Dovato

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

  



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1. NAME OF THE MEDICINAL PRODUCT 
 
Dovato 50 mg/300 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains dolutegravir sodium equivalent to 50 mg dolutegravir and 300 mg 
lamivudine. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Oval, biconvex, white, film coated tablet, approximately 18.5 x 9.5 mm, debossed with “SV 137” on one face. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Dovato is indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults 
and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the 
integrase inhibitor class, or lamivudine (see section 5.1). 
 
 
4.2 Posology and method of administration  
 
Dovato should be prescribed by physicians experienced in the management of HIV infection. 
 
Posology 
 
Adults and adolescents (above 12 years of age weighing at least 40 kg). 
 
The recommended dose of Dovato in adults and adolescents is one 50 mg/300 mg tablet once daily. 
 
Dose adjustments 
A separate preparation of dolutegravir is available where a dose adjustment is indicated due to drug-drug 
interactions (e.g. rifampicin, carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St. John’s wort, 
etravirine (without boosted protease inhibitors), efavirenz, nevirapine, or tipranavir/ritonavir, see sections 4.4 
and 4.5). In these cases the physician should refer to the individual product information for dolutegravir. 
 
Missed doses 
If the patient misses a dose of Dovato, the patient should take Dovato 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. 
 
Elderly 
There are limited data available on the use of Dovato in patients aged 65 years and over. No dose adjustment 
is necessary (see section 5.2). 
 
Renal impairment 



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Dovato is not recommended for use in patients with a creatinine clearance < 50 mL/min (see section 5.2). No 
dose adjustment is required in patients with mild renal impairment. 
 
Hepatic impairment 
No dosage adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh grade A 
or B). No data are available in patients with severe hepatic impairment (Child-Pugh grade C); therefore 
Dovato should be used with caution in these patients (see section 5.2). 
 
Paediatric population 
The safety and efficacy of Dovato in children aged less than 12 years or weighing less than 40 kg have not 
been established. No data are available. 
 
Method of administration 
 
Oral use.  
Dovato 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. 
 
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 
 
Hypersensitivity reactions have been reported with dolutegravir, and were characterized by rash, 
constitutional findings, and sometimes, organ dysfunction, including severe liver reactions. Dovato and other 
suspect medicinal products should be discontinued immediately if signs or symptoms of hypersensitivity 
reactions develop (including, but not limited to, severe rash or rash accompanied by raised liver enzymes, 
fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, 
eosinophilia, angioedema). Clinical status including liver aminotransferases and bilirubin should be 
monitored. Delay in stopping treatment with Dovato or other suspect active substances after the onset of 
hypersensitivity may result in a life-threatening allergic reaction. 
 
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. 
 
Liver disease 
 



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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. 
 
Dovato includes lamivudine, which is active against hepatitis B. Dolutegravir lacks 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 Dovato is used in patients co-infected with hepatitis B an 
additional antiviral is therefore generally needed. Reference should be made to treatment guidelines. 
 
If Dovato 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. 
 
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. 
 
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 ‘Liver disease’ 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 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. 
 
Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, biphosphonates, 
alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported 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. 



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Opportunistic infections 
 
Patients should be advised that dolutegravir, lamivudine 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 interactions 
 
The recommended dose of dolutegravir is 50 mg twice daily when co-administered with rifampicin, 
carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St. John’s wort, etravirine (without boosted 
protease inhibitors), efavirenz, nevirapine, or tipranavir/ritonavir (see section 4.5). 
 
Dovato should not be co-administered with polyvalent cation-containing antacids. Polyvalent cation-
containing antacids are recommended to be taken 2 hours after or 6 hours before Dovato (see section 4.5). 
 
When taken with food, Dovato and supplements or multivitamins containing calcium, iron or magnesium can 
be taken at the same time. If Dovato is administered under fasting conditions, supplements or multivitamins 
containing calcium, iron or magnesium are recommended to be taken 2 hours after or 6 hours before Dovato 
(see section 4.5). 
 
Dolutegravir increased metformin concentrations. A dose adjustment of metformin should be considered 
when starting and stopping coadministration of Dovato 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 Dovato. This combination may increase the risk for lactic acidosis in patients with 
moderate renal impairment (stage 3a creatinine clearance 45– 59 mL/min) and a cautious approach is 
recommended. Reduction of the metformin dose should be highly considered. 
 
The combination of Dovato with cladribine is not recommended (see section 4.5). 
 
Dovato should not be taken with any other medicinal product containing dolutegravir, lamivudine or 
emtricitabine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions (see 
section 4.5). 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No drug interaction studies have been conducted using Dovato. Dovato contains dolutegravir and 
lamivudine, therefore any interactions identified for these individually are relevant to Dovato. No clinically 
significant drug interactions are expected between dolutegravir and lamivudine. 
 
Effect of other medicinal products on the pharmacokinetics of dolutegravir 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 Dovato 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. 
 
The absorption of dolutegravir is reduced by certain metal cation-containing anti-acid substances and 
supplements (see Table 1). 
 
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 



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of these 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 relevant 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 lamivudine is a substrate of BCRP and P-gp in vitro, given its high absolute bioavailability, (see 
section 5.2), inhibitors of these efflux transporters are unlikely to result in a clinically relevant impact on 
lamivudine concentrations. 
 
Effect of dolutegravir and lamivudine on the pharmacokinetics of other medicinal products 
 
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 and section 4.3). 
 
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, 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, 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. The recommended dose 
of dolutegravir is 50 mg twice daily for 
patients taking etravirine without 
boosted protease inhibitors. As Dovato 
is a fixed-dose tablet, an additional 
50 mg tablet of dolutegravir should be 



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administered, approximately 12 hours 
after Dovato for the duration of the 
etravirine without boosted protease 
inhibitor co-administration (a separate 
formulation of dolutegravir is available 
for this dose adjustment, see section 
4.2).  

