HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
TRIUMEQ and TRIUMEQ PD safely and effectively. See full prescribing
information for TRIUMEQ and TRIUMEQ PD.

Pediatric
Population
Body Weight

Number of
Tablets(once daily)
Recommended Daily DoseTRIUMEQ 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 kg1
600 mg ABC, 50 mg DTG, and 300 mg 3TC
ABC = abacavir, DTG = dolutegravir, 3TC = lamivudine.

TRIUMEQ (abacavir, dolutegravir, and lamivudine) tablets, for oral use
TRIUMEQ PD (abacavir, dolutegravir, and lamivudine) tablets for oralsuspension
Initial U.S. Approval: 2014
WARNING: HYPERSENSITIVITY REACTIONS, AND
EXACERBATIONS OF HEPATITIS B
See full prescribing information for complete boxed warning.

•

Hypersensitivity Reactions• Serious and sometimes fatal hypersensitivity reactions have occurredwith abacavir-containing products. (5.1)• Hypersensitivity to abacavir is a multi-organ clinical syndrome. (5.1)• Patients who carry the HLA-B*5701 allele are at a higher risk ofexperiencing a hypersensitivity reaction to abacavir. (5.1)• TRIUMEQ and TRIUMEQ PD are contraindicated in patients with aprior hypersensitivity reaction to abacavir and in HLA-B*5701-positive
patients. (4)• Discontinue TRIUMEQ or TRIUMEQ PD as soon as a hypersensitivity
reaction is suspected. Regardless of HLA-B*5701 status, permanently
discontinue TRIUMEQ or TRIUMEQ PD if hypersensitivity cannot be
ruled out, even when other diagnoses are possible. (5.1)• Following a hypersensitivity reaction to TRIUMEQ or TRIUMEQ PD,
NEVER restart TRIUMEQ, TRIUMEQ PD, or any otherabacavir-containing product. (5.1)••

Do not substitute TRIUMEQ and TRIUMEQ PD on a milligram-permilligram basis. (2.3)
If dosing with certain UGT1A or CYP3A inducers, then therecommended dolutegravir dosage regimen should be adjusted. See Table
2 for complete dosing recommendations. (2.6)
Because TRIUMEQ and TRIUMEQ PD are fixed-dose tablets and cannot
be dose adjusted, TRIUMEQ and TRIUMEQ PD are not recommended inpatients with creatinine clearance <30 mL/min and pediatric patients witha similar degree of renal impairment based on age-appropriate assessmentof renal function, or patients with hepatic impairment. (2.7, 4)--------------------- DOSAGE FORMS AND STRENGTHS---------------------TRIUMEQ tablets: 600 mg of abacavir, 50 mg of dolutegravir, and
300 mg of lamivudine. (3)•
TRIUMEQ PD tablets for oral suspension: 60 mg of abacavir, 5 mg of
dolutegravir, and 30 mg of lamivudine. (3)•------------------------------ CONTRAINDICATIONS -----------------------------• 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)

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 withlamivudine-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 HBV have been reported in patients whoare co-infected with HBV and HIV-1 and have discontinued lamivudine,
a component of TRIUMEQ and TRIUMEQ PD. Closely monitor hepaticfunction in these patients and, if appropriate, initiate anti-HBV
treatment. (5.2)----------------------- WARNINGS AND PRECAUTIONS ----------------------• Hepatotoxicity has been reported in patients receiving a dolutegravircontaining regimen. Monitoring for hepatotoxicity is recommended. (5.3)• Lactic acidosis and severe hepatomegaly with steatosis, including fatal
cases, have been reported with the use of nucleoside analogues. (5.4)• Immune reconstitution syndrome has been reported in patients treatedwith combination antiretroviral therapy. (5.6)• TRIUMEQ tablets and TRIUMEQ PD tablets for oral suspension are notsubstitutable. (2.3, 5.7)--------------------------- RECENT MAJOR CHANGES --------------------------Dosage and Administration, (2.2)
4/2024
Warnings and Precautions, Embryo-Fetal Toxicity (5.5)
Removed 4/2024------------------------------ ADVERSE REACTIONS -----------------------------The most commonly reported adverse reactions of at least moderate intensity
and incidence at least 2% (in those receiving TRIUMEQ) were insomnia,
headache, and fatigue. (6.1)--------------------------- INDICATIONS AND USAGE---------------------------TRIUMEQ and TRIUMEQ PD are a combination of dolutegravir (integrase
strand transfer inhibitor [INSTI]), abacavir, and lamivudine (both nucleosideanalogue reverse transcriptase inhibitors) indicated for the treatment of HIV-1
infection in adults and in pediatric patients aged at least 3 months andweighing at least 6 kg. (1)Limitations of Use:
TRIUMEQ and TRIUMEQ PD alone are not recommended in patients withresistance-associated integrase substitutions or clinically suspected INSTI
resistance because the dose of dolutegravir in TRIUMEQ and TRIUMEQ PD
is insufficient in these subpopulations. See the dolutegravir prescribing
information. (1)To report SUSPECTED ADVERSE REACTIONS, contact ViiV
Healthcare at 1-877-844-8872 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
------------------------------ DRUG INTERACTIONS------------------------------Coadministration of TRIUMEQ or TRIUMEQ PD with other drugs can alter
the concentration of other drugs and other drugs may alter the concentrationsof TRIUMEQ or TRIUMEQ PD. The potential drug-drug interactions must be
considered prior to and during therapy. (4, 7, 12.3)----------------------- USE IN SPECIFIC POPULATIONS ----------------------• Pediatrics: Not recommended for patients aged <3 months or weighing<6 kg. (8.4)• TRIUMEQ and TRIUMEQ PD are not recommended in patients withcreatinine clearance less than 30 mL/min and pediatric patients with asimilar degree of renal impairment based on age-appropriate assessmentof renal function. (8.6)• If a dose reduction of abacavir, a component of TRIUMEQ andTRIUMEQ PD, is required for patients with mild hepatic impairment,
then the individual components should be used. (8.7)----------------------- DOSAGE AND ADMINISTRATION ----------------------• Before initiating TRIUMEQ or TRIUMEQ PD, screen for the
HLA-B*5701 allele because TRIUMEQ and TRIUMEQ PD containabacavir. (2.1).
• Prior to or when initiating TRIUMEQ or TRIUMEQ PD, test patients for
HBV infection. (2.2)• TRIUMEQ and TRIUMEQ PD may be taken with or without food. (2.4,
2.5)• Adults: One tablet of TRIUMEQ daily. (2.4)

See 17 for PATIENT COUNSELING INFORMATION and Medication
Guide.
Revised: 7/2024

1

FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: HYPERSENSITIVITY REACTIONS, AND
EXACERBATIONS OF HEPATITIS B
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Screening for HLA-B*5701 Allele prior to Initiating
TRIUMEQ
2.2 Testing prior to or When Initiating Treatment with
TRIUMEQ
2.3 Overview of TRIUMEQ Dosage Forms
2.4 Recommended Dosage in Adults
2.5 Recommended Dosage and Administration Instructions for
Pediatric Patients Weighing at Least 6 kg
2.6 Dosage Recommendation with Certain Concomitant
Medications
2.7 Not Recommended Due to Lack of Dosage Adjustment
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
5.2 Patients Co-infected with HIV-1 and HBV: Emergence of
Lamivudine-Resistant HBV and the Risk of Posttreatment
Exacerbations of HBV
5.3 Hepatotoxicity
5.4 Lactic Acidosis and Severe Hepatomegaly with Steatosis
5.5 Risk of Adverse Reactions or Loss of Virologic Response
Due to Drug Interactions
5.6 Immune Reconstitution Syndrome
5.7 Different Formulations Are Not Substitutable
5.8 Myocardial Infarction
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience

6.2 Postmarketing Experience
DRUG INTERACTIONS
7.1 Effect of Dolutegravir on the Pharmacokinetics of Other
Agents
7.2 Effect of Other Agents on the Pharmacokinetics of
Dolutegravir
7.3 Established and Other Potentially Significant Drug
Interactions
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Patients with Impaired Renal Function
8.7 Patients with Impaired Hepatic Function
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.4 Microbiology
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Adult Subjects
14.2 Pediatric Subjects
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are notlisted.
7

FULL PRESCRIBING INFORMATIONWARNING: HYPERSENSITIVITY REACTIONS, AND EXACERBATIONS OFHEPATITIS 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 haveoccurred in patients who do not carry the HLA-B*5701 allele [see Warnings andPrecautions (5.1)].
TRIUMEQ and TRIUMEQ PD are contraindicated in patients with a priorhypersensitivity reaction to abacavir and in HLA-B*5701-positive patients [seeContraindications (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 orreinitiation of therapy with TRIUMEQ or TRIUMEQ PD, unless patients have apreviously documented HLA-B*5701 allele assessment. Discontinue TRIUMEQ or
2

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 havealso occurred rarely following the reintroduction of abacavir-containing products inpatients 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 beenreported. 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 areco-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)].
1

INDICATIONS AND USAGE

TRIUMEQ and TRIUMEQ PD are indicated for the treatment of HIV-1 infection in adults andin pediatric patients aged at least 3 months and weighing at least 6 kg.
Limitations of Use:
TRIUMEQ and TRIUMEQ PD alone are not recommended in patients with resistance-associatedintegrase substitutions or clinically suspected integrase strand transfer inhibitor (INSTI)
resistance because the dose of dolutegravir in TRIUMEQ and TRIUMEQ PD is insufficient inthese subpopulations. See full prescribing information for TIVICAY (dolutegravir).
2

DOSAGE AND ADMINISTRATION

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 (5.1)].

3

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 [seeWarnings and Precautions (5.2)].
2.3

Overview of TRIUMEQ Dosage Forms

TRIUMEQ is available in two dosage forms. Do not substitute TRIUMEQ tablets andTRIUMEQ PD tablets for oral suspension on a milligram-per-milligram basis due todiffering pharmacokinetic profiles for the dolutegravir component [see Warnings andPrecautions (5.7), Clinical Pharmacology (12.3)].
•

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 [seeDosage and Administration (2.4, 2.5)].

•

TRIUMEQ PD tablets for oral suspension: 60 mg of abacavir, 5 mg of dolutegravir, and30 mg of lamivudine. TRIUMEQ PD is recommended in pediatric patients weighing 6 kg toless than 25 kg [see Dosage and Administration (2.5)].

•

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 andAdministration (2.4, 2.5)].

2.4

Recommended Dosage in Adults

TRIUMEQ 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 kg
The dosage and dosage form recommended for pediatric patients varies by weight as shown in
Table 1 below.
Table 1. Recommended Dosage of TRIUMEQ Tablets and TRIUMEQ PD Tablets for Oral
Suspension in Pediatric Patients
TRIUMEQ PDb
TRIUMEQ
Number ofaBody Weight
Tablets
Tablets
Total Daily Dose
6 kg to <10 kgNot
3 tablets once
180 mg abacavir, 15 mg dolutegravir,
recommended
daily
and 90 mg lamivudine once daily
10 kg to <14 kg Not
4 tablets once
240 mg abacavir, 20 mg dolutegravir,
recommended
daily
and 120 mg lamivudine once daily414 kg to <20 kg

Not
recommended
Not
recommended
1 tablet oncedaily

5 tablets oncedaily
6 tablets once
daily
Not
recommended

300 mg abacavir, 25 mg dolutegravir,
and 150 mg lamivudine once daily
20 kg to <25 kg
360 mg abacavir, 30 mg dolutegravir,
and 180 mg lamivudine once daily≥25 kg
600 mg of abacavir, 50 mg of
dolutegravir, and 300 mg oflamivudinea
TRIUMEQ is a fixed-dose combination product containing 600 mg of abacavir, 50 mg of
dolutegravir, and 300 mg of lamivudine.
b
TRIUMEQ PD is a fixed-dose combination product containing 60 mg of abacavir, 5 mg of
dolutegravir, and 30 mg of lamivudine.
Administer TRIUMEQ PD tablets for oral suspension with or without food. Instruct patients (orinstruct 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 oralsuspension) 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 forUse]. Do not swallow the tablets for oral suspension whole, and do not chew, cut, or crush thetablets.
For children unable to use the supplied cup, an appropriate-sized syringe may be used toadminister the oral suspension.
Administer TRIUMEQ tablet with or without food. Do not chew, cut, or crush the tablet.
2.6

Dosage Recommendation with Certain Concomitant Medications

The dolutegravir dose in TRIUMEQ (50 mg) and TRIUMEQ PD (5 mg) is insufficient whencoadministered with medications listed in Table 2 that may decrease dolutegravir concentrations;the following dolutegravir dosage regimen is recommended.

5

Table 2. Dosing Recommendations for TRIUMEQ and TRIUMEQ PD with
Coadministered Medications
Coadministered Drug
Dosing Recommendation
Efavirenz,
In adults and in pediatric patients weighing at least 25 kg, thefosamprenavir/ritonavir,
recommended dolutegravir dosage regimen is 50 mg twice daily.
tipranavir/ritonavir,
Thus, an additional TIVICAY 50-mg tablet, separated by 12 hours
carbamazepine, orfrom TRIUMEQ, should be taken.
rifampin
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.
2.7

Not Recommended Due to Lack of Dosage Adjustment

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 renal function assessment. There are no data
available on the use of lamivudine, a component of TRIUMEQ and TRIUMEQ PD, inpediatric patients with renal impairment [see Use in Specific Populations (8.4, 8.6)].

•

patients with mild hepatic impairment. TRIUMEQ and TRIUMEQ PD are contraindicated inpatients with moderate or severe hepatic impairment [see Contraindications (4), Use inSpecific Populations (8.7)].

3

DOSAGE FORMS AND STRENGTHSTRIUMEQ tablets are purple, biconvex, oval, and debossed with “572 Trı” on one side. Eachfilm-coated tablet contains 600 mg of abacavir (as abacavir sulfate), 50 mg of dolutegravir (asdolutegravir sodium), and 300 mg of lamivudine [see Description (11)].

6

TRIUMEQ PD tablets for oral suspension are yellow, capsule-shaped, strawberry creamflavored, biconvex, film-coated tablets debossed with “SV WTU” on one side. Each film-coatedtablet contains 60 mg of abacavir (as abacavir sulfate), 5 mg of dolutegravir (as dolutegravir
sodium), and 30 mg of lamivudine [see Description (11)].
4

CONTRAINDICATIONSTRIUMEQ 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 andthe risk for serious and/or life-threatening events with concomitant use of dolutegravir [seeDrug Interactions (7)].

•with moderate or severe hepatic impairment [see Use in Specific Populations (8.7)].

5

WARNINGS AND PRECAUTIONS

5.1

Hypersensitivity Reactions

Hypersensitivity reactions have been reported with the use of abacavir or dolutegravir,
components of TRIUMEQ and TRIUMEQ PD.
Abacavir
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 andtypically 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 (6.1)]. Patients who carry the HLA-B*5701 allele are at a higher risk ofabacavir hypersensitivity reactions; although, patients who do not carry the HLA-B*5701 allele
have developed hypersensitivity reactions. Hypersensitivity to abacavir was reported inapproximately 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 withabacavir:•

All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with7

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 otherabacavir-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 issuspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases suchas pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to othermedications). Clinical status, including liver chemistries, should be monitored andappropriate 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 inpatients 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 ofhypersensitivity have also experienced life-threatening reactions within hours of reinitiating
abacavir therapy. Therefore, reintroduction of TRIUMEQ or TRIUMEQ PD, or any otherabacavir-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.

