Triumeq

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Triumeq 50 mg/600 mg/300 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 50 mg dolutegravir (as sodium), 600 mg of abacavir (as sulfate) and 
300 mg of lamivudine. 
 
For the full list of excipients see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet) 
 
Purple, biconvex, film-coated oval tablets, approximately 22 x 11 mm, debossed with “572 Trı” on 
one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Triumeq is indicated for the treatment of Human Immunodeficiency Virus (HIV) infected adults and 
adolescents above 12 years of age weighing at least 40 kg (see sections 4.4 and 5.1).  
 
Before initiating treatment with abacavir-containing products, screening for carriage of the HLA-
B*5701 allele should be performed in any HIV-infected patient, irrespective of racial origin (see 
section 4.4). Abacavir should not be used in patients known to carry the HLA-B*5701 allele. 
 
4.2 Posology and method of administration 
 
Therapy should be prescribed by a physician experienced in the management of HIV infection. 
 
Posology 
 
Adults and adolescents (weighing at least 40kg)  
The recommended dose of Triumeq in adults and adolescents is one tablet once daily. 
 
Triumeq should not be administered to adults or adolescents who weigh less than 40 kg because it is a 
fixed-dose tablet that cannot be dose reduced. 
 
Triumeq is a fixed-dose tablet and should not be prescribed for patients requiring dose adjustments. 
Separate preparations of dolutegravir, abacavir or lamivudine are available in cases where 
discontinuation or dose adjustment of one of the active substances is indicated. In these cases the 
physician should refer to the individual product information for these medicinal products. 
 
Missed doses 
If the patient misses a dose of Triumeq, the patient should take it as soon as possible, providing the 
next dose is not due within 4 hours. If the next dose is due within 4 hours, the patient should not take 
the missed dose and simply resume the usual dosing schedule. 



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Elderly 
There are limited data available on the use of dolutegravir, abacavir and lamivudine in patients aged 
65 years and over. There is no evidence that elderly patients require a different dose than younger 
adult patients (see section 5.2). Special care is advised in this age group due to age associated changes 
such as the decrease in renal function and alteration of haematological parameters. 
 
Renal impairment  
Triumeq is not recommended for use in patients with a creatinine clearance < 50 ml/min (see section 
5.2). 
 
Hepatic impairment 
Abacavir is primarily metabolised by the liver. No clinical data are available in patients with moderate 
or severe hepatic impairment, therefore the use of Triumeq is not recommended unless judged 
necessary. In patients with mild hepatic impairment (Child-Pugh score 5-6) close monitoring is 
required, including monitoring of abacavir plasma levels if feasible (see sections 4.4 and 5.2). 
 
Paediatric population  
The safety and efficacy of Triumeq in children less than 12 years of age has not yet been established. 
No data are available. 
 
Method of administration 
 
Oral use 
Triumeq can be taken with or without food (see section 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. See sections 
4.4 and 4.8. 
 
Co-administration with medicinal products with narrow therapeutic windows, that are substrates of 
organic cation transporter (OCT) 2, including but not limited to fampridine (also known as 
dalfampridine; see section 4.5). 
 
4.4 Special warnings and precautions for use 
 
Transmission of HIV 
 
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce 
the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission 
should be taken in accordance with national guidelines. 
 
Hypersensitivity reactions (see section 4.8) 
 
Both abacavir and dolutegravir are associated with a risk for hypersensitivity reactions (HSR) (see 
section 4.8), and share some common features such as fever and/or rash with other symptoms 
indicating multi-organ involvement. Clinically it is not possible to determine whether a HSR with 
Triumeq would be caused by abacavir or dolutegravir. Hypersensitivity reactions have been observed 
more commonly with abacavir, some of which have been life-threatening, and in rare cases fatal, 
when not managed appropriately. The risk for abacavir HSR to occur is high for patients who test 
positive for the HLA-B*5701 allele. However, abacavir HSRs have been reported at a low frequency 
in patients who do not carry this allele.   



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Therefore, the following should always be adhered to: 
 
- HLA-B*5701 status must always be documented prior to initiating therapy. 
 
- Triumeq should never be initiated in patients with a positive HLA-B*5701 status, nor in patients 
with a negative HLA-B*5701 status who had a suspected abacavir HSR on a previous abacavir-
containing regimen.  
 
- Triumeq must be stopped without delay, even in the absence of the HLA-B*5701 allele, if an 
HSR is suspected. Delay in stopping treatment with Triumeq after the onset of hypersensitivity may 
result in an immediate and life-threatening reaction. Clinical status including liver aminotransferases 
and bilirubin should be monitored. 
 
- After stopping treatment with Triumeq for reasons of a suspected HSR, Triumeq or any other 
medicinal product containing abacavir or dolutegravir must never be re-initiated.  
 
- Restarting abacavir containing products following a suspected abacavir HSR can result in a prompt 
return of symptoms within hours. This recurrence is usually more severe than on initial presentation, 
and may include life-threatening hypotension and death.  
 
- In order to avoid restarting abacavir and dolutegravir, patients who have experienced a suspected 
HSR should be instructed to dispose of their remaining Triumeq tablets.  
  
Clinical description of HSRs 
 
Hypersensitivity reactions have been reported in <1% of patients treated with dolutegravir in clinical 
studies, and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, 
including severe liver reactions. 
 
Abacavir HSR has been well characterised through clinical studies and during post marketing follow-
up. Symptoms usually appeared within the first six weeks (median time to onset 11 days) of initiation 
of treatment with abacavir, although these reactions may occur at any time during therapy. 
 
Almost all HSR to abacavir will include fever and/or rash. Other signs and symptoms that have been 
observed as part of abacavir HSR are described in detail in section 4.8 (Description of selected 
adverse reactions), including respiratory and gastrointestinal symptoms. Importantly, such symptoms 
may lead to misdiagnosis of HSR as respiratory disease (pneumonia, bronchitis, pharyngitis), or 
gastroenteritis. The symptoms related to this HSR worsen with continued therapy and can be life- 
threatening. These symptoms usually resolve upon discontinuation of abacavir.  
 
Rarely, patients who have stopped abacavir for reasons other than symptoms of HSR have also 
experienced life-threatening reactions within hours of re- initiating abacavir therapy (see Section 4.8 
Description of selected adverse reactions).  Restarting abacavir in such patients must be done in a 
setting where medical assistance is readily available. 
 
Weight and metabolic parameters 
 
An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral 
therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in 
some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating 
this to any particular treatment. For monitoring of blood lipids and glucose reference is made to 
established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate. 



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Liver disease 
 
The safety and efficacy of Triumeq has not been established in patients with significant underlying 
liver disorders. Triumeq is not recommended in patients with moderate to severe hepatic impairment 
(see sections 4.2 and 5.2).  
 
Patients with pre-existing liver dysfunction, including chronic active hepatitis have an increased 
frequency of liver function abnormalities during combination antiretroviral therapy, and should be 
monitored according to standard practice. If there is evidence of worsening liver disease in such 
patients, interruption or discontinuation of treatment must be considered.  
 
Patients with chronic hepatitis B or C 
 
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an 
increased risk of severe and potentially fatal hepatic adverse reactions. In case of concomitant 
antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these 
medicinal products.  
 
Triumeq includes lamivudine, which is active against hepatitis B. Abacavir and dolutegravir lack such 
activity. Lamivudine monotherapy is generally not considered an adequate treatment for hepatitis B, 
since the risk for hepatitis B resistance development is high. If Triumeq is used in patients co-infected 
with hepatitis B an additional antiviral is, therefore, generally needed. Reference should be made to 
treatment guidelines.  
 
If Triumeq is discontinued in patients co-infected with hepatitis B virus, periodic monitoring of both 
liver function tests and markers of HBV replication is recommended, as withdrawal of lamivudine 
may result in an acute exacerbation of hepatitis. 
 
Immune Reactivation Syndrome 
 
In HIV-infected patients with severe immune deficiency at the time of institution of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, 
such reactions have been observed within the first few weeks or months of initiation of CART. 
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, 
and Pneumocystis jirovecii pneumonia (often referred to as PCP). Any inflammatory symptoms 
should be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves’ 
disease and autoimmune hepatitis) have also been reported to occur in the setting of immune 
reactivation; however, the reported time to onset is more variable and these events can occur many 
months after initiation of treatment. 
 
Liver chemistry elevations consistent with immune reconstitution syndrome were observed in some 
hepatitis B and/or C co-infected patients at the start of dolutegravir therapy.  Monitoring of liver 
chemistries is recommended in patients with hepatitis B and/or C co-infection. (See ‘Patients with 
chronic hepatitis B or C’ earlier in this section and also see section 4.8). 
 
Mitochondrial dysfunction following exposure in utero 
 
Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which 
is most pronounced with stavudine, didanosine and zidovudine. There have been reports of 
mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside 
analogues, these have predominantly concerned treatment with regimens containing zidovudine. The 



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main adverse reactions reported are haematological disorders (anaemia, neutropenia), and metabolic 
disorders (hyperlactatemia, hyperlipasemia). These reactions have often been transitory. Some late-
onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour). 
Whether such neurological disorders are transient or permanent is currently unknown. These findings 
should be considered for any child exposed in utero to nucleoside and nucleotide analogues, who 
presents with severe clinical findings of unknown aetiology, particularly neurologic findings.  These 
findings do not affect current national recommendations to use antiretroviral therapy in pregnant 
women to prevent vertical transmission of HIV. 
 
Myocardial infarction 
 
Observational studies have shown an association between myocardial infarction and the use of 
abacavir. Those studied were mainly antiretroviral experienced patients. Data from clinical trials 
showed limited numbers of myocardial infarction and could not exclude a small increase in risk.  
Overall the available data from observational cohorts and from randomised trials show some 
inconsistency so can neither confirm nor refute a causal relationship between abacavir treatment and 
the risk of myocardial infarction.  To date, there is no established biological mechanism to explain a 
potential increase in risk.  When prescribing Triumeq, action should be taken to try to minimize all 
modifiable risk factors (e.g. smoking, hypertension, and hyperlipidaemia). 
 
Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, 
bisphosphonates, alcohol consumption, severe immunosuppression, higher body mass index), cases of 
osteonecrosis have been reported particularly in patients with advanced HIV-disease and/or long-term 
exposure to CART. Patients should be advised to seek medical advice if they experience joint aches 
and pain, joint stiffness or difficulty in movement. 
 
Opportunistic infections 
 
Patients should be advised that Triumeq or any other antiretroviral therapy does not cure HIV 
infection and that they may still develop opportunistic infections and other complications of HIV 
infection. Therefore, patients should remain under close clinical observation by physicians 
experienced in the treatment of these associated HIV diseases. 
 
Drug resistance 
 
Since the recommended dose of dolutegravir is 50 mg twice daily for patients with resistance to 
integrase inhibitors, the use of Triumeq is not recommended for patients with integrase inhibitor 
resistance. 
 
Drug interactions 
 
Since the recommended dose of dolutegravir is 50 mg twice daily when co-administered with 
etravirine (without boosted protease inhibitors), efavirenz, nevirapine, rifampicin, tipranavir/ritonavir, 
carbamazepine, phenytoin, phenobarbital and St. John’s wort, the use of Triumeq is not recommended 
for patients taking these medicines (see section 4.5). 
 
Triumeq should not be co-administered with polyvalent cation-containing antacids. Triumeq is 
recommended to be administered 2 hours before or 6 hours after these medicinal products (see section 
4.5). 
 



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Triumeq is recommended to be administered 2 hours before or 6 hours after taking supplements or 
multivitamins containing calcium, iron or magnesium (see section 4.5). 
 
Dolutegravir increased metformin concentrations. A dose adjustment of metformin should be 
considered when starting and stopping coadministration of dolutegravir with metformin, to maintain 
glycaemic control (see section 4.5). Metformin is eliminated renally and therefore it is of importance 
to monitor renal function when co-treated with dolutegravir. This combination may increase the risk 
for lactic acidosis in patients with moderate renal impairment (stage 3a creatinine clearance [CrCl] 
45– 59 mL/min) and a cautious approach is recommended. Reduction of the metformin dose should 
be highly considered.   
 
The combination of lamivudine with cladribine is not recommended (see section 4.5). 
 
Triumeq should not be taken with any other medicinal products containing dolutegravir, abacavir, 
lamivudine or emtricitabine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Triumeq contains dolutegravir, abacavir and lamivudine, therefore any interactions identified for these 
individually are relevant to Triumeq. No clinically significant drug interactions are expected between 
dolutegravir, abacavir and lamivudine. 
 
Effect of other medicinal products on the pharmacokinetics of dolutegravir, abacavir and lamivudine 
 
Dolutegravir is eliminated mainly through metabolism by uridine diphosphate glucuronosyl 
transferase (UGT) 1A1. Dolutegravir is also a substrate of UGT1A3, UGT1A9, CYP3A4, P-
glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Co-administration of Triumeq and 
other medicinal products that inhibit UGT1A1, UGT1A3, UGT1A9, CYP3A4, and/or P-gp may 
therefore increase dolutegravir plasma concentration. Medicinal products that induce those enzymes 
or transporters may decrease dolutegravir plasma concentration and reduce the therapeutic effect of 
dolutegravir (see Table 1). 
 
The absorption of dolutegravir is reduced by certain anti-acid medicinal products (see Table 1).  
 
Abacavir is metabolised by UGT (UGT2B7) and alcohol dehydrogenase; co-administration of 
inducers (e.g. rifampicin, carbamazepine and phenytoin) or inhibitors (e.g. valproic acid) of UGT 
enzymes or with compounds eliminated through alcohol dehydrogenase could alter abacavir exposure.  
 
Lamivudine is cleared renally. Active renal secretion of lamivudine in the urine is mediated through 
the OCT2 and multidrug and toxin extrusion transporters (MATE1 and MATE2-K). Trimethoprim (an 
inhibitor of these drug transporters) has been shown to increase lamivudine plasma concentrations, 
however the resulting increase was not clinically significant (see Table 1).  Dolutegravir is an OCT2 
and MATE1 inhibitor; however, lamivudine concentrations were similar with or without co-
administration of dolutegravir based on a cross study analysis, indicating that dolutegravir has no 
effect on lamivudine exposure in vivo. Lamivudine is also substrate of the hepatic uptake transporter 
OCT1. As hepatic elimination plays a minor role in the clearance of lamivudine, drug interactions due 
to inhibition of OCT1 are unlikely to be of clinical significance. 
Although abacavir and lamivudine are substrates of BCRP and P-gp in vitro, given the high absolute 
bioavailability of abacavir and lamivudine, (see section 5.2), inhibitors of these efflux transporters are 
unlikely to result in a clinically relevant impact on abacavir or lamivudine concentrations.  
 
