Kivexa

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Kivexa 600 mg/300 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 600 mg of abacavir (as sulfate) and 300 mg lamivudine. 
 
Excipient(s) with known effect: sunset yellow FCF (E110) 1.7 mg per tablet 
 
For the full list of excipients see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Orange, film-coated, modified capsule shaped tablets, debossed with GS FC2 on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Kivexa is indicated in antiretroviral combination therapy for the treatment of Human 
Immunodeficiency Virus (HIV) infection in adults, adolescents and children weighing at least 25 kg 
(see sections 4.4 and 5.1).  
 
Before initiating treatment with abacavir, screening for carriage of the HLA-B*5701 allele should be 
performed in any HIV-infected patient, irrespective of racial origin (see section 4.4). Abacavir should 
not be used in patients known to carry the HLA-B*5701 allele. 
 
4.2 Posology and method of administration 
 
Therapy should be prescribed by a physician experienced in the management of HIV infection. 
 
Posology 
 
Adults, adolescents and children weighing at least 25 kg: 
 
The recommended dose of Kivexa is one tablet once daily. 
 
Children Under 25 kg:  
Kivexa should not be administered to children who weigh less than 25 kg because it is a fixed-dose 
tablet that cannot be dose reduced.  
 
Kivexa is a fixed-dose tablet and should not be prescribed for patients requiring dose adjustments. 
Separate preparations of abacavir or lamivudine are available in cases where discontinuation or dose 
adjustment of one of the active substances is indicated. In these cases the physician should refer to the 
individual product information for these medicinal products. 
 
Special Populations 
 
Elderly:  



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No pharmacokinetic data are currently available in patients over 65 years of age. Special care is 
advised in this age group due to age associated changes such as the decrease in renal function and 
alteration of haematological parameters. 
 
Renal impairment:  
Kivexa is not recommended for use in patients with a creatinine clearance < 50 ml/min as necessary 
dose adjustment cannot be made (see section 5.2). 
 
Hepatic impairment:  
Abacavir is primarily metabolised by the liver. No clinical data are available in patients with moderate 
or severe hepatic impairment, therefore the use of Kivexa is not recommended unless judged necessary. 
In patients with mild hepatic impairment (Child-Pugh score 5-6) close monitoring is required, including  
monitoring of abacavir plasma levels if feasible (see sections 4.4 and 5.2).  
 
Paediatric population:  
The safety and efficacy of Kivexa in children weighing less than 25 kg has not been established.  
 
Currently available data are described in section 4.8, 5.1 and 5.2 but no recommendation on posology 
can be made. 
 
Method of administration  
 
Oral use 
 
Kivexa can be taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. See sections 
4.4 and 4.8. 
 
 
4.4 Special warnings and precautions for use 
 
The special warnings and precautions relevant to abacavir and lamivudine are included in this section. 
There are no additional precautions and warnings relevant to Kivexa. 
 
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the 
risk of sexual transmission, a residual risk cannot be excluded.  Precautions to prevent transmission 
should be taken in accordance with national guidelines.   
 

Hypersensitivity reactions (see also section 4.8 ) 
 
Abacavir is associated with a risk for hypersensitivity reactions (HSR) (see section4.8) ) characterised 
by fever and/or rash with other symptoms indicating multi-organ involvement. HSRs have been 
observed with abacavir, some of which have been life-threatening, and in rare cases fatal, when not 
managed appropriately. 
 
The risk for abacavir HSR to occur is high for patients who test positive for the HLA-B*5701 allele. 
However, abacavir HSRs have been reported at a lower frequency in patients who do not carry this 
allele.   
 

Therefore the following should be adhered to: 



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• HLA-B*5701 status must always be documented prior to initiating therapy. 

• Kivexa should never be initiated in patients with a positive HLA-B*5701 status, nor in patients 
with a negative HLA-B*5701 status who had a suspected abacavir HSR on a previous abacavir-
containing regimen. (e.g. Ziagen, Trizivir, Triumeq)  

• Kivexa must be stopped without delay, even in the absence of the HLA-B*5701 allele, if an 
HSR is suspected. Delay in stopping treatment with Kivexa after the onset of hypersensitivity 
may result in a life-threatening reaction.  

• After stopping treatment with Kivexa for reasons of a suspected HSR, Kivexa or any other 
medicinal product containing abacavir (e.g. Ziagen, Trizivir, Triumeq) must never be re-
initiated.  

• Restarting abacavir containing products following a suspected abacavir HSR can result in a 
prompt return of symptoms within hours. This recurrence is usually more severe than on initial 
presentation, and may include life-threatening hypotension and death. 

• In order to avoid restarting abacavir, patients who have experienced a suspected HSR should be 
instructed to dispose of their remaining Kivexa tablets  

 
• Clinical Description of abacavir HSR 
 
Abacavir HSR has been well characterised through clinical studies and during post marketing follow-up. 
Symptoms usually appeared within the first six weeks (median time to onset 11 days) of initiation of 
treatment with abacavir, although these reactions may occur at any time during therapy. 
 
Almost all HSR to abacavir include fever and/or rash. Other signs and symptoms that have been 
observed as part of abacavir HSR are described in detail in section 4.8 (Description of selected adverse 
reactions), including respiratory and gastrointestinal symptoms. Importantly, such symptoms may lead 
to misdiagnosis of HSR as respiratory disease (pneumonia, bronchitis, pharyngitis), or 
gastroenteritis. 
 
The symptoms related to HSR worsen with continued therapy and can be life-threatening. These 
symptoms usually resolve upon discontinuation of abacavir.  
Rarely, patients who have stopped abacavir for reasons other than symptoms of HSR have also 
experienced life-threatening reactions within hours of re- initiating abacavir therapy (see Section 4.8 
Description of selected adverse reactions).  Restarting abacavir in such patients must be done in a 
setting where medical assistance is readily available. 

 
 
Weight and metabolic parameters 

An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. 
Such changes may in part be linked to disease control and life style. For lipids, there is in some cases 
evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any 
particular treatment. For monitoring of blood lipids and glucose reference is made to established HIV 
treatment guidelines. Lipid disorders should be managed as clinically appropriate. 

 
Pancreatitis  
 
Pancreatitis has been reported, but a causal relationship to lamivudine and abacavir is uncertain. 
 
Risk of virological failure  



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- Triple nucleoside therapy: There have been reports of a high rate of virological failure, and of 
emergence of resistance at an early stage when abacavir and lamivudine were combined with tenofovir 
disoproxil fumarate as a once daily regimen. 
- The risk of virological failure with Kivexa might be higher than with other therapeutic options (see 
section 5.1).  
 
