Abacavir, dolutegravir, and lamivudine
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Boxed warning
WARNING: HYPERSENSITIVITY REACTIONS, AND EXACERBATIONS OF HEPATITIS B Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir, a component of TRIUMEQ and TRIUMEQ PD (abacavir, dolutegravir, and lamivudine). Patients who carry the HLA ‑ B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir, although hypersensitivity reactions have occurred in patients who do not carry the HLA ‑ B*5701 allele [see Warnings and Precautions ( 5.1 )] .
TRIUMEQ and TRIUMEQ PD are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA ‑ B*5701-positive patients [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] . 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. Discontinue TRIUMEQ or TRIUMEQ PD immediately if a hypersensitivity reaction is suspected, regardless of HLA ‑ B*5701 status and even when other diagnoses are possible [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] .
Following a hypersensitivity reaction to TRIUMEQ or TRIUMEQ PD, NEVER restart TRIUMEQ or TRIUMEQ PD or any other abacavir ‑ containing product because more severe symptoms, including death can occur within hours. Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity [see Warnings and Precautions ( 5.1 )] . Exacerbations of Hepatitis B All patients with HIV-1 should be tested for the presence of hepatitis B virus (HBV) prior to or when initiating TRIUMEQ or TRIUMEQ PD.
Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If TRIUMEQ or TRIUMEQ PD 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 hepatitis B have been reported in patients who are co ‑ infected with HBV and HIV-1 and have discontinued lamivudine, a component of TRIUMEQ and TRIUMEQ PD. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment [see Warnings and Precautions ( 5.2 )].
WARNING: HYPERSENSITIVITY REACTIONS, AND EXACERBATIONS OF HEPATITIS B See full prescribing information for…
Handling and access
NIOSH hazardous drug
Table 2This product contains abacavir, which NIOSH lists as a hazardous drug. AHFS class: 8:18.08.20 HIV nucleoside and nucleotide reverse transcriptase inhibitors.
- Meets the NIOSH definition of a hazardous drug (carcinogenicity, developmental or reproductive toxicity, organ toxicity at low doses, or genotoxicity) without MSHI or a Group 1 or 2A carcinogen classification.
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor, Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor
Dosing in kidney impairment
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 , 4 ) 2.1 Screening for HLA−B*5701 Allele prior to Initiating TRIUMEQ Screen for the HLA‑B*5701 allele prior to initiating therapy with TRIUMEQ or TRIUMEQ PD [see Boxed Warning , Warnings and Precautions]. 2.2 Testing prior to or When Initiating Treatment with TRIUMEQ Prior to or when initiating TRIUMEQ or TRIUMEQ PD, test patients for HBV infection [see Warnings and Precautions] . 2.3 Overview of TRIUMEQ Dosage Forms TRIUMEQ is available in two dosage forms. 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 ( 8.4 , 8.6 )] .
Preparation and administration
Recommended Dosage and Administration Instructions for Pediatric Patients Weighing at Least 6 kg The dosage and dosage form recommended for pediatric patients varies by weight as shown in Table 1 below. [See table below.] . b TRIUMEQ PD is a fixed-dose combination product containing 60 mg of abacavir, 5 mg of dolutegravir, and 30 mg of lamivudine.
Body Weight TRIUMEQ Tablets a TRIUMEQ PD b Number of Tablets Total Daily Dose 6 kg to <10 kg Not recommended 3 tablets once daily 180 mg abacavir, 15 mg dolutegravir, and 90 mg lamivudine once daily 10 kg to <14 kg Not recommended 4 tablets once daily 240 mg abacavir, 20 mg dolutegravir, and 120 mg lamivudine once daily 14 kg to <20 kg Not recommended 5 tablets once daily 300 mg abacavir, 25 mg dolutegravir, and 150 mg lamivudine once daily 20 kg to <25 kg Not recommended 6 tablets once daily 360 mg abacavir, 30 mg dolutegravir, and 180 mg lamivudine once daily ≥25 kg 1 tablet once daily Not recommended 600 mg of abacavir, 50 mg of dolutegravir, and 300 mg of lamivudine Administer TRIUMEQ PD tablets for oral suspension with or without food.
Instruct patients (or instruct caregivers) to fully disperse 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.
Drug interactions
Check interactions
Add the patient's other drugs. Matches come from both FDA labels: by name, drug class, and enzyme or transporter pathway.