Effect of dolutegravir, abacavir and lamivudine on the pharmacokinetics of other medicinal products 
 



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In vivo, dolutegravir did not have an effect on midazolam, a CYP3A4 probe. Based on in vivo and/or 
in vitro data, dolutegravir is not expected to affect the pharmacokinetics of medicinal products that are 
substrates of any major enzyme or transporter such as CYP3A4, CYP2C9 and P-gp (for more 
information see section 5.2). 
 
In vitro, dolutegravir inhibited the renal transporters OCT2 and MATE1. In vivo, a 10-14% decrease 
of creatinine clearance (secretory fraction is dependent on OCT2 and MATE1 transport) was observed 
in patients. In vivo, dolutegravir may increase plasma concentrations of medicinal products in which 
excretion is dependent upon OCT2 and/or MATE1 (e.g. fampridine [also known as dalfampridine], 
metformin) (see Table 1).  
 
In vitro, dolutegravir inhibited the renal uptake organic anion transporters (OAT)1 and OAT3. Based 
on the lack of effect on the in vivo pharmacokinetics of the OAT substrate tenofovir, in vivo inhibition 
of OAT1 is unlikely. Inhibition of OAT3 has not been studied in vivo. Dolutegravir may increase 
plasma concentrations of medicinal products in which excretion is dependent upon OAT3.   
 
In vitro, abacavir was an inhibitor of MATE1; the clinical consequences are not known.  
 
In vitro, lamivudine was an inhibitor of OCT1 and OCT2; the clinical consequences are not known.  
 
Established and theoretical interactions with selected antiretrovirals and non-antiretroviral medicinal 
products are listed in Table 1. 
 
Interaction table  
 
Interactions between dolutegravir, abacavir, lamivudine and co-administered medical products are 
listed in Table 1 (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, area under the 
concentration versus time curve as “AUC”, maximum observed concentration as “Cmax”, 
concentration at end of dosing interval as “Cτ”). The table should not be considered exhaustive but is 
representative of the classes studied.  
 
Table 1:  Drug Interactions 
 
Medicinal products by 
therapeutic areas 

Interaction geometric 
mean change (%)  

Recommendations concerning co-
administration 

Antiretroviral medicinal products 
Non-nucleoside reverse transcriptase inhibitors 
Etravirine without boosted 
protease inhibitors / 
Dolutegravir 

Dolutegravir ↓ 
   AUC ↓ 71% 
   Cmax ↓ 52% 
   Cτ ↓ 88% 
 
Etravirine ↔ 
(induction of UGT1A1 
and CYP3A enzymes) 

Etravirine without boosted protease 
inhibitors decreased plasma dolutegravir 
concentration. Since the recommended 
dose of dolutegravir is 50 mg twice daily 
for patients taking etravirine without 
boosted protease inhibitors, Triumeq is 
not recommended for patients taking 
etravirine without co-administration of 
atazanavir/ritonavir, darunavir/ritonavir 
or lopinavir/ritonavir (see further below 
in table). 

Lopinavir+ritonavir+etravirine/ 
Dolutegravir 

Dolutegravir ↔ 
   AUC ↑ 11% 
   Cmax ↑ 7% 
   Cτ ↑ 28% 
 

No dose adjustment is necessary. 



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Lopinavir ↔ 
Ritonavir ↔ 
Etravirine ↔ 

Darunavir+ritonavir+etravirine/ 
Dolutegravir 

Dolutegravir ↓ 
   AUC ↓ 25% 
   Cmax ↓ 12% 
   Cτ ↓ 36% 
 
Darunavir ↔ 
Ritonavir ↔ 
Etravirine ↔ 

No dose adjustment is necessary. 

Efavirenz/Dolutegravir Dolutegravir ↓ 
   AUC ↓ 57% 
   Cmax ↓ 39% 
   Cτ ↓ 75% 
 
Efavirenz ↔ (historical 
controls) 
(induction of UGT1A1 
and CYP3A enzymes) 

Since the dose of dolutegravir is 50 mg 
twice daily when co-administered with 
efavirenz, the co-administration of 
efavirenz with Triumeq is not 
recommended (see section 4.4).  

Nevirapine/Dolutegravir Dolutegravir ↓ 
(Not studied, a similar 
reduction in exposure as 
observed with efavirenz is 
expected, due to 
induction) 

Co-administration with nevirapine may 
decrease dolutegravir plasma 
concentration due to enzyme induction 
and has not been studied. Effect of 
nevirapine on dolutegravir exposure is 
likely similar to or less than that of 
efavirenz. Since the dose of dolutegravir 
is 50 mg twice daily when co-
administered with nevirapine, the co-
administration of nevirapine with 
Triumeq is not recommended. 

Rilpivirine Dolutegravir ↔ 
   AUC ↑ 12% 
   Cmax ↑ 13% 
   Cτ ↑ 22% 
Rilpivirine ↔ 

No dose adjustment is necessary. 

Nucleoside reverse transcriptase inhibitors (NRTIs) 
Tenofovir  
 
 
 
 
 
Emtricitabine, didanosine, 
stavudine, zidovudine. 

Dolutegravir ↔ 
   AUC ↑ 1% 
   Cmax ↓ 3% 
   Cτ  ↓ 8% 
Tenofovir ↔ 
 
Interaction not studied 

No dose adjustment is necessary when 
Triumeq is combined with nucleoside 
reverse transcript inhibitors. 
 
 
 
Triumeq is not recommended for use in 
combination with emtricitabine 
containing products, since both 
lamivudine (in Triumeq) and 
emtricitabine are cytidine analogues (i.e. 
risk for intracellular interactions, (see 
section 4.4)) 

Protease inhibitors 
Atazanavir/Dolutegravir Dolutegravir ↑ 

   AUC ↑ 91% 
No dose adjustment is necessary. 



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   Cmax ↑ 50% 
   Cτ ↑ 180% 
 
Atazanavir ↔ (historical 
controls) 
(inhibition of UGT1A1 
and CYP3A enzymes) 

Atazanavir+ ritonavir/ 
Dolutegravir 

Dolutegravir ↑ 
   AUC ↑ 62% 
   Cmax ↑ 34% 
   Cτ ↑ 121% 
 
Atazanavir ↔ 
Ritonavir ↔ 

No dose adjustment is necessary. 

Tipranavir+ritonavir/ 
Dolutegravir 

Dolutegravir ↓ 
   AUC ↓ 59% 
   Cmax ↓ 47% 
   Cτ ↓ 76% 
 
Tipranavir ↔ 
Ritonavir ↔ 
(induction of UGT1A1 
and CYP3A enzymes) 

Since the recommended dose of 
dolutegravir is 50 mg twice daily when 
co-administered with 
tipranavir/ritonavir, the co-
administration of tipranavir/ritonavir 
with Triumeq is not recommended.  

Fosamprenavir+ritonavir/ 
Dolutegravir 

Dolutegravir↓ 
   AUC ↓ 35% 
   Cmax ↓ 24% 
   Cτ ↓ 49% 
 
Fosamprenavir↔ 
Ritonavir ↔ 
(induction of UGT1A1 
and CYP3A enzymes) 

Fosamprenavir/ritonavir decreases 
dolutegravir concentrations, but based 
on limited data, did not result in 
decreased efficacy in Phase III studies. 
No dose adjustment is necessary.  

Lopinavir+ritonavir/  
Dolutegravir 
 
 
 
 
 
 
Lopinavir+ritonavir/ 
Abacavir 

Dolutegravir ↔ 
   AUC  ↓ 4% 
   Cmax ↔ 0% 
   C24 ↓ 6% 
 
Lopinavir ↔ 
Ritonavir ↔ 
 
Abacavir                          
AUC ↓ 32% 

No dose adjustment is necessary. 

Darunavir+ritonavir/ 
Dolutegravir 

Dolutegravir ↓ 
   AUC ↓ 22%  
   Cmax ↓ 11% 
   Cτ ↓ 38% 
 
Darunavir ↔ 
Ritonavir ↔ 
(induction of UGT1A1 
and CYP3A enzymes) 

No dose adjustment is necessary. 

Other antiviral agents 



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Daclatasvir/Dolutegravir Dolutegravir ↔ 
   AUC ↑ 33%  
   Cmax ↑ 29% 
   Cτ ↑ 45% 
Daclatasvir ↔ 

Daclatasvir did not change dolutegravir 
plasma concentration to a clinically 
relevant extent.  Dolutegravir did not 
change daclatasvir plasma concentration. 
No dose adjustment is necessary. 

Anti-infective products 
Trimethoprim/sulfamethoxazole 
(Co-trimoxazole)/Abacavir 
 
Trimethoprim/sulfamethoxazole 
(Co-trimoxazole)/Lamivudine 
(160mg/800mg once daily for 5 
days/300mg single dose) 

Interaction not studied 
 
 
Lamivudine:  
   AUC ↑43% 
   Cmax ↑7% 
 
Trimethoprim:  
   AUC ↔ 
 
Sulfamethoxazole:  
   AUC ↔ 
 
(organic cation transporter 
inhibition) 

No Triumeq dosage adjustment 
necessary, unless patient has renal 
impairment (See Section 4.2). 
 
 

Antimycobacterials 
Rifampicin/Dolutegravir Dolutegravir ↓ 

   AUC ↓ 54% 
   Cmax ↓ 43% 
   Cτ ↓ 72% 
(induction of UGT1A1 
and CYP3A enzymes) 

Since the dose of dolutegravir is 50 mg 
twice daily when co-administered with 
rifampicin, the co-administration of 
rifampicin with Triumeq is not 
recommended.  

Rifabutin Dolutegravir ↔ 
   AUC ↓ 5% 
   Cmax ↑ 16% 
   Cτ ↓ 30% 
(induction of UGT1A1 
and CYP3A enzymes) 

No dose adjustment is necessary. 

Anticonvulsants 
Carbamazepine/Dolutegravir Dolutegravir ↓ 

   AUC ↓ 49% 
   Cmax ↓ 33% 
   Cτ ↓ 73% 
 

Since the recommended dose of 
dolutegravir is 50 mg twice daily when 
co-administered with carbamazepine, 
Triumeq is not recommended for 
patients taking carbamazepine. 

Phenobarbital/Dolutegravir 
Phenytoin/Dolutegravir 
Oxcarbazepine/Dolutegravir 
 

Dolutegravir↓ 
(Not studied, decrease 
expected due to induction 
of UGT1A1 and CYP3A 
enzymes, a similar 
reduction in exposure as 
observed with 
carbamazepine is 
expected) 

Since the recommended dose of 
dolutegravir is 50 mg twice daily when 
co-administered with these metabolic 
inducers, Triumeq is not recommended 
for patients taking these metabolic 
inducers. 

Antihistamines (histamine H2 receptor antagonists) 
Ranitidine Interaction not studied. 

 
Clinically significant 

No dosage adjustment necessary. 



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interaction unlikely. 
Cimetidine Interaction not studied. 

 
Clinically significant 
interaction unlikely. 

No dosage adjustment necessary. 

Cytotoxics 
Cladribine/Lamivudine Interaction not studied.  

 
In vitro lamivudine 
inhibits the intracellular 
phosphorylation of 
cladribine leading to a 
potential risk of cladribine 
loss of efficacy in case of 
combination in the 
clinical setting. Some 
clinical findings also 
support a possible 
interaction between 
lamivudine and cladribine 

Concomitant use of Triumeq with 
cladribine is not recommended (see 
section 4.4). 

Opioids 
Methadone/Abacavir 
(40 to 90mg once daily for 14 
days/600mg single dose, then 
600mg twice daily for 14 days) 

Abacavir:   
   AUC ↔ 
   Cmax ↓35% 
 
Methadone:  
   CL/F ↑22% 

Methadone dosage adjustment likely not 
needed in majority of patients; 
occasionally methadone re-titration may 
be required. 

Retinoids 
Retinoid compounds  
(e.g. Isotretinoin) 

Interaction not studied 
 
Possible interaction given 
common pathway of 
elimination via alcohol 
dehydrogenase (abacavir-
component). 

Insufficient data to recommend dosage 
adjustment. 

Miscellaneous 
Alcohol 
Ethanol/Dolutegravir 
Ethanol/Lamivudine 
 
 
Ethanol/Abacavir 
(0.7 g/kg single dose/600mg 
single dose) 

Interaction not studied 
(Inhibition of alcohol 
dehydrogenase) 
 
Abacavir:  
   AUC ↑ 41% 
Ethanol:  
   AUC ↔ 
 

No dosage adjustment necessary. 

Sorbitol   
Sorbitol solution (3.2 g, 10.2 g, 
13.4 g)/Lamivudine 

Single dose lamivudine 
oral solution 300 mg  

Lamivudine: 

AUC ↓ 14%; 32%; 36%  

Cmax ↓ 28%; 52%, 55%. 

When possible, avoid chronic 
coadministration of Triumeq with 
medicinal products containing sorbitol 
or other osmotic acting poly-alcohols or 
monosaccharide alcohols (eg: xylitol, 
mannitol, lactitol, maltitol). Consider 



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more frequent monitoring of HIV-1 viral 
load when chronic coadministration 
cannot be avoided. 

Potassium channel blockers 
Fampridine (also known as 
dalfampridine)/Dolutegravir 

Fampridine ↑ Co-administration of dolutegravir has 
the potential to cause seizures due to 
increased fampridine plasma 
concentration via inhibition of OCT2 
transporter; co-administration has not 
been studied. Fampridine co-
administration with Triumeq is 
contraindicated (see section 4.3). 

Antacids and supplements 
Magnesium/ 
aluminium-containing 
antacids/Dolutegravir 

Dolutegravir ↓ 
AUC ↓ 74%  
Cmax ↓ 72% 
 
(Complex binding to 
polyvalent ions) 

Magnesium/ aluminium-containing 
antacids should be taken well separated 
in time from the administration of 
Triumeq (minimum 2 hours after or 6 
hours before). 

Calcium 
supplements/Dolutegravir 

Dolutegravir ↓ 
   AUC ↓ 39%  
   Cmax ↓ 37% 
   C24 ↓ 39% 
(Complex binding to 
polyvalent ions) 

Supplements or multivitamins 
containing calcium, iron or magnesium 
should be taken well separated in time 
from the administration of Triumeq 
(minimum 2 hours after or 6 hours 
before). 

Iron supplements/Dolutegravir Dolutegravir ↓ 
   AUC ↓ 54%  
   Cmax ↓ 57% 
   C24 ↓ 56% 
(Complex binding to 
polyvalent ions) 

Multivitamins (containing 
calcium, iron and magnesium) 
/Dolutegravir 

Dolutegravir ↓ 
   AUC ↓ 33%  
   Cmax ↓ 35% 
   C24 ↓ 32% 

Corticosteroids 
Prednisone Dolutegravir ↔ 

   AUC ↑ 11% 
   Cmax ↑ 6% 
   Cτ ↑ 17% 

No dose adjustment is necessary. 