Lopinavir+ritonavir+etravirine/ 
Dolutegravir 

Dolutegravir ↔ 
   AUC ↑ 11% 
   Cmax ↑ 7% 
   Cτ ↑ 28% 
 
Lopinavir ↔ 
Ritonavir ↔ 
Etravirine ↔ 

No dose adjustment is necessary. 

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) 

The recommended dose of dolutegravir 
is 50 mg twice daily when 
co-administered with efavirenz. As 
Dovato is a fixed-dose tablet, an 
additional 50 mg tablet of dolutegravir 
should be administered, approximately 
12 hours after Dovato for the duration of 
the efavirenz co-administration (a 
separate formulation of dolutegravir is 
available for this dose adjustment, see 
section 4.2).  

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

The recommended dose of dolutegravir 
is 50 mg twice daily when 
co-administered with nevirapine. As 
Dovato is a fixed-dose tablet, an 
additional 50 mg tablet of dolutegravir 
should be administered, approximately 
12 hours after Dovato for the duration of 
the nevirapine co-administration (a 
separate formulation of dolutegravir is 
available for this dose adjustment, see 
section 4.2).  

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

No dose adjustment is necessary. 

Nucleoside reverse transcriptase inhibitors (NRTIs) 
Tenofovir disoproxil  
 
 
 

Dolutegravir ↔ 
   AUC ↑ 1% 
   Cmax ↓ 3% 
   Cτ ↓ 8% 

No dose adjustment is necessary when 
Dovato is combined with tenofovir, 
didanosine, stavudine or zidovudine. 
 



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Emtricitabine, didanosine, 
stavudine, tenofovir 
alafenamide, zidovudine 

Tenofovir ↔ 
 
 
Interaction not studied 
 

Dovato is not recommended for use in 
combination with emtricitabine 
containing products, since both 
lamivudine (in Dovato) and 
emtricitabine are cytidine analogues (i.e. 
risk for intracellular interactions), see 
section 4.4. 

Protease inhibitors 
Atazanavir/Dolutegravir Dolutegravir ↑ 

   AUC ↑ 91% 
   Cmax ↑ 50% 
   Cτ ↑ 180% 
 
Atazanavir ↔ (historical 
controls) 
(inhibition of UGT1A1 
and CYP3A enzymes) 

No dose adjustment is necessary. 

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) 

The recommended dose of dolutegravir 
is 50 mg twice daily when 
co administered with 
tipranavir/ritonavir. As Dovato is a 
fixed-dose tablet, an additional 50 mg 
tablet of dolutegravir should be 
administered, approximately 12 hours 
after Dovato for the duration of the 
tipranavir/ritonavir co-administration (a 
separate formulation of dolutegravir is 
available for this dose adjustment, see 
section 4.2).  

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 

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

No dose adjustment is necessary. 

Darunavir+ritonavir/ 
Dolutegravir 

Dolutegravir ↓ 
   AUC ↓ 22%  

No dose adjustment is necessary. 



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

Other antiviral active substances 
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. 

Ledipasvir/Sofosbuvir/ 
Lamivudine (with abacavir) 

Lamivudine ↔ 
Ledipasvir ↔ 
Sofosbuvir ↔ 

No dosage adjustment necessary. 

Sofosbuvir/ 
Velpatasvir/Dolutegravir 

Dolutegravir ↔ 
Sofosbuvir ↔ 
Velpatasvir↔ 

No dosage adjustment necessary. 

Ribavirin Interaction not studied. 
 
Clinically significant 
interaction unlikely. 

No dosage adjustment necessary. 

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

Lamivudine:  
   AUC ↑ 43% 
   Cmax ↑ 7% 
 
Trimethoprim:  
   AUC ↔ 
 
Sulfamethoxazole:  
   AUC ↔ 
 
(organic cation transporter 
inhibition) 

No dosage adjustment necessary. 

Antimycobacterials 
Rifampicin/Dolutegravir Dolutegravir ↓ 

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

The recommended dose of dolutegravir 
is 50 mg twice daily when 
co-administered with rifampicin. As 
Dovato is a fixed-dose tablet, an 
additional 50 mg tablet of dolutegravir 
should be administered, approximately 
12 hours after Dovato for the duration of 
the rifampicin co-administration (a 
separate formulation of dolutegravir is 
available for this dose adjustment, see 
section 4.2).  

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

No dose adjustment is necessary. 



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Anticonvulsants 
Carbamazepine/Dolutegravir Dolutegravir ↓ 

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

The recommended dose of dolutegravir 
is 50 mg twice daily when 
co-administered with these metabolic 
inducers. As Dovato is a fixed-dose 
tablet, an additional 50 mg tablet of 
dolutegravir should be administered, 
approximately 12 hours after Dovato for 
the duration of the co-administration 
with these metabolic inducers (a separate 
formulation of dolutegravir is available 
for this dose adjustment, see section 
4.2).  

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). 

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

 
Clinically significant 
interaction unlikely. 

No dosage adjustment necessary. 

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 Dovato with 
cladribine is not recommended (see 
section 4.4). 

Miscellaneous 
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 Dovato with 
medicinal products containing sorbitol 
or other osmotic acting poly-alcohols or 
monosaccharide alcohols (eg: xylitol, 
mannitol, lactitol, maltitol). Consider 
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 



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transporter; co-administration has not 
been studied. Fampridine co-
administration with Dovato 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 
Dovato (minimum 2 hours after or 
6 hours before). 

Calcium 
supplements/Dolutegravir 
(fasted intake) 

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

- When taken with food, Dovato and 
supplements or multivitamins containing 
calcium, iron or magnesium can be taken 
at the same time.  
- If Dovato is taken in a fasted state, 
such supplements should be taken a 
minimum 2 hours after or 6 hours before 
the intake of Dovato. 
 
The stated reductions in dolutegravir 
exposure were observed with the intake 
of dolutegravir and these supplements 
during fasted conditions. In fed state, the 
changes in exposure following intake 
together with calcium or iron 
supplements were modified by the food 
effect, resulting in an exposure similar to 
that obtained with dolutegravir 
administered in the fasted state. 