Liver disease  
 
The safety and efficacy of Kivexa has not been established in patients with significant underlying liver 
disorders. Kivexa is not recommended in patients with moderate or severe hepatic impairment (see 
sections 4.2 and 5.2).  
 
Patients with pre-existing liver dysfunction, including chronic active hepatitis have an increased 
frequency of liver function abnormalities during combination antiretroviral therapy, and should be 
monitored according to standard practice. If there is evidence of worsening liver disease in such 
patients, interruption or discontinuation of treatment must be considered.  
 
Patients co-infected with chronic hepatitis B or C virus 
 
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.  
 
If lamivudine is being used concomitantly for the treatment of HIV and hepatitis B virus (HBV), 
additional information relating to the use of lamivudine in the treatment of hepatitis B infection can be 
found in the Summary of Product Characteristics for  products containing lamivudine that are indicated 
for the treatment of HBV. 
 
If Kivexa is discontinued in patients co-infected with HBV, 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 (see the Summary of Product Characteristics for products containing 
lamivudine that are indicated for the treatment of HBV). 
 
 
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. 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  nucleotide and nucleotide  analogues, who 
presents with severe clinical findings of unknown etiology, particularly neurologic findings.. These 
findings do not affect current national recommendations to use antiretroviral therapy in pregnant 
women to prevent vertical transmission of HIV. 
 
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 



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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. 
 
Osteonecrosis  
 
Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV-disease and/or long-term exposure to CART. 
Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness 
or difficulty in movement. 
 
 
Opportunistic infections  
 
Patients should be advised that Kivexa 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. 

Myocardial infarction  

Observational studies have shown an association between myocardial infarction and the use of 
abacavir. Those studied were mainly antiretroviral experienced patients. Data from clinical trials 
showed limited numbers of myocardial infarction and could not exclude a small increase in risk.  
Overall the available data from observational cohorts and from randomised trials show some 
inconsistency so can neither confirm nor refute a causal relationship between abacavir treatment and 
the risk of myocardial infarction.  To date, there is no established biological mechanism to explain a 
potential increase in risk.  When prescribing Kivexa, action should be taken to try to minimize all 
modifiable risk factors (e.g. smoking, hypertension, and hyperlipidaemia). 

Drug Interactions: 

Kivexa should not be taken with any other medicinal products containing lamivudine or medicinal 
products containing emtricitabine. 
 
The combination of lamivudine with cladribine is not-recommended (see section 4.5). 
 
Excipients 
 
Kivexa contains the azo colouring agent sunset yellow, which may cause allergic reactions. 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Kivexa contains abacavir and lamivudine, therefore any interactions identified for these individually 
are relevant to Kivexa. Clinical studies have shown that there are no clinically significant interactions 
between abacavir and lamivudine. 
 
Abacavir is metabolised by UDP-glucuronyltransferase (UGT) enzymes and alcohol dehydrogenase; 
co-administration of inducers or inhibitors of UGT enzymes or with compounds eliminated through 
alcohol dehydrogenase could alter abacavir exposure. Lamivudine is cleared renally. Active renal 



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secretion of lamivudine in the urine is mediated through organic cation transporters (OCTs); 
co-administration of lamivudine with OCT inhibitors may increase lamivudine exposure.  
 
Abacavir and lamivudine are not significantly metabolised by cytochrome P450 enzymes (such as CYP 
3A4, CYP 2C9 or CYP 2D6) nor do they inhibit or induce this enzyme system. Therefore, there is little 
potential for interactions with antiretroviral protease inhibitors, non-nucleosides and other medicinal 
products metabolised by major P450 enzymes.  
 
Kivexa should not be taken with any other medicinal products containing lamivudine (see section 4.4). 
 
The list below should not be considered exhaustive but is representative of the classes studied. 
 
 

Drugs by Therapeutic Area 
 

Interaction 
Geometric mean change (%) 
(Possible mechanism) 

Recommendation concerning 
co-administration 

ANTIRETROVIRAL MEDICINAL PRODUCTS 
Didanosine /Abacavir Interaction not studied. No dosage adjustment 

necessary. Didanosine/Lamivudine Interaction not studied. 
Zidovudine/Abacavir Interaction not studied 
Zidovudine/Lamivudine  
Zidovudine 300 mg single dose  
Lamivudine 150 mg single dose   

Lamivudine: AUC  ↔ 
Zidovudine : AUC  ↔ 

Emtricitabine/Lamivudine  Due to similarities, Kivexa 
should not be administered 
concomitantly with other 
cytidine analogues, such as 
emtricitabine. 

ANTI-INFECTIVE PRODUCTS 
Trimethoprim/sulfamethoxazole 
(Co-trimoxazole)/Abacavir 

Interaction not studied. No Kivexa dosage adjustment 
necessary. 
 
When concomitant 
administration with 
co-trimoxazole is warranted, 
patients should be monitored 
clinically.  High doses of 
trimethoprim/ 
sulfamethoxazole for the 
treatment of Pneumocystis  
jirovecii  pneumonia (PCP) 
and toxoplasmosis have not 
been studied and should be 
avoided 

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

Lamivudine: AUC ↑40% 
 
Trimethoprim: AUC ↔ 
Sulfamethoxazole: AUC ↔ 
 
(organic cation transporter 
inhibition) 

ANTIMYCOBACTERIALS 
Rifampicin/Abacavir Interaction not studied. 

 
Potential to slightly decrease 
abacavir plasma concentrations 
through UGT induction. 

Insufficient data to recommend 
dosage adjustment. 

Rifampicin/Lamivudine Interaction not studied. 
ANTICONVULSANTS 
Phenobarbital/Abacavir Interaction not studied. 

 
Insufficient data to recommend 
dosage adjustment. 



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Potential to slightly decrease 
abacavir plasma concentrations 
through UGT induction. 

 

Phenobarbital/Lamivudine Interaction not studied. 
Phenytoin/Abacavir Interaction not studied. 

 
Potential to slightly decrease 
abacavir plasma concentrations 
through UGT induction. 

Insufficient data to recommend 
dosage adjustment. 
 
Monitor phenytoin 
concentrations. 

Phenytoin/Lamivudine Interaction not studied. 



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Drugs by Therapeutic Area 
 

Interaction 
Geometric mean change (%) 
(Possible mechanism) 

Recommendation concerning 
co-administration 

ANTIHISTAMINES (HISTAMINE H2 RECEPTOR ANTAGONISTS) 
Ranitidine/Abacavir Interaction not studied. No dosage adjustment 

necessary. Ranitidine/Lamivudine Interaction not studied. 
 