Antidiabetics 
Metformin/Dolutegravir Metformin ↑ 

Dolutegravir ↔ 
When co-administered 
with dolutegravir 50mg 
QD: 
Metformin 
   AUC ↑ 79%  
   Cmax ↑ 66% 
When co-administered 
with dolutegravir 50mg 
BID:  

A dose adjustment of metformin should 
be considered when starting and 
stopping coadministration of 
dolutegravir with metformin, to maintain 
glycaemic control. In patients with 
moderate renal impairment a dose 
adjustment of metformin should be 
considered when coadministered with 
dolutegravir, because of the increased 
risk for lactic acidosis in patients with 
moderate renal impairment due to 



14 

   Metformin 
   AUC ↑ 145 %  
   Cmax ↑ 111% 

increased metformin concentration 
(section 4.4). 

Herbal products   
St. John’s wort/Dolutegravir 
 

Dolutegravir↓ 
(Not studied, decrease 
expected due to induction 
of UGT1A1 and CYP3A 
enzymes, a similar 
reduction in exposure as 
observed with 
carbamazepine is 
expected) 

Since the recommended dose of 
dolutegravir is 50 mg twice daily when 
co-administered with St. John’s wort, 
Triumeq is not recommended. 

Oral contraceptives 
Ethinyl estradiol (EE) and 
Norgestromin 
(NGMN)/Dolutegravir 

Effect of dolutegravir: 
EE ↔ 
   AUC ↑ 3%  
   Cmax ↓ 1% 
 
Effect of dolutegravir: 
NGMN ↔ 
   AUC ↓ 2%  
   Cmax ↓ 11% 

Dolutegravir had no Pharmacodynamic 
effect on Luteinizing Hormone (LH), 
Follicle Stimulating Hormone (FSH) and 
progesterone. No dose adjustment of 
oral contraceptives is necessary when 
co-administered with Triumeq. 

 
Paediatric population 
 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential (WOCBP) should be counselled about the potential risk of neural 
tube defects with dolutegravir (a component of Triumeq, see below), including consideration of 
effective contraceptive measures. 
 
If a woman plans pregnancy, the benefits and the risks of continuing treatment with Triumeq should 
be discussed with the patient. 
 
Pregnancy  
 
Human experience from a birth outcome surveillance study in Botswana shows a small increase of 
neural tube defects; 7 cases in 3,591 deliveries (0.19%; 95% CI 0.09%, 0.40%) to mothers taking 
dolutegravir-containing regimens at the time of conception compared to 21 cases in 19,361 deliveries 
(0.11%: 95% CI 0.07%, 0.17%) to women exposed to non-dolutegravir regimens at the time of 
conception. 
 
The incidence of neural tube defects in the general population ranges from 0.5-1 case per 1,000 live 
births (0.05-0.1%). Most neural tube defects occur within the first 4 weeks of embryonic development 
after conception (approximately 6 weeks after the last menstrual period). If a pregnancy is confirmed 
in the first trimester while on Triumeq, the benefits and risks of continuing Triumeq versus switching 
to another antiretroviral regimen should be discussed with the patient taking the gestational age and 
the critical time period of neural tube defect development into account. 



15 

 
Data analysed from the Antiretroviral Pregnancy Registry do not indicate an increased risk of major 
birth defects in over 600 women exposed to dolutegravir during pregnancy but are currently 
insufficient to address the risk of neural tube defects. 
 
In animal reproductive toxicology studies with dolutegravir, no adverse development outcomes, 
including neural tube defects, were identified (see section 5.3). Dolutegravir was shown to cross the 
placenta in animals. 
 
More than 1000 outcomes from exposure to dolutegravir during second and third trimester pregnancy 
indicate no evidence of increased risk of foeto/neonatal toxicity. Triumeq may be used during the 
second and third trimester of pregnancy when the expected benefit justifies the potential risk to the 
foetus. 
 
Concerning lamivudine, a large amount of data (more than 5200 outcomes from first trimester) 
indicates no malformative toxicity. A moderate amount of data (more than 1200 outcomes from first 
trimester) indicates no malformative toxicity for abacavir.  
 
Abacavir and lamivudine may inhibit cellular DNA replication and abacavir has been shown to be 
carcinogenic in animal models (see section 5.3). The clinical relevance of these findings is unknown. 
 
Mitochondrial dysfunction  
Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable 
degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in HIV-
negative infants exposed in utero and/or post-natally to nucleoside analogues (see section 4.4). 
 
Breast-feeding 
 
Dolutegravir is excreted in human milk in small amounts. There is insufficient information on the 
effects of dolutegravir in neonates/infants.  
 
Abacavir and its metabolites are excreted into the milk of lactating rats. Abacavir is also excreted into 
human milk. 
 
Based on more than 200 mother/child pairs treated for HIV, serum concentrations of lamivudine in 
breastfed infants of mothers treated for HIV are very low (< 4% of maternal serum concentrations) 
and progressively decrease to undetectable levels when breastfed infants reach 24 weeks of age. There 
are no data available on the safety of abacavir and lamivudine when administered to babies less than 
three months old. 
 
It is recommended that HIV infected women do not breast-feed their infants under any circumstances 
in order to avoid transmission of HIV. 
 
Fertility 
 
There are no data on the effects of dolutegravir, abacavir or lamivudine on human male or female 
fertility. Animal studies indicate no effects of dolutegravir, abacavir or lamivudine on male or female 
fertility (see section 5.3).   
 
4.7 Effects on ability to drive and use machines 
 
Patients should be informed that dizziness has been reported during treatment with dolutegravir. The 
clinical status of the patient and the adverse reaction profile of Triumeq should be borne in mind when 



16 

considering the patient’s ability to drive or operate machinery. 
 
4.8 Undesirable effects  
 
Summary of the safety profile  
 
The most frequently reported adverse reactions considered possibly or probably related to 
dolutegravir and abacavir/lamivudine were nausea (12%), insomnia (7%), dizziness (6%) and 
headache (6%). 
 
Many of the adverse reactions listed in the table below occur commonly (nausea, vomiting, diarrhoea, 
fever, lethargy, rash) in patients with abacavir hypersensitivity. Therefore, patients with any of these 
symptoms should be carefully evaluated for the presence of this hypersensitivity (see section 4.4). 
Very rarely cases of erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis 
have been reported where abacavir hypersensitivity could not be ruled out. In such cases medicinal 
products containing abacavir should be permanently discontinued. 
 
The most severe adverse event possibly related to the treatment with dolutegravir and 
abacavir/lamivudine, seen in individual patients, was a hypersensitivity reaction that included rash 
and severe liver effects (see section 4.4 and Description of selected adverse reactions in this section).  
 
Tabulated list of adverse reactions 
 
The adverse reactions considered at least possibly related to treatment with the components of 
Triumeq from clinical study and post-marketing experience are listed in Table 2 by body system, 
organ class and absolute frequency. Frequencies are defined as very common (≥ 1/10), common 
(≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare 
(< 1/10,000). 
 
Table 2: Tabulated summary of adverse reactions associated with the combination of dolutegravir 
+ abacavir/lamivudine in an analysis of pooled data from: Phase IIb to Phase IIIb clinical trials or 
post-marketing experience; and adverse reactions to treatment with dolutegravir, abacavir and 
lamivudine from clinical studies and post-marketing experience when used with other antiretrovirals 
 
Frequency Adverse reaction 

Blood and lymphatic systems disorders: 

Uncommon: Neutropenia1, anaemia1, thrombocytopenia1 

Very rare: pure red cell aplasia1 

Immune system disorders: 

Common hypersensitivity (see section 4.4) 

Uncommon: immune reconstitution syndrome (see section 4.4) 

Metabolism and nutrition disorders: 

Common: anorexia1 

Uncommon: hypertriglyceridaemia, hyperglycaemia 

Very rare: lactic acidosis1 

Psychiatric disorders:  

Very common: insomnia 



17 

Common: abnormal dreams, depression, anxiety1, nightmare, sleep 
disorder 

Uncommon suicidal ideation or suicide attempt (particularly in patients 
with a pre-existing history of depression or psychiatric 
illness) 

Nervous system disorders:  

Very common: headache 

Common: dizziness, somnolence, lethargy1 

Very rare: peripheral neuropathy1, paraesthesia1 

Respiratory, thoracic and mediastinal disorders: 

Common: cough1, nasal symptoms1 

Gastrointestinal disorders:  

Very common: nausea, diarrhoea 

Common: vomiting, flatulence, abdominal pain, abdominal pain upper, 
abdominal distension, abdominal discomfort, gastro-
oesophageal reflux disease, dyspepsia 

Rare: pancreatitis1 

Hepatobiliary disorders: 

Uncommon: hepatitis 

Rare acute hepatic failure1 

Skin and subcutaneous tissue disorders:  

Common: rash, pruritus, alopecia1 

Very rare: erythema multiform1, Stevens-Johnson syndrome1, toxic 
epidermal necrolysis1 

Musculoskeletal and connective tissue disorders: 

Common: Arthralgia1, muscle disorders1(including myalgia1) 

Rare: rhabdomyolysis1 

General disorders and administration site conditions:  

Very common: fatigue 

Common: asthenia, fever1, malaise1 

Investigations: 

Common: CPK elevations, ALT/AST elevations 

Rare: amylase elevations1 
1This adverse reaction was identified from clinical studies or post-marketing experience 
for dolutegravir, abacavir or lamivudine when used with other antiretrovirals or post-
marketing experience with Triumeq.  
 
Description of selected adverse reactions 
 



18 

Hypersensitivity reactions 
Both abacavir and dolutegravir are associated with a risk for hypersensitivity reactions (HSR), which 
were observed more commonly with abacavir. Hypersensitivity reaction observed for each of these 
medicinal products (described below) share some common features such as fever and/or rash with 
other symptoms indicating multi-organ involvement. Time to onset was typically 10-14 days for both 
abacavir and dolutegravir-associated reactions, although reactions to abacavir may occur at any time 
during therapy. Treatment with Triumeq must be stopped without delay if HSR cannot be ruled out on 
clinical grounds, and therapy with Triumeq or other abacavir or dolutegravir containing products must 
never be re-initiated. Please refer to section 4.4 for further details on patient management in the event 
of a suspected HSR to Triumeq. 
 
Dolutegravir hypersensitivity 
Symptoms have included rash, constitutional findings, and sometimes, organ dysfunction, including 
severe liver reactions. 
 
Abacavir hypersensitivity 
The signs and symptoms of this HSR are listed below. These have been identified either from clinical 
studies or post marketing surveillance. Those reported in at least 10% of patients with a 
hypersensitivity reaction are in bold text. 
 
Almost all patients developing hypersensitivity reactions will have fever and/or rash (usually 
maculopapular or urticarial) as part of the syndrome, however reactions have occurred without rash or 
fever. Other key symptoms include gastrointestinal, respiratory or constitutional symptoms such as 
lethargy and malaise.  
 
Skin Rash (usually maculopapular or urticarial) 

 
Gastrointestinal tract Nausea, vomiting, diarrhoea, abdominal pain, mouth ulceration 

 
Respiratory tract Dyspnoea, cough, sore throat, adult respiratory distress syndrome, 

respiratory failure 
 

Miscellaneous Fever, lethargy, malaise, oedema, lymphadenopathy, hypotension, 
conjunctivitis, anaphylaxis 
 

Neurological/Psychiatry Headache, paraesthesia 
 

Haematological Lymphopenia 
 

Liver/pancreas Elevated liver function tests, hepatitis, hepatic failure 
 

Musculoskeletal Myalgia, rarely myolysis, arthralgia, elevated creatine phosphokinase 
 

Urology Elevated creatinine, renal failure 
 

Symptoms related to this HSR worsen with continued therapy and can be life-threatening and in rare 
instance, have been fatal. 
 
Restarting abacavir following an abacavir HSR results in a prompt return of symptoms within hours. 
This recurrence of the HSR is usually more severe than on initial presentation, and may include life-
threatening hypotension and death. Similar reactions have also occurred infrequently after restarting 
abacavir in patients who had only one of the key symptoms of hypersensitivity (see above) prior to 
stopping abacavir; and on very rare occasions have also been seen in patients who have restarted 



19 

therapy with no preceding symptoms of a HSR (i.e., patients previously considered to be abacavir 
tolerant). 
 
Metabolic parameters 
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see section 
4.4) 
 
Osteonecrosis 
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk 
factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown 
(see section 4.4). 
 
Immune reactivation syndrome  
In HIV-infected patients with severe immune deficiency at the time of initiation of CART, an 
inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune 
disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported; however, the 
reported time to onset is more variable and these events can occur many months after initiation of 
treatment (see section 4.4). 
 
Changes in laboratory chemistries 
 
Increases in serum creatinine occurred within the first week of treatment with dolutegravir and 
remained stable through 96 weeks. In the SINGLE study a mean change from baseline of 12.6 µmol/L 
was observed after 96 weeks of treatment. These changes are not considered to be clinically relevant 
since they do not reflect a change in glomerular filtration rate. 
 
Asymptomatic creatine phosphokinase (CPK) elevations mainly in association with exercise have also 
been reported with dolutegravir therapy. 
 
Co-infection with Hepatitis B or C 
 
In dolutegravir Phase III studies patients with hepatitis B and/or C co-infection were permitted to 
enrol provided that baseline liver chemistry tests did not exceed 5 times the upper limit of normal 
(ULN). Overall, the safety profile in patients co-infected with hepatitis B and/or C was similar to that 
observed in patients without hepatitis B or C co-infection, although the rates of AST and ALT 
abnormalities were higher in the subgroup with hepatitis B and/or C co-infection for all treatment 
groups. 
 
Paediatric population 
 
There are no clinical study data on the effects of Triumeq in the paediatric population. Individual 
components have been investigated in adolescents (12 to 17 years). 
 
Based on limited available data with the dolutegravir single entity used in combination with other 
antiretroviral agents to treat adolescents (12 to 17 years), there were no additional types of adverse 
reactions beyond those observed in the adult population. 
The individual preparations of abacavir and lamivudine have been investigated separately, and as a 
dual nucleoside backbone, in combination antiretroviral therapy to treat ART- naive and ART- 
experienced HIV- infected paediatric patients (data available on the use of abacavir and lamivudine in 
infants less than three months are limited).  No additional types of adverse reactions have been 
observed beyond those characterised for the adult population. 
 
Reporting of suspected adverse reactions 



20 

 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No specific symptoms or signs have been identified following acute overdose with dolutegravir, 
abacavir or lamivudine, apart from those listed as adverse reactions. 
 
Further management should be as clinically indicated or as recommended by the national poisons 
centre, where available.  There is no specific treatment for an overdose of Triumeq. If overdose 
occurs, the patient should be treated supportively with appropriate monitoring, as necessary. Since 
lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdose, 
although this has not been studied. It is not known whether abacavir can be removed by peritoneal 
dialysis or haemodialysis. As dolutegravir is highly bound to plasma proteins, it is unlikely that it will 
be significantly removed by dialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, antivirals for treatment of HIV infections, 
combinations. ATC code: J05AR13 
 
Mechanism of action 
 
Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand 
transfer step of retroviral Deoxyribonucleic acid (DNA) integration which is essential for the HIV 
replication cycle. 
 