Dolutegravir
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).
8

Clinical status, including liver aminotransferases, should be monitored and appropriate therapy
initiated. Delay in stopping treatment with TRIUMEQ or TRIUMEQ PD or other suspect agentsafter 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 havestopped therapy with TRIUMEQ or TRIUMEQ PD due to a hypersensitivity reaction.
5.2
Patients Co-infected with HIV-1 and HBV: Emergence of Lamivudine-Resistant
HBV and the Risk of Posttreatment Exacerbations of HBVAll patients with HIV-1 should be tested for the presence of HBV prior to or when initiating
TRIUMEQ or TRIUMEQ PD.
Emergence of Lamivudine Resistant HBV
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 withresistance 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 in Patients Co-infected with HIV-1 and HBVSevere 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 withdiscontinuation of TRIUMEQ or TRIUMEQ PD. Patients who are co-infected with HIV-1 andHBV who discontinue TRIUMEQ or TRIUMEQ PD should be closely monitored with bothclinical 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 ofhepatitis may lead to hepatic decompensation and liver failure.
5.3

Hepatotoxicity

Hepatic adverse events have been reported in patients receiving a dolutegravir-containing
regimen [see Adverse Reactions (6.1, 6.2)]. Patients with underlying hepatitis B or C may be atincreased risk for worsening or development of transaminase elevations with use of TRIUMEQ
or TRIUMEQ PD [see Adverse Reactions (6.1)]. In some cases, the elevations in transaminases
were consistent with immune reconstitution syndrome or hepatitis B reactivation particularly inthe setting where anti-hepatitis therapy was withdrawn. Cases of hepatic toxicity, including
elevated serum liver biochemistries, hepatitis, and acute liver failure, have also been reported inpatients, including pediatric patients receiving a dolutegravir-containing regimen who had no9

pre-existing hepatic disease or other identifiable risk factors. Drug-induced liver injury leading toliver transplant has been reported with TRIUMEQ. Monitoring for hepatotoxicity is
recommended.
5.4

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reportedwith the use of nucleoside analogues, including abacavir and lamivudine (components of
TRIUMEQ and TRIUMEQ PD). A majority of these cases have been in women. Female sex andobesity may be risk factors for the development of lactic acidosis and severe hepatomegaly withsteatosis in patients treated with antiretroviral nucleoside analogues. See full prescribing
information for ZIAGEN (abacavir) and EPIVIR (lamivudine). Treatment with TRIUMEQ or
TRIUMEQ PD should be suspended in any patient who develops clinical or laboratory findings
suggestive of lactic acidosis or pronounced hepatotoxicity, which may include hepatomegaly andsteatosis even in the absence of marked transaminase elevations.
5.5

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

The concomitant use of TRIUMEQ or TRIUMEQ PD and other drugs may result in known or
potentially significant drug interactions, some of which may lead to [see Contraindications (4),Drug Interactions (7.3)]:•

Loss of therapeutic effect of TRIUMEQ or TRIUMEQ PD and possible development ofresistance.

•

Possible clinically significant adverse reactions from greater exposures of concomitant drugs.

See Table 6 for steps to prevent or manage these possible and known significant druginteractions, including dosing recommendations. Consider the potential for drug interactions
prior to and during therapy with TRIUMEQ or TRIUMEQ PD, review concomitant medications
during therapy with TRIUMEQ or TRIUMEQ PD, and monitor for the adverse reactions
associated with the concomitant drugs.
5.6

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination
antiretroviral therapy, including TRIUMEQ or TRIUMEQ PD. During the initial phase of
combination antiretroviral treatment, patients whose immune systems respond may develop an
inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium
avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis),which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome,autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution;
however, the time to onset is more variable, and can occur many months after initiation oftreatment.
10

5.7

Different Formulations Are Not Substitutable

TRIUMEQ and TRIUMEQ PD are not bioequivalent and are not substitutable on a milligramper-milligram basis [see Clinical Pharmacology (12.3)]. If a pediatric patient switches from thetablets for oral suspension to the tablets, the dosage must be adjusted [see Dosage andAdministration (2.3, 2.5)]. Incorrect dosing of a given formulation may result in underdosing andloss of therapeutic effect and possible development of resistance or possible clinically significant
adverse reactions from greater exposure to the individual components.
5.8

Myocardial Infarction

Several prospective, observational, epidemiological studies have reported an association with theuse of abacavir and the risk of myocardial infarction (MI). Meta-analyses of randomized,
controlled clinical trials have observed no excess risk of MI in abacavir-treated subjects ascompared with control subjects. To date, there is no established biological mechanism to explain
a potential increase in risk. In totality, the available data from the observational studies and fromcontrolled clinical trials show inconsistency; therefore, evidence for a causal relationshipbetween abacavir and the risk of MI is inconclusive.
As a precaution, the underlying risk of coronary heart disease should be considered whenprescribing antiretroviral therapies, including abacavir, and action taken to minimize all
modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).
6

ADVERSE REACTIONS

The following adverse reactions are discussed in other sections of the labeling:•

Serious and sometimes fatal hypersensitivity reaction [see Boxed Warning, Warnings andPrecautions (5.1)].

•

Exacerbations of hepatitis B [see Boxed Warning, Warnings and Precautions (5.3)].

•

Hepatotoxicity [see Warnings and Precautions (5.3)].

•

Lactic acidosis and severe hepatomegaly with steatosis [see Warnings and Precautions(5.4)].

•

Immune reconstitution syndrome [see Warnings and Precautions (5.6)].

•

Myocardial infarction [see Warnings and Precautions (5.8)].

6.1

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared with rates in the clinical
trials of another drug and may not reflect the rates observed in clinical practice.

11

Clinical Trials in Adults
Serious and Fatal Abacavir-Associated Hypersensitivity Reactions: In clinical trials, serious andsometimes fatal hypersensitivity reactions have occurred with abacavir, a component of
TRIUMEQ and TRIUMEQ PD [see Boxed Warning, Warnings and Precautions (5.1)]. These
reactions have been characterized by 2 or more of the following signs or symptoms: (1) fever; (2)rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, or abdominal pain);(4) constitutional symptoms (including generalized malaise, fatigue, or achiness); (5) respiratory
symptoms (including dyspnea, cough, or pharyngitis). Almost all abacavir hypersensitivity
reactions include fever and/or rash as part of the syndrome.
Other signs and symptoms have included lethargy, headache, myalgia, edema, arthralgia, andparesthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distresssyndrome, respiratory failure, myolysis, and death have occurred in association with these
hypersensitivity reactions. Physical findings have included lymphadenopathy, mucous membranelesions (conjunctivitis and mouth ulcerations), and maculopapular or urticarial rash (althoughsome patients had other types of rashes and others did not have a rash). There were reports oferythema multiforme. Laboratory abnormalities included elevated liver chemistries, elevatedcreatine phosphokinase, elevated creatinine, and lymphopenia and abnormal chest x-ray findings(predominantly infiltrates, which were localized).
Serious Dolutegravir Hypersensitivity Reactions: In clinical trials, hypersensitivity reactions
have occurred with dolutegravir, a component of TRIUMEQ and TRIUMEQ PD [see Warnings
and Precautions (5.1)]. These hypersensitivity reactions have been characterized by rash,constitutional findings, and sometimes organ dysfunction, including liver injury.
Additional Treatment-Emergent Adverse Drug Reactions (ADRs) with Use of TRIUMEQ: The
safety assessment of TRIUMEQ is primarily based on the analyses of data from a randomized,
international, multicenter, double-blind, active-controlled trial, SINGLE (ING114467) andsupported by data in treatment-experienced, INSTI-naive subjects from SAILING (ING111762)
and by data from other treatment-naive trials. See full prescribing information for TIVICAY.
Treatment-Naive Subjects: In SINGLE, 833 adult subjects were randomized and received
at least one dose of either dolutegravir (TIVICAY) 50 mg with fixed-dose abacavir andlamivudine (EPZICOM) once daily (n = 414) or fixed-dose efavirenz/emtricitabine/tenofovir(ATRIPLA) once daily (n = 419) (study treatment was blinded through Week 96 and open-label
from Week 96 through Week 144). Through 144 weeks, the rate of adverse events leading todiscontinuation was 4% in subjects receiving TIVICAY + EPZICOM and 14% in subjects
receiving ATRIPLA once daily.
Treatment-emergent ADRs of moderate to severe intensity observed in at least 2% of subjects ineither treatment arm of SINGLE are provided in Table 3.

12

Table 3. Treatment-Emergent Adverse Drug Reactions of at Least Moderate Intensity(Grades 2 to 4) and at Least 2% Frequency in Treatment-Naive Subjects in SINGLE(Week 144 Analysis)
TIVICAY + EPZICOMATRIPLA
Once Daily
Once Daily
Adverse Reaction(n = 414)(n = 419)
PsychiatricInsomnia
3%
3%
Depression
1%
2%
Abnormal dreams<1%
2%
Nervous System
Dizziness<1%
5%
Headache2%2%
Gastrointestinal
Nausea<1%
3%
Diarrhea<1%
2%
General Disorders
Fatigue2%2%Skin and Subcutaneous Tissue
Rasha
<1%
6%
Ear and Labyrinth
Vertigo02%aIncludes pooled terms: rash, rash generalized, rash macular, rash maculo-papular, rash pruritic,
and drug eruption.
Treatment-Experienced Subjects: SAILING is an international, double-blind trial in
INSTI-naive, antiretroviral treatment-experienced adult subjects. Subjects were randomized andreceived either TIVICAY 50 mg once daily or raltegravir 400 mg twice daily with investigatorselected background regimen consisting of up to 2 agents, including at least one fully active
agent. At 48 weeks, the rate of adverse events leading to discontinuation was consistent with thatseen in the overall treatment-naive patient population. See full prescribing information for
TIVICAY.
The ADRs observed in the subset of subjects who received TIVICAY + EPZICOM weregenerally consistent with those seen in the overall treatment-naive patient population.
Less Common Adverse Reactions Observed in Clinical Trials: The following adverse reactions
occurred in <2% of treatment-naive or treatment-experienced subjects in any one trial. These
events have been included because of their seriousness and/or assessment of potential causal
relationship.

13

Gastrointestinal Disorders: Abdominal pain, abdominal distention, abdominal
discomfort, dyspepsia, flatulence, gastroesophageal reflux disease, upper abdominal pain,
vomiting.
General Disorders: Fever, lethargy.
Hepatobiliary Disorders: Hepatitis.
Metabolism and Nutrition Disorders: Anorexia, hypertriglyceridemia.
Musculoskeletal Disorders: Arthralgia, myositis.
Nervous System Disorders: Somnolence.
Psychiatric Disorders: Suicidal ideation, attempt, behavior, or completion. These eventswere observed primarily in subjects with a pre-existing history of depression or other psychiatricillness. Nightmare and sleep disorder.
Renal and Urinary Disorders: Renal impairment.
Skin and Subcutaneous Tissue Disorders: Pruritus.
Laboratory Abnormalities: Treatment-Naive Subjects: Selected laboratory abnormalities (Grades
2 to 4) with a worsening grade from baseline and representing the worst-grade toxicity in at least
2% of subjects in SINGLE are presented in Table 4. The mean change from baseline observed
for selected lipid values is presented in Table 5.

14

Table 4. Selected Laboratory Abnormalities (Grades 2 to 4) in Treatment-Naive
Subjects in SINGLE (Week 144 Analysis)
TIVICAY + EPZICOMATRIPLA
Once Daily
Once Daily
Laboratory Abnormality(n = 414)(n = 419)
ALT
3%
5%
Grade 2 (>2.5-5.0 x ULN)
1%
<1%
Grade 3 to 4 (>5.0 x ULN)
AST
3%
4%
Grade 2 (>2.5-5.0 x ULN)
1%
3%
Grade 3 to 4 (>5.0 x ULN)
Creatine kinase
5%
3%
Grade 2 (6.0-9.9 x ULN)
7%
8%
Grade 3 to 4 (≥10.0 x ULN)
Hyperglycemia
9%6%Grade 2 (126-250 mg/dL)
2%<1%
Grade 3 (>250 mg/dL)
Lipase11%11%Grade 2 (>1.5-3.0 x ULN)
5%
4%
Grade 3 to 4 (>3.0 ULN)
Total neutrophils
4%5%Grade 2 (0.75-0.99 x 109)9
3%
3%
Grade 3 to 4 (<0.75 x 10 )
ALT = Alanine aminotransferase, AST = Aspartate aminotransferase, ULN = upper limit of
normal.
Table 5. Mean Change from Baseline in Fasted Lipid Values in Treatment-Naive
Subjects in SINGLE (Week 144 Analysisa)
TIVICAY + EPZICOMATRIPLA
Once Daily
Once Daily
Lipid(n = 414)(n = 419)
24.0
26.7
Cholesterol (mg/dL)
5.4
7.2
HDL cholesterol (mg/dL)
16.0
14.6
LDL cholesterol (mg/dL)
13.6
31.9
Triglycerides (mg/dL)
HDL = High-density lipoprotein, LDL = Low-density lipoprotein.
aSubjects on lipid-lowering agents at baseline were excluded from these analyses(TIVICAY + EPZICOM: n = 30 and ATRIPLA: n = 27). Seventy-two subjects initiated alipid-lowering agent post-baseline; their last fasted on-treatment values (prior to starting theagent) were used regardless of whether they discontinued the agent (TIVICAY + EPZICOM:n = 36 and ATRIPLA: n = 36).
15