Clinically significant interaction 
unlikely.  Ranitidine eliminated 
only in part by renal organic 
cation transport system. 

Cimetidine/Abacavir Interaction not studied. No dosage adjustment 
necessary. Cimetidine/Lamivudine Interaction not studied. 

 
Clinically significant interaction 
unlikely.  Cimetidine eliminated 
only in part by renal organic 
cation transport system. 

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 

Therefore, the concomitant use 
of lamivudine with cladribine 
is not recommended (see 
section 4.4). 

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

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

No Kivexa dosage adjustment 
necessary.   
 
Methadone dosage adjustment 
unlikely in majority of 
patients; occasionally 
methadone re-titration may be 
required. 

Methadone/Lamivudine Interaction not studied. 

 
RETINOIDS 
Retinoid compounds  
(e.g. isotretinoin)/Abacavir 

Interaction not studied. 
 
Possible interaction given 
common pathway of elimination 
via alcohol dehydrogenase. 

Insufficient data to 
recommend dosage 
adjustment. 

Retinoid compounds  
(e.g. isotretinoin)/Lamivudine 
No drug interaction studies 

Interaction not studied.  



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Abbreviations: ↑ = Increase; ↓ = decrease; ↔ = no significant change; AUC = area under the concentration versus time curve; 
Cmax = maximum observed concentration; CL/F = apparent oral clearance 
 
Paediatric population 
 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy  
 
As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in 
pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, 
the animal data as well as the clinical experience in pregnant women should be taken into account.  
 
Animal studies with abacavir have shown toxicity to the developing embryo and foetus in rats, but not 
in rabbits. Animal studies with lamivudine showed an increase in early embryonic deaths in rabbits but 
not in rats. (see section 5.3). The active ingredients of Kivexa may inhibit cellular DNA replication and 
abacavir has been shown to be carcinogenic in animal models (see section 5.3). The clinical relevance 
of these findings is unknown. Placental transfer of abacavir and lamivudine has been shown to occur in 
humans.  
 
In pregnant women treated with abacavir, more than 800 outcomes after first trimester exposure and 
more than 1000 outcomes after second and third trimester exposure indicate no malformative and 
foetal/neonatal effect. In pregnant women treated with lamivudine, more than 1000 outcomes from first 
trimester and more than 1000 outcomes from second and third trimester exposure indicate no 
malformative and foeto/neonatal effect. There are no data on the use of Kivexa in pregnancy, however 
the malformative risk is unlikely in humans based on those data. 
 
For patients co-infected with hepatitis who are being treated with a lamivudine containing medicinal 
product such as Kivexa and subsequently become pregnant, consideration should be given to the 
possibility of a recurrence of hepatitis on discontinuation of lamivudine.  
 

Drugs by Therapeutic Area 
 

Interaction 
Geometric mean change (%) 
(Possible mechanism) 

Recommendation concerning 
co-administration 

MISCELLANEOUS 
Ethanol/Abacavir 
(0.7 g/kg single dose/600 mg 
single dose) 

Abacavir: AUC ↑41% 
Ethanol: AUC ↔ 
 
(Inhibition of alcohol 
dehydrogenase) 

No dosage adjustment 
necessary. 

Ethanol/Lamivudine Interaction not studied. 
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 Kivexa 
with medicinal products 
containing sorbitol or other 
osmotic acting poly-alcohols 
or monosaccharide alcohols 
(e.g. xylitol, mannitol, lactitol, 
maltitol). Consider more 
frequent monitoring of HIV-1 
viral load when chronic 
coadministration cannot be 
avoided. 



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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 
 
Abacavir and its metabolites are excreted into the milk of lactating rats. Abacavir is also excreted into 
human milk.  
 
Based on more than 200 mother/child pairs treated for HIV, serum concentrations of lamivudine in 
breastfed infants of mothers treated for HIV are very low (< 4% of maternal serum concentrations) and 
progressively decrease to undetectable levels when breastfed infants reach 24 weeks of age. There are 
no data available on the safety of abacavir and lamivudine when administered to babies less than three 
months old.  
 
It is recommended that HIV infected women do not breast-feed their infants under any circumstances 
in order to avoid transmission of HIV. 
 
Fertility 
 
Studies in animals showed that neither abacavir nor lamivudine had any effect on fertility (see section 
5.3).   
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on ability to drive and use machines have been performed. The clinical status 
of the patient and the adverse reaction profile of Kivexa 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 adverse reactions reported for Kivexa were consistent with the known safety profiles of abacavir 
and lamivudine when given as separate medicinal products. For many of these adverse reactions it is 
unclear whether they are related to the active substance, the wide range of other medicinal products 
used in the management of HIV infection, or whether they are a result of the underlying disease 
process. 
Many of the adverse reactions listed in the table below occur commonly (nausea, vomiting, diarrhoea, 
fever, lethargy, rash) in patients with abacavir hypersensitivity. Therefore, patients with any of these 
symptoms should be carefully evaluated for the presence of this hypersensitivity (see section 4.4). Very 
rarely cases of erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis have 
been reported where abacavir hypersensitivity could not be ruled out. In such cases medicinal products 
containing abacavir should be permanently discontinued. 
 
Tabulated list of adverse reactions 
 
The adverse reactions considered at least possibly related to abacavir or lamivudine are listed by body 
system, organ class and absolute frequency. Frequencies are defined as very common (> 1/10), 
common (> 1/100 to < 1/10), uncommon (> 1/1000 to < 1/100), rare (> 1/10,000 to < 1/1000), very rare 
(< 1/10,000). 
  



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Body system Abacavir Lamivudine 
 

Blood and lymphatic systems 
disorders 
 

 Uncommon: Neutropenia and 
anaemia (both occasionally 
severe), thrombocytopenia 
Very rare: Pure red cell aplasia 
 

Immune system disorders Common: hypersensitivity 
 

 

Metabolism and nutrition 
disorders 
 

Common: anorexia 
Very rare: lactic acidosis 

Very rare: lactic acidosis 

Nervous system disorders 
 

Common: headache Common: Headache, insomnia. 
Very rare: Cases of peripheral 
neuropathy (or paraesthesia) 
have been reported 

Respiratory, thoracic and 
mediastinal disorders 
 

 Common: Cough, nasal 
symptoms 

Gastrointestinal disorders 
 

Common: nausea, vomiting, 
diarrhoea  
Rare: pancreatitis has been 
reported, but a causal 
relationship to abacavir 
treatment is uncertain 

Common: Nausea, vomiting, 
abdominal pain or cramps, 
diarrhoea 
Rare: Rises in serum amylase. 
Cases of pancreatitis have been 
reported 
 

Hepatobiliary disorders 
 

 Uncommon: Transient rises in 
liver enzymes (AST, ALT),  
Rare: Hepatitis 

Skin and subcutaneous tissue 
disorders 
 

Common: rash (without 
systemic symptoms) 
Very rare: erythema 
multiforme, Stevens-Johnson 
syndrome and toxic epidermal 
necrolysis 

Common: Rash, alopecia 
Rare: Angioedema 

Musculoskeletal and connective 
tissue disorders 
 

 Common: Arthralgia, muscle 
disorders  
Rare: Rhabdomyolysis 
 

General disorders and 
administration site conditions 
 

Common: fever, lethargy, 
fatigue. 