Abacavir and lamivudine are potent selective inhibitors of HIV-1 and HIV-2. Both abacavir and 
lamivudine are metabolised sequentially by intracellular kinases to the respective 5'-triphosphates 
(TP) which are the active moieties with extended intracellular half-lives supporting once daily dosing 
(see section 5.2). Lamivudine-TP (an analogue for cytidine) and carbovir-TP (the active triphosphate 
form of abacavir, an analogue for guanosine) are substrates for and competitive inhibitors of HIV 
reverse transcriptase (RT). However, their main antiviral activity is through incorporation of the 
monophosphate form into the viral DNA chain, resulting in chain termination. Abacavir and 
lamivudine triphosphates show significantly less affinity for host cell DNA polymerases. 
 
Pharmacodynamic effects 
 
Antiviral activity in vitro 
Dolutegravir, abacavir and lamivudine have been shown to inhibit replication of lab-strains and 
clinical isolates of HIV in a number of cell types, including transformed T cell lines, 
monocyte/macrophage derived lines and primary cultures of activated peripheral blood mononuclear 
cells (PMBCs) and monocyte/macrophages.  The concentration of active substance necessary to effect 
viral replication by 50% (IC50 - half maximal inhibitory concentration) varied according to virus and 
host cell type. 
 

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21 

The IC50 for dolutegravir in various lab-strains using PBMC was 0.5 nM, and when using MT-4 cells 
it ranged from 0.7-2 nM. Similar IC50s were seen for clinical isolates without any major difference 
between subtypes; in a panel of 24 HIV-1 isolates of clades A, B, C, D, E, F and G and group O the 
mean IC50 value was 0.2 nM (range 0.02-2.14). The mean IC50 for 3 HIV-2 isolates was 0.18 nM 
(range 0.09-0.61). 
 
The mean IC50 for abacavir against lab-strains of HIV-1IIIB and HIV-1HXB2 ranged from 1.4 to 
5.8 µM. The median or mean IC50 values for lamivudine against lab-strains of HIV-1 ranged from 
0.007 to 2.3 µM. The mean IC50 against lab-strains of HIV-2 (LAV2 and EHO) ranged from 1.57 to 
7.5 µM for abacavir and from 0.16 to 0.51 µM for lamivudine.  
 
The IC50 values of abacavir against HIV-1 Group M subtypes (A-G) ranged from 0.002 to 1.179 µM, 
against Group O from 0.022 to 1.21 µM, and against HIV-2 isolates, from 0.024 to 0.49 µM. For 
lamivudine, the IC50 values against HIV-1 subtypes (A-G) ranged from 0.001 to 0.170 µM, against 
Group O from 0.030 to 0.160 µM and against HIV-2 isolates from 0.002 to 0.120 µM in peripheral 
blood mononuclear cells. 
 
HIV-1 isolates (CRF01_AE, n=12; CRF02_AG, n=12; and Subtype C or CRF_AC, n=13) from 37 
untreated patients in Africa and Asia were susceptible to abacavir (IC50 fold changes < 2.5), and 
lamivudine (IC50 fold changes < 3.0), except for two CRF02_AG isolates with fold changes of 2.9 and 
3.4 for abacavir.  Group O isolates from antiviral naïve patients tested for lamivudine activity were 
highly sensitive. 
 
The combination of abacavir and lamivudine has demonstrated antiviral activity in cell culture against 
non-subtype B isolates and HIV-2 isolates with equivalent antiviral activity as for subtype B isolates.  
 
Antiviral activity in combination with other antiviral agents 
No antagonistic effects in vitro were seen with dolutegravir and other antiretrovirals (tested agents: 
stavudine, abacavir, efavirenz, nevirapine, lopinavir, amprenavir, enfuvirtide, maraviroc, adefovir and 
raltegravir).  In addition, ribavirin had no apparent effect on dolutegravir activity.   
 
The antiviral activity of abacavir in cell culture was not antagonized when combined with the 
nucleoside reverse transcriptase inhibitors (NRTIs) didanosine, emtricitabine, lamivudine, stavudine, 
tenofovir, zalcitabine or zidovudine, the non-nucleoside reverse transcriptase inhibitor (NNRTI) 
nevirapine, or the protease inhibitor (PI) amprenavir.  
 
No antagonistic effects in vitro were seen with lamivudine and other antiretrovirals (tested agents: 
abacavir, didanosine, nevirapine, zalcitabine, and zidovudine). 
 
Effect of human serum 
In 100% human serum, the mean fold shift for dolutegravir activity was 75-fold, resulting in protein 
adjusted IC90 of 0.064 ug/mL. Plasma protein binding studies in vitro indicate that abacavir binds only 
low to moderately (~49%) to human plasma proteins at therapeutic concentrations.  Lamivudine 
exhibits linear pharmacokinetics over the therapeutic dose range and displays low plasma protein 
binding (less than 36%). 
 
Resistance 
 
Resistance in vitro: (dolutegravir) 
Serial passage is used to study resistance evolution in vitro. When using the lab-strain HIVIII during 
passage over 112 days, mutations selected appeared slowly, with substitutions at positions S153Y and 
F. These mutations were not selected in patients treated with dolutegravir in the clinical studies.  
Using strain NL432 mutations E92Q (fold change 3) and G193E (fold change 3) were selected. These 



22 

mutations have been selected in patients with pre-existing raltegravir resistance and who were then 
treated with dolutegravir (listed as secondary mutations for dolutegravir).  
 
In further selection experiments using clinical isolates of subtype B, mutation R263K was seen in all 
five isolates (after 20 weeks and onwards). In subtype C (n=2) and A/G (n=2) isolates the integrase 
substitution R263K was selected in one isolate, and G118R in two isolates.  R263K was reported from 
two individual patients with subtype B and subtype C in the clinical program for ART experienced, 
INI naive subjects, but without effects on dolutegravir susceptibility in vitro. G118R lowers the 
susceptibility to dolutegravir in site directed mutants (fold change 10), but was not detected in patients 
receiving dolutegravir in the Phase III program.   
 
Primary mutations for raltegravir/elvitegravir (Q148H/R/K, N155H, Y143R/H/C, E92Q, T66I) do not 
affect the in vitro susceptibility of dolutegravir as single mutations. When mutations listed as 
secondary integrase inhibitor associated mutations (for raltegravir/elvitegravir) are added to primary 
mutations (excluding at Q148) in experiments with site directed mutants, dolutegravir susceptibility 
remains at or near wildtype level.  In the case of the Q148-mutation viruses, increasing dolutegravir 
fold change is seen as the number of secondary mutations increase. The effect of the Q148-based 
mutations (H/R/K) was also consistent with in vitro passage experiments with site directed mutants.  
In serial passage with strain NL432-based site directed mutants at N155H or E92Q, no further 
selection of resistance was seen (fold change unchanged around 1). In contrast, starting passage with 
mutants with mutation Q148H (fold change 1), a variety of raltegravir associated secondary mutations 
accumulated with a consequent increase of fold change to values >10.  
A clinically relevant phenotypic cut-off value (fold change vs wild type virus) has not been 
determined; genotypic resistance was a better predictor for outcome. 
 
Seven hundred and five raltegravir resistant isolates from raltegravir experienced patients were 
analyzed for susceptibility to dolutegravir.  Dolutegravir has a <10-fold change against 94% of the 
705 clinical isolates. 
 
Resistance in vivo: (dolutegravir) 
In previously untreated patients receiving dolutegravir + 2 NRTIs in Phase IIb and Phase III, no 
development of resistance to the integrase class, or to the NRTI class was seen (n=876, follow-up of 
48-96 weeks).  
 
In patients with prior failed therapies, but naïve to the integrase class (SAILING study), integrase 
inhibitor substitutions were observed in 4/354 patients (follow-up 48 weeks) treated with dolutegravir, 
which was given in combination with an investigator selected background regimen (BR). Of these 
four, two subjects had a unique R263K integrase substitution, with a maximum fold change of 1.93, 
one subject had a polymorphic V151V/I integrase substitution, with maximum fold change of 0.92, 
and one subject had pre-existing integrase mutations and is assumed to have been integrase 
experienced or infected with integrase resistant virus by transmission. The R263K mutation was also 
selected in vitro (see above). 
 
Resistance in vitro and in vivo: (abacavir and lamivudine) 
Abacavir-resistant isolates of HIV-1 have been selected in vitro and in vivo and are associated with 
specific genotypic changes in the RT codon region (codons M184V, K65R, L74V and Y115F). 
During in vitro abacavir selection the M184V mutation occurred first and resulted in about a 2-fold 
increase in IC50, below the abacavir clinical cut-off of 4.5-fold change.  Continued passage in 
increasing concentrations of drug resulted in selection for double RT mutants 65R/184V and 
74V/184V or triple RT mutant 74V/115Y/184V. Two mutations conferred a 7 to 8-fold change in 
abacavir susceptibility and combinations of three mutations were required to confer more than an 
8-fold change in susceptibility. 
  



23 

HIV-1 resistance to lamivudine involves the development of a M184I or M184V amino acid change 
close to the active site of the viral RT. This variant arises both in vitro and in HIV-1 infected patients 
treated with lamivudine-containing antiretroviral therapy.  M184V mutants display greatly reduced 
susceptibility to lamivudine and show diminished viral replicative capacity in vitro. M184V is 
associated with about a 2-fold increase in abacavir resistance but does not confer clinical resistance 
for abacavir. 
 
Isolates resistant to abacavir may also show reduced sensitivity to lamivudine.  The combination of 
abacavir/lamivudine has demonstrated decreased susceptibility to viruses with the substitutions K65R 
with or without the M184V/I substitution, and to viruses with L74V plus the M184V/I substitution. 
 
Cross-resistance between dolutegravir or abacavir or lamivudine and antiretrovirals from other classes 
e.g. PIs or NNRTIs is unlikely.  
 
Effects on electrocardiogram 
 
No relevant effects were seen on the QTc interval, with doses of dolutegravir exceeding the clinical 
dose by approximately 3-fold.  Similar studies were not conducted with either abacavir or lamivudine. 
 
Clinical efficacy and safety 
 
The efficacy of Triumeq in HIV-infected, therapy naive subjects is based on the analyses of data from 
a number of trials. The analyses included two randomized, international, double-blind, active-
controlled trials, SINGLE (ING114467) and SPRING-2 (ING113086), the international, open-label, 
active-controlled trial FLAMINGO (ING114915), and the randomized, open-label, active-controlled, 
multicentre, non-inferiority study ARIA (ING117172).  
 
The STRIIVING study (201147), was a randomized, open-label, active-controlled, multicentre, non-
inferiority switch study in virologically suppressed subjects with no documented history of resistance 
to any class.  
 
In SINGLE, 833 patients were treated with dolutegravir 50 mg once daily plus fixed-dose abacavir-
lamivudine (DTG + ABC/3TC) or fixed-dose efavirenz-tenofovir-emtricitabine (EFV/TDF/FTC). At 
baseline, median patient age was 35 years, 16% were female, 32% non-white, 7% had hepatitis C co-
infection and 4% were CDC Class C, these characteristics were similar between treatment groups. 
Week 48 outcomes (including outcomes by key baseline covariates) are shown in Table 3. 
 
Table 3:  Virologic Outcomes of Randomized Treatment of SINGLE at 48 Weeks (Snapshot  
 algorithm) 
 48 weeks 
 DTG 50 mg + ABC/3TC 

once daily 
N=414 

EFV/TDF/FTC 
once daily 

N=419 
HIV-1 RNA <50 copies/mL 88% 81% 
  Treatment Difference* 7.4% (95% CI: 2.5%, 12.3%) 
Virologic non response†  5% 6% 
No virologic data at Weeks 
48 window  7% 13% 

Reasons   
Discontinued study/study 
drug due to adverse event or 
death‡  

2% 10% 

Discontinued study/study 5% 3% 



24 

drug for other reasons§ 
Missing data during window 
but on study 0 <1% 

HIV-1 RNA <50 copies/mL by baseline covariates 
Baseline Plasma Viral 
Load (copies/mL) n / N (%) n / N (%) 

  ≤100,000  253 / 280 (90%) 238 / 288 (83%)  
  >100,000  111 / 134 (83%) 100 / 131 (76%) 
Baseline CD4+ (cells/ mm3)   
  <200  45 / 57 (79%) 48 / 62 (77%)  
  200 to <350  143 / 163 (88%) 126 / 159 (79%) 
  ≥350 176 / 194 (91%) 164 / 198 (83%) 
Gender   
  Male  307 / 347 (88%) 291 / 356 (82%)  
  Female  57 / 67 (85%) 47 / 63 (75%) 
Race    
  White  255 / 284 (90%) 238 /285 (84%)  
  African-American/African   
  Heritage/Other 109 / 130 (84%) 99 / 133 (74%) 

Age (years)   
  <50 319 / 361 (88%) 302 / 375 (81%)  
  ≥50 45 / 53 (85%) 36 / 44 (82%) 

* Adjusted for baseline stratification factors. 
† Includes subjects who discontinued prior to Week 48 for lack or loss of efficacy and subjects 
who are ≥50 copies in the 48 week window.  
‡ Includes subjects who discontinued due to an adverse event or death at any time point from  
Day 1 through the Week 48 analysis window if this resulted in no virologic data on treatment 
during the analysis window.  
§ Includes reasons such as withdrew consent, loss to follow-up, moved, protocol deviation.  
Notes: ABC/3TC = abacavir 600 mg, lamivudine 300 mg in the form of Kivexa/Epzicom fixed 
dose combination (FDC) 
EFV/TDF/FTC = efavirenz 600 mg, tenofovir disoproxil 245 mg, emtricitabine 200 mg in the 
form of Atripla FDC. 

 
In the primary 48 weeks analysis, the proportion of patients with virologic suppression in the 
dolutegravir + ABC/3TC arm, was superior to the EFV/TDF/FTC arm, p=0.003, the same treatment 
difference was observed in subjects defined by baseline HIV RNA level (< or > 100,000 copies/mL). 
The median time to viral suppression was shorter with ABC/3TC + DTG (28 vs 84 days, p<0.0001). 
The adjusted mean change in CD4+ T cell count from baseline were 267 cells versus 208 cells/mm3, 
respectively (p<0.001). Both the time to viral suppression and change from baseline analyses were 
pre-specified and adjusted for multiplicity. At 96 weeks, the response was 80% vs 72%, respectively. 
The difference in the endpoint remained statistically significant (p=0.006).  The statistically higher 
responses on DTG+ABC/3TC were driven by a higher rate of withdrawals due to AEs in the 
EFV/TDF/FTC arm, irrespective of viral load strata. Overall treatment differences at Week 96 are 
applicable to patients with high and low Baseline viral loads. At 144 weeks in the open-label phase of 
SINGLE, virologic suppression was maintained, the DTG +ABC/3TC arm (71%) was superior to the 
EFV/TDF/FTC arm (63%), treatment difference was 8.3% (2.0, 14.6). 
 