Treatment-Experienced Subjects: Laboratory abnormalities observed in SAILING weregenerally similar compared with observations seen in the treatment-naive trials.
Hepatitis C Virus Co-infection: In SINGLE, the pivotal Phase 3 trial, subjects with hepatitis C
virus co-infection were permitted to enroll provided that baseline liver chemistry tests did notexceed 5 times the upper limit of normal; subjects with hepatitis B co-infection were excluded.
Overall, the safety profile in subjects with hepatitis C virus co-infection was similar to thatobserved in subjects without hepatitis C co-infection, although the rates of aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) abnormalities were higher in thesubgroup with hepatitis C virus co-infection for both treatment groups. Grades 2 to 4 ALT
abnormalities in hepatitis C co-infected compared with HIV mono-infected subjects receiving
TRIUMEQ were observed in 15% and 2% (vs. 24% and 4% of subjects treated with ATRIPLA)(Week 96 analysis), respectively [see Warnings and Precautions (5.2)]. See also full prescribing
information for TIVICAY.
Changes in Serum Creatinine: Dolutegravir has been shown to increase serum creatinine
due to inhibition of tubular secretion of creatinine without affecting renal glomerular function[see Clinical Pharmacology (12.2)]. Increases in serum creatinine occurred within the first
4 weeks of treatment and remained stable through 144 weeks. In SINGLE, a mean change frombaseline of 0.14 mg/dL (range: -0.25 mg/dL to 0.81 mg/dL) was observed after 144 weeks oftreatment. Creatinine increases were similar in treatment-experienced subjects.
Abacavir and Lamivudine: Laboratory abnormalities observed in clinical trials of ZIAGEN (incombination with other antiretroviral treatment) were anemia, neutropenia, liver function test
abnormalities, and elevations of creatine phosphokinase (CPK), blood glucose, and triglycerides.
Additional laboratory abnormalities observed in clinical trials of EPIVIR (in combination withother antiretroviral treatment) were thrombocytopenia and elevated levels of bilirubin, amylase,and lipase.
Clinical Trials Experience in Pediatric Subjects
Abacavir, Dolutegravir and Lamivudine: The safety of TRIUMEQ PD and TRIUMEQ inpediatric subjects with HIV-1 infection weighing at least 6 kg was evaluated in the IMPAACT
2019 trial. This was a multicenter, open-label, non-comparative trial of pediatric subjects with
HIV-1 infection, younger than 12 years of age. Fifty-seven subjects weighing at least 6 kg to lessthan 40 kg were enrolled in this trial [see Use in Specific Populations (8.4), ClinicalPharmacology (12.3), Clinical Studies (14.2)]. Overall, the safety data in this pediatric study was
similar to that seen in adults.
The safety analysis through Week 48 included 57 subjects weighing at least 6 kg at enrollment
who received the recommended dose (determined by weight) and formulation. This analysis
showed that 26% of subjects experienced clinical adverse reactions. The most common adverse
reactions were classified as laboratory abnormalities and included decreased glomerular filtration
rate (n = 13, 23%), increased blood creatinine (n = 10, 18%), and increased ALT (n = 3, 5%). All
16other adverse reactions occurred at a rate of <2% of participants. Two subjects reported Grade 3
or 4 adverse reactions. One subject, an 8-year-old female who weighed 22 kg at baseline,
experienced Grade 3 increased blood creatinine and Grade 3 decreased glomerular filtration rate.
By Week 48, the glomerular filtration rate was improving, and the events did not lead to drug
discontinuation. Another subject, a 7-year-old male who weighed 20 kg at baseline, experienced
drug-induced liver injury with Grade 4 increased ALT and AST following 36 weeks of treatment
with TRIUMEQ PD. Clinical signs or symptoms of hepatitis were not reported, and ALT and
AST values normalized after TRIUMEQ PD was discontinued.
Abacavir and Lamivudine: The safety of once-daily compared with twice-daily dosing of
abacavir and lamivudine, administered as either single products or as EPZICOM, was assessed in
the ARROW trial (n = 336). Primary safety assessment in the ARROW (COL105677) trial was
based on Grade 3 and Grade 4 adverse events. One event of Grade 4 hepatitis in the once-daily
cohort was considered as uncertain causality by the investigator and all other Grade 3 or 4
adverse events were considered not related by the investigator. No additional safety issues wereidentified in pediatric subjects compared with historical data in adults.
Dolutegravir: The safety of dolutegravir in pediatric subjects with HIV-1 infection weighing atleast 6 kg was evaluated in the IMPAACT P1093 trial [see Use in Specific Populations (8.4),
Clinical Pharmacology (12.3)]. Overall, the safety data in this pediatric study was similar to thatseen in adults.
IMPAACT P1093 is an ongoing multicenter, open-label, non-comparative trial of pediatricsubjects with HIV-1 infection, aged <18 years. One hundred and forty-two subjects weighing atleast 6 kg were enrolled in this trial [see Use in Specific Populations (8.4), ClinicalPharmacology (12.3), Clinical Studies (14.2)].
The safety analysis through Week 24 included 60 subjects weighing at least 6 kg at enrollment
who received the recommended dose (determined by weight and age) and formulation. This
analysis showed that 13% of subjects experienced adverse reactions. Grade 1 to 2 adverse
reactions reported by more than one subject was immune reconstitution inflammatory syndrome(n = 2). There were no Grade 3 or 4 adverse reactions reported. No adverse reactions led to
discontinuation.
The Grade 3 or 4 laboratory abnormalities reported in more than one subject weighing at least
6 kg at enrollment were decreased neutrophil count (n = 5), decreased blood bicarbonate (n = 3),increased lipase (n = 2), and increased blood potassium (n = 2). These laboratory events were notconsidered to be drug related. Changes in median serum creatinine were similar to thoseobserved in adults.
6.2

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions havebeen identified during postmarketing use with one or more of the components of TRIUMEQ and17

TRIUMEQ PD. Because these reactions are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate their frequency or establish a causal
relationship to drug exposure.
Blood and Lymphatic Systems
Aplastic anemia, anemia (including pure red cell aplasia and severe anemias progressing on
therapy), lymphadenopathy, splenomegaly.
Digestive
Stomatitis.
Gastrointestinal
Pancreatitis.
GeneralWeakness.
Hepatobiliary Disorders
Acute liver failure, liver transplant [see Warnings and Precautions (5.3)].
Hypersensitivity
Sensitization reactions (including anaphylaxis), urticaria [see Warnings and Precautions (5.1),
Adverse Reactions (6.1)].
Investigations
Weight increased.
Metabolism and Nutrition Disorders
Hyperlactemia.
Musculoskeletal
CPK elevation, muscle weakness, myalgia, rhabdomyolysis.
Nervous
Paresthesia, peripheral neuropathy, seizures.
PsychiatricAnxiety.
Respiratory
Abnormal breath sounds/wheezing.

18

Skin
Alopecia, erythema multiforme. Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination
with medications known to be associated with SJS and TEN, respectively. Because of theoverlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN,
and the possibility of multiple drug sensitivities in some patients, abacavir should be
discontinued and not restarted in such cases [see Adverse Reactions (6.1)].
7

DRUG INTERACTIONS

7.1

Effect of Dolutegravir on the Pharmacokinetics of Other Agents

In 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) [seeContraindications (4), Drug Interactions (7.3)].
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 notalter the plasma concentrations of tenofovir or para-amino hippurate, substrates of OAT1 andOAT3.
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 theresults of drug interaction trials, dolutegravir is not expected to affect the pharmacokinetics ofdrugs that are substrates of these enzymes or transporters.
In drug interaction trials, dolutegravir did not have a clinically relevant effect on thepharmacokinetics of the following drugs: tenofovir, methadone, midazolam, rilpivirine, and oral
contraceptives containing norgestimate and ethinyl estradiol. Using cross-study comparisons tohistorical pharmacokinetic data for each interacting drug, dolutegravir did not appear to affectthe 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 isalso a substrate of UGT1A3, UGT1A9, BCRP, and P-gp in vitro. Drugs that induce those19

enzymes and transporters may decrease dolutegravir plasma concentrations and reduce thetherapeutic 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 tobe mitigated by atazanavir/ritonavir (Table 6) [see Drug Interactions (7.3), ClinicalPharmacology (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, andlamivudine 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 druginteraction trials or predicted interactions due to the expected magnitude of interaction andpotential for serious adverse events or loss of efficacy. [See Contraindications (4), ClinicalPharmacology (12.3).]

20

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
Concomitant Drug Class:Effect on
Drug Name
Concentration
Clinical Comment
HIV-1 Antiviral Agents
Non-nucleoside reverse↓Dolutegravir
Use of TRIUMEQ or TRIUMEQ PD
transcriptase inhibitor:
with etravirine without coadministrationa
Etravirineof atazanavir/ritonavir,
darunavir/ritonavir, or
lopinavir/ritonavir is not recommended.
Non-nucleoside reverse↓Dolutegravir
In adults and in pediatric patientstranscriptase inhibitor:
weighing at least 25 kg, adjustaEfavirenz
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 doseof dolutegravir should be given
separated by 12 hours from TRIUMEQ
PD.
• 6 to <10 kg: administer an additional
15-mg dose of dolutegravir (3TIVICAY PD tablets for oralsuspension), 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
21

for oral suspension), 12 hours after
TRIUMEQ PD.

Non-nucleoside reverse
transcriptase inhibitor:
Nevirapine↓Dolutegravir

Protease inhibitor:
Fosamprenavir/ritonavira
Tipranavir/ritonavira↓Dolutegravir

22

Avoid coadministration with
TRIUMEQ or TRIUMEQ PD because
there are insufficient data to makedosing recommendations.
In adults and in pediatric patientsweighing at least 25 kg, adjust
dolutegravir dose to 50 mg twice daily.
An additional TIVICAY 50-mg doseshould be taken, separated by 12 hours
from TRIUMEQ.
In pediatric patients weighing 10 to<25 kg, an additional weight-based doseof dolutegravir should be given
separated by 12 hours from TRIUMEQ
PD.
• 6 to <10 kg: administer an additional
15-mg dose of dolutegravir (3TIVICAY PD tablets for oralsuspension), 12 hours after
TRIUMEQ PD,• 10 to <14 kg: administer an
additional 20-mg dose of

Antiarrhythmic:
Dofetilide
Potassium channel
blocker:
Dalfampridine

Carbamazepinea

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↑Dofetilide
Coadministration is contraindicatedwith TRIUMEQ and TRIUMEQ PD[see Contraindications (4)].
↑Dalfampridine
Elevated levels of dalfampridine
increase the risk of seizures. The
potential benefits of taking
dalfampridine concurrently with
TRIUMEQ or TRIUMEQ PD should beconsidered against the risk of seizures inthese patients.
↓Dolutegravir
In adults and in pediatric patientsweighing at least 25 kg, adjust
dolutegravir dose to 50 mg twice daily.
An additional TIVICAY 50-mg doseshould be taken, separated by 12 hours
from TRIUMEQ.
In pediatric patients weighing 6 to < 25kg, 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 (3TIVICAY PD tablets for oralsuspension), 12 hours after
TRIUMEQ PD,
23

Oxcarbazepine
Phenytoin
Phenobarbital
St. John’s wort (Hypericum
perforatum)
Medications containing
polyvalent cations(e.g., Mg or Al):
Cation-containing
antacidsa or laxatives
Sucralfate
Buffered medications
Oral calcium and ironsupplements, including
multivitamins containing
calcium or irona↓Dolutegravir

Metformina↑Metformin• 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.
Avoid coadministration with
TRIUMEQ or TRIUMEQ PD because
there are insufficient data to makedosing recommendations.

↓Dolutegravir

Administer TRIUMEQ or TRIUMEQ
PD 2 hours before or 6 hours after
taking medications containing
polyvalent cations.

↓Dolutegravir

When taken with food, TRIUMEQ or
TRIUMEQ PD and supplements or
multivitamins containing calcium oriron 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.
Refer to the prescribing information for
metformin for assessing the benefit andrisk of concomitant use of TRIUMEQ
or TRIUMEQ PD and metformin.

24

Rifampina

In adults and in pediatric patientsweighing 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 doseof dolutegravir should be given
separated by 12 hours from TRIUMEQ
PD.
• 6 to <10 kg: administer an additional
15-mg dose of dolutegravir (3TIVICAY PD tablets for oralsuspension), 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.
a
See Clinical Pharmacology (12.3) Table 8 or Table 10 for magnitude of interaction.
↓Dolutegravir

Methadone
Abacavir: 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 (12.3)]. This alteration will not result in amethadone dose modification in the majority of patients; however, an increased methadone dose
may be required in a small number of patients.

25

Sorbitol
Lamivudine: Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol
dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitolcontaining medicines with lamivudine-containing medicines [see Clinical Pharmacology (12.3)].
Riociguat
Abacavir: Coadministration with TRIUMEQ resulted in increased riociguat exposure, which
may increase the risk of riociguat adverse reactions [see Clinical Pharmacology (12.3)]. The
riociguat dose may need to be reduced. See full prescribing information for ADEMPAS(riociguat).
8

USE IN SPECIFIC POPULATIONS

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 bycalling 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 ofneural tube defects among infants born to individuals taking dolutegravir at the time ofconception compared to those born to individuals taking non-dolutegravir-containing regimens atconception 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 datafrom the APR with the individual components of TRIUMEQ do not indicate an increased risk ofbirth defects (see Data). The background risk for major birth defects for the indicated populationis 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 humandose (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 thehuman exposure (AUC) at the RHD. No adverse developmental effects were observed following
oral administration of abacavir to pregnant rabbits during organogenesis at exposuresapproximately 9 times the human exposure (AUC) at the RHD. Oral administration oflamivudine to pregnant rabbits during organogenesis resulted in embryolethality at a human26

exposure (AUC) similar to the RHD; however, no adverse development effects were observedwith oral administration of lamivudine to pregnant rats during organogenesis at plasma
concentrations (Cmax) 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 dolutegravir was administered at the time of conception and inearly pregnancy. A subsequent analysis was conducted based on a larger cohort from the birthoutcome surveillance study in Botswana and included over 9,460 individuals exposed to
dolutegravir at conception, 23,664 individuals exposed to non-dolutegravir-containing regimens,
and 170,723 HIV-negative pregnant individuals. The prevalence of neural tube defects in infantsdelivered to individuals taking dolutegravir at conception was 0.11% (95% CI: 0.05-0.19%). The
observed prevalence rate did not differ significantly from that of infants delivered to individuals
taking non-dolutegravir-containing regimens (0.11%, 95% CI: 0.07-0.16%), or to HIV-negative
individuals (0.06%, 95% CI: 0.05-0.08%).
The Eswatini birth outcome surveillance study includes 9,743 individuals exposed to
dolutegravir at conception, 1,838 individuals exposed to non-dolutegravir-containing regimens,
and 32,259 HIV-negative pregnant individuals. The prevalence of neural tube defects in infantsdelivered to individuals taking dolutegravir at conception was 0.08% (95% CI: 0.04-0.16%). The
observed prevalence rate did not differ significantly from that of infants delivered to individuals
taking non-dolutegravir-containing regimens (0.22%, 95% CI: 0.06-0.56%) or to HIV-negative
individuals (0.08%, 95% CI: 0.06-0.12%). The observed prevalence of neural tube defects ininfants delivered to individuals taking non-dolutegravir-containing regimens had a wide
confidence interval due to low sample size.
Limitations of these birth outcome surveillance studies include insufficient data to determine if
baseline characteristics were balanced between the study groups or to assess other factors such as
the use of folic acid during the preconception or first trimester periods.
Antiretroviral Pregnancy Registry: Based on prospective reports to the APR, of over
1,300 exposures to dolutegravir during pregnancy resulting in live births (including 874 exposedin the first trimester), the prevalence of defects in live births was 3.3% (95% CI: 2.2% to 4.7%)
following first-trimester exposure to dolutegravir-containing regimens and 5.0% (95% CI: 3.2%
to 7.3%) following second-/third-trimester exposure to dolutegravir-containing regimens. In the
U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP),
the background birth defect rate was 2.7%.

27

Dolutegravir has been shown to cross the placenta. In a clinical trial in Uganda and South Africa
in women during the last trimester of pregnancy receiving dolutegravir 50 mg once daily, theratio of median dolutegravir concentration in fetal umbilical cord to that in maternal peripheral
plasma was 1.21 (range 0.51-2.11) (n = 15).
Abacavir: Based on prospective reports to the APR of over 2,800 exposures to abacavirduring pregnancy resulting in live births (including 1,455 exposed in the first trimester), there
was no difference between the overall risk of birth defects for abacavir compared with thebackground birth defect rate of 2.7% in the U.S. reference population of the MACDP. The
prevalence of defects in live births was 3.2% (95% CI: 2.4% to 4.3%) following first trimester
exposure to abacavir-containing regimens and 3.0% (95% CI: 2.2% to 4.1%) following
second/third trimester exposure to abacavir-containing regimens.
Abacavir has been shown to cross the placenta and concentrations in neonatal plasma at birthwere essentially equal to those in maternal plasma at delivery [see Clinical Pharmacology(12.3)].
Lamivudine: Based on prospective reports to the APR of over 13,000 exposures tolamivudine during pregnancy resulting in live births (including 5,613 exposed in the firsttrimester), there was no difference between the overall risk of birth defects for lamivudine
compared with the background birth defect rate of 2.7% in the U.S. reference population of the
MACDP. The prevalence of birth defects in live births was 3.1% (95% CI: 2.6% to 3.6%)
following first trimester exposure to lamivudine-containing regimens and 2.9% (95% CI: 2.5%,3.3%) following second/third trimester exposure to lamivudine-containing regimens.
Lamivudine pharmacokinetics were studied in pregnant women during 2 clinical trials conductedin South Africa. The trials assessed pharmacokinetics in 16 women at 36 weeks’ gestation using
150 mg lamivudine twice daily with zidovudine, 10 women at 38 weeks’ gestation using 150 mg
lamivudine twice daily with zidovudine, and 10 women at 38 weeks’ gestation using lamivudine
300 mg twice daily without other antiretrovirals. These trials were not designed or powered toprovide efficacy information. Lamivudine concentrations were generally similar in maternal,
neonatal, and umbilical cord serum samples. In a subset of subjects, amniotic fluid specimens
were collected following natural rupture of membranes and confirmed that lamivudine crosses
the placenta in humans. Based on limited data at delivery, median (range) amniotic fluid
concentrations of lamivudine were 3.9-fold (1.2- to 12.8-fold) greater compared with paired
maternal serum concentration (n = 8).
Animal Data:
Dolutegravir: Dolutegravir was administered orally to pregnant rats and rabbits (up to
1,000 mg/kg/day) on Gestation Days 6 to 17 and 6 to 18, respectively, and to rats on Gestation
Day 6 to lactation/post-partum Day 20. No adverse effects on embryo-fetal (rats and rabbits) or
pre/post-natal (rats) development were observed up to the highest dose tested. Duringorganogenesis, systemic exposures (AUC) to dolutegravir in rabbits were less than the exposure28