Common: fatigue, malaise, 
fever. 

 
Description of selected adverse reactions 
 
Abacavir hypersensitivity 
The signs and symptoms of this HSR are listed below. These have been identified either from clinical 
studies or post marketing surveillance. Those reported in at least 10% of patients with a 
hypersensitivity reaction are in bold text. 
 
Almost all patients developing hypersensitivity reactions will have fever and/or rash (usually 
maculopapular or urticarial) as part of the syndrome, however reactions have occurred without rash or 
fever. Other key symptoms include gastrointestinal, respiratory or constitutional symptoms such as 
lethargy and malaise.  
 



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Skin Rash (usually maculopapular or urticarial) 
 

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

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

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

Neurological/Psychiatry Headache, paraesthesia 
 

Haematological Lymphopenia 
 

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

Musculoskeletal Myalgia, rarely myolysis, arthralgia, elevated creatine phosphokinase 
 

Urology Elevated creatinine, renal failure 
 

Symptoms related to this HSR worsen with continued therapy and can be life- threatening and in rare 
instance, have been fatal. 
 
Restarting abacavir following an abacavir HSR results in a prompt return of symptoms within hours. 
This recurrence of the HSR is usually more severe than on initial presentation, and may include life-
threatening hypotension and death. Similar reactions have also occurred infrequently after restarting 
abacavir in patients who had only one of the key symptoms of hypersensitivity (see above) prior to 
stopping abacavir; and on very rare occasions have also been seen in patients who have restarted 
therapy with no preceding symptoms of a HSR (i.e., patients previously considered to be abacavir 
tolerant). 
 
Metabolic parameters                                                                                                                         
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see section 
4.4) 

 
Immune reactivation syndrome  
In HIV-infected patients with severe immune deficiency at the time of initiation of combination 
antiretroviral therapy, an inflammatory reaction to asymptomatic or residual opportunistic infections 
may arise. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been 
reported to occur in the setting of immune reconstitution; however, the reported time to onset is more 
variable and these events can occur many months after initiation of treatment (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). 
 
Paediatric population 

The safety database to support once daily dosing in paediatric patients comes from the ARROW Trial 
(COL105677) in which 669 HIV-1 infected paediatric subjects (from 12 months to ≤17 years old). 
received abacavir and lamivudine either once or twice daily (see section 5.1). Within this population, 
104 HIV-1 infected paediatric subjects weighing at least 25 kg received abacavir and lamivudine as 



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Kivexa once daily. No additional safety issues have been identified in paediatric subjects receiving 
either once or twice daily dosing compared to adults. 

 
 
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 abacavir or 
lamivudine, apart from those listed as undesirable effects.  
 
If overdose occurs the patient should be monitored for evidence of toxicity (see section 4.8), and 
standard supportive treatment applied as necessary. Since lamivudine is dialysable, continuous 
haemodialysis could be used in the treatment of overdose, although this has not been studied. It is not 
known whether abacavir can be removed by peritoneal dialysis or haemodialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, antivirals for treatment of HIV infections, 
combinations. ATC code: J05AR02.  
 
Mechanism of action: Abacavir and lamivudine are NRTIs, and are potent selective inhibitors of HIV-1 
and HIV-2 (LAV2 and EHO) replication. Both abacavir and lamivudine are metabolised sequentially 
by intracellular kinases to the respective 5'-triphosphate (TP) which are the active moieties. 
Lamivudine-TP and carbovir-TP (the active triphosphate form of abacavir) are substrates for and 
competitive inhibitors of HIV reverse transcriptase (RT). However, their main antiviral activity is 
through incorporation of the monophosphate form into the viral DNA chain, resulting in chain 
termination. Abacavir and lamivudine triphosphates show significantly less affinity for host cell DNA 
polymerases. 
 
 No antagonistic effects in vitro were seen with lamivudine and other antiretrovirals (tested 
agents:didanosine, nevirapine and zidovudine). The antiviral activity of abacavir in cell culture was not 
antagonized when combined with the nucleoside reverse transcriptase inhibitors (NRTIs) didanosine, 
emtricitabine,  stavudine, tenofovir  or zidovudine, the non-nucleoside reverse transcriptase inhibitor 
(NNRTI) nevirapine, or the protease inhibitor (PI) amprenavir.   
 
Antiviral Activity in vitro  
 
Both abacavir and lamivudine have been shown to inhibit replication of laboratory 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 lymphocytes (PBLs) and 
monocyte/macrophages.  The concentration of drug necessary to effect viral replication by 50% (EC50) 
or 50% inhibitory concentration (IC50) varied according to virus and host cell type.   
 
The mean EC50 for abacavir against laboratory strains of HIV-1IIIB and HIV-1HXB2 ranged from 1.4 
to 5.8 µM. The median or mean EC50 values for lamivudine against laboratory strains of HIV-1 ranged 
from 0.007 to 2.3 µM. The mean EC50 against laboratory strains of HIV-2 (LAV2 and EHO) ranged 
from 1.57 to 7.5 µM for abacavir and from 0.16 to 0.51 µM for lamivudine.  

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


15 

 
The EC50 values of abacavir against HIV-1 Group M subtypes (A-G) ranged from 0.002 to 1.179 µM, 
against Group O from 0.022 to 1.21 µM, and against HIV-2 isolates, from 0.024 to 0.49 µM. For 
lamivudine, the EC50 values against HIV-1 subtypes (A-G) ranged from 0.001 to 0.170 µM, against 
Group O from 0.030 to 0.160 µM and against HIV-2 isolates from 0.002 to 0.120 µM in peripheral 
blood mononuclear cells. 
 
Baseline HIV-1 samples from therapy-naive subjects with no amino acid substitutions associated with 
resistance have been evaluated using either the multi-cycle Virco Antivirogram™ assay (n=92 from 
COL40263) or the  the single cycle  Monogram Biosciences PhenoSense™ assay (n=138 from 
ESS30009). These resulted in median EC50 values of 0.912 µM (range: 0.493 to 5.017 µM) and 1.26 
µM (range 0.72 to 1.91 µM) respectively for abacavir, and median EC50 values of 0.429 µM (range: 
0.200 to 2.007 µM) and 2.38 µM (1.37 to 3.68 µM) respectively for lamivudine.  
 