- Abacavir, dolutegravir, and lamivudine
Label text (17 paragraphs)
Coadministration 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. ( 4 , 7 , 12.3 )
7.1 Effect of Dolutegravir on the Pharmacokinetics of Other Agents In vitro, dolutegravir inhibited the renal organic cation transporters (OCT)2 (IC 50 = 1.93 microM) and multidrug and toxin extrusion transporter (MATE)1 (IC 50 = 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 ( 4 ), Drug Interactions ( 7.3 )] . In vitro, dolutegravir inhibited the basolateral renal transporters, organic anion transporter (OAT) 1 (IC 50 = 2.12 microM) and OAT3 (IC 50 = 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 (IC 50 >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 Dolutegravir Dolutegravir 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 ( Table 6 ) [see Drug Interactions ( 7.3 ), Clinical Pharmacology ( 12.3 )] . 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 Interactions There 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 ( 4 ), Clinical Pharmacology ( 12.3 ).] 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 ( 12.3 ) Table 8 or Table 10 for magnitude of interaction. Concomitant Drug Class: Drug Name Effect on Concentration Clinical Comment HIV-1 Antiviral Agents Non-nucleoside reverse transcriptase inhibitor: Etravirine a ↓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: Efavirenz a ↓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/ritonavir a Tipranavir/ritonavir a ↓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 Agents Antiarrhythmic: Dofetilide ↑Dofetilide Coadministration is contraindicated with TRIUMEQ and TRIUMEQ PD [see Contraindications ( 4 )] . 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.
Carbamazepine a ↓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 antacids a or 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 iron a ↓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.
Metformin a ↑Metformin Refer to the prescribing information for metformin…
Supplement interactions
Dietary supplement interactions
1 noted- Dolutegravir (Dovato, Tivicay) is an HIV integrase inhibitor used in adults and children. Concomitant use of calcium supplements and dolutegravir can reduce blood levels of dolutegravir substantially, apparently through chelation.
Contraindications
4 CONTRAINDICATIONS TRIUMEQ and TRIUMEQ PD are contraindicated in patients: • who have the HLA-B*5701 allele [see Warnings and Precautions ( 5.1 )] . • with prior hypersensitivity reaction to abacavir, dolutegravir [see Warnings and Precautions ( 5.1 )] , 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 ( 7 )] . • with moderate or severe hepatic impairment [see Use in Specific Populations ( 8.7 )] . • Presence of HLA-B*5701 allele. ( 4 ) • Prior hypersensitivity reaction to abacavir, dolutegravir, or lamivudine.
( 4 ) • Coadministration with dofetilide. ( 4 ) • Moderate or severe hepatic impairment. ( 4 , 8.7 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for abacavir, dolutegravir, and lamivudine. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to TRIUMEQ during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1‑800‑258‑4263.
Risk Summary Data from two, ongoing birth outcome surveillance studies in Botswana and Eswatini which together include over 14,000 individuals evaluated during pregnancy show similar prevalence of neural tube defects among infants born to individuals taking dolutegravir at the time of conception compared to those born to individuals taking non-dolutegravir-containing regimens at conception or infants born to HIV-negative individuals (see Data). There are insufficient human data on the use of TRIUMEQ during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage.
However, available human data from the APR with the individual components of TRIUMEQ do not indicate an increased risk of birth defects (see Data) . The background risk for major birth defects for the indicated population is unknown. In the U.S. general population, the estimated background rate for major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
In animal reproduction studies, no evidence of adverse developmental outcomes (including neural tube defects) was observed with dolutegravir at systemic exposures (AUC) less than (rabbits) and approximately 50 times (rats) the exposure in humans at the recommended human dose (RHD) (see Data) . Oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (AUC) at the RHD. No adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis at exposures approximately 9 times the human exposure (AUC) at the RHD.
Oral administration of lamivudine to pregnant rabbits during organogenesis resulted in embryolethality at a human exposure (AUC) similar to the RHD; however, no adverse development effects were observed with oral administration of lamivudine to pregnant rats during organogenesis at plasma concentrations (C max ) 35 times the RHD (see Data). Data Human Data: Dolutegravir: Observational studies: The first interim analysis from an ongoing birth outcome surveillance study in Botswana identified an association between dolutegravir and an increased risk of neural tube defects when…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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