In SPRING-2, 822 patients were treated with either dolutegravir 50 mg once daily or raltegravir 400 
mg twice daily (blinded), both with fixed-dose ABC/3TC (around 40%) or TDF/FTC (around 60%), 
given open label. Baseline demographics and outcomes are summarised in Table 4.  Dolutegravir was 



25 

non-inferior to raltegravir, including within the subset of patients with the abacavir/lamivudine 
background regimen.  
 
Table 4:  Demographics and virologic outcomes of randomized treatment of SPRING-2 (snapshot 
algorithm) 
 DTG 50 mg 

once daily 
+ 2 NRTI  

N=411 

RAL 400mg 
 twice daily 
+ 2 NRTI 

N=411 
Demographics 
     Median Age (years) 37 35 
     Female 15% 14% 
    Non-white 16% 14% 
    Hepatitis B and/or C 13% 11% 
    CDC class C 2% 2% 
    ABC/3TC backbone 41% 40% 
Week 48 efficacy results 
HIV-1 RNA <50 copies/mL 88% 85% 
Treatment difference* 2.5% (95% CI: -2.2%, 7.1%) 
     Virologic non response†  5% 8% 
     No virologic data at Weeks 48 window  7% 7% 
         Reasons   

Discontinued study/study drug due to adverse event or 
death‡  2% 1% 

Discontinued study/study drug for other reasons§ 5% 6% 
HIV-1 RNA <50 copies/mL for those on ABC/3TC 86% 87% 
Week 96 efficacy results 
HIV-1 RNA <50 copies/mL 81% 76% 
Treatment difference* 4.5% (95% CI: -1.1%, 10.0%) 
  HIV-1 RNA <50 copies/mL for those on ABC/3TC 74% 76% 
* Adjusted for baseline stratification factors. 
† Includes subjects who discontinued prior to Week 48 for lack or loss of efficacy and subjects who 
are ≥50 copies in the 48 week window.  
‡ Includes subjects who discontinued due to an adverse event or death at any time point from Day 1 
through the Week 48 analysis window if this resulted in no virologic data on treatment during the 
analysis window.  
§ Includes reasons such as protocol deviation, lost to follow up, and withdrew consent.  
Notes: DTG = dolutegravir, RAL = raltegravir. 
 
 
In FLAMINGO, 485 patients were treated with dolutegravir 50 mg once daily or darunavir/ritonavir 
(DRV/r) 800 mg/100 mg once daily, both with ABC/3TC (around 33%) or TDF/FTC (around 67%). 
All treatments were given open-label.  Main demographics and outcomes are summarised in Table 5.  
 



26 

Table 5:  Demographics and Week 48 virologic outcomes of randomized treatment of FLAMINGO 
(snapshot algorithm)  
 
 DTG 50 mg  

once daily 
 + 2 NRTI 

 
N=242 

DRV+RTV 
800mg + 100mg 

once daily 
+2 NRTI 

N=242 
Demographics  
     Median Age (years) 34 34 
     Female  13% 17% 
     Non-white  28% 27% 
     Hepatitis B and/or C 11% 8% 
     CDC class C  4% 2% 
     ABC/3TC backbone  33% 33% 
Week 48 Efficacy Results   
HIV-1 RNA <50 copies/mL 90% 83% 
Treatment Difference* 7.1% (95% CI: 0.9%, 13.2%) 
      Virologic non response†  6% 7% 
      No virologic data at Weeks 48 window  4% 10% 

Reasons   
Discontinued study/study drug due to adverse event or 
death‡  1% 4% 

Discontinued study/study drug for other reasons§ 2% 5% 
Missing data during window but on study <1% 2% 

HIV-1 RNA <50copies/mL for those on ABC/3TC 90% 85% 
Median time to viral suppression** 28 days 85 days 
* Adjusted for baseline stratification factors, p=0.025. 
† Includes subjects who discontinued prior to Week 48 for lack or loss of efficacy and subjects who are 
≥50 copies in the 48 week window.  
‡ Includes subjects who discontinued due to an adverse event or death at any time point from Day 1 
through the Week 48 analysis window if this resulted in no virologic data on treatment during the 
analysis window.  
§ Includes reasons such as withdrew consent, loss to follow-up, protocol deviation. 
** p<0.001. 
Notes: DRV+RTV = darunavir + ritonavir, DTG = dolutegravir. 
 
At 96 weeks, virologic suppression in the dolutegravir group (80%) was superior to the DRV/r group 
(68%), (adjusted treatment difference [DTG-(DRV+RTV)]: 12.4%; 95% CI: [4.7, 20.2]). Response 
rates at 96 weeks were 82% for DTG+ABC/3TC and 75% for DRV/r+ABC/3TC. 
 
In ARIA (ING117172), a randomized, open-label, active-controlled, multicenter, parallel group, non-
inferiority study; 499 HIV-1 infected ART naïve adult women were randomized 1:1 to receive either; 
DTG/ABC/3TC FDC 50 mg/600 mg/300 mg; or atazanavir 300 mg plus ritonavir 100 mg plus 
tenofovir disproxil / emtricitabine 245 mg/200 mg (ATV+RTV+TDF/FTC FDC), all administered 
once daily.  
 



27 

Table 6: Demographics and Week 48 virologic outcomes of randomized treatment of ARIA  
(snapshot algorithm) 
 
 DTG/ABC/3TC 

FDC 
N=248 

ATV+RTV+TDF/FTC 
FDC 

N=247 
Demographics   
    Median Age (years) 37 37 

 Female 100 % 100 % 
 Non-white 54 % 57 % 
 Hepatitis B and/ or C 6 % 9% 
 CDC class C 4 % 4 % 

Week 48 Efficacy Results  
 HIV-1 RNA <50 copies/mL 82 % 71 % 
 Treatment difference 10.5 (3.1% to 17.8%) [p=0.005]. 
   Virologic Failure  6 % 14 % 
       Reasons   

    Data in window not below 50 c/mL threshold 2 % 6 % 
    Discontinued for lack of efficacy 2 % <1 % 
    Discontinued for other reason while not 
below threshold 

3 % 7 % 

No Virologic Data  12 % 15 % 

Discontinued due to AE or death 4 % 7 % 
Discontinued for other reasons 6 % 6 % 
Missing data during window but on study 2 % 2 % 

AE = Adverse event. 
HIV-1 - human immunodeficiency virus type 1 
DTG/ABC/3TC FDC - abacavir/dolutegravir/lamivudine fixed-dose combination 
ATV+RTV+TDF/FTC FDC -atazanavir plus ritonavir plus tenofovir disproxil/emtricitabine fixed-
dose combination 

 
 
STRIIVING (201147) is a 48-week, randomized, open-label, active controlled, multicenter, non-
inferiority study in patients without any prior treatment failure, and without any documented 
resistance to any class. Virologically suppressed (HIV-1 RNA <50 c/mL) subjects were randomly 
assigned (1:1) to continue their current ART regimen (2 NRTIs plus either a PI, NNRTI, or INI), or 
switch to ABC/DTG/3TC FDC once daily (Early Switch). Hepatitis B co-infection was one of main 
exclusion criteria.  
Patients were mainly white (66%) or black (28%) of male sex (87%). Main prior transmission routes 
were homosexual (73%) or heterosexual (29%) contact. The proportion with a positive HCV serology 
was 7%. The median time from first starting ART was around 4.5 years. 
 



28 

Table 7: Outcomes of randomized treatment of STRIIVING (snapshot algorithm) 
 

Study Outcomes (Plasma HIV-1 RNA <50 c/mL) at Week 24 and Week 48 – Snapshot Analysis (ITT-E 
Population) 

 

ABC/DTG/3TC 
FDC 

N=275 
n (%) 

Current ART 
 

N=278 
n (%) 

Early Switch 
ABC/DTG/3TC 

FDC 
N=275 
n (%) 

Late Switch 
ABC/DTG/3TC 

FDC 
N=244 
n (%) 

Outcome Time Point Day 1 to W 24 Day 1 to W 24 Day 1 to W48 W24 to W48 
Virologic Success 85 % 88 % 83 % 92 % 
Virologic Failure 1 % 1 % <1 % 1 % 
  Reasons  

Data in window not below 
threshold 

1 % 1 % <1 % 1 % 

No Virologic Data 14 % 10 % 17 % 7 % 
Discontinued due to AE or 
death 

4 % 0 % 4 % 2 % 

Discontinued for other 
reasons 

9 % 10 % 12 % 3 % 

Missing data during 
window but on study 

1 % <1 % 2 % 2 % 

ABC/DTG/3TC FDC = abacavir/dolutegravir/lamivudine fixed-dose combination; AE = adverse event; 
ART = antiretroviral therapy; HIV-1 = human immunodeficiency virus type 1; ITT-E = intent-to-treat 
exposed; W = week. 

Virologic suppression (HIV-1 RNA <50 copies/mL) in the ABC/DTG/3TC FDC group (85%) was 
statistically non-inferior to the current ART groups (88%) at 24 weeks. The adjusted difference in 
proportion and 95% CI [ABC/DTG/3TC vs current ART] were 3.4%; 95% CI: [-9.1, 2.4]. After 24 
weeks all remaining subjects switched to ABC/DTG/3TC FDC (Late Switch). Similar levels of 
virologic suppression were maintained in both the Early and Late Switch groups at 48 weeks. 
 
De novo resistance in patients failing therapy in SINGLE, SPRING-2 and FLAMINGO 
 
De novo resistance was not detected to the integrase class or the NRTI class in any patients who were 
treated with dolutegravir + abacavir/lamivudine in the three studies mentioned.   
For the comparators typical resistance was detected with TDF/FTC/EFV (SINGLE; six with NNRTI 
associated resistance and one with major NRTI resistance) and with 2 NRTIs + raltegravir (SPRING-
2; four with major NRTI resistance and one with raltegravir resistance), while no de novo resistance 
was detected in patients treated with 2 NRTIs + DRV/RTV (FLAMINGO). 
 
Paediatric population 
 
In a Phase I/II 48 week multicentre, open-label study (P1093/ING112578), the pharmacokinetic 
parameters, safety, tolerability and efficacy of dolutegravir was evaluated in combination regimens in 
HIV-1 infected infants, children and adolescents. 
 
At 24 weeks, 16 of 23 (69%) adolescents (12 to 17 years of age) treated with dolutegravir once daily 
(35 mg n=4; 50 mg n=19) plus OBR achieved viral load less than 50 copies/mL. 
Twenty out of 23 children and adolescents (87%) had >1 log10 c/mL decrease from Baseline in HIV-1 
RNA or HIV-1 RNA <400 c/mL at Week 24. Four subjects had virologic failure none of which had 
INI resistance at the time of virologic failure.  
 



29 

5.2 Pharmacokinetic properties 
 
The Triumeq tablet has been shown to be bioequivalent to dolutegravir single entity tablet and 
abacavir/lamivudine fixed-dose combination tablet (ABC/3TC FDC) administered separately. This 
was demonstrated in a single dose, 2-way crossover bioequivalence study of Triumeq (fasted) versus 
1 x 50 mg dolutegravir tablet, plus 1 x 600mg abacavir/300 mg lamivudine tablet (fasted) in healthy 
subjects (n=66). The effect of a high fat meal on the Triumeq tablet was evaluated in a subgroup of 
subjects in this study (n=12). Plasma Cmax and AUC of dolutegravir following administration of 
Triumeq with a high fat meal were 37% and 48% higher, respectively, than those following 
administration of Triumeq in the fasted state. This is not considered clinically significant (see 
Absorption). The effect of food on plasma exposures of abacavir and lamivudine following 
administration of Triumeq with a high fat meal were very similar to prior food effects observed with 
ABC/3TC FDC. These results indicate that Triumeq can be taken with or without food. 
 
The pharmacokinetic properties of dolutegravir, lamivudine and abacavir are described below. 
 
Absorption 
 
Dolutegravir, abacavir and lamivudine are rapidly absorbed following oral administration. The 
absolute bioavailability of dolutegravir has not been established. The absolute bioavailability of oral 
abacavir and lamivudine in adults is about 83% and 80-85% respectively. The mean time to maximal 
serum concentrations (tmax) is about 2 to 3 hours (post dose for tablet formulation), 1.5 hours and 
1.0 hour for dolutegravir, abacavir and lamivudine, respectively. 
 
Exposure to dolutegravir was generally similar between healthy subjects and HIV-1–infected subjects. 
In HIV-1–infected adult subjects following dolutegravir 50 mg once daily, the steady-state 
pharmacokinetic parameters (geometric mean [%CV]) based on population pharmacokinetic analyses 
were AUC(0-24) = 53.6 (27) µg.h/mL, Cmax = 3.67 (20) µg/mL, and Cmin = 1.11 (46) µg/mL. Following 
a single dose of 600 mg of abacavir, the mean (CV) Cmax is 4.26 µg/ml (28%) and the mean (CV) 
AUC∞ is 11.95 µg.h/ml (21%). Following multiple-dose oral administration of lamivudine 300 mg 
once daily for seven days, the mean (CV) steady-state Cmax is 2.04 µg/ml (26%) and the mean (CV) 
AUC24 is 8.87 µg.h/ml (21%). 
 
Plasma Cmax and AUC of dolutegravir following administration of Triumeq with a high fat meal were 
37% and 48% higher, respectively, than those following administration of Triumeq in the fasted 
state). For abacavir there was a decrease in Cmax with 23% and AUC was unchanged. The exposure of 
lamivudine was similar with and without food. These results indicate that Triumeq can be taken with 
or without food. 
 
Distribution 
 
The apparent volume of distribution of dolutegravir (following oral administration of suspension 
formulation, Vd/F) is estimated at 12.5 L.  Intravenous studies with abacavir and lamivudine showed 
that the mean apparent volume of distribution is 0.8 and 1.3 l/kg respectively. 
 
Dolutegravir is highly bound (> 99%) to human plasma proteins based on in vitro data.  Binding of 
dolutegravir to plasma proteins is independent of dolutegravir concentration.  Total blood and plasma 
drug-related radioactivity concentration ratios averaged between 0.441 to 0.535, indicating minimal 
association of radioactivity with blood cellular components. The unbound fraction of dolutegravir in 
plasma is increased at low levels of serum albumin (<35 g/L) as seen in subjects with moderate 
hepatic impairment. Plasma protein binding studies in vitro indicate that abacavir binds only low to 
moderately (~49%) to human plasma proteins at therapeutic concentrations. Lamivudine exhibits 



30 

linear pharmacokinetics over the therapeutic dose range and displays limited plasma protein binding 
in vitro (< 36%). 
 
Dolutegravir, abacavir and lamivudine are present in cerebrospinal fluid (CSF).   
 