Iron supplements/Dolutegravir 
(fasted intake) 

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

Multivitamins (containing 
calcium, iron and magnesium) 
/Dolutegravir 
(fasted intake) 

Dolutegravir ↓ 
   AUC ↓ 33%  
   Cmax ↓ 35% 
   C24 ↓ 32% 
(Complex binding to 
polyvalent ions) 

Proton pump inhibitors 
Omeprazole Dolutegravir ↔ No dosage adjustment necessary. 
Corticosteroids 
Prednisone/Dolutegravir Dolutegravir ↔ 

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

No dose adjustment is necessary. 

Antidiabetics 
Metformin/Dolutegravir Metformin ↑ 

Dolutegravir ↔ 
When co-administered 
with dolutegravir 50 mg 
QD: 
Metformin 
   AUC ↑ 79%  
   Cmax ↑ 66% 
When co-administered 
with dolutegravir 50 mg 
BID:  
   Metformin 
   AUC ↑ 145 %  
   Cmax ↑ 111% 

A dose adjustment of metformin should 
be considered when starting and 
stopping coadministration of Dovato 
with metformin, to maintain glycaemic 
control. In patients with moderate renal 
impairment a dose adjustment of 
metformin should be considered when 
coadministered with Dovato, because of 
the increased risk for lactic acidosis in 
patients with moderate renal impairment 
due to increased metformin 
concentration (section 4.4). 

Herbal products   



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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). 

The recommended dose of dolutegravir 
is 50 mg twice daily when co-
administered with St. John’s wort. As 
Dovato is a fixed-dose tablet, an 
additional 50 mg tablet of dolutegravir 
should be administered, approximately 
12 hours after Dovato for the duration of 
the St. John’s wort co-administration (a 
separate formulation of dolutegravir is 
available for this dose adjustment, see 
section 4.2).  

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 Dovato. 

 
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 Dovato, see below), including consideration of effective 
contraceptive measures. 
 
If a woman plans pregnancy, the benefits and the risks of continuing treatment with Dovato should be 
discussed with the patient. 
 
Pregnancy 
 
The safety and efficacy of a dual regimen has not been studied in 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 Dovato, the benefits and risks of continuing Dovato 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. 
 



13 

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. Dovato may be used during the second and 
third trimester of pregnancy when the expected benefit justifies the potential risk to the foetus. 
 
A large amount of data on the use of lamivudine in pregnant women (more than 5200 outcomes from first 
trimester) indicates no malformative toxicity.  
 
Animal studies showed lamivudine may inhibit cellular DNA replication (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  
 
It is unknown whether dolutegravir is excreted in human milk. Available toxicological data in animals has 
shown excretion of dolutegravir in milk. In lactating rats that received a single oral dose of 50 mg/kg at 
10 days postpartum, dolutegravir was detected in milk at concentrations typically higher than blood.  
 
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 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 or lamivudine on human male or female fertility. Animal 
studies indicate no effects of dolutegravir or lamivudine on male or female fertility (see section 5.3).  
 
4.7 Effects on ability to drive and use machines  
 
Dovato has no or negligible influence on the ability to drive and use machines. Patients should be informed 
that dizziness and somnolence has been reported during treatment with dolutegravir. The clinical status of 
the patient and the adverse reaction profile of Dovato should be borne in mind when 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 are headache (3%), diarrhoea (2%), nausea (2%) and 
insomnia (2%).  
 



14 

The most severe adverse reaction reported with dolutegravir was a hypersensitivity reaction that included 
rash and severe liver effects (see section 4.4). 
 
Tabulated list of adverse reactions 
 
The adverse reactions 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 (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not 
known (cannot be estimated from the available data). 
 
Table 2: Tabulated summary of adverse reactions to Dovato based on clinical study and post-

marketing experience with Dovato and its individual components  
Frequency Adverse reaction 

Blood and lymphatic systems disorders: 

Uncommon: neutropenia, anaemia, thrombocytopenia 

Very rare: pure red cell aplasia 

Immune system disorders: 

Uncommon: hypersensitivity (see section 4.4), immune reconstitution 
syndrome (see section 4.4) 

Metabolism and nutrition disorders: 

Very rare: lactic acidosis 

Psychiatric disorders:  

Common: depression, anxiety, insomnia, abnormal dreams 

Uncommon suicidal ideation*, suicide attempt* 
 
*particularly in patients with a pre-existing history of 
depression or psychiatric illness. 

Nervous system disorders:  

Very common: headache 

Common: dizziness, somnolence 

Very rare: peripheral neuropathy, paraesthesia 

Gastrointestinal disorders:  

Very common: nausea, diarrhoea 

Common: vomiting, flatulence, abdominal pain/ discomfort 

Rare: pancreatitis 

Hepatobiliary disorders: 

Uncommon: hepatitis 

Rare acute hepatic failure1 

Skin and subcutaneous tissue disorders:  

Common: rash, pruritus, alopecia 

Rare: angioedema 

Musculoskeletal and connective tissue disorders: 



15 

Common: arthralgia, muscle disorders (including myalgia) 

Rare: rhabdomyolysis 

General disorders and administration site conditions:  

Common: fatigue 

Investigations: 

Common: creatine phosphokinase (CPK) elevations 
alanine aminotransferase (ALT) and/or aspartate 
aminotransferase (AST) elevations 

Rare: amylase elevations 
1 This adverse reaction was identified through post-marketing surveillance for 
dolutegravir in combination with other ARVs. The frequency category of rare was 
estimated based on post-marketing reports. 

 
Description of selected adverse reactions 
 
Changes in laboratory biochemistries 
Dolutegravir has been associated with an increase in serum creatinine occuring in the first week of treatment 
when administered with other antiretroviral medicinal products. Increases in serum creatinine occurred 
within the first four weeks of treatment with dolutegravir plus lamivudine and remained stable through 
48 weeks. In the pooled GEMINI studies a mean change from baseline of 10.3 µmol/L (range: -36.3 µmol/L 
to 55.7 µmol/L) was observed after 48 weeks of treatment. These changes are linked to the inhibiting effect 
of dolutegravir on renal tubular transporters of creatinine. The changes are not considered to be clinically 
relevant and do not reflect a change in glomerular filtration rate. 
 