in humans at the RHD and in rats were approximately 50 times the exposure in humans at the
RHD. In the rat pre/post-natal development study, decreased body weight of the developing
offspring was observed during lactation at a maternally toxic dose (approximately 50 times
human exposure at the RHD).
Abacavir: Abacavir was administered orally to pregnant rats (at 100, 300, and
1,000 mg/kg/day) and rabbits (at 125, 350, or 700 mg/kg/day) during organogenesis (onGestation Days 6 through 17 and 6 through 20, respectively). Fetal malformations (increased
incidences of fetal anasarca and skeletal malformations) or developmental toxicity (decreased
fetal body weight and crown-rump length) were observed in rats at doses up to 1,000 mg/kg/day,resulting in exposures approximately 35 times the human exposure (AUC) at the RHD. No
developmental effects were observed in rats at 100 mg/kg/day, resulting in exposures (AUC) 3.5
times the human exposure at the recommended daily dose. In a fertility and early embryo-fetal
development study conducted in rats (at 60, 160, or 500 mg/kg/day), embryonic and fetal
toxicities (increased resorptions, decreased fetal body weights) or toxicities to the offspring(increased incidence of stillbirth and lower body weights) occurred at doses up to
500 mg/kg/day. No developmental effects were observed in rats at 60 mg/kg/day, resulting in
exposures (AUC) approximately 4 times the human exposure at the RHD. Studies in pregnant
rats showed that abacavir is transferred to the fetus through the placenta. In pregnant rabbits, nodevelopmental toxicities and no increases in fetal malformations occurred at up to the highest
dose evaluated, resulting in exposures (AUC) approximately 9 times the human exposure at theRHD.
Lamivudine: Lamivudine was administered orally to pregnant rats (at 90, 600, and
4,000 mg/kg/day) and rabbits (at 90, 300 and 1,000 mg/kg/day and at 15, 40, and 90 mg/kg/day)during organogenesis (on Gestation Days 7 through 16 [rat] and 8 through 20 [rabbit]). No
evidence of fetal malformations due to lamivudine was observed in rats and rabbits at doses
producing plasma concentrations (Cmax) approximately 35 times higher than human exposure at
the recommended daily dose. Evidence of early embryolethality was seen in the rabbit atsystemic exposures (AUC) similar to those observed in humans, but there was no indication ofthis effect in the rat at plasma concentrations (Cmax) 35 times higher than human exposure at therecommended daily dose. Studies in pregnant rats showed that lamivudine is transferred to thefetus through the placenta. In the fertility/pre- and postnatal development study in rats,
lamivudine was administered orally at doses of 180, 900, and 4,000 mg/kg/day (from prior tomating through postnatal Day 20). In the study, development of the offspring, including fertility
and reproductive performance, were not affected by the maternal administration of lamivudine.

29

8.2

Lactation

Risk Summary
Abacavir, dolutegravir and lamivudine are present in human milk. There is no information on theeffects of TRIUMEQ or its components on the breastfed infant or the effects of the drug on milk
production.
Potential risks of breastfeeding include: (1) HIV-1 transmission (in HIV-1–negative infants), (2)developing viral resistance (in HIV-1–positive infants), and (3) adverse reactions in a breastfed
infant similar to those seen in adults.
8.4

Pediatric Use

The 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 individualcomponents:• 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 (6.1), Clinical Pharmacology (12.3), Clinical Studies(14.2)].
• The safety and efficacy of once-daily abacavir and lamivudine were established with arandomized, multicenter trial (ARROW [COL105677]) in HIV-1–infected, treatment-naive
subjects aged 3 months to 17 years with a first-line regimen containing abacavir andlamivudine, using either the combination of EPIVIR and ZIAGEN or EPZICOM [seeAdverse Reactions (6.1), Clinical Studies (14.2)].
• 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 atleast 3 kg were treated with TIVICAY or TIVICAY PD plus optimized background therapy[see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.2)].
• 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 nucleosidereverse transcriptase inhibitors (NRTIs) (mainly abacavir and lamivudine) compared withstandard of care in HIV-1–infected pediatric subjects younger than 18 years [see ClinicalPharmacology (12.3)].
Overall, the safety, and efficacy profile of TRIUMEQ and TRIUMEQ PD in pediatric patients iscomparable to that observed in adults. There are no data available on the use of lamivudine in30pediatric patients with renal impairment [see Dosage and Administration (2.7), Warnings andPrecautions (5.3), Adverse Reactions (6.1), Use in Specific Populations (8.6), ClinicalPharmacology (12.3), Clinical Studies (14.2)].
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.
8.5

Geriatric Use

Clinical trials of abacavir, dolutegravir, or lamivudine did not include sufficient numbers ofsubjects aged 65 and over to determine whether they respond differently from younger subjects.
In general, caution should be exercised in the administration of TRIUMEQ in elderly patientsreflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of
concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)].
8.6

Patients with Impaired Renal Function

TRIUMEQ 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 ageappropriate 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 patientswith 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 individualcomponents should be used [see Clinical Pharmacology (12.3)].
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 wereassociated 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 patientswith 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 isindicated, TRIUMEQ or TRIUMEQ PD should be discontinued, and the individual components
should be used to construct the treatment regimen.

31

8.7

Patients with Impaired Hepatic Function

TRIUMEQ and TRIUMEQ PD are fixed-dose combinations, and the dosage of the individualcomponents cannot be adjusted. If a dose reduction of abacavir, a component of TRIUMEQ andTRIUMEQ PD, is required for patients with mild hepatic impairment (Child-Pugh Score A), thenthe individual components should be used [see Clinical Pharmacology (12.3)].
The safety, efficacy, and pharmacokinetic properties of abacavir have not been established inpatients with moderate (Child-Pugh Score B) or severe (Child-Pugh Score C) hepatic
impairment; therefore, TRIUMEQ and TRIUMEQ PD are contraindicated in these patients [seeContraindications (4)].
10

OVERDOSAGE

There is no known specific treatment for overdose with TRIUMEQ or TRIUMEQ PD. If
overdose occurs, the patient should be monitored, and standard supportive treatment applied as
required.
Dolutegravir
As dolutegravir is highly bound to plasma proteins, it is unlikely that it will be significantly
removed by dialysis.
Abacavir
It is not known whether abacavir can be removed by peritoneal dialysis or hemodialysis.
Lamivudine
Because a negligible amount of lamivudine was removed via (4-hour) hemodialysis, continuous
ambulatory peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuous
hemodialysis would provide clinical benefit in a lamivudine overdose event.
11

DESCRIPTIONTRIUMEQ and TRIUMEQ PD
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
32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.
Abacavir Sulfate
The chemical name of abacavir sulfate is (1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). It has a molecular formula of(C14H18N6O)2•H2SO4 and a molecular weight of 670.76 g/mol. It has the following structural
formula:Abacavir sulfate is a white to off-white solid and is soluble in water.
Dolutegravir Sodium
The chemical name of dolutegravir sodium is sodium (4R,12aS)-9-{[(2,4difluorophenyl)methyl]carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2Hpyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate. The empirical formula is C20H18F2N3NaO5
and the molecular weight is 441.36 g/mol. It has the following structural formula:

ONa O
F

F

H
N

O

CH3
N

N
O

H

O

Dolutegravir sodium is a white to light yellow powder and is slightly soluble in water.

33

Lamivudine
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.
12

CLINICAL PHARMACOLOGY

12.1

Mechanism of Action

TRIUMEQ and TRIUMEQ PD are a fixed-dose combination of the HIV-1 antiretroviral agentsabacavir, dolutegravir, and lamivudine [see Microbiology (12.4)].
12.2

Pharmacodynamics

Effects on Electrocardiogram
A thorough QT trial has been conducted for dolutegravir. Neither the effects of abacavir nor
lamivudine as single entities or the combination of abacavir, dolutegravir, and lamivudine on the
QT interval have been evaluated.
In a randomized, placebo-controlled, cross-over trial, 42 healthy subjects received single-dose
oral administrations of placebo, dolutegravir 250-mg suspension (exposures approximately 3–
fold of the 50-mg once-daily dose at steady state), and moxifloxacin 400 mg (active control) in
random sequence. After baseline and placebo adjustment, the maximum mean QTc change basedon Fridericia correction method (QTcF) for dolutegravir was 2.4 msec (1-sided 95% upper CI:
4.9 msec). Dolutegravir did not prolong the QTc interval over 24 hours postdose.

34

Effects on Renal Function
The effect of dolutegravir on renal function was evaluated in an open-label, randomized, 3-arm,parallel, placebo-controlled trial in healthy subjects (n = 37) who received dolutegravir 50 mg
once daily (n = 12), dolutegravir 50 mg twice daily (n = 13), or placebo once daily (n = 12) for
14 days. A decrease in creatinine clearance, as determined by 24-hour urine collection, wasobserved with both doses of dolutegravir after 14 days of treatment in subjects who received
50 mg once daily (9% decrease) and 50 mg twice daily (13% decrease). Neither dose of
dolutegravir had a significant effect on the actual glomerular filtration rate (determined by theclearance of probe drug, iohexol) or effective renal plasma flow (determined by the clearance ofprobe drug, para-amino hippurate) compared with the placebo.
12.3

Pharmacokinetics

Pharmacokinetics in Adults
One TRIUMEQ tablet was bioequivalent to one dolutegravir (TIVICAY) tablet (50 mg) plus one
abacavir and lamivudine fixed-dose combination tablet (EPZICOM) under fasted conditions inhealthy subjects (n = 62).
TRIUMEQ tablets and TRIUMEQ PD tablets for oral suspension are bioequivalent for theabacavir and lamivudine components, but not for the dolutegravir component. The relative
dolutegravir bioavailability of TRIUMEQ PD is approximately 1.7-fold higher than TRIUMEQ;
therefore, the 2 dosage forms are not substitutable on a milligram-per-milligram basis [seeDosage and Administration (2.3), Warnings and Precautions (5.7)]. The relative dolutegravir
bioavailability is expected to be similar between TRIUMEQ PD and TIVICAY PD.
Abacavir: Following oral administration, abacavir is rapidly absorbed and extensively
distributed. After oral administration of a single dose of 600 mg of abacavir in 20 subjects, Cmax
was 4.26 ± 1.19 mcg/mL (mean ± SD) and AUC∞ was 11.95 ± 2.51 mcg•hour/mL. Binding of
abacavir to human plasma proteins is approximately 50% and was independent of concentration.
Total blood and plasma drug-related radioactivity concentrations are identical, demonstratingthat abacavir readily distributes into erythrocytes. The primary routes of elimination of abacavir
are metabolism by alcohol dehydrogenase to form the 5′-carboxylic acid and glucuronyltransferase to form the 5′-glucuronide. In single-dose trials, the observed elimination half-life(t½) was 1.54 ± 0.63 hours. After intravenous administration, total clearance was 0.80 ± 0.24
L/h/kg (mean ± SD).
Dolutegravir: Following oral administration of dolutegravir, peak plasma concentrations wereobserved 2 to 3 hours postdose. With once-daily dosing, pharmacokinetic steady state isachieved within approximately 5 days with average accumulation ratios for AUC, Cmax, and C24 hranging from 1.2 to 1.5. Dolutegravir is a P-gp substrate in vitro. The absolute bioavailability of
dolutegravir has not been established. Dolutegravir is highly bound (≥98.9%) to human plasma
proteins based on in vivo data and binding is independent of plasma concentration of35

dolutegravir. The apparent volume of distribution (Vd/F) following 50-mg once-dailyadministration is estimated at 17.4 L based on a population pharmacokinetic analysis.
Dolutegravir is primarily metabolized via UGT1A1 with some contribution from CYP3A. Aftera single oral dose of [14C] dolutegravir, 53% of the total oral dose is excreted unchanged in thefeces. Thirty-one percent of the total oral dose is excreted in the urine, represented by an ether
glucuronide of dolutegravir (18.9% of total dose), a metabolite formed by oxidation at the
benzylic carbon (3.0% of total dose), and its hydrolytic N-dealkylation product (3.6% of total
dose). Renal elimination of unchanged drug was <1% of the dose. Dolutegravir has a terminal
half-life of approximately 14 hours and an apparent clearance (CL/F) of 1.0 L/h based on
population pharmacokinetic analyses.
The pharmacokinetic properties of dolutegravir have been evaluated in healthy adult subjects andHIV-1–infected adult subjects. Exposure to dolutegravir was generally similar between healthy
subjects and HIV-1–infected subjects.
Table 7. Dolutegravir Steady-State Pharmacokinetic Parameter Estimates in HIV-1–
Infected Adults
50 mg Once Daily
Parameter
Geometric Mean (%CV)
AUC(0-24) (mcg•h/mL)
53.6 (27)Cmax (mcg/mL)
3.67 (20)Cmin (mcg/mL)
1.11 (46)
Cerebrospinal Fluid (CSF): In 11 treatment-naive subjects on dolutegravir 50 mg dailyplus abacavir/lamivudine, the median dolutegravir concentration in CSF was 18 ng/mL (range:
4 ng/mL to 23.2 ng/mL) 2 to 6 hours postdose after 2 weeks of treatment. The clinical relevanceof this finding has not been established.
Lamivudine: Following oral administration, lamivudine is rapidly absorbed and extensively
distributed. After multiple-dose oral administration of lamivudine 300 mg once daily for 7 days
to 60 healthy subjects, steady-state Cmax (Cmax,ss) was 2.04 ± 0.54 mcg/mL (mean ± SD) and the
24-hour steady-state AUC (AUC24,ss) was 8.87 ± 1.83 mcg•hour/mL. Binding to plasma protein
is low. Approximately 70% of an intravenous dose of lamivudine is recovered as unchanged
drug in the urine. Metabolism of lamivudine is a minor route of elimination. In humans, the only
known metabolite is the trans-sulfoxide metabolite (approximately 5% of an oral dose after
12 hours). In most single-dose trials with plasma sampling up to 48 or 72 hours after dosing, theobserved mean elimination half-life (t½) ranged from 13 to 19 hours. In HIV-1–infected subjects,
total clearance was 398.5 ± 69.1 mL/min (mean ± SD).
Effect of Food on Oral Absorption
TRIUMEQ or TRIUMEQ PD may be taken with or without food. Overall, when compared withfasted conditions, administration of TRIUMEQ to healthy adult subjects with a high-fat meal36