In 13 treatment-naïve subjects on a stable dolutegravir plus abacavir/lamivudine regimen, dolutegravir 
concentration in CSF averaged 18 ng/mL (comparable to unbound plasma concentration, and above 
the IC50). Studies with abacavir demonstrate a CSF to plasma AUC ratio of between 30 to 44%. The 
observed values of the peak concentrations are 9-fold greater than the IC50 of abacavir of 0.08 µg/ml 
or 0.26 µM when abacavir is given at 600 mg twice daily. The mean ratio of CSF/serum lamivudine 
concentrations 2-4 hours after oral administration was approximately 12%. The true extent of CNS 
penetration of lamivudine and its relationship with any clinical efficacy is unknown. 
 
Dolutegravir is present in the female and male genital tract.  AUC in cervicovaginal fluid, cervical 
tissue and vaginal tissue were 6-10% of those in corresponding plasma at steady state. AUC in semen 
was 7% and 17% in rectal tissue of those in corresponding plasma at steady state. 
 
Biotransformation 
 
Dolutegravir is primarily metabolized via UGT1A1 with a minor CYP3A component (9.7% of total 
dose administered in a human mass balance study).  Dolutegravir is the predominant circulating 
compound in plasma; renal elimination of unchanged active substance is low (< 1% of the dose).  
Fifty-three percent of total oral dose is excreted unchanged in the faeces. It is unknown if all or part of 
this is due to unabsorbed active substance or biliary excretion of the glucuronidate conjugate, which 
can be further degraded to form the parent compound in the gut lumen.  Thirty-two percent of the total 
oral dose is excreted in the urine, represented by ether glucuronide of dolutegravir (18.9% of total 
dose), N-dealkylation metabolite (3.6% of total dose), and a metabolite formed by oxidation at the 
benzylic carbon (3.0% of total dose). 
 
Abacavir is primarily metabolised by the liver with approximately 2% of the administered dose being 
renally excreted, as unchanged compound. The primary pathways of metabolism in man are by 
alcohol dehydrogenase and by glucuronidation to produce the 5’-carboxylic acid and 5’-glucuronide 
which account for about 66% of the administered dose. These metabolites are excreted in the urine. 
 
Metabolism of lamivudine is a minor route of elimination. Lamivudine is predominately cleared by 
renal excretion of unchanged lamivudine. The likelihood of metabolic drug interactions with 
lamivudine is low due to the small extent of hepatic metabolism (5-10%). 
 
Drug interactions 
 
In vitro, dolutegravir demonstrated no direct, or weak inhibition (IC50>50 μM) of the enzymes 
cytochrome P450 (CYP)1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A, 
UGT1A1 or UGT2B7, or the transporters Pgp, BCRP, BSEP, organic anion transporting polypeptide 
1B1 (OATP1B1), OATP1B3, OCT1, MATE2-K, multidrug resistance-associated protein 2 (MRP2) 
or MRP4. In vitro, dolutegravir did not induce CYP1A2, CYP2B6 or CYP3A4. Based on this data, 
dolutegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of 
major enzymes or transporters (see section 4.5). 
 
In vitro, dolutegravir was not a substrate of human OATP 1B1, OATP 1B3 or OCT 1. 
 
In vitro, abacavir did not inhibit or induce CYP enzymes (such as CYP3A4, CYP2C9 or CYP2D6) 
and demonstrates no or weak inhibition of OATP1B1, OAT1B3, OCT1, OCT2, BCRP and P-gp or 



31 

MATE2-K.  Abacavir is therefore not expected to affect the plasma concentrations of drugs that are 
substrates of these enzymes or transporters. 
 
Abacavir was not significantly metabolised by CYP enzymes.  In vitro, abacavir was 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 affect abacavir plasma concentrations.  
 
In vitro, lamivudine did not inhibit or induce CYP enzymes (such as CYP3A4, CYP2C9 or CYP2D6) 
and demonstrated no or weak inhibition of OATP1B1, OAT1B3, OCT3, BCRP, P-gp, MATE1 or 
MATE2-K.  Lamivudine is therefore not expected to affect the plasma concentrations of drugs that 
are substrates of these enzymes or transporters. 
 
Lamivudine was not significantly metabolised by CYP enzymes.  
 
Elimination 
 
Dolutegravir has a terminal half-life of ~14 hours. The apparent oral clearance (CL/F) is 
approximately 1 L/hr in HIV-infected patients based on a population pharmacokinetic analysis. 
 
The mean half-life of abacavir is about 1.5 hours. The geometric mean terminal half-life of 
intracellular active moiety carbovirtriphosphate (TP) at steady-state is 20.6 hours. Following multiple 
oral doses of abacavir 300 mg twice a day there is no significant accumulation of abacavir. 
Elimination of abacavir is via hepatic metabolism with subsequent excretion of metabolites primarily 
in the urine. The metabolites and unchanged abacavir account for about 83% of the administered 
abacavir dose in the urine. The remainder is eliminated in the faeces. 
 
The observed lamivudine half-life of elimination is 5 to 7 hours. For patients receiving lamivudine 
300 mg once daily, the terminal intracellular half-life of lamivudine-TP was 16 to 19 hours. The mean 
systemic clearance of lamivudine is approximately 0.32 l/h/kg, predominantly by renal clearance 
(> 70%) via the organic cationic transport system. Studies in patients with renal impairment show 
lamivudine elimination is affected by renal dysfunction. Dose reduction is required for patients with 
creatinine clearance < 50 ml/min (see section 4.2).  
 
Pharmacokinetic/pharmacodynamic relationship(s) 
 
In a randomized, dose-ranging trial, HIV-1–infected subjects treated with dolutegravir monotherapy 
(ING111521) demonstrated rapid and dose-dependent antiviral activity with mean decline in HIV-1 
RNA of 2.5 log10 at day 11 for 50 mg dose. This antiviral response was maintained for 3 to 4 days 
after the last dose in the 50 mg group. 
 
Intracellular pharmacokinetics  
 
The geometric mean terminal carbovir-TP intracellular half-life at steady-state was 20.6 hours, 
compared to the geometric mean abacavir plasma half-life of 2.6 hours. The terminal intracellular 
half-life of lamivudine-TP was prolonged to 16-19 hours, compared to the plasma lamivudine half-life 
of 5-7 hours, supporting once daily dosing of ABC and 3TC. 
 
Special patient populations 
 
Hepatic impairment 
Pharmacokinetic data has been obtained for dolutegravir, abacavir and lamivudine separately.  
 



32 

Dolutegravir is primarily metabolized and eliminated by the liver. A single dose of 50 mg of 
dolutegravir was administered to 8 subjects with moderate hepatic impairment (Child-Pugh class B) 
and to 8 matched healthy adult controls. While the total dolutegravir concentration in plasma was 
similar, a 1.5 to 2-fold increase in unbound exposure to dolutegravir was observed in subjects with 
moderate hepatic impairment compared to healthy controls. No dosage adjustment is considered 
necessary for patients with mild to moderate hepatic impairment. The effect of severe hepatic 
impairment on the pharmacokinetics of dolutegravir has not been studied. 
 
Abacavir is metabolised primarily by the liver. The pharmacokinetics of abacavir have been studied in 
patients with mild hepatic impairment (Child-Pugh score 5-6) receiving a single 600 mg dose. The 
results showed that there was a mean increase of 1.89-fold [1.32; 2.70] in the abacavir AUC, and 1.58 
[1.22; 2.04] fold in the elimination half-life. No recommendation on dose reduction is possible in 
patients with mild hepatic impairment due to substantial variability of abacavir exposure.  
 
Data obtained in patients with moderate to severe hepatic impairment show that lamivudine 
pharmacokinetics are not significantly affected by hepatic dysfunction. 
 
Based on data obtained for abacavir, Triumeq is not recommended in patients with moderate and 
severe hepatic impairment. 
 
Renal impairment 
Pharmacokinetic data have been obtained for dolutegravir, lamivudine and abacavir separately. 
 
Renal clearance of unchanged active substance is a minor pathway of elimination for dolutegravir. A 
study of the pharmacokinetics of dolutegravir was performed in subjects with severe renal impairment 
(CLcr <30 mL/min). No clinically important pharmacokinetic differences between subjects with 
severe renal impairment (CLcr <30 mL/min) and matching healthy subjects were observed. 
Dolutegravir has not been studied in patients on dialysis, though differences in exposure are not 
expected. 
 
Abacavir is primarily metabolised by the liver with approximately 2% of abacavir excreted unchanged 
in the urine. The pharmacokinetics of abacavir in patients with end-stage renal disease is similar to 
patients with normal renal function. 
 
Studies with lamivudine show that plasma concentrations (AUC) are increased in patients with renal 
dysfunction due to decreased clearance.  
 
Based on the lamivudine data, Triumeq is not recommended for patients with creatinine clearance of 
< 50 ml/min. 
 
Elderly 
Population pharmacokinetic analysis of dolutegravir using data in HIV-1 infected adults showed that 
there was no clinically relevant effect of age on dolutegravir exposure. 
 
Pharmacokinetic data for dolutegravir, abacavir and lamivudine in subjects >65 years of age are 
limited. 
 
Paediatric population 
The pharmacokinetics of dolutegravir in 10 antiretroviral treatment-experienced HIV-1 infected 
adolescents (12 to 17 years) showed that dolutegravir 50 mg once daily dosage resulted in 
dolutegravir exposure comparable to that observed in adults who received dolutegravir 50 mg once 
daily.  
 



33 

Limited data are available in adolescents receiving a daily dose of 600 mg of abacavir and 300 mg of 
lamivudine.  Pharmacokinetic parameters are comparable to those reported in adults. 
 
Polymorphisms in drug metabolising enzymes 
There is no evidence that common polymorphisms in drug metabolising enzymes alter dolutegravir 
pharmacokinetics to a clinically meaningful extent. In a meta-analysis using pharmacogenomics 
samples collected in clinical studies in healthy subjects, subjects with UGT1A1 (n=7) genotypes 
conferring poor dolutegravir metabolism had a 32% lower clearance of dolutegravir and 46% higher 
AUC compared with subjects with genotypes associated with normal metabolism via UGT1A1 
(n=41).  
 
Gender 
Population PK analyses using pooled pharmacokinetic data from Phase IIb and Phase III adult trials 
revealed no clinically relevant effect of gender on the exposure of dolutegravir. There is no evidence 
that a dose adjustment of dolutegravir, abacavir or lamivudine would be required based on the effects 
of gender on PK parameters. 
 
Race 
Population PK analyses using pooled pharmacokinetic data from Phase IIb and Phase III adult trials 
revealed no clinically relevant effect of race on the exposure of dolutegravir. The pharmacokinetics of 
dolutegravir following single dose oral administration to Japanese subjects appear similar to observed 
parameters in Western (US) subjects. There is no evidence that a dose adjustment of dolutegravir, 
abacavir or lamivudine would be required based on the effects of race on PK parameters. 
 
Co-infection with Hepatitis B or C 
Population pharmacokinetic analysis indicated that hepatitis C virus co-infection had no clinically 
relevant effect on the exposure to dolutegravir. There are limited pharmacokinetic data on subjects 
with hepatitis B co-infection (see section 4.4). 
 
5.3 Preclinical safety data 
 
There are no data available on the effects of the combination of dolutegravir, abacavir and lamivudine 
in animals, except a negative in vivo rat micronucleus test which tested the effects of the combination 
of abacavir and lamivudine.   
 
Mutagenicity and carcinogenicity 
 
Dolutegravir was not mutagenic or clastogenic using in vitro tests in bacteria and cultured mammalian 
cells, and an in vivo rodent micronucleus assay. 
 
Neither abacavir nor lamivudine were mutagenic in bacterial tests, but consistent with other 
nucleoside analogues, inhibit cellular DNA replication in in vitro mammalian tests such as the mouse 
lymphoma assay. The results of an in vivo rat micronucleus test with abacavir and lamivudine in 
combination were negative.  
 
Lamivudine has not shown any genotoxic activity in the in vivo studies. Abacavir has a weak potential 
to cause chromosomal damage both in vitro and in vivo at high tested concentrations.  
 
The carcinogenic potential of a combination of dolutegravir, abacavir and lamivudine has not been 
tested. Dolutegravir was not carcinogenic in long term studies in the mouse and rat. In long-term oral 
carcinogenicity studies in rats and mice, lamivudine did not show any carcinogenic potential. 
Carcinogenicity studies with orally administered abacavir in mice and rats showed an increase in the 
incidence of malignant and non-malignant tumours. Malignant tumours occurred in the preputial 



34 

gland of males and the clitoral gland of females of both species, and in rats in the thyroid gland of 
males and in the liver, urinary bladder, lymph nodes and the subcutis of females.  
 
The majority of these tumours occurred at the highest abacavir dose of 330 mg/kg/day in mice and 
600 mg/kg/day in rats. The exception was the preputial gland tumour which occurred at a dose of 
110 mg/kg in mice. The systemic exposure at the no effect level in mice and rats was equivalent to 3 
and 7 times the human systemic exposure during therapy. While the clinical relevance of these 
findings is unknown, these data suggest that a potential carcinogenic risk to humans is outweighed by 
the clinical benefit. 
 
Repeat-dose toxicity 
 
The effect of prolonged daily treatment with high doses of dolutegravir has been evaluated in repeat 
oral dose toxicity studies in rats (up to 26 weeks) and in monkeys (up to 38 weeks).  The primary 
effect of dolutegravir was gastrointestinal intolerance or irritation in rats and monkeys at doses that 
produce systemic exposures approximately 38 and 1.5 times the 50 mg human clinical exposure based 
on AUC, respectively.  Because gastrointestinal (GI) intolerance is considered to be due to local 
active substance administration, mg/kg or mg/m2 metrics are appropriate determinates of safety cover 
for this toxicity.  GI intolerance in monkeys occurred at 30 times the human mg/kg equivalent dose 
(based on 50 kg human), and 11 times the human mg/m2 equivalent dose for a total daily clinical dose 
of 50 mg.   
 
In toxicology studies abacavir was shown to increase liver weights in rats and monkeys. The clinical 
relevance of this is unknown. There is no evidence from clinical studies that abacavir is hepatotoxic. 
Additionally, autoinduction of abacavir metabolism or induction of the metabolism of other medicinal 
products hepatically metabolised has not been observed in humans. 
 
Mild myocardial degeneration in the heart of mice and rats was observed following administration of 
abacavir for two years. The systemic exposures were equivalent to 7 to 21 times the expected 
systemic exposure in humans. The clinical relevance of this finding has not been determined. 
 
Reproductive toxicology 
 
In reproductive toxicity studies in animals, dolutegravir, lamivudine and abacavir were shown to cross 
the placenta. 
 
Oral administration of dolutegravir to pregnant rats at doses up to 1000 mg/kg daily from days 6 to 17 
of gestation did not elicit maternal toxicity, developmental toxicity or teratogenicity (50 times the 
50 mg human clinical exposure when administered in combination with abacavir and lamivudine 
based on AUC). 
 