Co-infection with Hepatitis B or C 
In the Phase III studies for the dolutegravir single agent, 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. Liver chemistry 
elevations consistent with immune reconstitution syndrome were observed in some subjects with hepatitis B 
and/or C co-infection at the start of dolutegravir therapy, particularly in those whose anti-hepatitis B therapy 
was withdrawn (see section 4.4). 
 
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 response syndrome 
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral 
therapy (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). 
 
Paediatric population 
 



16 

There are no clinical study data on the effects of Dovato 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 or lamivudine 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. 
 
Reporting of suspected adverse reactions 
 
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 or 
lamivudine, apart from those listed as adverse reactions. 
 
There is no specific treatment for an overdose of Dovato. 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. 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: J05AR25 
 
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. 
 
Lamivudine, via its active metabolite 5'-triphosphates (TP) (an analogue for cytidine), inhibits reverse 
transcriptase of HIV-1 and HIV-2 through incorporation of the monophosphate form into the viral DNA 
chain, resulting in chain termination. Lamivudine triphosphate shows significantly less affinity for host cell 
DNA polymerases. 
 
Pharmacodynamic effects 
 
Antiviral activity in cell culture  
Dolutegravir 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. 
 
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). 
 

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


17 

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 0.16 to 0.51 µM for lamivudine. 
The IC50 values of lamivudine 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 lamivudine (IC50 fold changes < 3.0). Group O isolates from 
antiviral naïve patients tested for lamivudine activity were highly sensitive. 
 
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 µg/mL. Lamivudine exhibits linear pharmacokinetics over the therapeutic dose range and 
displays low plasma protein binding (less than 36%).  
 
Resistance 
 
Dovato is indicated in the absence of documented or suspected resistance to the integrase inhibitor class and 
to lamivudine (see section 4.1). For information around in vitro resistance, and cross resistance to other 
agents of the integrase- and NRTI class, please refer to the SmPCs of dolutegravir and lamivudine.  
 
None of the eleven subjects in the dolutegravir plus lamivudine group or the seven subjects in the 
dolutegravir plus tenofovir disoproxil/emtricitabine FDC group that met virological withdrawal criteria 
through Week 96 across the GEMINI-1 (204861) and GEMINI-2 (205543) studies had treatment emergent 
integrase inhibitor or NRTI class resistance. 
 
In previously untreated patients receiving dolutegravir + 2 NRTIs in Phase IIb and Phase III, no development 
of resistance to the integrase inhibitor class, or to the NRTI class was seen (n=1118 follow-up of 
48-96 weeks).  
 
Effects on electrocardiogram 
 
No relevant effects were seen with dolutegravir on the QTc interval, with doses exceeding the clinical dose 
by approximately three fold. A similar study was not conducted with lamivudine. 
 
Clinical efficacy and safety  

Antiretroviral naïve subjects  

The efficacy of Dovato is supported by data from 2 identical 148-week, Phase III, randomised, double-blind, 
multicentre, parallel-group, non-inferiority controlled trials GEMINI-1 (204861) and GEMINI-2 (205543). A 
total of 1433 HIV-1 infected antiretroviral treatment-naïve adult subjects received treatment in the trials. 
Subjects were enrolled with a screening plasma HIV-1 RNA of 1000 c/mL to ≤500,000 c/mL. Subjects were 
randomised to a two-drug regimen of dolutegravir 50 mg plus lamivudine 300 mg once daily or dolutegravir 
50 mg plus tenofovir disoproxil/emtricitabine 245/200 mg once daily. The primary efficacy endpoint for 
each GEMINI trial was the proportion of subjects with plasma HIV-1 RNA <50 copies/mL at Week 48 
(Snapshot algorithm for the ITT-E population). Double blind therapy will continue up to week 96, followed 
by open label therapy up to week 148. 
 
At baseline, in the pooled analysis, the median age of subjects was 33 years, 15% were female, 69% were 
white, 9% were CDC Stage 3 (AIDS), 20% had HIV-1 RNA >100,000 copies/mL, and 8% had CD4+ cell 
count less than 200 cells per mm3; these characteristics were similar between studies and treatment arms.  
 
In the primary week 48 analysis, dolutegravir plus lamivudine was non-inferior to dolutegravir plus tenofovir 
disoproxil/emtricitabine FDC in GEMINI-1 and GEMINI-2 studies. This was supported by the pooled 
analysis, see Table 3. 



18 

Table 3 Virologic Outcomes of Randomised Treatment of GEMINI at Week 48 (Snapshot 
algorithm) 

 GEMINI-1 and GEMINI-2 Pooled 
Data* 

DTG + 3TC 
N=716 

DTG + TDF/FTC 
N=717 

HIV-1 RNA <50 copies/mL 91% 93% 
 Treatment Difference† (95% confidence intervals) -1.7 (-4.4, 1.1) 
Virologic non response 3% 2% 
Reasons   

Data in window and ≥50 copies/mL  1% <1% 
Discontinued for lack of efficacy <1% <1% 
Discontinued for other reasons and ≥50 copies/mL <1% <1% 
Change in ART <1% <1% 

No virologic data at Week 48 window 6% 5%  
Reasons   

Discontinued study due to adverse event or death  1% 2% 
Discontinued study for other reasons 4% 3%  
Missing data during window but on study <1% 0% 

HIV-1 RNA <50 copies/mL by baseline covariates 
 n/N (%) n/N (%) 
Baseline Plasma Viral Load (copies/mL) 
≤100,000 
>100,000 

 
526 / 576 (91%) 
129 / 140 (92%) 

 
531 / 564 (94%) 
138 / 153 (90%) 