(53% fat, 869 calories) resulted in decreased Cmax for abacavir and increased Cmax and AUC for
dolutegravir. Lamivudine exposures were not affected by food. With a high-fat meal, the Cmax ofabacavir decreased 23% and the Cmax and AUC of dolutegravir increased 37% and 48%,
respectively. When compared with fasted conditions, administration of TRIUMEQ PD to healthy
adult subjects with a high-fat meal (50% fat, 917 calories) resulted in decreased Cmax for abacavir(55%), dolutegravir (29%) and lamivudine (36%). AUCs for all 3 components were not affectedby food.
Specific Populations
Patients with Renal Impairment: The pharmacokinetics for the individual components of
TRIUMEQ and TRIUMEQ PD have been evaluated in patients with renal impairment (see theU.S. prescribing information for the individual abacavir, dolutegravir, and lamivudine
components).
Patients with Hepatic Impairment: The pharmacokinetics for the individual components of
TRIUMEQ and TRIUMEQ PD have been evaluated in patients with varying degrees of hepatic
impairment (see the U.S. prescribing information for the individual abacavir, dolutegravir, andlamivudine components).
Pregnant women: Abacavir: Abacavir pharmacokinetics were studied in 25 pregnant women
during the last trimester of pregnancy receiving abacavir 300 mg twice daily. Abacavir exposure(AUC) during pregnancy was similar to those in postpartum and in HIV-infected non-pregnant
historical controls. Consistent with passive diffusion of abacavir across the placenta, abacavir
concentrations in neonatal plasma cord samples at birth were essentially equal to those inmaternal plasma at delivery.
Lamivudine: Lamivudine pharmacokinetics were studied in 36 pregnant women during 2
clinical trials conducted in South Africa. Lamivudine pharmacokinetics in pregnant women weresimilar to those seen in non-pregnant adults and in postpartum women. Lamivudine
concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples.
Pediatric Patients: The pharmacokinetics of TRIUMEQ, TRIUMEQ PD (abacavir, dolutegravir,
and lamivudine) and their individual components have been evaluated in pediatric subjects.
Abacavir, Dolutegravir and Lamivudine: The pharmacokinetics of TRIUMEQ andTRIUMEQ PD were evaluated in the IMPAACT 2019 trial. Steady-state plasma exposure atdoses by weight band are summarized in Table 8 [see Use in Specific Populations (8.4), ClinicalStudies (14.2)].
Overall, exposures of abacavir, dolutegravir and lamivudine at the recommended doses for
TRIUMEQ PD and TRIUMEQ are within the observed exposure ranges at the recommended
doses of individual products in adults and pediatrics. Refer to the prescribing information for
EPIVIR, TIVICAY, and ZIAGEN for pharmacokinetic information on lamivudine, dolutegravir,
and abacavir, respectively, in pediatric patients.
37

Table 8. Summary of Pharmacokinetic Parameters in Pediatric HIV-1–Infected Subjects(IMPAACT 2019 Trial)

Drug
Abacavir

Weight Band

Dosea of single
entities in
TRIUMEQ or
TRIUMEQ PD

Pharmacokinetic Parameter
Geometric Mean (%CV)
nCmax(mcg/mL)

AUC0-24h(mcg∙h/mL)

C24h(ng/mL)

6 to <10 kg

180 mg once daily
TRIUMEQ PD

77.30 (20)

17.7 (34)

3 (128)10 to <14 kg

240 mg once daily
TRIUMEQ PD

78.36 (44)19.8 (51)

5 (127)14 to <20 kg

300 mg once daily
TRIUMEQ PD

7

6.26 (31)15.1 (40)

3 (108)20 to <25 kg

360 mg once daily
TRIUMEQ PD

76.65 (28)17.4 (19)

4 (85)

25 to <40 kg

600 mg once daily
TRIUMEQ

79.04 (22)25.7 (15)

11 (229)

Dolutegravir 6 to <10 kg

15 mg once daily
TRIUMEQ PD

77.40 (28)75.9 (34)910 (68)

10 to <14 kg

20 mg once daily
TRIUMEQ PD

78.85 (21)91.0 (36)1220 (77)

14 to <20 kg

25 mg once daily
TRIUMEQ PD

77.04 (17)71.4 (23)790 (44)

20 to <25 kg

30 mg once daily
TRIUMEQ PD

77.29 (17)84.4 (26)1350 (95)

25 to <40 kg

50 mg once daily
TRIUMEQ

7

6.25 (21)71.8 (14)980 (28)

6 to <10 kg

90 mg once daily
TRIUMEQ PD

72.29 (40)10.7 (46)55 (39)10 to <14 kg

120 mg once daily
TRIUMEQ PD

73.55 (19)14.2 (24)46 (48)14 to <20 kg

150 mg once daily
TRIUMEQ PD

72.92 (23)13.0 (16)58 (37)20 to <25 kg

180 mg once daily
TRIUMEQ PD

72.99 (32)14.5 (17)60 (18)25 to <40 kg

300 mg once daily
TRIUMEQ

7

4.15 (29)21.7 (26)84 (35)

Lamivudine%CV, coefficient of variation expressed as a percentage.
38

a

The relative dolutegravir bioavailability of TRIUMEQ PD tablets for oral suspension is ~1.7fold that of TRIUMEQ tablets.

Geriatric Patients: Population analyses using pooled pharmacokinetic data from adult trials
indicated age had no clinically relevant effect on the pharmacokinetics of dolutegravir. The
pharmacokinetics of abacavir or lamivudine have not been studied in subjects older than
65 years.
Male and Female Patients: There are no significant or clinically relevant gender differences in
the pharmacokinetics of the individual components (dolutegravir, abacavir, or lamivudine) basedon the available information that was analyzed for each of the individual components.
Racial Groups: There are no significant or clinically relevant racial differences inpharmacokinetics of the individual components (dolutegravir, abacavir, or lamivudine) based on
the available information that was analyzed for each of the individual components.
Drug Interaction Studies
The drug interaction trials described were conducted with dolutegravir, abacavir, and/or
lamivudine as single entities; no drug interaction trials have been conducted using the
combination of abacavir, dolutegravir, and lamivudine. No clinically significant drug interactions
are expected between dolutegravir, abacavir, and lamivudine.
Dosing recommendations as a result of established and other potentially significant drug-druginteractions with the individual components of TRIUMEQ and TRIUMEQ PD are provided in
Section 7.3 [see Drug Interactions (7)].
Table 9. Summary of Effect of Dolutegravir on the Pharmacokinetics of Coadministered
Drugs
Geometric Mean Ratio(90% CI) of Pharmacokinetic
Parameters of
Coadministered Drugwith/without Dolutegravir
No Effect = 1.00
Coadministered
Dose ofDrug(s) and Dose(s) Dolutegravir
Ethinyl estradiol
50 mg
0.035 mgtwice daily
Metformin
50 mg
500 mg twice daily
once daily

n
15

15a

Cmax
0.99
(0.91 to 1.08)
1.66(1.53 to 1.81)

39

AUC
1.03
(0.96 to 1.11)
1.79(1.65 to 1.93)

Cτ or C24
1.02
(0.93 to 1.11)_

Metformin
50 mg
15a
2.11
2.45
_
500 mg twice daily twice daily(1.91 to 2.33) (2.25 to 2.66)
Methadone
50 mg
11
1.00
0.98
0.99
16 to 150 mg
twice daily(0.94 to 1.06) (0.91 to 1.06) (0.91 to 1.07)
Midazolam
25 mg
10
_
0.95
_
3 mg
once daily(0.79 to 1.15)
Norelgestromin
50 mg
15
0.89
0.98
0.93
0.25 mgtwice daily(0.82 to 0.97) (0.91 to 1.04) (0.85 to 1.03)
Rilpivirine
50 mg
16
1.10
1.06
1.21
25 mg once daily
once daily(0.99 to 1.22) (0.98 to 1.16) (1.07 to 1.38)
Tenofovir disoproxil
50 mg
15
1.09
1.12
1.19
fumarate
once daily(0.97 to 1.23) (1.01 to 1.24) (1.04 to 1.35)
300 mg once dailyaThe number of subjects represents the maximum number of subjects that were evaluated.
Table 10. Summary of Effect of Coadministered Drugs on the Pharmacokinetics of
Dolutegravir
Geometric Mean Ratio (90% CI) of
Dolutegravir Pharmacokinetic
Parameters with/without
Coadministered Drugs
No Effect = 1.00
Coadministered Drug(s)Dose ofand Dose(s)Atazanavir
400 mg once daily
Atazanavir/ritonavir
300/100 mg once daily
Darunavir/ritonavir
600/100 mg twice daily
Efavirenz
600 mg once daily
Etravirine
200 mg twice daily
Etravirine +darunavir/ritonavir
200 mg +600/100 mg
twice daily

Dolutegravir
30 mg
once daily
30 mg
once daily
30 mg
once daily
50 mg
once daily
50 mg
once daily
50 mg
once daily

n
12
12
15
12
16
9

40

Cmax
1.50
(1.40 to 1.59)
1.34(1.25 to 1.42)
0.89(0.83 to 0.97)
0.61(0.51 to 0.73)
0.48(0.43 to 0.54)
0.88(0.78 to 1.00)

AUC
1.91
(1.80 to 2.03)
1.62(1.50 to 1.74)
0.78(0.72 to 0.85)
0.43(0.35 to 0.54)
0.29(0.26 to 0.34)
0.75(0.69 to 0.81)

Cτ or C24
2.80
(2.52 to 3.11)
2.21(1.97 to 2.47)
0.62(0.56 to 0.69)
0.25(0.18 to 0.34)
0.12(0.09 to 0.16)
0.63(0.52 to 0.76)

Etravirine +lopinavir/ritonavir
200 mg + 400/100 mg
twice daily
Fosamprenavir/ritonavir
700 mg/100 mg twice
daily
Lopinavir/ritonavir
400/100 mg twice daily
Rilpivirine
25 mg once daily
Tenofovir
300 mg once daily
Tipranavir/ritonavir
500/200 mg twice daily
Antacid (MAALOX)
simultaneousadministration
Antacid (MAALOX)
2 h after dolutegravir
Boceprevir
800 mg every 8 h
Calcium carbonate
1,200 mg
simultaneousadministration (fasted)
Calcium carbonate
1,200 mg
simultaneousadministration (fed)
Calcium carbonate
1,200 mg
2 h after dolutegravir
Carbamazepine
300 mg twice daily
Ferrous fumarate 324 mg
simultaneousadministration (fasted)

50 mg
once daily

8

1.07(1.02 to 1.13)

1.11(1.02 to 1.20)

1.28(1.13 to 1.45)

50 mg
once daily

12

0.76
(0.63 to 0.92)

0.65(0.54 to 0.78)

0.51(0.41 to 0.63)

30 mg
once daily
50 mg
once daily
50 mg
once daily
50 mg
once daily
50 mg
single dose

15

1.00
(0.94 to 1.07)
1.13(1.06 to 1.21)
0.97(0.87 to 1.08)
0.54(0.50 to 0.57)
0.28(0.23 to 0.33)

0.97(0.91 to 1.04)
1.12(1.05 to 1.19)
1.01(0.91 to 1.11)
0.41(0.38 to 0.44)
0.26(0.22 to 0.32)

0.94(0.85 to 1.05)
1.22(1.15 to 1.30)
0.92(0.82 to 1.04)
0.24(0.21 to 0.27)
0.26(0.21 to 0.31)

50 mg
single dose
50 mg
once daily
50 mg
single dose

16

0.82
(0.69 to 0.98)
1.05(0.96 to 1.15)
0.63(0.50 to 0.81)

0.74(0.62 to 0.90)
1.07(0.95 to 1.20)
0.61(0.47 to 0.80)

0.70(0.58 to 0.85)
1.08(0.91 to 1.28)
0.61(0.47 to 0.80)

50 mg
single dose

11

1.07
(0.83 to 1.38)

1.09(0.84 to 1.43)

1.08(0.81 to 1.42)

50 mg
single dose

11

1.00
(0.78 to 1.29)

0.94(0.72 to 1.23)

0.90(0.68 to 1.19)

50 mg
once daily
50 mg
single dose

16c

0.67
(0.61 to 0.73)
0.43(0.35 to 0.52)

0.51(0.48 to 0.55)
0.46(0.38 to 0.56)

0.27(0.24 to 0.31)
0.44(0.36 to 0.54)

16
15
14
16

13
12

11

41

Ferrous fumarate 324 mg
50 mg
11
1.03
0.98
1.00
simultaneous
single dose
(0.84 to 1.26) (0.81 to 1.20) (0.81 to 1.23)
administration (fed)
Ferrous fumarate 324 mg
50 mg
10
0.99
0.95
0.92
2 h after dolutegravir
single dose
(0.81 to 1.21) (0.77 to 1.15) (0.74 to 1.13)
Multivitamin (One-A-Day)
50 mg
16
0.65
0.67
0.68
simultaneous
single dose
(0.54 to 0.77) (0.55 to 0.81) (0.56 to 0.82)
administration
Omeprazole
50 mg
12
0.92
0.97
0.95
40 mg once daily
single dose
(0.75 to 1.11) (0.78 to 1.20) (0.75 to 1.21)
Prednisone
50 mg
12
1.06
1.11
1.17
60 mg once daily withonce daily(0.99 to 1.14) (1.03 to 1.20) (1.06 to 1.28)
taper
Rifampina
50 mg
11
0.57
0.46
0.28
600 mg once daily
twice daily(0.49 to 0.65) (0.38 to 0.55) (0.23 to 0.34)bRifampin
50 mg
11
1.18
1.33
1.22
600 mg once daily
twice daily(1.03 to 1.37) (1.15 to 1.53) (1.01 to 1.48)
Rifabutin
50 mg
9
1.16
0.95
0.70
300 mg once daily
once daily(0.98 to 1.37) (0.82 to 1.10) (0.57 to 0.87)aComparison is rifampin taken with dolutegravir 50 mg twice daily compared with dolutegravir
50 mg twice daily.
bComparison is rifampin taken with dolutegravir 50 mg twice daily compared with dolutegravir
50 mg once daily.
c
The number of subjects represents the maximum number of subjects that were evaluated.
Abacavir or Lamivudine: The drug interactions described are based on trials conducted withabacavir or lamivudine as single entities.
Effect of Abacavir and Lamivudine on the Pharmacokinetics of Other Agents: In vitro
studies have shown that abacavir has potential to inhibit CYP1A1 and limited potential to inhibit
metabolism mediated by CYP3A4. Lamivudine does not inhibit or induce CYP3A4. Abacavirand lamivudine do not inhibit or induce other CYP enzymes (such as CYP2C9 or CYP2D6).
Based on in vitro study results, abacavir and lamivudine at therapeutic drug exposures are notexpected to affect the pharmacokinetics of drugs that are substrates of the following transporters:
OATP1B1/3, BCRP or P-gp, OCT1, OCT2, OCT3 (lamivudine only), or MATE1 andMATE2-K.
Abacavir, Dolutegravir, and Lamivudine: Coadministration of a single dose of riociguat (0.5 mg)
to HIV-1–infected subjects receiving TRIUMEQ is reported to increase riociguat AUC(∞)
compared with riociguat AUC(∞) reported in healthy subjects due to CYP1A1 inhibition byabacavir. The exact magnitude of increase in riociguat exposure has not been fully characterizedbased on findings from two studies [see Drug Interactions (7.3)].
42