Phenotypic susceptibility analyses of clinical isolates from antiretroviral-naïve patients with  HIV-1 
Group M non-B subtypes in three studies have each reported that all viruses were fully susceptible to 
both abacavir and lamivudine; one study of 104 isolates that included subtypes A and A1 (n=26), 
C (n=1), D (n=66), and the circulating recombinant forms (CRFs)  AD (n=9), CD (n=1), and a complex 
inter-subtype recombinant_cpx (n=1),  a second study of 18 isolates including subtype G (n=14) and 
CRF_AG (n=4) from Nigeria, and a third study of  six isolates (n=4 CRF_AG, n=1 A and n=1 
undetermined) from Abidjan (Côte d'Ivoire).  
  
HIV-1 isolates (CRF01_AE, n=12; CRF02_AG, n=12; and Subtype C or CRF_AC, n=13) from 37 
untreated patients in Africa and Asia were susceptible to abacavir (IC50 fold changes <2.5), and 
lamivudine (IC50 fold changes<3.0), except for two CRF02_AG isolates with fold-changes of 2.9 and 
3.4 for abacavir.  Group O isolates from antiviral naïve patients tested for lamivudine activity were 
highly sensitive.   
 
The combination of abacavir and lamivudine has demonstrated antiviral activity in cell culture against 
non-subtype B isolates and HIV-2 isolates with equivalent antiviral activity as for subtype B isolates.  
 
Resistance 
 
In vivo resistance  
 
Abacavir-resistant isolates of HIV-1 have been selected in-vitro in wild-type strain HIV-1 (HXB2) and 
are associated with specific genotypic changes in the RT codon region (codons M184V, K65R, L74V 
and Y115).  Selection for the M184V mutation occurred first and resulted in a two fold increase in IC50.  
Continued passage in increasing concentrations of drug resulted in selection for double RT mutants 
65R/184V and 74V/184V or triple RT mutant 74V/115Y/184V.  Two mutations conferred a 7- to 
8-fold change in abacavir susceptibility and combinations of three mutations were required to confer 
more than an 8-fold change in susceptibility.  Passage with a zidovudine resistant clinical isolate 
RTMC also selected for the 184V mutation. 
 
HIV-1 resistance to lamivudine involves the development of a M184I or, more commonly, M184V 
amino acid change close to the active site of the viral RT. Passage of HIV-1 (HXB2) in the presence of 
increasing 3TC concentrations results in high-level (>100 to >500-fold) lamivudine-resistant viruses 
and the RT M184I or V mutation is rapidly selected.  The IC50 for wild-type HXB2 is 0.24 to 0.6 µM, 
while the IC50 for M184V containing HXB2 is >100 to 500 µM.  
 
Antiviral therapy According to Genotypic/Phenotypic Resistance 
 
In vivo resistance (Therapy-naïve patients)  
 
The M184V or M184I variants arise in HIV-1 infected patients treated with lamivudine-containing 
antiretroviral therapy. 



16 

 
Isolates from most patients experiencing virological failure with a regimen containing abacavir in 
pivotal clinical trials showed either no NRTI-related changes from baseline (45%) or only M184V or 
M184I selection (45%).  The overall selection frequency for M184V or M184I was high (54%), and 
less common was the selection of L74V (5%), K65R (1%) and Y115F (1%) (see table below).  The 
inclusion of zidovudine in the regimen has been found to reduce the frequency of L74V and K65R 
selection in the presence of abacavir (with zidovudine: 0/40, without zidovudine: 15/192, 8%). 
 

Therapy 
 

Abacavir + 
Combivir1 

Abacavir + 
lamivudine + 

NNRTI 

Abacavir + 
lamivudine + 

PI (or 
PI/ritonavir) 

Total 

Number of 
Subjects 282 1094 909 2285 

Number of 
Virological 

Failures 
43 90 158 306 

Number of On-
Therapy  

Genotypes 
40 (100%) 51 (100%)2 141 (100%) 232 (100%) 

K65R 0 1 (2%) 2 (1%) 3 (1%) 

L74V 0 9 (18%) 3 (2%) 12 (5%) 
Y115F 0 2 (4%) 0 2 (1%) 

M184V/I 34 (85%) 22 (43%) 70 (50%) 126 (54%) 
TAMs3 3 (8%) 2 (4%) 4 (3%) 9 (4%) 

1. Combivir is a fixed dose combination of lamivudine and zidovudine 
2. Includes three non-virological failures and four unconfirmed virological failures. 
3. Number of subjects with ≥1 Thymidine Analogue Mutations (TAMs). 
 
TAMs might be selected when thymidine analogs are associated with abacavir. In a meta-analysis of 
six clinical trials, TAMs were not selected by regimens containing abacavir without zidovudine 
(0/127), but were selected by regimens containing abacavir and the thymidine analogue zidovudine 
(22/86, 26%). 
 
In vivo resistance (Therapy experienced patients)   
 
The M184V or M184I variants arise in HIV-1 infected patients treated with lamivudine-containing 
antiretroviral therapy and confer high-level resistance to lamivudine. In vitro data tend to suggest that 
the continuation of lamivudine in anti-retroviral regimen despite the development of M184V might 
provide residual anti-retroviral activity (likely through impaired viral fitness).  The clinical relevance of 
these findings is not established.  Indeed, the available clinical data are very limited and preclude any 
reliable conclusion in the field.  In any case, initiation of susceptible NRTIs should always be preferred 
to maintenance of lamivudine therapy. Therefore, maintaining lamivudine therapy despite emergence 
of M184V mutation should only be considered in cases where no other active NRTIs are available. 
 
Clinically significant reduction of susceptibility to abacavir has been demonstrated in clinical isolates 
of patients with uncontrolled viral replication, who have been pre-treated with and are resistant to other 
nucleoside inhibitors. In a meta-analysis of five clinical trials where ABC was added to intensify 
therapy, of 166 subjects, 123 (74%) had M184V/I, 50 (30%) had T215Y/F, 45 (27%) had M41L, 30 
(18%) had K70R and 25 (15%) had D67N.  K65R was absent and L74V and Y115F were uncommon 
(≤3%).  Logistic regression modelling of the predictive value for genotype (adjusted for baseline 
plasma HIV-1RNA [vRNA], CD4+ cell count, number and duration of prior antiretroviral therapies) 
showed that the presence of 3 or more NRTI resistance-associated mutations was associated with 
reduced response at Week 4 (p=0.015) or 4 or more mutations at median Week 24 (p≤0.012). In 
addition, the 69 insertion complex or the Q151M mutation, usually found in combination with A62V, 



17 

V75I, F77L and F116Y, cause a high level of resistance to abacavir. 
 