Baseline CD4+ (cells/ mm3)   
≤200  50 / 63 (79%) 51 / 55 (93%) 
 >200 605 / 653 (93%) 618 / 662 (93%) 
HIV-1 subtype   
 B 424 / 467 (91%) 452 / 488 (93%) 
 A 84 / 86 (98%) 74 / 78 (95%) 
 Other 147 / 163 (90%) 143 / 151 (95%) 
Gender   
 Male  555 / 603 (92%) 580 / 619 (94%) 
 Female  100 / 113 (88%) 89 / 98 (91%) 
Race    
 White  451 / 484 (93%) 473 / 499 (95%) 
 African-American/African Heritage/Other 204 / 232 (88%) 196 / 218 (90%) 
* The results of the pooled analysis are in line with those of the individual studies, for which the primary 
endpoint (difference in proportion <50 copies/mL plasma HIV-1 RNA at Week 48 based on the 
Snapshot algorithm for dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil 
/emtricitabine FDC) was met. The adjusted difference was -2.6 (95% CI: -6.7; 1.5) for GEMINI-1 and -
0.7 (95% CI: -4.3; 2.9) for GEMINI-2 with a prespecified non-inferiority margin of 10%. 
† Based on CMH-stratified analysis adjusting for the following baseline stratification factors: Plasma 
HIV-1 RNA (≤100,000 c/mL vs. >100,000 c/mL) and CD4+ cell count 
(≤200 cells/mm3 vs. >200 cells/mm3). Pooled analysis also stratified by study. Assessed using a 
non-inferiority margin of 10%. 
N = Number of subjects in each treatment group 

 
At 96 weeks in the GEMINI-1 and GEMINI-2 studies, the dolutegravir plus lamivudine group (86% with 
plasma HIV-1 RNA < 50 copies/mL [pooled data]) remained non-inferior to the dolutegravir plus 
tenofovir/emtricitabine FDC group (90% with plasma HIV-1 RNA < 50 copies/mL [pooled data]). The 
adjusted difference in proportions and 95% CI was -3.4% (-6.7, 0.0). The results of the pooled analysis were 
in line with those of the individual studies, for which the secondary endpoint (difference in proportion <50 
copies/mL plasma HIV-1 RNA at week 96 based on the Snapshot algorithm for dolutegravir plus lamivudine 
versus dolutegravir plus tenofovir/emtricitabine FDC) was met. The adjusted differences 



19 

of -4.9 (95% CI: -9.8; 0.0) for GEMINI-1 and -1.8 (95% CI: -6.4; 2.7) for GEMINI-2 were within the 
prespecified non-inferiority margin of -10%.  
 
The mean increase in CD4+ T-cell counts was 269 in the dolutegravir plus lamivudine arm and 259 in the 
dolutegravir plus tenofovir/emtricitabine arm, at week 96. 
 
Virologically suppressed subjects 
 
The efficacy of dolutegravir/lamivudine in virologically suppressed subjects is supported by data from a 
randomised, open-label, trial (TANGO [204862]). A total of 741 adult HIV-1 infected subjects, without any 
evidence of resistance to the NRTI or integrase inhibitor (INSTI) class and who were on a stable suppressive 
tenofovir alafenamide based regimen (TBR) received treatment in the studies. Subjects were randomised in a 
1:1 ratio to receive dolutegravir/lamivudine FDC or continue with TBR for up to 200 weeks. Randomisation 
was stratified by baseline core agent class (protease inhibitor [PI], INSTI, or non-nucleoside reverse 
transcriptase inhibitor [NNRTI]). The primary efficacy endpoint was the proportion of subjects with plasma 
HIV-1 RNA ≥50 c/mL (virologic non-response) as per the FDA Snapshot category at Week 48 (adjusted for 
randomisation stratification factor). 
 
At baseline the median age of subjects was 39 years, 8% were female and 21% non-white, 5% were CDC 
Class C (AIDS) and 98% subjects had Baseline CD4+ cell count ≥200 cells/mm3; these characteristics were 
similar between treatment arms. Subjects had been on ART for a median of around 3 years prior to Day 1 
Around 80% were on INSTI-based TBR (mainly elvitegravir/c) at baseline. 
 
The primary analysis demonstrated that dolutegravir/lamivudine is non-inferior to TBR, with <1% of 
subjects in both arms experiencing virologic failure (HIV-1 RNA ≥50 c/mL) at Week 48 (Table 4). 
 
Table 4 Virologic Outcomes of Randomised Treatment of TANGO at Week 48 (Snapshot 

algorithm) 
 DTG/3TC 

N=369 
TBR 

N=372 
HIV-1 RNA <50 copies/mL* 93% 93% 
Virologic non response (≥50 copies/mL)** <1% <1% 
Treatment Difference† (95% confidence intervals) -0.3 (-1.2, 0.7) 
Reasons for virologic non response:   

Data in window and ≥50 copies/mL  0% 0% 
Discontinued for lack of efficacy 0% <1% 
Discontinued for other reasons and ≥50 copies/mL <1% 0% 
Change in ART 0% 0% 

No virologic data at Week 48 window 7% 6%  
Reasons   

Discontinued study due to adverse event or death  3% <1% 
Discontinued study for other reasons 3% 6%  
Missing data during window but on study 0% <1% 

*Based on an 8% non-inferiority margin, DTG/3TC is non-inferior to TBR at Week 48 in the secondary 
analysis (proportion of subjects achieving <50 copies/mL plasma HIV-1 RNA). 
**Based on a 4% non-inferiority margin, DTG/3TC is non-inferior to TBR at Week 48 in the primary 
analysis (proportion of subjects with plasma HIV-1 RNA ≥50 c/mL).  
†Based on CMH-stratified analysis adjusting for Baseline third agent class (PI, NNRTI, INSTI).  
N = Number of subjects in each treatment group; TBR = tenofovir alafenamide based regimen.  
 