Effect of Other Agents on the Pharmacokinetics of Abacavir or Lamivudine: In vitro,
abacavir is not a substrate of OATP1B1, OATP1B3, OCT1, OCT2, OAT1, MATE1, MATE2-K,
MRP2 or MRP4; therefore, drugs that modulate these transporters are not expected to affectabacavir plasma concentrations. Abacavir is a substrate of BCRP and P-gp in vitro; however,considering its absolute bioavailability (83%), modulators of these transporters are unlikely toresult in a clinically relevant impact on abacavir concentrations.
Lamivudine is a substrate of MATE1, MATE2-K, and OCT2 in vitro. Trimethoprim (an inhibitorof these drug transporters) has been shown to increase lamivudine plasma concentrations. This
interaction is not considered clinically significant as no dose adjustment of lamivudine is needed.
Lamivudine is a substrate of P-gp and BCRP; however, considering its absolute bioavailability(87%), it is unlikely that these transporters play a significant role in the absorption oflamivudine. Therefore, coadministration of drugs that are inhibitors of these efflux transporters is
unlikely to affect the disposition and elimination of lamivudine.
Ethanol: Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol
decreases the elimination of abacavir causing an increase in overall exposure.
Interferon Alfa: There was no significant pharmacokinetic interaction between
lamivudine and interferon alfa in a trial of 19 healthy male subjects.
Methadone: In a trial of 11 HIV-1–infected subjects receiving methadone-maintenancetherapy (40 mg and 90 mg daily), with 600 mg of abacavir twice daily (twice the currently
recommended dose), oral methadone clearance increased 22% (90% CI: 6% to 42%) [see Drug
Interactions (7.3)]. The addition of methadone has no clinically significant effect on thepharmacokinetic properties of abacavir.
Ribavirin: In vitro data indicate ribavirin reduces phosphorylation of lamivudine,stavudine, and zidovudine. However, no pharmacokinetic (e.g., plasma concentrations or
intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (e.g., lossof HIV-1/HCV [hepatitis C virus] virologic suppression) interaction was observed whenribavirin and lamivudine (n = 18), stavudine (n = 10), or zidovudine (n = 6) were coadministeredas part of a multi-drug regimen to HIV-1/HCV co-infected subjects.
Sorbitol (Excipient): Lamivudine and sorbitol solutions were coadministered to 16
healthy adult subjects in an open-label, randomized-sequence, 4-period, crossover trial. Eachsubject received a single 300-mg dose of lamivudine oral solution alone or coadministered with asingle dose of 3.2 g, 10.2 g, or 13.4 g of sorbitol in solution. Coadministration of lamivudinewith sorbitol resulted in dose-dependent decreases of 20%, 39%, and 44% in the AUC(0-24); 14%,32%, and 36% in the AUC(∞); and 28%, 52%, and 55% in the Cmax; of lamivudine, respectively.
Abacavir, Lamivudine, Zidovudine: Fifteen HIV-1–infected subjects were enrolled in acrossover-designed drug interaction trial evaluating single doses of abacavir (600 mg),lamivudine (150 mg), and zidovudine (300 mg) alone or in combination. Analysis showed no43

clinically relevant changes in the pharmacokinetics of abacavir with the addition of lamivudine
or zidovudine or the combination of lamivudine and zidovudine. Lamivudine exposure (AUC
decreased 15%) and zidovudine exposure (AUC increased 10%) did not show clinically relevantchanges with concurrent abacavir.
Lamivudine and Zidovudine: No clinically significant alterations in lamivudine or zidovudine
pharmacokinetics were observed in 12 asymptomatic HIV-1–infected adult patients given asingle dose of zidovudine (200 mg) in combination with multiple doses of lamivudine (300 mg
every 12 hours).
The effects of other coadministered drugs on abacavir or lamivudine are provided in Table 11.
Table 11. Effect of Coadministered Drugs on Abacavir or Lamivudine
Concentrations of
Abacavir or Lamivudine
Coadministered Drug
Drug andand Dose
Dosen
AUC
Variability
24
90% CI:↑41%
Ethanol
Abacavir
35% to 48%
0.7 g/kg
Single 600 mg
11
95% CI:↑10%
Nelfinavir
Lamivudine
1% to 20%750 mg every 8 h x 7
Single 150 mg
to 10 days
14
90% CI:
Trimethoprim 160 mg/
Lamivudine↑43%
32% to 55%
Sulfamethoxazole
Single 300 mg
800 mg daily x 5 days
↑ = Increase; ↔ = No significant change.
a
The drug-drug interaction was only evaluated in males.
12.4

Concentration of
Coadministered
Drug
↔a
↔
↔

Microbiology

Mechanism of Action
Dolutegravir: Dolutegravir inhibits HIV integrase by binding to the integrase active site andblocking the strand transfer step of retroviral DNA integration which is essential for the HIV
replication cycle. Strand transfer biochemical assays using purified recombinant HIV-1 integrase
and pre-processed substrate DNA resulted in IC50 values of 2.7 nM and 12.6 nM.
Abacavir: Abacavir is a carbocyclic synthetic nucleoside analogue. Abacavir is converted bycellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of
deoxyguanosine-5′-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse
transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation
into viral DNA.
Lamivudine: Lamivudine is a synthetic nucleoside analogue. Intracellularly lamivudine is
phosphorylated to its active 5′-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The

44

principal mode of action of 3TC-TP is inhibition of RT via DNA chain termination afterincorporation of the nucleotide analogue.
Antiviral Activity in Cell Culture
Dolutegravir: Dolutegravir exhibited antiviral activity against laboratory strains of wild-type
HIV-1 with mean concentration of drug necessary to affect viral replication by 50% (EC50)
values of 0.5 nM (0.21 ng/mL) to 2.1 nM (0.85 ng/mL) in peripheral blood mononuclear cells(PBMCs) and MT-4 cells. Dolutegravir exhibited antiviral activity against 13 clinically diverse
clade B isolates with a median EC50 value of 0.54 nM (range: 0.41 to 0.60 nM) in a viralsusceptibility assay using the integrase coding region from clinical isolates. Dolutegravir
demonstrated antiviral activity in cell culture against a panel of HIV-1 clinical isolates withmedian EC50 values of 0.18 nM (n = 3, range: 0.09 to 0.5 nM), 0.08 nM (n = 5, range: 0.05 to
2.14 nM), 0.12 nM (n = 4, range: 0.05 to 0.51 nM), 0.17 nM (n = 3, range: 0.16 to 0.35 nM),
0.24 nM (n = 3, range: 0.09 to 0.32 nM), 0.17 nM (n = 4, range: 0.07 to 0.44 nM), 0.2 nM (n = 3,
range: 0.02 to 0.87 nM), and 0.42 nM (n = 3, range: 0.41 to 1.79 nM) for clades A, B, C, D, E, F,
and G, and group O viruses, respectively. Dolutegravir EC50 values against three HIV-2 clinicalisolates in PBMC assays ranged from 0.09 nM to 0.61 nM.
Abacavir: The antiviral activity of abacavir against HIV-1 was assessed in a number of cell lines
including in primary monocytes/macrophages and PBMCs. EC50 values ranged from 3,700 to
5,800 nM (1 nM = 0.28 ng/mL) and 70 to 1,000 nM against HIV-1IIIB and HIV-1BaL,
respectively, and the mean EC50 value was 260 ± 180 nM against 8 clinical isolates. The median
EC50 values of abacavir were 344 nM (range: 14.8 to 676 nM), 16.9 nM (range: 5.9 to 27.9 nM),
8.1 nM (range: 1.5 to 16.7 nM), 356 nM (range: 35.7 to 396 nM), 105 nM (range: 28.1 to
168 nM), 47.6 nM (range: 5.2 to 200 nM), 51.4 nM (range: 7.1 to 177 nM), and 282 nM (range:
22.4 to 598 nM) against HIV-1 clades A-G and group O viruses (n = 3 except n = 2 for clade B),
respectively. The EC50 values against HIV-2 isolates (n = 4), ranged from 24 to 490 nM.
Lamivudine: The antiviral activity of lamivudine against HIV-1 was assessed in a number of celllines including monocytes and PBMCs using standard susceptibility assays. EC50 values were in
the range of 3 to 15,000 nM (1 nM = 0.23 ng/mL). The median EC50 values of lamivudine were
60 nM (range: 20 to 70 nM), 35 nM (range: 30 to 40 nM), 30 nM (range: 20 to 90 nM), 20 nM(range: 3 to 40 nM), 30 nM (range: 1 to 60 nM), 30 nM (range: 20 to 70 nM), 30 nM (range: 3 to
70 nM), and 30 nM (range: 20 to 90 nM) against HIV-1 clades A-G and group O viruses (n = 3
except n = 2 for clade B) respectively. The EC50 values against HIV-2 isolates (n = 4) from 3 to
120 nM in PBMCs. Ribavirin (50,000 nM) used in the treatment of chronic HCV infection
decreased the anti-HIV-1 activity of lamivudine by 3.5-fold in MT-4 cells.
Antiviral Activity in Combination with Other Antiviral Agents
Neither dolutegravir, abacavir, nor lamivudine were antagonistic to all tested anti-HIV agents.
See full prescribing information for ZIAGEN (abacavir), TIVICAY (dolutegravir), and EPIVIR(lamivudine).
45

Resistance in Cell Culture
Dolutegravir: Dolutegravir-resistant viruses were selected in cell culture starting from different
wild-type HIV-1 strains and clades. Amino acid substitutions E92Q, G118R, S153F or Y, G193E
or R263K emerged in different passages and conferred decreased susceptibility to dolutegravir of
up to 4-fold.
Abacavir and Lamivudine: HIV-1 isolates with reduced susceptibility to the combination of
abacavir and lamivudine have been selected in cell culture with amino acid substitutions K65R,
L74V, Y115F, and M184V/I in HIV-1 RT. M184V or I substitutions resulted in high-level
resistance to lamivudine and approximately 2-fold decrease in susceptibility to abacavir.
Substitutions K65R, L74V, or Y115F with M184V or I conferred a 7- to 8-fold reduction inabacavir susceptibility, and combinations of three substitutions were required to confer morethan an 8-fold reduction in susceptibility.
Resistance in Clinical Subjects
No subjects in the treatment arm receiving dolutegravir + EPZICOM in SINGLE (treatmentnaive trial) had a detectable decrease in susceptibility to dolutegravir or background NRTIs in
the resistance analysis subset (n = 11 with HIV-1 RNA >400 copies/mL at failure or last visitand having resistance data). Two virologic failure subjects in SINGLE had treatment-emergent
G/D/E193D and G193G/E integrase substitutions at Week 84 and Week 108, respectively, and 1
subject with 275 copies/mL HIV-1 RNA had a treatment-emergent Q157Q/P integrase
substitution detected at Week 24. None of these subjects had a corresponding decrease in
dolutegravir susceptibility. No treatment-emergent genotypic resistance to abacavir andlamivudine, components of TRIUMEQ and TRIUMEQ PD, was observed in the arm receiving
dolutegravir + EPZICOM in the SINGLE trial through Week 144. One ART-naïve subject
receiving TRIUMEQ PD in the pediatric IMPAACT 2019 trial experienced confirmed virologic
failure at Week 24 but subsequently suppressed to 76 copies/mL by Week 48 while on continued
study treatment. The subject’s entry specimen (HIV-1 subtype AE) had the presence of baseline
integrase substitution L74I polymorphism. Genotypic sequencing and phenotypic analyses failed
at the confirmed virologic failure timepoint for this subject.
Cross-Resistance
Dolutegravir: Cross-resistance has been observed among INSTIs. The single INSTI-resistancesubstitutions T66K, I151L, and S153Y conferred a >2-fold decrease in dolutegravir
susceptibility (range: 2.3-fold to 3.6-fold from reference). Combinations of multiple substitutions
T66K/L74M, E92Q/N155H, G140C/Q148R, G140S/Q148H, R or K, Q148R/N155H,
T97A/G140S/Q148, and substitutions at E138/G140/Q148 showed a >2-fold decrease in
dolutegravir susceptibility (range: 2.5-fold to 21-fold from reference). In HIV-2 mutants,
combinations of substitutions A153G/N155H/S163G and E92Q/T97A/N155H/S163D conferred
4-fold decreases in dolutegravir susceptibility, and E92Q/N155H and G140S/Q148R showed
8.5-fold and 17-fold decreases in dolutegravir susceptibility, respectively.
46

Abacavir and Lamivudine: Cross-resistance has been observed among NRTIs. The combinationof abacavir/lamivudine has demonstrated decreased susceptibility to viruses with a K65R
substitution with or without an M184V/I substitution, viruses with L74V plus the M184V/I
substitution, and viruses with thymidine analog mutation (TAM) substitutions (M41L, D67N,
K70R, L210W, T215Y/F, K219 E/R/H/Q/N) plus M184V. An increasing number of TAMs is
associated with a progressive reduction in abacavir susceptibility.
13

NONCLINICAL TOXICOLOGY

13.1

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity
Dolutegravir: Two-year carcinogenicity studies in mice and rats were conducted withdolutegravir. Mice were administered doses of up to 500 mg/kg, and rats were administereddoses of up to 50 mg/kg. In mice, no significant increases in the incidence of drug-related
neoplasms were observed at the highest doses tested, resulting in dolutegravir AUC exposuresapproximately 26-fold higher than those in humans at the recommended dose of 50 mg once
daily. In rats, no increases in the incidence of drug-related neoplasms were observed at thehighest dose tested, resulting in dolutegravir AUC exposures 17-fold and 30-fold higher in males
and females, respectively, than those in humans at the recommended dose of 50 mg once daily.
Abacavir: Abacavir was administered orally at 3 dosage levels to separate groups of mice andrats in 2-year carcinogenicity studies. Results showed an increase in the incidence of malignant
and non-malignant tumors. Malignant tumors occurred in the preputial gland of males and theclitoral gland of females of both species, and in the liver of female rats. In addition,
non-malignant tumors also occurred in the liver and thyroid gland of female rats. Theseobservations were made at systemic exposures in the range of 7 to 28 times the human exposure
at the recommended dose of 600 mg.
Lamivudine: Long-term carcinogenicity studies with lamivudine in mice and rats showed noevidence of carcinogenic potential at exposures up to 12 times (mice) and 57 times (rats) the
human exposures at the recommended dose of 300 mg.
Mutagenicity
Dolutegravir: Dolutegravir was not genotoxic in the bacterial reverse mutation assay, mouse
lymphoma assay, or in the in vivo rodent micronucleus assay.
Abacavir: Abacavir induced chromosomal aberrations both in the presence and absence of
metabolic activation in an in vitro cytogenetic study in human lymphocytes. Abacavir was
mutagenic in the absence of metabolic activation, although it was not mutagenic in the presenceof metabolic activation in an L5178Y mouse lymphoma assay. Abacavir was clastogenic inmales and not clastogenic in females in an in vivo mouse bone marrow micronucleus assay.

47

Abacavir was not mutagenic in bacterial mutagenicity assays in the presence and absence of
metabolic activation.
Lamivudine: Lamivudine was mutagenic in an L5178Y mouse lymphoma assay and clastogenic
in a cytogenetic assay using cultured human lymphocytes. Lamivudine was not mutagenic in a
microbial mutagenicity assay, in an in vitro cell transformation assay, in a rat micronucleus test,
in a rat bone marrow cytogenetic assay, and in an assay for unscheduled DNA synthesis in rat
liver.
Impairment of Fertility
Dolutegravir, abacavir, or lamivudine did not affect male or female fertility in rats at doses
associated with exposures approximately 44, 9, or 112 times (respectively) higher than the
exposures in humans at the doses of 50 mg, 600 mg, and 300 mg (respectively).
13.2

Animal Toxicology and/or Pharmacology

Myocardial degeneration was found in mice and rats following administration of abacavir for
2 years. The systemic exposures were equivalent to 7 to 21 times the expected systemic exposurein humans at a dose of 600 mg. The clinical relevance of this finding has not been determined.
14

CLINICAL STUDIES

14.1

Adult Subjects

The efficacy of TRIUMEQ is supported by data from a randomized, controlled trial (doubleblind through 96 weeks and open-label phase from 96 to 144 weeks) in antiretroviral treatmentnaive subjects, SINGLE (ING114467, NCT01263015) and other trials in treatment-naive
subjects. See full prescribing information for TIVICAY. The efficacy of dolutegravir, in
combination with at least two active background regimens in treatment-experienced, INSTInaive subjects is supported by data from SAILING (ING111762, NCT01231516) (refer to theprescribing information for TIVICAY).
Treatment-Naive Subjects
In SINGLE, 833 subjects were randomized and received at least 1 dose of either TIVICAY
50 mg once daily with fixed-dose abacavir and lamivudine (EPZICOM) or fixed-dose
efavirenz/emtricitabine/tenofovir disoproxil fumarate (ATRIPLA). At baseline, the median ageof subjects was 35 years, 16% female, 32% non-white, 7% had hepatitis C co-infection (hepatitis
B virus co-infection was excluded), 4% were CDC Class C (AIDS), 32% had HIV-1 RNA>100,000 copies/mL, and 53% had CD4+ cell count <350 cells/mm3; these characteristics weresimilar between treatment groups.
Week 144 (open-label-phase analysis which followed the Week 96 double-blind phase)outcomes for SINGLE are provided in Table 12.