Baseline Reverse 
Transcriptase 

Mutation 

Week 4 
(n = 166) 

n 
Median 

Change vRNA 
(log10 c/mL) 

Percent with 
<400 copies/mL vRNA 

None 15 -0.96 40% 
M184V alone  75 -0.74 64% 

Any one NRTI 
mutation 82 -0.72 65% 

Any two NRTI-
associated mutations  22 -0.82 32% 

Any three NRTI-
associated mutations 19 -0.30 5% 

Four or more NRTI-
associated mutations 28 -0.07 11% 

 
Phenotypic resistance and cross-resistance   
 
Phenotypic resistance to abacavir requires M184V with at least one other abacavir-selected mutation, 
or M184V with multiple TAMs. Phenotypic cross-resistance to other NRTIs with M184V or M184I 
mutation alone is limited. Zidovudine, didanosine, stavudine and tenofovir maintain their antiretroviral 
activities against such HIV-1 variants. The presence of M184V with K65R does give rise to cross-
resistance between abacavir, tenofovir, didanosine and lamivudine, and M184V with L74V gives rise 
to cross-resistance between abacavir, didanosine and lamivudine. The presence of M184V with Y115F 
gives rise to cross-resistance between abacavir and lamivudine. Readily available genotypic drug 
resistance interpretation algorithms and commercially available susceptibility tests have established 
clinical cut offs for reduced activity for abacavir and lamivudine as separate drug entities that predict 
susceptibility, partial susceptibility or resistance based upon either direct measurement of susceptibility 
or by calculation of the HIV-1 resistance phenotype from the viral genotype.  Appropriate use of 
abacavir and lamivudine can be guided using these currently recommended resistance algorithms. 
 
Cross-resistance between abacavir or lamivudine and antiretrovirals from other classes e.g. PIs or 
NNRTIs is unlikely.  
 
Clinical experience 
 
Clinical experience with the combination of abacavir and lamivudine as a once daily regimen is mainly 
based on four studies in treatment-naïve subjects, CNA30021, EPZ104057 (HEAT study), ACTG5202, 
and CNA109586 (ASSERT study) and two studies in treatment-experienced subjects, CAL30001 and 
ESS30008. 
 
Therapy-naïve patients 
  
The combination of abacavir and lamivudine as a once daily regimen is supported by a 48 weeks 
multi-centre, double-blind, controlled study (CNA30021) of 770 HIV-infected, therapy-naïve adults. 
These were primarily asymptomatic HIV infected patients (CDC stage A). They were randomised to 
receive either abacavir (ABC) 600 mg once daily or 300 mg twice daily, in combination with 
lamivudine 300 mg once daily and efavirenz 600 mg once daily. The results are summarised by 
subgroup in the table below: 
 



18 

Efficacy Outcome at Week 48 in CNA30021 by baseline HIV-1 RNA and CD4 Categories (ITTe 
TLOVR ART naïve subjects). 
 

 ABC QD 
+3TC+EFV 
(n=384) 
 

ABC BID +3TC+EFV 
(n=386) 

ITT-E Population 
TLOVR analysis 

Proportion with HIV-1 RNA <50 copies/ml 

All Subjects 253/384 (66%)    261/386  (68%) 

Baseline RNA category    
<100,000 copies/mL 

141/217 (65%)    145/217  (67%) 
 

Baseline RNA category 
>=100,000 copies/mL    

112/167  (67%)      116/169  (69%) 

Baseline CD4 category <50                                                      3/ 6 (50%)      4/6  (67%) 
 

Baseline CD4 category 50-100                                                 21/40 (53%)     23/37  (62%) 

Baseline CD4 category  101-200                                                57/ 85 (67%)     43/67  (64%) 

Baseline CD4 category  201-350                                               101/143 (71%)    114/170  (67%) 
 

Baseline CD4 category >350                                                    71/109 (65%)     76/105  (72%) 
 

>1 log reduction in HIV RNA  or 
<50 cp/mL 
All Patients                               

372/384 (97%)    373/386  (97%) 
 

 
Similar clinical success (point estimate for treatment difference: -1.7, 95% CI –8.4, 4.9) was observed 
for both regimens. From these results, it can be concluded with 95% confidence that the true difference 
is no greater than 8.4% in favour of the twice daily regimen. This potential difference is sufficiently small 
to draw an overall conclusion of non-inferiority of abacavir once daily over abacavir twice daily. 
 
There was a low, similar overall incidence of virologic failure (viral load > 50 copies/ml) in both the 
once and twice daily treatment groups (10% and 8% respectively). In the small sample size for 
genotypic analysis, there was a trend toward a higher rate of NRTI-associated mutations in the once 
daily versus the twice daily abacavir regimens. No firm conclusion could be drawn due to the limited 
data derived from this study.  
 
There are conflicting data in some comparative studies with Kivexa i.e. HEAT, ACTG5202 and 
ASSERT: 
 
EPZ104057 (HEAT study) was a randomised, double-blind, placebo-matched, 96 week, multi-centre 
study with the primary objective of evaluating the relative efficacy of abacavir/lamivudine (ABC/3TC, 
600mg/300mg) and tenofovir /emtricitabine (TDF/FTC, 300mg/200mg), each given once-daily in 
combination with lopinavir/ritonavir (LPV/r, 800mg/200mg) in HIV-infected, therapy-naive adults.  
The primary efficacy analysis was performed at week 48 with study continuation to week 96 and 
demonstrated non-inferiority.  The results are summarised below: 
 



19 

Virologic Response Based on Plasma HIV-1 RNA < 50 copies/ml  
ITT-Exposed Population M=F switch included 

Virologic Response 
ABC/3TC +LPV/r  

(N = 343) 
TDF/FTC + LPV/r 

(N = 345) 
Week 48 Week 96 Week 48 Week 96 

Overall response (stratified by 
baseline HIV-1 RNA) 

231/343 
(68%) 

205/343 
(60%) 

232/345 
(67%) 

200/345 
(58%) 

Response by Baseline HIV-1 RNA 
<100,000 c/ml 

134/188 
(71%) 

118/188 
(63%) 

141/205 
(69%) 

119/205 
(58%) 

Response by Baseline HIV-1 RNA 
≥100,000 c/ml 

97/155 
(63%) 

87/155 
(56%) 

91/140 
(65%) 

81/140 
(58%) 

 
A similar virologic response was observed for both regimens (point estimate for treatment difference at 
week 48: 0.39%, 95% CI: -6.63, 7.40). 
 