Treatment outcomes between treatment arms at week 48 were similar across the stratification factor, baseline 
third agent class and across subgroups by age, sex, race, baseline CD4+ cell count, CDC HIV disease stage, 
and countries. The median change from baseline in CD4+ count at Week 48 was 22.5 cells per mm3 in 
subjects who switched to dolutegravir/lamivudine and 11.0 cells per mm3 in subjects who stayed on TBR. 
 



20 

Paediatric population 
The efficacy of Dovato, or the dual combination of dolutegravir plus lamivudine (as single entities) has not 
been studied in children or adolescents. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with Dovato in 
one or more subsets of the paediatric population in the treatment of HIV infection. 
 
 
5.2 Pharmacokinetic properties 
 
When administered in fasted state, bioequivalence regarding Cmax was achieved for dolutegravir, when 
comparing Dovato to dolutegravir 50 mg co-administered with lamivudine 300 mg. Dolutegravir AUC0-t was 
16% higher for Dovato than for dolutegravir 50 mg co-administered with lamivudine 300 mg. This increase 
is not considered clinically relevant. 
 
When administered in fasted state, bioequivalence was achieved for lamivudine AUC, when comparing 
Dovato to lamivudine 300 mg co-administered with dolutegravir 50 mg. Lamivudine Cmax for Dovato was 
32% higher than lamivudine 300 mg co-administered with dolutegravir 50 mg. The higher lamivudine Cmax, 
is not considered clinically relevant. 
 
Absorption  
 
Dolutegravir and lamivudine are rapidly absorbed following oral administration. The absolute bioavailability 
of dolutegravir has not been established. The absolute bioavailability of oral lamivudine in adults is 
approximately 80-85%. For Dovato, the median time to maximal plasma concentration (tmax) is 2.5 hours for 
dolutegravir and 1.0 hour for lamivudine, when dosed under fasted conditions. 
 
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 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) AUC(0-24) is 8.87 µg.h/mL (21%). 
 
Administration of a single Dovato tablet with a high fat meal increased dolutegravir AUC(0-∞) and Cmax by 
33% and 21%, respectively, and decreased the lamivudine Cmax by 30% compared to fasted conditions. The 
lamivudine AUC(0-∞) was not affected by a high fat meal. These changes are not clinically significant. Dovato 
may be administered with or without food. 
 
Distribution  
 
The apparent volume of distribution of dolutegravir (Vd/F) is 17-20 L. Intravenous studies with lamivudine 
showed that the mean apparent volume of distribution is 1.3 L/kg. 
 
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. Lamivudine 
exhibits linear pharmacokinetics over the therapeutic dose range and displays limited plasma protein binding 
in vitro (< 16%- 36% to serum albumin). 
 
Dolutegravir 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). The mean ratio of CSF/serum 



21 

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). 
 
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 (OATP) 1B1, 
OATP1B3, OCT1, MATE2-K, multidrug resistance-associated protein (MRP) 2 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, 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 medicinal products 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 observed lamivudine half-life of elimination is 18 to 19 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) 
 



22 

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. 
 
Special patient populations 
 
Children 
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.  
 
Limited data are available in adolescents receiving a daily dose of 300 mg of lamivudine. Pharmacokinetic 
parameters are comparable to those reported in adults. 
 
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 and lamivudine in subjects >65 years of age are limited. 
 
Renal impairment 
Pharmacokinetic data have been obtained for dolutegravir and lamivudine 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. 
 
Studies with lamivudine show that plasma concentrations (AUC) are increased in patients with renal 
dysfunction due to decreased clearance.  
 
Based on the lamivudine data, Dovato is not recommended for patients with creatinine clearance of 
< 50 mL/min. 
 
Hepatic impairment 
Pharmacokinetic data has been obtained for dolutegravir and lamivudine separately.  
 
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. 
 
Data obtained in patients with moderate to severe hepatic impairment show that lamivudine 
pharmacokinetics are not significantly affected by hepatic dysfunction. 
 
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). 



23 

 
Gender 
Population PK analyses using pooled pharmacokinetic data from clinical studies where dolutegravir or 
lamivudine was administered to adults in combination with other ARVs revealed no clinically relevant effect 
of gender on the exposure of dolutegravir or lamivudine. There is no evidence that a dose adjustment of 
dolutegravir or lamivudine would be required based on the effects of gender on PK parameters. 
 
Race  
Population PK analyses using pooled pharmacokinetic data from clinical studies where dolutegravir was 
administered to adults in combination with other ARVs 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 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 and lamivudine in animals. 
 
Carcinogenesis and mutagenesis 
 
Dolutegravir was not mutagenic or clastogenic using in vitro tests in bacteria and cultured mammalian cells, 
and an in vivo rodent micronucleus assay. Lamivudine was not mutagenic in bacterial tests, but consistent 
with other nucleoside analogues, inhibits cellular DNA replication in in vitro mammalian tests such as the 
mouse lymphoma assay. The results from two in vivo rat micronucleus tests with lamivudine were negative. 
Lamivudine has not shown any genotoxic activity in the in vivo studies.  
 
The carcinogenic potential of a combination of dolutegravir 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.  
 
Reproductive toxicology studies 
 
In reproductive toxicity studies in animals, dolutegravir and lamivudine 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 (37.2 times the 50 mg 
human clinical exposure, based on AUC following single dose in the fasted state). 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 (0.55 times the 50 mg human clinical exposure, based on AUC 
following single dose in the fasted state). In rabbits, maternal toxicity (decreased food consumption, scant/no 
faeces/urine, suppressed body weight gain) was observed at 1000 mg/kg (0.55 times the 50 mg human 
clinical exposure, based on AUC following single dose in the fasted state). 
 
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. 
 
Fertility studies in rats have shown that dolutegravir or lamivudine have no effect on male or female fertility. 
 