48

Table 12. Virologic Outcomes of Randomized Treatment in SINGLE at 144 Weeks(Snapshot Algorithm)
TIVICAY + EPZICOMATRIPLA
Once Daily
Once Daily(n = 414)(n = 419)71%
63%
HIV-1 RNA <50 copies/mL
Treatment differencea
8.3% (95% CI: 2.0%, 14.6%)d
Virologic nonresponse
10%
7%
4%
<1%
Data in window not <50 copies/mL
Discontinued for lack of efficacy
3%3%Discontinued for other reasons while not
3%
4%
suppressed
No virologic data
18%
30%
Reasons
Discontinued study/study drug due to4%
14%badverse event or death
Discontinued study/study drug for other
12%
13%
c
reasons
Missing data during window but on study
2%
3%
Proportion (%) of Subjects with HIV-1 RNA <50 copies/mL by Baseline Category
Plasma viral load (copies/mL)
73%
64%≤100,000≥100,00069%
61%
GenderMale
72%
66%
Female
69%
48%
Race
White
72%
71%
African American/African Heritage/Other
71%
47%
a
Adjusted for pre-specified stratification factors.
bIncludes subjects who discontinued due to an adverse event or death at any time point if thisresulted in no virologic data on treatment during the analysis window.
c
Other includes reasons such as withdrew consent, loss to follow-up, moved, and protocol
deviation.
d
The primary endpoint was assessed at Week 48 and the virologic success rate was 88% in thegroup receiving TIVICAY and 81% in the ATRIPLA group, with a treatment difference of
7.4% and 95% CI of (2.5%, 12.3%).
Treatment differences were maintained across baseline characteristics including baseline viralload, CD4+ cell count, age, gender, and race. The adjusted mean changes in CD4+ cell counts
from baseline were 378 cells/mm3 in the group receiving TIVICAY + EPZICOM and332 cells/mm3 for the ATRIPLA group at 144 weeks. The adjusted difference between treatment

49

arms and 95% CI was 46.9 cells/mm3 (15.6 cells/mm3, 78.2 cells/mm3) (adjusted for prespecified stratification factors: baseline HIV-1 RNA, and baseline CD4+ cell count).
Treatment-Experienced
In SAILING, there were 715 subjects included in the efficacy and safety analyses (see fullprescribing information for TIVICAY). At Week 48, 71% of subjects randomized to TIVICAY
plus background regimen versus 64% of subjects randomized to raltegravir plus backgroundregimen had HIV-1 RNA <50 copies/mL (treatment difference and 95% CI: 7.4% [0.7%,
14.2%]).
14.2

Pediatric Subjects

The efficacy of TRIUMEQ, TRIUMEQ PD and/or their individual components for the treatment
of HIV-1 infection was evaluated in pediatric patients enrolled in the IMPAACT 2019 trial(NCT03760458), ARROW trial (NCT02028676) and IMPAACT P1093 trial (NCT01302847),
as summarized below.
•

TRIUMEQ and TRIUMEQ PD were evaluated in treatment-naive or treatment-experienced,
HIV-1–infected subjects younger than 12 years in an open-label, multicenter clinical trial(IMPAACT 2019). Subjects were stratified by weight band and enrolled in one of fivegroups. Fifty-seven subjects, with a median age of 6.4 years (range: 1 to 11.3) and medianweight of 17 kg (range: 8.2 to 39.3), received the recommended dose (determined by weight)
and formulation, and contributed to the efficacy analysis at Week 48. At this timepoint, 79%of subjects achieved HIV-1 RNA less than 50 copies/mL and 95% achieved HIV-1 RNA lessthan 200 copies/mL (Snapshot algorithm).

•

Abacavir and lamivudine once daily, in combination with a third antiretroviral drug, were
evaluated in a randomized, multicenter trial (ARROW) in treatment-naive pediatric subjects
with HIV-1 infection. Subjects randomized to once-daily dosing (n = 336) and who weighed
at least 25 kg received abacavir 600 mg and lamivudine 300 mg, as either the single entities
or as EPZICOM. At Week 96, 67% of subjects receiving abacavir and lamivudine once-daily
in combination with a third antiretroviral drug, had HIV-1 RNA <80 copies/mL.
Dolutegravir (TIVICAY or TIVICAY PD), in combination with other antiretroviral drugs,
was evaluated in treatment-naive or treatment-experienced, INSTI-naive, HIV-1–infectedsubjects aged at least 4 weeks to 18 years in an ongoing open-label, multicenter, dose-finding
clinical trial, IMPAACT P1093. Subjects were stratified by age from 4 weeks to younger
than 18 years and enrolled in one of five age cohorts.Thirty-six subjects weighing at least
6 kg who received the recommended dose (determined by weight and age) and formulation
contributed to the efficacy analysis at Week 48. At this timepoint, 72% (26/36) of subjects
weighing at least 6 kg achieved HIV-1 RNA <50 copies/mL (Snapshot algorithm).

•

50

16

HOW SUPPLIED/STORAGE AND HANDLINGTRIUMEQ tablets
TRIUMEQ tablets are purple, oval, film-coated, biconvex tablets debossed with “572 Tri” on
one side and contain 600 mg of abacavir (as abacavir sulfate), 50 mg of dolutegravir (asdolutegravir sodium), and 300 mg lamivudine.
Bottle of 30 tablets with desiccant and child-resistant closure. NDC 49702-231-13.
Store and dispense in the original package, protect from moisture, and keep the bottle tightly
closed. Do not remove desiccant.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to86°F). [See USP Controlled Room Temperature].
TRIUMEQ PD tablets for oral suspension
TRIUMEQ PD tablets for oral suspension, are yellow, capsule-shaped, strawberry creamflavored, film-coated, biconvex tablets debossed with “SV WTU” on one side and contain 60 mg
of abacavir (as abacavir sulfate), 5 mg of dolutegravir (as dolutegravir sodium), and 30 mg
lamivudine.
Bottle of 90 tablets (NDC 49702-272-59) with desiccant and child-resistant closure. Each bottle
is packaged as a kit (NDC 49702-258-37) with one 40-mL dosing cup.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to86°F). [See USP Controlled Room Temperature]. Store and dispense in the original bottle,
protect from moisture, and keep the bottle tightly closed. Do not remove desiccant.
17

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions
for Use).
Drug Interactions
TRIUMEQ or TRIUMEQ PD may interact with many drugs; therefore, advise patients to reportto their healthcare provider the use of any other prescription or nonprescription medication or
herbal products, including St. John’s wort [see Contraindications (4), Warnings and Precautions(5.5), Drug Interactions (7)].
Hypersensitivity Reaction
Inform patients:•that a Medication Guide and Warning Card summarizing the symptoms of the abacavir
hypersensitivity reaction and other product information will be dispensed by the pharmacist
with each new prescription and refill of TRIUMEQ or TRIUMEQ PD, and instruct thepatient to read the Medication Guide and Warning Card every time to obtain any new51

information that may be present about TRIUMEQ or TRIUMEQ PD. The complete text of
the Medication Guide is reprinted at the end of this document.
•

to carry the Warning Card with them.

•

how to identify a hypersensitivity reaction [see Warnings and Precautions (5.1), Medication
Guide].

•

that if they develop symptoms consistent with a hypersensitivity reaction they should calltheir healthcare provider right away to determine if they should stop taking TRIUMEQ or
TRIUMEQ PD.

•

that a hypersensitivity reaction can worsen and lead to hospitalization or death if TRIUMEQ
or TRIUMEQ PD is not immediately discontinued.

•

to not restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing productfollowing a hypersensitivity reaction because more severe symptoms can occur within hours
and may include life-threatening hypotension and death.

•that if they have a hypersensitivity reaction, they should dispose of any unused TRIUMEQ or
TRIUMEQ PD to avoid restarting abacavir.

•

that a hypersensitivity reaction is usually reversible if it is detected promptly and TRIUMEQ
or TRIUMEQ PD is stopped right away.

•that if they have interrupted TRIUMEQ or TRIUMEQ PD for reasons other than symptomsof hypersensitivity (for example, those who have an interruption in drug supply), a serious or
fatal hypersensitivity reaction may occur with reintroduction of abacavir.

•

to not restart TRIUMEQ or TRIUMEQ PD or any other abacavir-containing product without
medical consultation and only if medical care can be readily accessed by the patient orothers.

•to not restart TRIUMEQ or TRIUMEQ PD or any other dolutegravir-containing productfollowing a hypersensitivity reaction to TRIUMEQ or TRIUMEQ PD.

Hepatotoxicity
Inform patients that hepatotoxicity has been reported with dolutegravir, a component of
TRIUMEQ and TRIUMEQ PD [see Warnings and Precautions (5.3), Adverse Reactions (6.1)].
Inform patients that monitoring for hepatotoxicity during therapy with TRIUMEQ or TRIUMEQ
PD is recommended.
Severe Acute Exacerbations of Hepatitis in Patients with HBV Co-infection
Advise all patients with HIV-1 to be tested for the presence of HBV prior to or when initiating
TRIUMEQ or TRIUMEQ PD. Advise patients co-infected with HIV-1 and HBV that worseningof liver disease has occurred in some cases when treatment with lamivudine was discontinued.
52

Advise patients to discuss any changes in regimen with their physician [see Warnings andPrecautions (5.2)].
Lactic Acidosis/Hepatomegaly
Inform patients that some HIV medicines, including TRIUMEQ and TRIUMEQ PD, can cause arare, but serious condition called lactic acidosis with liver enlargement (hepatomegaly) [seeBoxed Warning, Warnings and Precautions (5.4)].
Immune Reconstitution Syndrome
Advise patients to inform their healthcare provider immediately of any signs and symptoms ofinfection as inflammation from previous infection may occur soon after combination
antiretroviral therapy, including when TRIUMEQ or TRIUMEQ PD is started [see Warnings
and Precautions (5.6)].
TRIUMEQ Tablets and TRIUMEQ PD Tablets for Oral Suspension Are Not Bioequivalent
Advise patients that TRIUMEQ and TRIUMEQ PD are not bioequivalent and are notsubstitutable on a milligram-per-milligram basis. Advise patients or their care provider thatpatients switching from the tablets for oral suspension to the tablets must adjust the dose [seeDosage and Administration (2.3) and Warnings and Precautions (5.7)].
Pregnancy Registry
Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes inthose exposed to TRIUMEQ during pregnancy [see Use in Specific Populations (8.1)].
Lactation
Inform individuals with HIV-1 infection that the potential risks of breastfeeding include: (1)HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–
positive infants), and (3) adverse reactions in a breastfed infant similar to those seen in adults[see Use in Specific Populations (8.2)].
Administration Instructions
To avoid a dosing error from using the wrong formulation of TRIUMEQ, strongly advise
patients and caregivers to visually inspect the tablets to verify the correct formulation each time
the prescription is filled [see Dosage and Administration (2), Warnings and Precautions (5.7),
How Supplied/Storage and Handling (16)].
Inform patients and caregivers that TRIUMEQ PD tablets for oral suspension should be
dispersed in drinking water and should not be chewed, cut, crushed, or swallowed whole [seeDosage and Administration (2.5)]. Inform patients and caregivers that an appropriate-sizedsyringe may be used to administer the oral suspension if the patient is unable to use the suppliedcup [see Dosage and Administration (2.5)].
53

Instruct patients and caregivers that if a dose of TRIUMEQ or TRIUMEQ PD is missed, to takeit as soon as they remember. Advise patients and caregivers not to double the next dose or takemore than the prescribed dose [see Dosage and Administration (2)].
Availability of Medication Guide
Instruct patients and caregivers to read the Medication Guide before starting TRIUMEQ or
TRIUMEQ PD and to re-read it each time the prescription is renewed. Instruct patients to informtheir physician or pharmacist if they develop any unusual symptom, or if any known symptom
persists or worsens.
Storage
Instruct patients and caregivers to store TRIUMEQ and TRIUMEQ PD tablets for oralsuspension in the original package, protect from moisture, and keep the bottle tightly closed. Do
not remove desiccant.
EPIVIR, EPZICOM, TIVICAY, TIVICAY PD, TRIUMEQ, TRIUMEQ PD, and ZIAGEN are
trademarks owned by or licensed to the ViiV Healthcare group of companies.
EPIVIR-HBV is a trademark owned by or licensed to the GSK group of companies.
The other brands listed are trademarks owned by or licensed to their respective owners and are
not owned by or licensed to the ViiV Healthcare group of companies. The makers of thesebrands are not affiliated with and do not endorse the ViiV Healthcare group of companies or its
products.

Manufactured for:

ViiV Healthcare
Durham, NC 27701©2024 ViiV Healthcare group of companies or its licensor.
TRM:18PI

54

MEDICATION GUIDETRIUMEQ (TRI-u-meck)

TRIUMEQ PD (TRI-u-meck Pe De)(abacavir, dolutegravir, and lamivudine)(abacavir, dolutegravir, and lamivudine)tablets

tablets for oral suspension

What is the most important information I should know about TRIUMEQ and TRIUMEQ PD?
TRIUMEQ and TRIUMEQ PD can cause serious side effects, including:• Serious allergic reactions (hypersensitivity reaction) that can cause death have happened with
TRIUMEQ or TRIUMEQ PD and other abacavir-containing products. Your risk of this allergic
reaction to abacavir is much higher if you have a gene variation called HLA-B*5701. Your
healthcare provider can determine with a blood test if you have this gene variation.
If you get a symptom from 2 or more of the following groups while taking TRIUMEQ or
TRIUMEQ PD, call your healthcare provider right away to find out if you should stop taking
TRIUMEQ or TRIUMEQ PD.
Symptom(s)Group 1

Fever

Group 2

Rash

Group 3

Nausea, vomiting, diarrhea, abdominal (stomach area) pain

Group 4Generally ill feeling, extreme tiredness, or achinessGroup 5

Shortness of breath, cough, sore throat

A list of these symptoms is on the Warning Card your pharmacist gives you. Carry this Warning
Card with you at all times.
If you stop TRIUMEQ or TRIUMEQ PD because of an allergic reaction, never take TRIUMEQ,
TRIUMEQ PD (abacavir, dolutegravir and lamivudine), or any other medicine that contains
abacavir or dolutegravir (DOVATO, EPZICOM, JULUCA, TIVICAY, TIVICAY PD, TRIZIVIR, or
ZIAGEN) again.
oo

If you have an allergic reaction, dispose of any unused TRIUMEQ or TRIUMEQ PD. Ask yourpharmacist how to properly dispose of medicines.
If you take TRIUMEQ, TRIUMEQ PD or any other abacavir-containing medicine again after
you have had an allergic reaction, within hours you may get life-threatening symptoms that
may include very low blood pressure or death.

o

If you stop TRIUMEQ or TRIUMEQ PD for any other reason, even for a few days, and you are
not allergic to TRIUMEQ or TRIUMEQ PD, talk with your healthcare provider before taking it
again. Taking TRIUMEQ or TRIUMEQ PD again can cause a serious allergic or life-threatening
reaction, even if you never had an allergic reaction to it before.

1

If your healthcare provider tells you that you can take TRIUMEQ or TRIUMEQ PD again, starttaking it when you are around medical help or people who can call a healthcare provider if
you need one.
• Worsening of Hepatitis B virus (HBV) infection. Your healthcare provider will test you for HBV
infection before you start treatment with TRIUMEQ or TRIUMEQ PD. If you have HBV infection andtake TRIUMEQ or TRIUMEQ PD, your HBV may get worse (flare-up) if you stop taking TRIUMEQ
or TRIUMEQ PD. A “flare-up” is when your HBV infection suddenly returns in a worse way than
before.
o

Do not run out of TRIUMEQ or TRIUMEQ PD. Refill your prescription or talk to your healthcareo

Do not stop TRIUMEQ or TRIUMEQ PD without first talking to your healthcare provider.

oprovider before your TRIUMEQ or TRIUMEQ PD is all gone.
If you stop taking TRIUMEQ or TRIUMEQ PD, your healthcare provider will need to check yourhealth often and do blood tests regularly for several months to check your liver function andmonitor your HBV infection. It may be necessary to give you a medicine to treat hepatitis B.
Tell your healthcare provider about any new or unusual symptoms you may have after you
stop taking TRIUMEQ or TRIUMEQ PD.