ACTG 5202 study was a, multi-centre, comparative, randomised study of double-blind 
abacavir/lamivudine or emtricitabine/tenofovir in combination with open-label efavirenz or 
atazanavir/ritonavir in treatment-naïve HIV-1 infected patients. Patients were stratified at screening 
based on plasma HIV-1 RNA levels < 100,000 and ≥ 100,000 copies/mL. 
  
An interim analysis from ACTG 5202 revealed that abacavir/lamivudine was associated with a 
statistically significantly higher risk of virological failure as compared to emtricitabine/tenofovir 
(defined as viral load >1000 copies/mL at or after 16 weeks and before 24 weeks or HIV-RNA level 
>200 copies/mL at or after 24 weeks) in subjects with a screening viral load ≥100,000 copies/mL 
(estimated hazard ratio: 2.33, 95% CI: 1.46, 3.72, p=0.0003). The Data Safety Monitoring Board 
(DSMB) recommended that consideration be given to change in the therapeutic management of all 
subjects in the high viral load stratum due to the efficacy differences observed. The subjects in the low 
viral load stratum remained blinded and on-study. 

Analysis of the data from subjects in the low viral load stratum showed no demonstrable difference 
between the nucleoside backbones in the proportion of patients free of virological failure at week 96. 
The results are presented below: 

- 88.3% with ABC/3TC vs 90.3% with TDF/FTC when taken with atazanavir/ritonovir as third 
drug, treatment difference -2.0% (95% CI -7.5%, 3.4%), 
- 87.4% with ABC/3TC vs 89.2% with TDF/FTC, when taken with efavirenz as third drug, 
treatment difference -1.8% (95% CI -7.5%, 3.9%). 

 
CNA109586 (ASSERT study), a multi-centre, open label, randomised study of abacavir/lamivudine 
(ABC/3TC, 600mg/300mg) and tenofovir/emtricitabine (TDF/FTC, 300mg/200mg), each given once 
daily with efavirenz (EFV, 600mg) in ART naïve, HLA-B*5701 negative, HIV-1 infected adults.The 
virologic results are summarised in the table below: 
Virologic Response at Week 48 ITT-Exposed Population < 50 copies/ml TLOVR 

 ABC/3TC + EFV (N =192) 
TDF/FTC + EFV 

(N =193) 
Overall response 114/192 

(59%) 
137/193 
(71%) 

Response by Baseline 
HIV-1 RNA <100,000 
c/mL 

61/95 
(64%) 

62/83 
(75%) 

Response by Baseline 
HIV-1 RNA ≥100,000 
c/mL 

53/97 
(55%) 

75/110 
(68%) 

 



20 

At week 48, a lower rate of virologic response was observed for ABC/3TC compared to TDF/FTC 
(point estimate for the treatment difference: 11.6%, 95% CI: 2.2, 21.1). 
 
Therapy-experienced patients 
 
Data from two studies, CAL30001 and ESS30008 demonstrated that Kivexa once daily has similar 
virological efficacy to abacavir 300 mg twice daily plus lamivudine 300 mg once daily or 150 mg twice 
daily in therapy-experienced patients. 
 
In study CAL30001, 182 treatment-experienced patients with virologic failure were randomised and 
received treatment with either Kivexa once daily or abacavir 300 mg twice daily plus lamivudine 
300 mg once daily, both in combination with tenofovir and a PI or an NNRTI for 48 weeks. Similar 
reductions in HIV-1 RNA as measured by average area under the curve minus baseline were observed,  
indicating that the Kivexa group was non-inferior to the abacavir plus lamivudine twice daily group 
(AAUCMB, -1.65 log10 copies/ml versus -1.83 log10 copies/ml respectively, 95% CI -0.13, 0.38). 
Proportions with HIV-1 RNA < 50 copies/ml (50% versus 47%) and < 400 copies/ml (54% versus 
57%) at week 48 were also similar in each group (ITT population). However, as there were only 
moderately experienced patients included in this study with an imbalance in baseline viral load between 
the arms, these results should be interpreted with caution. 
 
In study ESS30008, 260 patients with virologic suppression on a first line therapy regimen containing 
abacavir 300 mg plus lamivudine 150 mg, both given twice daily and a PI or NNRTI, were randomised 
to continue this regimen or switch to Kivexa plus a PI or NNRTI for 48 weeks. Results at 48 weeks 
indicated that the Kivexa group was associated with a similar virologic outcome (non-inferior) 
compared to the abacavir plus lamivudine group, based on proportions of subjects with HIV-1 RNA 
< 50 copies/ml (90% and 85% respectively, 95% CI  -2.7, 13.5). 
 
A genotypic sensitivity score (GSS) has not been established by the MAH for the abacavir/lamivudine 
combination.  The proportion of treatment-experienced patients in the CAL30001 study with HIV-
RNA <50 copies/mL at Week 48 by genotypic sensitivity score in optimized background therapy 
(OBT) are tabulated  The impact of major IAS-USA defined mutations to abacavir or lamivudine and 
multi-NRTI resistance associated mutations to the number of baseline mutations on response was also 
evaluated. The GSS was obtained from the Monogram reports with susceptible virus ascribed the 
values ‘1-4’ based upon the numbers of drugs in the regimen and with virus with reduced susceptibility 
ascribed the value ‘0’.  Genotypic sensitivity scores were not obtained for all patients at baseline.  
Similar proportions of patients in the once-daily and twice-daily abacavir arms of CAL30001 had GSS 
scores of <2 or ≥2 and successfully suppressed to <50 copies/mL by Week 48. 
 
Proportion of Patients in CAL30001 with <50 copies/mL at Week 48 by Genotypic Sensitivity 
Score in OBT and Number of Baseline Mutations 
 

 ABC/3TC FDC QD 
(n=94) 

 
Number of Baseline Mutations1 

ABC BID 
+3TC QD 
(n=88) 

Genotypic 
SS in OBT 

All 0-1 2-5 6+ All 

≤2 10/24 (42%) 3/24 (13%) 7/24 (29%) 0 12/26 (46%) 
>2 29/56 (52%) 21/56 (38%) 8/56 (14%) 0 27/56 (48%) 
Unknown 8/14 (57%) 6/14 (43%) 2/14 (14%) 0 2/6 (33%) 
All 47/94 (50%) 30/94 (32%) 17/94 (18%) 0 41/88 (47%) 
1 Major IAS-USA defined mutations to Abacavir or Lamivudine and multi-NRTI resistance associated mutations 
 

For the CNA109586 (ASSERT) and CNA30021 studies in treatment-naïve patients, genotype data was 
obtained for only a subset of patients at screening or at baseline, as well as for those patients who met 
virologic failure criteria.  The partial patient subset of data available for CNA30021 is tabulated below, 



21 

but must be interpreted with caution.  Drug susceptibility scores were assigned for each patient’s viral 
genotype utilising the ANRS 2009 HIV-1 genotypic drug resistance algorithm.  Each susceptible drug 
in the regimen received a score of 1 and drugs for which the ANRS algorithm predicts resistance were 
ascribed the value ‘0’. 
 
