacavir:In a trial of 11 HIV-1–infected subjects receiving methadone-maintenance therapy with 600 mg of abacavir twice daily (twice the currently recommended dose), oral methadone clearance increased[see Clinical Pharmacology ]. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.SorbitolLamivudine:Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine-containing medicines[see Clinical Pharmacology ].RiociguatAbacavir:Coadministration with TRIUMEQ resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions[see Clinical Pharmacology ]. The riociguat dose may need to be reduced. See full prescribing information for ADEMPAS (riociguat).• with moderate or severe hepatic impairment[see Use in Specific Populations (.)]8.7 Patients with Impaired Hepatic FunctionTRIUMEQ and TRIUMEQ PD are fixed-dose combinations, and the dosage of the individual components cannot be adjusted. If a dose reduction of abacavir, a component of TRIUMEQ and TRIUMEQ PD, is required for patients with mild hepatic impairment (Child-Pugh Score A), then the individual components should be used
[see Clinical Pharmacology ].The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate (Child-Pugh Score B) or severe (Child-Pugh Score C) hepatic impairment; therefore, TRIUMEQ and TRIUMEQ PD are contraindicated in these patients
[see Contraindications ].