Repeated dose toxicity 



24 

 
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 28.5 and 1.1 times the 50 mg human clinical exposure following single dose in the 
fasted state 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. 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Microcrystalline cellulose  
Sodium starch glycolate 
Magnesium Stearate 
Mannitol (E421) 
Povidone (K29/32) 
Sodium stearyl fumarate 
 
Tablet coating 
 
Hypromellose (E464) 
Macrogol 
Titanium dioxide (E171) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container  
 
Opaque, white HDPE (high density polyethylene) bottles closed with child resistant polypropylene closures, 
with a polyethylene faced induction heat seal liner. Each pack consists of one bottle containing 30 film-
coated tablets. 
 
Multipacks containing 90 (3 packs of 30) film-coated tablets. 
 
6.6 Special precautions for disposal  
 
No special requirements for disposal. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 



25 

ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1370/001 
EU/1/19/1370/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorization: 1st July 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/


26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

 

A. MANUFACTURERS 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 

 

 



27 

A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer(s) responsible for batch release  
 
GLAXO WELLCOME, S.A. 
Avda. Extremadura, 3 
09400 Aranda De Duero 
Burgos 
Spain 

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.  

  



28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



30 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (INDIVIDUAL PACKS ONLY) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Dovato 50 mg/300 mg film-coated tablets 
dolutegravir/lamivudine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains dolutegravir sodium equivalent to 50 mg dolutegravir and 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 
 
 
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 
 



31 

ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1370/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
dovato  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN:  
 
 



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON (MULTIPACKS ONLY – WITH BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Dovato 50 mg/300 mg film-coated tablets 
dolutegravir/lamivudine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains dolutegravir sodium equivalent to 50 mg dolutegravir and 300 mg 
lamivudine. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 90 (3 packs of 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 
 
 
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 
 



33 

ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1370/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
dovato 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN:  
 
 
  



34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INTERMEDIATE CARTON (WITHOUT BLUE BOX – COMPONENT OF MULTIPACK) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Dovato 50 mg/300 mg film-coated tablets 
dolutegravir/lamivudine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains dolutegravir sodium equivalent to 50 mg dolutegravir and 300 mg 
lamivudine. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 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 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
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 
 



35 

ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1370/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
dovato 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 
  



36 

 
 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Dovato 50 mg/300 mg tablets 
dolutegravir/lamivudine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains dolutegravir sodium equivalent to 50 mg dolutegravir and 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 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



37 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1370/001 
EU/1/19/1370/002 
 
 
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 
 
 
  



38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



39 

Package leaflet: Information for the patient 
 

Dovato 50 mg/300 mg film-coated tablets 
dolutegravir/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 Dovato is and what it is used for  
2. What you need to know before you take Dovato  
3. How to take Dovato 
4. Possible side effects  
5. How to store Dovato  
6. Contents of the pack and other information 
 
 
1. What Dovato is and what it is used for 
 
Dovato is a medicine that contains two active ingredients used to treat human immunodeficiency virus (HIV) 
infection: dolutegravir and lamivudine. Dolutegravir belongs to a group of anti-retroviral medicines called 
integrase inhibitors (INIs), and lamivudine belongs to a group of anti-retroviral medicines called nucleoside 
analogue reverse transcriptase inhibitors (NRTIs). 
 
Dovato is used to treat HIV in adults and adolescents over 12 years old who weigh at least 40 kg. 
 
Dovato does not cure HIV infection; it keeps the amount of virus in your body at a low level. This helps 
maintain 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 Dovato in the same way. Your doctor will monitor the effectiveness 
of your treatment. 
 
 
2. What you need to know before you take Dovato 
 
Do not take Dovato: 

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

• 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 
Some people taking Dovato 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 



40 

• if you have ever had liver disease, including hepatitis B or C (if you have hepatitis B infection, don’t 
stop Dovato without your doctor’s advice, as your hepatitis may come back) 

• if you have a kidney problem. 
→ Talk to your doctor before using Dovato if any of these apply to you. You may need extra check-
ups, including blood tests, while you’re taking your medicine. See section 4 for more information. 

 
Allergic reactions 
Dovato contains dolutegravir. Dolutegravir can cause a serious allergic reaction known as a hypersensitivity 
reaction. You need to know about important signs and symptoms to look out for while you’re taking Dovato. 

→ Read the information ‘Allergic reactions’ in section 4 of this leaflet. 
 
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 Dovato. 
→ Read the information ‘Other possible side effects’ 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. Discuss with your doctor the precautions 
needed to avoid infecting other people. 
 
Children 
This medicine is not for use in children under 12 years of age, because it has not been studied in these 
patients. 
 
Other medicines and Dovato 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Don't take Dovato with the following medicine: 

• fampridine (also known as dalfampridine), used in multiple sclerosis. 
 
Some medicines can affect how Dovato works or make it more likely that you will have side effects. Dovato 
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 Dovato, or for at least 2 hours after you take it (see also section 3, ‘How to 
take Dovato’) 

• supplements or multivitamins containing calcium, iron or magnesium. If you take Dovato with 
food, you can take supplements or multivitamins containing calcium, iron or magnesium at the same 
time as Dovato. If you do not take Dovato with food, do not take a supplement or multivitamin 
containing calcium, iron or magnesium during the 6 hours before you take Dovato, or for at least 
2 hours after you take it (see also section 3, ‘How to take Dovato’) 

• 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 
• cladribine, to treat leukaemia or multiple sclerosis  
• rifampicin, to treat tuberculosis (TB) and other bacterial infections 
• phenytoin and phenobarbital, to treat epilepsy 
• oxcarbazepine and carbamazepine, to treat epilepsy or bipolar disorder 
• St. John’s wort (Hypericum perforatum), a herbal remedy to treat depression. 



41 

 → 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 check ups. 

 
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 Dovato. 
 
Taking Dovato at the time of becoming pregnant or during the first six weeks of pregnancy, may increase the 
risk of a birth defect, called neural tube defect, such as spina bifida (malformed spinal cord). 
 
If you could get pregnant while taking Dovato: 
 → Talk to your doctor and discuss whether there is a need for contraception, such as condom or 
pills. 
 