• Resistant HBV. If you have human immunodeficiency virus-1 (HIV-1) and HBV, the HBV canchange (mutate) during your treatment with TRIUMEQ or TRIUMEQ PD and become harder to treat(resistant). Your healthcare provider may give you other medicines to treat HBV infection if you
have HIV-1 and HBV infections and take TRIUMEQ or TRIUMEQ PD.
• For more information about side effects, see “What are the possible side effects of TRIUMEQ
or TRIUMEQ PD?”
What is TRIUMEQ and TRIUMEQ PD?
TRIUMEQ and TRIUMEQ PD are prescription medicines used to treat HIV-1 infection in adults andchildren who are at least 3 months of age and weigh at least 13.2 pounds (6 kg).
HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).
TRIUMEQ and TRIUMEQ PD contain the prescription medicines abacavir, dolutegravir, andlamivudine.
• TRIUMEQ or TRIUMEQ PD should not be used by itself in people who have resistance to certain
types of medicines.
It is not known if TRIUMEQ PD is safe and effective in children who are less than 3 months of age or
weigh less than 13.2 pounds (6 kg).
Do not take TRIUMEQ or TRIUMEQ PD if you:• have a certain type of gene variation called the HLA-B*5701 allele. Your healthcare provider will test
you for this before prescribing treatment with TRIUMEQ or TRIUMEQ PD.
• are allergic to abacavir, dolutegravir, lamivudine, or any of the ingredients in TRIUMEQ or
TRIUMEQ PD. See the end of this Medication Guide for a complete list of ingredients in TRIUMEQ
and TRIUMEQ PD.

2• take dofetilide. Taking TRIUMEQ or TRIUMEQ PD and dofetilide can cause side effects that may beserious or life-threatening.
• have certain liver problems.
Before you take TRIUMEQ or TRIUMEQ PD, tell your healthcare provider about all of your
medical conditions, including if you:• have been tested and know whether or not you have a particular gene variation called HLA-B*5701.
• have or have had liver problems, including hepatitis B or C virus infection.
• have kidney problems.
• have heart problems, smoke, or have diseases that increase your risk of heart disease such as highblood pressure, high cholesterol, or diabetes.
• drink alcohol or take medicines that contain alcohol.
• are pregnant or plan to become pregnant. Talk to your healthcare provider about the benefits andrisks of treatment with TRIUMEQ during pregnancy.
Pregnancy Registry. There is a pregnancy registry for those who take TRIUMEQ during pregnancy.
The purpose of this registry is to collect information about the health of you and your baby. Talk withyour healthcare provider about how you can take part in this registry.
• are breastfeeding or plan to breastfeed. TRIUMEQ passes to your baby in your breast milk. Talk
with your healthcare provider about the following risks to your baby from breastfeeding during
treatment with TRIUMEQ:ooothe HIV-1 virus may pass to your baby if your baby does not have HIV-1 infection.
the HIV-1 virus may become harder to treat if your baby has HIV-1 infection.
your baby may get side effects from TRIUMEQ.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.
Some medicines interact with TRIUMEQ or TRIUMEQ PD. Keep a list of your medicines to show yourhealthcare provider and pharmacist when you get a new medicine.
• You can ask your healthcare provider or pharmacist for a list of medicines that interact with
TRIUMEQ or TRIUMEQ PD.
• Do not start taking a new medicine without telling your healthcare provider. Your healthcare
provider can tell you if it is safe to take TRIUMEQ or TRIUMEQ PD with other medicines.
How should I take TRIUMEQ or TRIUMEQ PD?
Read the Instructions for Use at the end of this Medication Guide for detailed instructions on
how to prepare a dose of TRIUMEQ PD tablets for oral suspension.
• Take TRIUMEQ or TRIUMEQ PD exactly as your healthcare provider tells you to take it.
• Do not change your dose, switch medicines or stop taking TRIUMEQ or TRIUMEQ PD without
talking with your healthcare provider first.
• TRIUMEQ tablets are not the same as TRIUMEQ PD tablets for oral suspension and cannot
be substituted for each other. Check to make sure you receive the correct dosage form eachtime you or your child’s prescription is filled to avoid using the wrong medicine.

3• Your child’s healthcare provider will prescribe TRIUMEQ or TRIUMEQ PD based on your child’s
weight.
• TRIUMEQ PD tablets for oral suspension should be dispersed in drinking water.
• Do not chew, cut, or crush TRIUMEQ tablets or TRIUMEQ PD tablets for oral suspension. Do not
swallow TRIUMEQ PD tablets for oral suspension whole.
• TRIUMEQ or TRIUMEQ PD may be taken with or without food.
• If you take antacids, laxatives, or other medicines that contain aluminum, magnesium, or buffered
medicines, TRIUMEQ or TRIUMEQ PD should be taken at least 2 hours before or 6 hours after
you take these medicines.
• If you need to take iron or calcium supplements, or multivitamin supplements that contain iron or
calcium, by mouth during treatment with TRIUMEQ or TRIUMEQ PD:
o If you take TRIUMEQ or TRIUMEQ PD with food, you may take these supplements at the sametime that you take TRIUMEQ or TRIUMEQ PD.

o If you do not take TRIUMEQ or TRIUMEQ PD with food, take TRIUMEQ or TRIUMEQ PD atleast 2 hours before or 6 hours after you take these supplements.

• If you miss a dose of TRIUMEQ or TRIUMEQ PD, take it as soon as you remember. Do not take 2
doses at the same time or take more than your healthcare provider tells you to take.
• Stay under the care of a healthcare provider during treatment with TRIUMEQ or TRIUMEQ PD.
• Do not run out of TRIUMEQ or TRIUMEQ PD. The virus in your blood may increase and the virus
may become harder to treat. When your supply starts to run low, get more from your healthcare
provider or pharmacy.
• If you take too much TRIUMEQ or TRIUMEQ PD, call your healthcare provider or go to the nearest
hospital emergency room right away.
What are the possible side effects of TRIUMEQ or TRIUMEQ PD?
TRIUMEQ or TRIUMEQ PD can cause serious side effects, including:• See “What is the most important information I should know about TRIUMEQ and TRIUMEQ
PD?”• Liver problems. People with a history of hepatitis B or C virus may have an increased risk ofdeveloping new or worsening changes in certain liver function tests during treatment with TRIUMEQ
or TRIUMEQ PD. Liver problems including liver failure have also happened with TRIUMEQ or
TRIUMEQ PD in people without a history of liver disease or other risk factors. Liver failure resulting
in liver transplant has also been reported with TRIUMEQ. Your healthcare provider may do blood
tests to check your liver. Call your healthcare provider right away if you develop any of thesigns or symptoms of liver problems listed below.
oyour skin or the white part of your eyesodark or “tea-colored” urineoturns yellow (jaundice)oloss of appetiteopain, aching, or tenderness on the right sideolight colored stools (bowel movements)

4nausea or vomitingof your stomach area• Too much lactic acid in your blood (lactic acidosis). Too much lactic acid is a serious medical
emergency that can lead to death. Call your healthcare provider right away if you get any of thefollowing symptoms that could be signs of lactic acidosis:
o feel very weak or tiredo feel cold, especially in your arms and legs

o unusual (not normal) muscle paino feel dizzy or lightheadedo trouble breathingo have a fast or irregular heartbeato stomach pain with nausea and vomiting• Lactic acidosis can also lead to severe liver problems, which can lead to death. Your liver may
become large (hepatomegaly), and you may develop fat in your liver (steatosis). Call yourhealthcare provider right away if you get any of the signs or symptoms of liver problems
which are listed above under “Liver problems”.
• You may be more likely to get lactic acidosis or severe liver problems if you are female orvery overweight (obese).
• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you
start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections
that have been hidden in your body for a long time. Tell your healthcare provider right away if you
start having new symptoms after you start taking TRIUMEQ or TRIUMEQ PD.
• Heart attack. Some HIV-1 medicines including TRIUMEQ or TRIUMEQ PD may increase your riskof heart attack.
• The most common side effects of TRIUMEQ include:otrouble sleepingoheadache

These are not all the possible side effects of TRIUMEQ or TRIUMEQ PD.

otiredness

Call your doctor for medical advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.
How should I store TRIUMEQ or TRIUMEQ PD?
• Store TRIUMEQ and TRIUMEQ PD at room temperature between 68°F to 77°F (20°C to 25°C) in
the original bottle. Keep the bottle tightly closed and protect it from moisture.
• The bottle of TRIUMEQ and TRIUMEQ PD contains a desiccant packet to help keep your medicine
dry (protect it from moisture). Do not remove the desiccant packet from the bottle.
Keep TRIUMEQ, TRIUMEQ PD, and all medicines out of the reach of children.
General information about the safe and effective use of TRIUMEQ or TRIUMEQ PD.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do
not use TRIUMEQ or TRIUMEQ PD for a condition for which it was not prescribed. Do not give
TRIUMEQ or TRIUMEQ PD to other people, even if they have the same symptoms that you have. It
may harm them. You can ask your pharmacist or healthcare provider for information about TRIUMEQ
or TRIUMEQ PD that is written for health professionals.
What are the ingredients in TRIUMEQ and TRIUMEQ PD?
Active ingredients: abacavir, dolutegravir, and lamivudine
Inactive ingredients:

5

TRIUMEQ tablets: D-mannitol, magnesium stearate, microcrystalline cellulose, povidone, and sodium
starch glycolate. Tablet film-coating contains: iron oxide black, iron oxide red, macrogol/PEG, polyvinyl
alcohol–part hydrolyzed, talc, and titanium oxide.
TRIUMEQ PD tablets for oral suspension: acesulfame potassium, crospovidone, mannitol,
microcrystalline cellulose, povidone K29/32, silicified microcrystalline cellulose, sodium starchglycolate, sodium stearyl fumarate, strawberry cream flavor, and sucralose.
Tablet film-coating contains: ferric oxide yellow, macrogol/PEG, polyvinyl alcohol-part hydrolyzed, talc,
and titanium dioxide.
Manufactured for:

ViiV Healthcare
Durham, NC 27701
DOVATO, EPZICOM, JULUCA, TIVICAY, TIVICAY PD, TRIUMEQ, TRIUMEQ PD, TRIZIVIR, and ZIAGEN are trademarks
owned by or licensed to the ViiV Healthcare group of companies.
©2024 ViiV Healthcare group of companies or its licensor. TRM:17MG
For more information go to www.TRIUMEQ.com or call 1-877-844-8872.
This Medication Guide has been approved by the U.S. Food and Drug Administration.

6

Revised: 4/2024

INSTRUCTIONS FOR USE
TRIUMEQ PD (TRI-u-meck Pe De)(abacavir, dolutegravir, and lamivudine)tablets for oral suspension
This Instructions for Use contains information on how to take TRIUMEQ PD.
Read this Instructions for Use before your child starts taking TRIUMEQ PD for the first time and eachtime you get a refill. There may be new information. This information does not take the place oftalking to your healthcare provider about your child’s medical condition or treatment. Talk to yourhealthcare provider or pharmacist if you have any questions on how to prepare or give the prescribed
dose of TRIUMEQ PD.
Important Information You Need to Know Before Giving TRIUMEQ PD•

Give TRIUMEQ PD exactly as your healthcare provider tells you.

•

Each time you receive your child’s prescription, check the bottle to make sure that you
received TRIUMEQ PD. TRIUMEQ tablets are not the same as TRIUMEQ PD tablets for oralsuspension and cannot be substituted for each other. Contact your pharmacist or
healthcare provider if you did not receive the correct dosage form.

•

Do not chew, cut, crush, or swallow whole the tablets for oral suspension.

•

If you forget to give a dose of TRIUMEQ PD, give it as soon as you remember. Do not give 2
doses at the same time or give more than your healthcare provider has prescribed.

•

If your child does not or cannot take the full dose, call your healthcare provider.

•If you give too much TRIUMEQ PD, get emergency medical help right away.

•

For more information about TRIUMEQ PD, read the Medication Guide.

Your pack contains:• A bottle containing 90 TRIUMEQ PD
tablets for oral suspension• Dosing cup

Supply not included in the pack• Oral syringe (optional)
If your child cannot use the supplied dosing cup, you may need an oral syringe to give themedicine. Talk to your healthcare provider for advice about the size of oral syringe you should use togive TRIUMEQ PD.

1

You will also need:• Clean drinking water.

Preparing to Give TRIUMEQ PD
Step 1. Pour water• Pour clean drinking water into the cup.
The Water Volume Guide in Figure A
shows the amount of water needed for theprescribed dose
See Figure A.
Use drinking water only.
Do not use any other drink or food to prepare
the dose.

Figure A

TRIUMEQ PD tablets for oral suspension
must be dispersed in drinking water before
you give them to your child.

Step 2. Prepare the medicine• Add the prescribed number of tablet(s) to
the water. See Figure B.
• Swirl the cup gently for 1 to 2 minutes todisperse the tablet(s). The medicine will
become cloudy. Take care not to spill anyof the medicine. See Figure C.
• Check that the medicine is ready. If there
Figure B

are any lumps of tablet, swirl the cup until

Figure C

they are gone.

If you spill any medicine, clean up the spill.
Throw away the rest of the prepared medicine and make a new dose.
You must give the dose of medicine within 30 minutes of preparing the dose. If it has been
more than 30 minutes, wash away all the dose in the cup using water and prepare a new dose of
medicine.

Giving TRIUMEQ PD
Step 3. Give the medicine

2• Make sure that the child is upright. Give all
the prepared medicine to the child. See
Figure D.
• Add another 15 mL or less of drinking
water to the cup, swirl, and give it all to thechild.
• Repeat if any medicine remains in the
cup to make sure the child gets the full
dose.
Figure D• Place the tip of the oral syringe into the
prepared medicine and draw up all the
medicine into the oral syringe by pulling up
on the plunger. See Figure E.
• Place the tip of the oral syringe against theinside of the child’s cheek. Gently pushdown the plunger to give the dose slowly.
See Figure F.
• Add another 15 mL or less of drinking
Figure E

water to the cup and swirl. Draw up the

Figure Fremaining medicine into the oral syringe
and give it all to the child.
• Repeat if any medicine remains in theoral syringe to make sure the child getsthe full dose.
Allow time for the medicine to be swallowed.

Cleaning the Dosing Items
Step 4. Clean the dosing items you used to give TRIUMEQ PD• Wash all the dosing items with water. See
Figure G and Figure H.
• If using and oral syringe, pull theplunger out of the syringe parts
separately in water. Allow parts to drycompletely before reassembling andstoring. See Figure H.
• All parts will need to be clean before
preparing the next dose.
Figure G

Figure H

3

Storing TRIUMEQ PD•

Store TRIUMEQ PD tablets for oral suspension at room temperature between 68°F to 77°F
(20°C to 25°C) in the original bottle. Keep the bottle tightly closed and protect from moisture.

•

The TRIUMEQ PD bottle contains a desiccant packet to help keep your medicine dry (protect itfrom moisture). Do not remove the desiccant packet from the bottle.

Keep TRIUMEQ PD and all medicines out of the reach of children.

Disposing of TRIUMEQ PD
When all the tablets in the bottle have been taken or are no longer needed, throw away thebottle, cup, and oral syringe. Dispose of them using your local household waste guidelines.
You will get a new cup in your next pack.
Manufactured for:

ViiV Healthcare
Durham, NC 27701
Trademarks are owned by or licensed to the ViiV Healthcare group of companies.
©2023 ViiV Healthcare group of companies or its licensor.
TRM:3IFU
This Instructions for Use has been approved by the U.S. Food and Drug Administration.

4

Revised: 6/2023