Oral administration of dolutegravir to pregnant rabbits at doses up to 1000 mg/kg daily from days 6 to 
18 of gestation did not elicit developmental toxicity or teratogenicity (0.74 times the 50mg human 
clinical exposure when administered in combination with abacavir and lamivudine based on AUC).  
In rabbits, maternal toxicity (decreased food consumption, scant/no faeces/urine, suppressed body 
weight gain) was observed at 1000 mg/kg (0.74 times the 50 mg human clinical exposure when 
administered in combination with abacavir and lamivudine based on AUC). 
 
Lamivudine was not teratogenic in animal studies but there were indications of an increase in early 
embryonic deaths in rabbits at relatively low systemic exposures, comparable to those achieved in 
humans. A similar effect was not seen in rats even at very high systemic exposure. 
 



35 

Abacavir demonstrated toxicity to the developing embryo and foetus in rats, but not in rabbits. These 
findings included decreased foetal body weight, foetal oedema, and an increase in skeletal 
variations/malformations, early intra-uterine deaths and still births. No conclusion can be drawn with 
regard to the teratogenic potential of abacavir because of this embryo-foetal toxicity. 
 
Fertility studies in rats have shown that dolutegravir, abacavir and lamivudine have no effect on male 
or female fertility. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core  
Mannitol (E421) 
Microcrystalline cellulose 
Povidone (K29/32) 
Sodium starch glycollate 
Magnesium stearate 
 
Tablet coating 
Poly(vinyl) alcohol – partially hydrolysed  
titanium dioxide  
macrogol 
talc 
iron oxide black 
iron oxide red 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from moisture. Keep the bottle tightly closed. Do not 
remove the desiccant. 
 
This medicinal product does not require any special temperature storage conditions. 
 
6.5 Nature and contents of container 
 
White HDPE (high density polyethylene) bottles closed with polypropylene child-resistant closures, 
with a polyethylene faced induction heat seal liner. Each bottle contains 30 film-coated tablets and a 
desiccant. 
 
Multipacks containing 90 (3 packs of 30) film-coated tablets. Each pack of 30 film-coated tablets 
contains a desiccant. 
 
Not all pack sizes may be marketed. 



36 

 
6.6 Special precautions for disposal  
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/14/940/001 
EU/1/14/940/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorization: 2nd September 2014 
Date of latest renewal: 20th June 2019 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu  
 
 

http://www.ema.europa.eu/


37 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE 
AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 



38 

A.  MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer(s) responsible for batch release 
 
GLAXO WELLCOME, S.A., 
Avda. Extremadura, 3  
Pol. Ind. Allendeduero  
Aranda de Duero  
Burgos, 09400  
Spain 
 
Or 
 
GlaxoSmithKline Pharmaceuticals S.A., UL.Grunwaldzka 189, 60-322 Poznan, Poland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports  

The requirements for submission of periodic safety update reports for this medicinal product are  set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of an 
important (pharmacovigilance or risk minimisation) milestone being reached.  



39 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



40 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



41 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
BOTTLE CARTON (INDIVIDUAL PACKS ONLY) 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Triumeq 50 mg/600 mg/300 mg film-coated tablets 
dolutegravir/abacavir/lamivudine 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 50 mg dolutegravir (as sodium), 600 mg abacavir (as sulfate), 
300 mg lamivudine. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Detach enclosed Alert Card, it contains important safety information. 
 
WARNING  
 
In case of any symptoms suggesting hypersensitivity reactions, contact your doctor IMMEDIATELY. 
 
Push here (with Alert card attached) 
 
 
8. EXPIRY DATE 
 
EXP 



42 

 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. Keep the bottle tightly closed. Do not 
remove the desiccant. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/940/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
triumeq 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC: 
SN: 
NN:  



43 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
BOTTLE CARTON (MULTIPACKS ONLY – WITH BLUE BOX) 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Triumeq 50 mg/600 mg/300 mg film-coated tablets 
dolutegravir/abacavir/lamivudine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 50 mg dolutegravir (as sodium), 600 mg abacavir (as sulfate), 
300 mg lamivudine. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 90 (3 packs of 30) film-coated tablets  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
WARNING! In case of any symptoms suggesting hypersensitivity reactions, contact your doctor 
IMMEDIATELY. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
 



44 

9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. Keep the bottle tightly closed. Do not 
remove the desiccant. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/940/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
triumeq 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC: 
SN: 
NN:  



45 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 
 
INTERMEDIATE CARTON (WITHOUT BLUE BOX – COMPONENT OF MULTIPACK) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Triumeq 50 mg/600 mg/300 mg film-coated tablets 
dolutegravir/abacavir/lamivudine 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 50 mg dolutegravir (as sodium), 600 mg abacavir (as sulfate), 
300 mg lamivudine. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets. Component of a multipack, can’t be sold separately. 

 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
  
Detach enclosed Alert Card, it contains important safety information. 
 
WARNING  
 
In case of any symptoms suggesting hypersensitivity reactions, contact your doctor IMMEDIATELY. 
 
Push here (with Alert card attached) 
 
 
8. EXPIRY DATE 
 
EXP 



46 

 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. Keep the bottle tightly closed. Do not 
remove the desiccant. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/940/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
triumeq 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
 



47 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Triumeq 50 mg/600 mg/300 mg tablets 
dolutegravir/abacavir/lamivudine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 50 mg dolutegravir (as sodium), 600 mg abacavir (as sulfate), 
300 mg lamivudine. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. Keep the bottle tightly closed. Do not 
remove the desiccant. 
 



48 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/940/001 
EU/1/14/940/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
 



49 

TRIUMEQ TABLETS PATIENT ALERT CARD 
 
SIDE 1 

 
IMPORTANT  -  PATIENT ALERT CARD 

Triumeq (dolutegravir / abacavir / lamivudine) tablets 
Carry this card with you at all times 

 
Since Triumeq contains abacavir some patients taking Triumeq may develop a hypersensitivity 
reaction (serious allergic reaction). This reaction can be life-threatening if treatment with Triumeq is 
continued. CONTACT YOUR DOCTOR IMMEDIATELY for advice on whether you should 
stop taking Triumeq if:  
1) you get a skin rash OR 
2) you get one or more symptoms from at least TWO of the following groups 
- fever 
- shortness of breath, sore throat or cough 
- nausea or vomiting or diarrhoea or abdominal pain 
- severe tiredness or achiness or generally feeling ill 
 
If you have discontinued Triumeq due to this reaction, YOU MUST NEVER TAKE Triumeq, or any 
medicine containing abacavir again as within hours you may experience a life-threatening lowering 
of your blood pressure or death.  
 

 (see reverse of card) 
 
SIDE 2 
 
You should immediately contact your doctor if you think you are having a hypersensitivity reaction to 
Triumeq. Write your doctor's details below:  
 
Doctor:.......................…………………… Tel:...................………… 
 
If your doctor is not available, you must urgently seek alternative medical advice (e.g. the 
emergency unit of the nearest hospital). 
 
For general Triumeq information enquiries, contact:  
 

 
 
 
 



50 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



51 

Package leaflet: Information for the patient 
 

Triumeq 50 mg/600 mg/300 mg film-coated tablets  
dolutegravir/abacavir/lamivudine 

 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Triumeq is and what it is used for  
2. What you need to know before you take Triumeq  
3. How to take Triumeq 
4. Possible side effects  
5. How to store Triumeq 
6. Contents of the pack and other information 
 
 
1. What Triumeq is and what it is used for 
 
Triumeq is a medicine that contains three active ingredients used to treat HIV infection: abacavir, 
lamivudine and dolutegravir. Abacavir and lamivudine belong to a group of anti-retroviral medicines 
(medicines used to treat HIV infection) called nucleoside analogue reverse transcriptase inhibitors 
(NRTIs), and dolutegravir belongs to a group of anti-retroviral medicines called integrase inhibitors 
(INIs). 
 
Triumeq is used to treat HIV (human immunodeficiency virus) infection in adults and children over 
12 years old who weigh at least 40 kg. 
 
Before you are prescribed Triumeq your doctor will arrange a test to find out whether you carry a 
particular type of gene called HLA-B*5701. Triumeq should not be used in patients who are known to 
carry the HLA-B*5701 gene. Patients with this gene are at a high risk of developing a serious 
hypersensitivity (allergic) reaction if they use Triumeq (see ‘hypersensitivity reactions’ in section 4). 
 
Triumeq does not cure HIV infection; it reduces the amount of virus in your body, and keeps it at a 
low level. It also increases the number of CD4 cells in your blood. CD4 cells are a type of white blood 
cells that are important in helping your body to fight infection. 
 
Not everyone responds to treatment with Triumeq in the same way. Your doctor will monitor the 
effectiveness of your treatment. 
 
 
2. What you need to know before you take Triumeq 
 
Do not take Triumeq: 

• if you are allergic (hypersensitive) to dolutegravir, abacavir (or any other medicine containing 
abacavir), or lamivudine, or any of the other ingredients of this medicine (listed in section 6). 



52 

Carefully read all the information about hypersensitivity reactions in Section 4. 
• If you are taking a medicine called fampridine (also known as dalfampridine; used in multiple 

sclerosis). 
→ If you think any of these apply to you, tell your doctor. 

 
Warnings and precautions  

IMPORTANT — Hypersensitivity reactions 

Triumeq contains abacavir and dolutegravir. Both of these active ingredients can cause a serious 
allergic reaction known as a hypersensitivity reaction. You should never take abacavir or abacavir-
containing products again if you have a hypersensitivity reaction: it can be life threatening. 
 
You must carefully read all the information under ‘Hypersensitivity reactions’ in the panel in 
Section 4. 

The Triumeq pack includes an Alert Card to remind you and medical staff about hypersensitivity. 
Detach this card and keep it with you at all times. 
 
Some people taking Triumeq or other combination treatments for HIV are more at risk of serious side 
effects than others. You need to be aware of the extra risks: 
 
• if you have moderate or severe liver disease 
• if you have ever had liver disease, including hepatitis B or C (if you have hepatitis B infection, 

don’t stop Triumeq without your doctor’s advice, as your hepatitis may come back)  
• if you have a kidney problem 

→ Talk to your doctor if any of these apply to you before using Triumeq. You may need 
extra check-ups, including blood tests, while you’re taking your medicine. See Section 4 for 
more information.  

 
Abacavir hypersensitivity reactions 
Even patients who don’t have the HLA-B*5701 gene may still develop a hypersensitivity reaction (a 
serious allergic reaction). 

→ Carefully read all the information about hypersensitivity reactions in Section 4 of this 
leaflet. 

 
Risk of heart attack 
The possibility that abacavir increases the risk of having a heart attack cannot be excluded. 

→ Tell your doctor if you have heart problems, if you smoke, or have other illnesses that may 
increase your risk of heart disease such as high blood pressure or diabetes. Don’t stop taking 
Triumeq unless your doctor advises you to do so. 

 
Look out for important symptoms 
Some people taking medicines for HIV infection develop other conditions, which can be serious. 
These include: 

• symptoms of infections and inflammation 
• joint pain, stiffness and bone problems 

You need to know about important signs and symptoms to look out for while you’re taking Triumeq. 
→ Read the information ‘Other possible side effects of combination therapy for HIV’ in 
Section 4 of this leaflet. 

 
Protect other people 
HIV infection is spread by sexual contact with someone who has the infection, or by transfer of 
infected blood (for example, by sharing injection needles). You can still pass on HIV when taking this 
medicine, although the risk is lowered by effective antiretroviral therapy, so it is important you take 



53 

your medicine exactly as your doctor has told you. Discuss with your doctor the precautions needed to 
avoid infecting other people. 
 
Children 
This medicine is not for children under 12 years of age. The use of Triumeq in children under 12 
years of age has not yet been studied. 
 
Other medicines and Triumeq 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Don't take Triumeq with the following medicine: 

• fampridine (also known as dalfampridine), used in multiple sclerosis. 
 
Some medicines can affect how Triumeq works, or make it more likely that you will have side effects.  
Triumeq can also affect how some other medicines work.  
Tell your doctor if you are taking any of the medicines in the following list: 

• metformin, to treat diabetes 
• medicines called antacids, to treat indigestion and heartburn. Do not take an antacid during 

the 6 hours before you take Triumeq, or for at least 2 hours after you take it. (See also 
Section 3). 

• supplements or multivitamins containing calcium, iron or magnesium. Do not take 
supplements or multivitamins containing calcium, iron or magnesium during the 6 hours 
before you take Triumeq, or for at least 2 hours after you take it (see also Section 3). 

• emtricitabine, etravirine, efavirenz, nevirapine or tipranavir/ritonavir, to treat HIV infection 
• medicines (usually liquids) containing sorbitol and other sugar alcohols (such as xylitol, 

mannitol, lactitol or maltitol), if taken regularly 
• other medicines containing lamivudine, used to treat HIV infection or hepatitis B infection 
• cladribine, used to treat hairy cell leukaemia 
• rifampicin, to treat tuberculosis (TB) and other bacterial infections 
• trimethoprim/sulfamethoxazole, an antibiotic to treat bacterial infections 
• phenytoin and phenobarbital, to treat epilepsy 
• oxcarbazepine and carbamazepine, to treat epilepsy and bipolar disorder 
• St. John’s wort (Hypericum perforatum), a herbal remedy to treat depression 
• methadone, used as a heroin substitute.  Abacavir increases the rate at which methadone is 

removed from the body. If you are taking methadone, you will be checked for any withdrawal 
symptoms. Your methadone dose may need to be changed.  
 

 → Tell your doctor or pharmacist if you are taking any of these. Your doctor may decide to 
adjust your dose or that you need extra checkups. 

 
Pregnancy 
If you are pregnant, think you may be pregnant, or if you are planning to have a baby: 
 → Talk to your doctor about the risks and benefits of taking Triumeq. 
 
Taking Triumeq at the time of becoming pregnant or during the first six weeks of pregnancy, may 
increase the risk of a type of birth defect, called neural tube defect, such as spina bifida (malformed 
spinal cord). 
 
If you could get pregnant while receiving Triumeq: 
 → Talk to your doctor and discuss whether there is a need for contraception, such as condom 
or pills. 
 



54 

Tell your doctor immediately if you become pregnant or are planning to become pregnant. Your 
doctor will review your treatment. Do not stop taking Triumeq without consulting your doctor, as this 
may harm you and your unborn child.  
 
Breast-feeding 
It is recommended women who are HIV-positive do not breast-feed because HIV infection can be 
passed on to the baby in breast milk. 
 
A small amount of the ingredients in Triumeq can also pass into your breast milk. 
If you are breast-feeding, or thinking about breast-feeding: 
 → Talk to your doctor immediately.  
 
Driving and using machines 
Triumeq can make you dizzy and have other side effects that make you less alert. 
 → Don’t drive or operate machinery unless you are sure your alertness has not been affected.  
 
Important information about the contents of Triumeq tablets. 
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially 
‘sodium-free’. 
 