Tell your doctor immediately if you become pregnant or are planning to become pregnant. Your doctor will 
review your treatment. Do not stop taking Dovato without consulting your doctor, as this may harm you and 
your unborn child.  
 
Breast-feeding 
Women who are HIV-positive must not breast feed because HIV infection can be passed on to the baby in 
breast milk.  
 
A small amount of the ingredients in Dovato 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 
Dovato can make you dizzy, and have other side effects that make you less alert. 
 → Don’t drive or operate machinery unless you are sure you’re not affected. 
 
 
3. How to take Dovato 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you 
are not sure. 
 

• The recommended dose of Dovato is one tablet once a day. 
 
Swallow the tablet with some liquid. Dovato can be taken with or without food. 
 
Use in adolescents 
Adolescents aged between 12 and 17 years and weighing at least 40 kg can take the adult dose of one tablet 
once a day. 
 
Antacid medicines 
Antacids, to treat indigestion and heartburn, can stop Dovato being absorbed into your body and make it less 
effective. 
Do not take an antacid during the 6 hours before you take Dovato, or for at least 2 hours after you take it. 
You can take other acid-lowering medicines like ranitidine and omeprazole at the same time as Dovato. 
 → Talk to your doctor for further advice on taking acid-lowering medicines with Dovato. 
 
Supplements or multivitamins containing calcium, iron or magnesium 
Supplements or multivitamins containing calcium, iron or magnesium can stop Dovato being absorbed into 
your body and make it less effective. 



42 

If you take Dovato with food, you can take supplements or multivitamins containing calcium, iron or 
magnesium at the same time as Dovato. If you do not take Dovato with food, do not take a supplement or 
multivitamin containing calcium, iron or magnesium during the 6 hours before you take Dovato, 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 Dovato. 
 
If you take more Dovato than you should 
If you take too many tablets of Dovato contact your doctor or pharmacist for advice. If possible, show 
them the Dovato pack. 
 
If you forget to take Dovato 
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. 
 →Do not take a double dose to make up for a forgotten dose. 
 
Don’t stop taking Dovato without advice from your doctor 
Take Dovato for as long as your doctor recommends. Don’t stop unless your doctor tells you to. Stopping 
Dovato can affect your health and how future treatment works. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects   
 
Like all medicines, this medicine can cause side effects, although not everybody gets them, so it is very 
important to talk to your doctor about any changes in your health. 
 
Allergic reactions 
Dovato contains dolutegravir. Dolutegravir can cause a serious allergic reaction known as a hypersensitivity 
reaction. This is an uncommon reaction (may affect up to 1 in 100 people) in people taking dolutegravir. If 
you get any of the following symptoms: 

• skin rash 
• a high temperature (fever) 
• lack of energy (fatigue) 
• swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
• muscle or joint aches. 
→ See a doctor straight away. Your doctor may decide to carry out tests to check your liver, kidneys or 
blood, and may tell you to stop taking Dovato. 

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

• headache 
• diarrhoea 
• feeling sick (nausea).  

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

• depression (feelings of deep sadness and unworthiness) 
• rash 
• itching (pruritus) 
• being sick (vomiting) 
• stomach (abdominal) pain or discomfort 
• wind (flatulence) 
• dizziness 
• feeling drowsy 



43 

• difficulty sleeping (insomnia) 
• abnormal dreams 
• lack of energy (fatigue) 
• hair loss 
• anxiety 
• joint pain 
• muscle pain. 

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

• increase in the level of liver enzymes (aminotransferases) 
• increase in the level of enzymes produced in the muscles (creatine phosphokinase). 

 
Uncommon side effects  
These may affect up to 1 in 100 people: 

• inflammation of the liver (hepatitis) 
• suicidal attempt (particularly in patients who have had depression or mental health problems before) 
• suicidal thoughts (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). 

 
Rare side effects  
These may affect up to 1 in 1000 people: 

• liver failure (signs may include yellowing of the skin and the whites of the eyes or unusually dark 
urine) 

• swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing 
• inflammation of the pancreas (pancreatitis) 
• breakdown of muscle tissue. 

 
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: 

• lactic acidosis (excess lactic acid in the blood) 
• numbness, tingly feelings in the skin (pins and needles) 
• sensation of weakness in the limbs. 

 
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). 
 
Other possible side effects 

People taking combination therapy for HIV may get other side effects. 
 
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 



44 

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 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. 
 
Joint pain, stiffness and bone problems 

Some people taking combination therapy for HIV develop a condition called osteonecrosis. With this 
condition, parts of the bone tissue are permanently damaged 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 in the joints (especially in the hip, knee or shoulder) 
• difficulty moving. 

If you notice any of these symptoms: 
 → Tell your doctor. 
 
Weight, blood lipid and blood glucose 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 lifestyle, and in the case of blood lipids sometimes to the HIV medicines 
themselves. Your doctor will test for these changes. 
 
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 Dovato 
 
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. The expiry 
date refers to the last day of that month. 
 
This medicine does not require any special 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. 
 

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


45 

6. Contents of the pack and other information 
 
What Dovato contains  
• The active substances are dolutegravir and lamivudine. Each tablet contains dolutegravir sodium 

equivalent to 50 mg dolutegravir and 300 mg lamivudine. 
• The other ingredients are microcrystalline cellulose, sodium starch glycolate, magnesium stearate, 

mannitol (E421), povidone (K29/32), sodium stearyl fumarate, hypromellose (E464), macrogol, 
titanium dioxide (E171). 

• This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’. 

 
What Dovato looks like and contents of the pack 
 
Dovato film-coated tablets are oval, biconvex, white tablets debossed with 'SV 137' on one face. 
 
The film-coated tablets are provided in bottles closed with child-resistant closures. 
 
Each bottle contains 30 film-coated tablets. 
 
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 
 
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 

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



46 

dk-info@gsk.com 
 
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 
 

 
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 16051 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 397000 
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  

 

mailto:viiv.med.info@viivhealthcare.com
mailto:es-ci@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com


47 

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.  


	ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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