 
3. How to take Triumeq 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 

• The usual dose is one tablet once a day 
 
Swallow the tablet with some liquid. Triumeq can be taken with or without food. 
 
Use in children and adolescents 
Children and adolescents aged between 12 and 17 years and weighing at least 40 kg can take the adult 
dose of one tablet once a day. 
 
Do not take an antacid during the 6 hours before you take Triumeq, or for at least 2 hours after you 
take it.  Other acid-lowering medicines like ranitidine and omeprazole can be taken at the same time 
as Triumeq.  
  → Talk to your doctor for further advice on taking antacid medicines with Triumeq. 
 
Do not take supplements or multivitamins containing calcium, iron or magnesium during the 6 
hours before you take Triumeq, or for at least 2 hours after you take it. 
 →Talk to your doctor for further advice on taking supplements or multivitamins containing 
calcium, iron or magnesium with Triumeq. 
 
If you take more Triumeq than you should 
If you take too many tablets of Triumeq, contact your doctor or pharmacist for advice. If possible, 
show them the Triumeq pack. 
 
If you forget to take Triumeq 
If you miss a dose, take it as soon as you remember.  But if your next dose is due within 4 hours, skip 
the dose you missed and take the next one at the usual time. Then continue your treatment as before.  
 → Don't take a double dose to make up for a missed dose. 
 
If you have stopped taking Triumeq 



55 

If you have stopped taking Triumeq for any reason — especially because you think you are having 
side effects, or because you have another illness: 

Talk to your doctor before you start taking it again. Your doctor will check whether your 
symptoms were related to a hypersensitivity reaction. If the doctor thinks they may be related to a 
hypersensitivity reaction, you will be told never again to take Triumeq, or any other medicine 
containing abacavir or dolutegravir. It is important that you follow this advice. 

If your doctor advises that you can start taking Triumeq again, you may be asked to take your first 
doses in a place where you will have ready access to medical care if you need it. 
 
 
4. Possible side effects 
 
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.  

 
Like all medicines, this medicine can cause side effects, but not everybody gets them.  
 
When you’re being treated for HIV, it can be hard to tell whether a symptom is a side effect of 
Triumeq or other medicines you are taking, or an effect of the HIV disease itself. So it is very 
important to talk to your doctor about any changes in your health. 
 

Abacavir can cause a hypersensitivity reaction (a serious allergic reaction), especially in people 
who carry a particular type of gene called HLA-B*5701. Even patients who don’t have the HLA-
B*5701 gene may still develop a hypersensitivity reaction, described in this leaflet in the panel 
headed ‘Hypersensitivity reactions’. It is very important that you read and understand the 
information about this serious reaction. 

 
As well as the side effects listed below for Triumeq, other conditions can develop during 
combination therapy for HIV.  

It is important to read the information in this section under the heading ‘Other possible side effects 
of combination therapy for HIV’. 
 



56 

Hypersensitivity Reactions  
 
Triumeq contains abacavir and dolutegravir. Both of these active ingredients can cause a serious 
allergic reaction known as a hypersensitivity reaction.  
 
These hypersensitivity reactions have been seen more frequently in people taking medicines that 
contain abacavir.  
 
Who gets these reactions? 
 
Anyone taking Triumeq could develop a hypersensitivity reaction, which could be life threatening if 
they continue to take Triumeq. 
 
You are more likely to develop this reaction if you have a gene called HLA-B*5701 (but you can get 
a reaction even if you don’t have this gene). You should have been tested for this gene before 
Triumeq was prescribed for you. If you know you have this gene, tell your doctor. 
 
What are the symptoms? 
 
The most common symptoms are: 
fever (high temperature) and skin rash. 
Other common symptoms are: 
nausea (feeling sick), vomiting (being sick), diarrhoea, abdominal (stomach) pain, severe tiredness. 
 
Other symptoms include: 
 



57 

pains in the joints or muscles, swelling of the neck, shortness of breath, sore throat, cough, occasional 
headaches, inflammation of the eye (conjunctivitis), mouth ulcers, low blood pressure, tingling or 
numbness of the hands or feet. 
 
When do these reactions happen? 
 
Hypersensitivity reactions can start at any time during treatment with Triumeq, but are more likely 
during the first 6 weeks of treatment. 
 
Contact your doctor immediately: 
1 if you get a skin rash, OR 
2 if you get symptoms from at least 2 of the following groups: 
 - fever  
 - shortness of breath, sore throat or cough 
 - nausea or vomiting, diarrhoea or abdominal pain 
 - severe tiredness or aches and pains, or generally feeling ill. 
 
Your doctor may advise you to stop taking Triumeq. 
 
If you have stopped taking Triumeq 
 
If you have stopped taking Triumeq because of a hypersensitivity reaction, you must NEVER 
AGAIN take Triumeq, or any other medicine containing abacavir. If you do, within hours, your 
blood pressure could fall dangerously low, which could result in death. You should also never again 
take medicines containing dolutegravir. 
 
If you have stopped taking Triumeq for any reason — especially because you think you are having 
side effects, or because you have other illness: 
 
Talk to your doctor before you start again. Your doctor will check whether your symptoms were 
related to a hypersensitivity reaction. If the doctor thinks they may have been, you will then be told 
never again to take Triumeq, or any other medicine containing abacavir. You may also be told 
never again to take any other medicine containing dolutegravir. It is important that you follow this 
advice. 
 
Occasionally, hypersensitivity reactions have developed in people who start taking abacavir 
containing products again, but who had only one symptom on the Alert Card before they stopped 
taking it. 
 
Very rarely, patients who have taken medicines containing abacavir in the past without any symptoms 
of hypersensitivity have developed a hypersensitivity reaction when they start taking these medicines 
again.  
 
If your doctor advises that you can start taking Triumeq again, you may be asked to take your first 
doses in a place where you will have ready access to medical care if you need it. 
 
If you are hypersensitive to Triumeq, return all your unused Triumeq tablets for safe disposal. Ask 
your doctor or pharmacist for advice. 
 
The Triumeq pack includes an Alert Card, to remind you and medical staff about hypersensitivity 
reactions. Detach this card and keep it with you at all times. 



58 

 
Very common side effects  
These may affect more than 1 in 10 people: 

• headache 
• diarrhoea 
• feeling sick (nausea)  
• difficulty in sleeping (insomnia) 
• lack of energy (fatigue) 

 
Common side effects  
These may affect up to 1 in 10 people: 

• hypersensitivity reaction (see ‘Hypersensitivity reactions’ earlier in this section) 
• loss of appetite 
• rash 
• itching (pruritus) 
• being sick (vomiting) 
• stomach (abdominal) pain 
• stomach (abdominal) discomfort 
• indigestion 
• wind (flatulence) 
• dizziness 
• abnormal dreams 
• nightmares 
• depression (feelings of deep sadness and unworthiness) 
• anxiety 
• tiredness 
• feeling drowsy 
• fever (high temperature) 
• cough 
• irritated or runny nose 
• hair loss 
• muscle pain and discomfort 
• joint pain 
• feeling weak 
• general feeling of being unwell 

 
Common side effects that may show up in blood tests are: 

• an increase in the level of liver enzymes 
 
Uncommon side effects  
These may affect up to 1 in 100 people: 

• inflammation of the liver (hepatitis)  
• suicidal thoughts and behaviours (particularly in patients who have had depression or mental 

health problems before) 
 

Uncommon side effects that may show up in blood tests are: 
• a decreased number of cells involved in blood clotting (thrombocytopenia). 
• a low red blood cell count (anaemia) or low white blood cell count (neutropenia) 
• an increase in sugar (glucose) in the blood 
• an increase in triglycerides (type of fat) in the blood 

 



59 

Rare side effects 
These may affect up to 1 in 1000 people: 
• inflammation of the pancreas (pancreatitis) 
• breakdown of muscle tissue 
• liver failure (signs may include yellowing of the skin and the whites of the eyes or unusually dark 

urine). 
 

Rare side effects that may show up in blood tests are: 
• increase in an enzyme called amylase 

 
Very rare side effects 
These may affect up to 1 in 10,000 people: 
• numbness, tingly feelings in the skin (pins and needles) 
• sensation of weakness in the limbs 
• skin rash, which may form blisters and looks like small targets (central dark spots surrounded by a 

paler area, with a dark ring around the edge) (erythema multiforme) 
• a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and 

genitals (Stevens–Johnson syndrome), and a more severe form causing skin peeling in more than 
30% of the body surface (toxic epidermal necrolysis) 

• lactic acidosis (excess lactic acid in the blood). 
 

 
Very rare side effects that may show up in blood tests are:  
• a failure of the bone marrow to produce new red blood cells (pure red cell aplasia).  
 
If you get any side effects 

→ Talk to your doctor. This includes any possible side effects not listed in this leaflet. 
 
Other possible side effects of combination therapy for HIV 

Combination therapy such as Triumeq may cause other conditions to develop during HIV treatment. 
 
Symptoms of infection and inflammation  

People with advanced HIV infection or AIDS have weak immune systems, and are more likely to 
develop serious infections (opportunistic infections). Such infections may have been “silent” and not 
detected by the weak immune system before treatment was started. After starting treatment, the 
immune system becomes stronger, and may attack the infections, which can cause symptoms of 
infection or inflammation. Symptoms usually include fever, plus some of the following: 

• headache 
• stomach ache 
• difficulty breathing 

In rare cases, as the immune system becomes stronger, it can also attack healthy body tissue 
(autoimmune disorders).  The symptoms of autoimmune disorders may develop many months after 
you start taking medicine to treat your HIV infection. Symptoms may include: 

• palpitations (rapid or irregular heartbeat) or tremor 
• hyperactivity (excessive restlessness and movement)  
• weakness beginning in the hands and feet and moving up towards the trunk of the body. 

 
If you get any symptoms of infection and inflammation or if you notice any of the symptoms above: 
 → Tell your doctor immediately. Don’t take other medicines for the infection without your 
doctor’s advice. 
 
 



60 

Joint pain, stiffness and bone problems 

Some people taking combination therapy for HIV develop a condition called osteonecrosis. In this 
condition, parts of the bone tissue die because of reduced blood supply to the bone. People may be 
more likely to get this condition: 

• if they have been taking combination therapy for a long time 
• if they are also taking anti-inflammatory medicines called corticosteroids 
• if they drink alcohol 
• if their immune systems are very weak 
• if they are overweight. 

Signs of osteonecrosis include: 
• stiffness in the joints 
• aches and pains (especially in the hip, knee or shoulder) 
• difficulty moving. 

If you notice any of these symptoms: 
 → Tell your doctor. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety 
of this medicine. 
 
5. How to store Triumeq 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and bottle after EXP. 
 
Store in the original package in order to protect from moisture. Keep the bottle tightly closed. Do not 
remove the desiccant. 
 
This medicine does not require any special temperature storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
6. Contents of the pack and other information 
 
What Triumeq contains  
- The active substances are dolutegravir, abacavir and lamivudine. Each tablet contains 

dolutegravir sodium equivalent to 50 mg dolutegravir, 600 mg abacavir (as sulfate) and 300 mg 
lamivudine. 

- The other ingredients are mannitol (E421), microcrystalline cellulose, povidone (K29/32), 
sodium starch glycolate, magnesium stearate, poly(vinyl) alcohol – partially hydrolysed, 
titanium dioxide, macrogol/PEG, talc, iron oxide black and iron oxide red). 

 
What Triumeq looks like and contents of the pack 
Triumeq film-coated tablets are purple, biconvex, oval tablets, debossed with “572 Trı” on one side. 
The film-coated tablets are provided in bottles containing 30 tablets.   
The bottle contains a desiccant to reduce moisture. Once the bottle has been opened keep the 
desiccant in the bottle, do not remove it.  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


61 

Multipacks containing 90 film-coated tablets (3 packs of 30 film-coated tablets) are also available. 
Not all pack sizes may be available in your country. 
 
Marketing Authorisation Holder 
ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands. 
 
Manufacturer  
Glaxo Wellcome, S.A., Avda. Extremadura 3, 09400 Aranda De Duero, Burgos, Spain 
OR 
GlaxoSmithKline Pharmaceuticals S.A., UL.Grunwaldzka 189, 60-322 Poznan, Poland. 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
ViiV Healthcare srl/bv  
Tél/Tel: + 32 (0) 10 85 65 00 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

България 
ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
ViiV Healthcare srl/bv  
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 65 00 
 

Česká republika 
GlaxoSmithKline, s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 
 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 

Deutschland 
ViiV Healthcare GmbH  
Tel.: + 49 (0)89 203 0038-10  
viiv.med.info@viivhealthcare.com  
 

Nederland 
ViiV Healthcare BV  
Tel: + 31 (0)33 2081199 
 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 
Τηλ: + 30 210 68 82 100 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
Laboratorios ViiV Healthcare, S.L.  
Tel: + 34 900 923 501  
es-ci@viivhealthcare.com 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 
 

mailto:dk-info@gsk.com
mailto:viiv.med.info@viivhealthcare.com
mailto:es-ci@viivhealthcare.com


62 

France 
ViiV Healthcare SAS  
Tél.: + 33 (0)1 39 17 69 69 
Infomed@viivhealthcare.com 
 

Portugal 
VIIVHIV HEALTHCARE, UNIPESSOAL, LDA  
Tel: + 351 21 094 08 01  
viiv.fi.pt@viivhealthcare.com 
 

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: + 385 1 6051 999 
 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
ViiV Healthcare S.r.l  
Tel: + 39 (0)45 9212611 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 

United Kingdom 
ViiV Healthcare UK Limited 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com  
  

  
 
This leaflet was last revised in {month YYYY}. 
 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 

mailto:Infomed@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com
http://www.ema.europa.eu/


63 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 

 
 
 
 
 
 
 
 
 
 
 
 
  



64 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for dolutegravir, dolutegravir / 
abacavir / lamivudine, dolutegravir / lamivudine, the scientific conclusions of the CHMP are as 
follows: 
  
In view of data from the publication by Waitt et al. 2019 regarding the transfer of dolutegravir into 
breast milk, the PRAC concluded that the product information of products containing dolutegravir 
should be amended with this updated information. It should be noted, that the package leaflet of both 
Dovato and Triumeq already include the following sentence: A small amount of the ingredients in 
Dovato/Triumeq can also pass into your breast milk. Therefore, these leaflets do not need to be 
updated in this regard. 

The CHMP agrees with the scientific conclusions made by the PRAC. 
 
 
Grounds for the variation to the terms of the Marketing Authorisation(s)  
 
On the basis of the scientific conclusions for dolutegravir, dolutegravir / abacavir / lamivudine, 
dolutegravir / lamivudine the CHMP is of the opinion that the benefit-risk balance of the medicinal 
product(s) containing dolutegravir, dolutegravir / abacavir / lamivudine, dolutegravir / lamivudine is 
unchanged subject to the proposed changes to the product information. 
 
The CHMP recommends that the terms of the Marketing Authorisation(s) should be varied. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMSOF THE MARKETING AUTHORISATION(S)