Proportion of Patients in CNA30021with <50 cps/mL at Week 48 by Genotypic Sensitivity Score 
in OBT and Number of Baseline Mutations 
 

 ABC QD + 3TC QD + EFV QD 
(N=384) 

Number of Baseline Mutations1 

ABC BID+ 
3TC QD + 
EFV QD 
(N=386) 

Genotypic 
SS in OBT 

All 0-1 2-5 6+ All 

≤2 2/6 (33%) 2/6 (33%) 0 0 3/6 (50%) 
>2 58/119 (49%) 57/119 (48%) 1/119 (<1%) 0 57/114 (50%) 
All 60/125 (48%) 59/125 (47%) 1/125 (<1%) 0 60/120 (50%) 
1 Major IAS-USA (Dec 2009) defined mutations for Abacavir or Lamivudine 

 
Paediatric population 
 
A comparison of a regimen including once daily versus  twice daily dosing of abacavir and lamivudine 
was undertaken within a randomised, multicentre, controlled study of HIV-infected, paediatric patients. 
1206 paediatric patients aged 3 months to 17 years enrolled in the ARROW Trial (COL105677) and 
were dosed according to the weight - band dosing recommendations in the World Health Organisation 
treatment guidelines (Antiretroviral therapy of HIV infection in infants and children, 2006). After 36 
weeks on a regimen including twice daily abacavir and lamivudine, 669 eligible subjects were 
randomised to either continue twice daily dosing or switch to once daily abacavir and lamivudine for at 
least an additional 96 weeks.  Within this population, 104 patients, weighing at least 25 kg, received 
600 mg abacavir and 300 mg lamivudine as Kivexa once daily, with a median duration of exposure of 
596 days.  
 
Among the 669 subjects randomized in this study (from 12 months to ≤17 years old), the 
abacavir/lamivudine once daily dosing group was demonstrated to be non-inferior to the twice daily 
group according to the pre-specified non-inferiority margin of -12%, for the primary endpoint of <80 
c/mL at Week 48 as well as at Week 96 (secondary endpoint) and all other thresholds tested 
(<200c/mL, <400c/mL, <1000c/mL), which all fell well within this non-inferiority margin. Subgroup 
analyses testing for heterogeneity of once versus twice daily demonstrated no significant effect of sex, 
age, or viral load at randomisation. Conclusions supported non-inferiority regardless of analysis 
method. 
 
Among the 104 patients who received Kivexa, including the ones who were between 40 kg and 25 kg, 
the viral suppression was similar 
 
5.2 Pharmacokinetic properties 
 
The fixed-dose combination tablet of abacavir/lamivudine (FDC) has been shown to be bioequivalent 
to lamivudine and abacavir administered separately. This was demonstrated in a single dose, 3-way 
crossover bioequivalence study of FDC (fasted) versus 2 x 300 mg abacavir tablets plus 2 x 150 mg 
lamivudine tablets (fasted) versus FDC administered with a high fat meal, in healthy volunteers 
(n = 30). In the fasted state there was no significant difference in the extent of absorption, as measured 
by the area under the plasma concentration-time curve (AUC) and maximal peak concentration (Cmax), 
of each component. There was also no clinically significant food effect observed between 
administration of FDC in the fasted or fed state. These results indicate that FDC can be taken with or 
without food. The pharmacokinetic properties of lamivudine and abacavir are described below. 



22 

Absorption 
 
Abacavir and lamivudine are rapidly and well absorbed from the gastro-intestinal tract following oral 
administration. The absolute bioavailability of oral abacavir and lamivudine in adults is about 83% and 
80-85% respectively. The mean time to maximal serum concentrations (tmax) is about 1.5 hours and 
1.0 hour for abacavir and lamivudine, respectively. Following a single dose of 600 mg of abacavir, the 
mean (CV) Cmax is 4.26 µg/ml (28%) and the mean (CV) AUC∞ is 11.95 µg.h/ml (21%). Following 
multiple-dose oral administration of lamivudine 300 mg once daily for seven days, the mean (CV) 
steady-state Cmax is 2.04 µg/ml (26%) and the mean (CV) AUC24 is 8.87 µg.h/ml (21%). 
 
Distribution 
 
Intravenous studies with abacavir and lamivudine showed that the mean apparent volume of 
distribution is 0.8 and 1.3 l/kg respectively. Plasma protein binding studies in vitro indicate that 
abacavir binds only low to moderately (~49%) to human plasma proteins at therapeutic concentrations. 
Lamivudine exhibits linear pharmacokinetics over the therapeutic dose range and displays limited 
plasma protein binding in vitro (< 36%). This indicates a low likelihood for interactions with other 
medicinal products through plasma protein binding displacement. 
 
Data show that abacavir and lamivudine penetrate the central nervous system (CNS) and reach the 
cerebrospinal fluid (CSF). Studies with abacavir demonstrate a CSF to plasma AUC ratio of between 
30 to 44%. The observed values of the peak concentrations are 9 fold greater than the IC50 of abacavir 
of 0.08 µg/ml or 0.26 µM when abacavir is given at 600 mg twice daily. The mean ratio of CSF/serum 
lamivudine concentrations 2-4 hours after oral administration was approximately 12%. The true extent 
of CNS penetration of lamivudine and its relationship with any clinical efficacy is unknown.  
 
Biotransformation 
 
Abacavir is primarily metabolised by the liver with approximately 2% of the administered dose being 
renally excreted, as unchanged compound. The primary pathways of metabolism in man are by alcohol 
dehydrogenase and by glucuronidation to produce the 5’-carboxylic acid and 5’-glucuronide which 
account for about 66% of the administered dose. These metabolites are excreted in the urine. 
 
Metabolism of lamivudine is a minor route of elimination. Lamivudine is predominately cleared by 
renal excretion of unchanged lamivudine. The likelihood of metabolic drug interactions with 
lamivudine is low due to the small extent of hepatic metabolism (5-10%). 
 
Elimination 
 
The mean half-life of abacavir is about 1.5 hours. Following multiple oral doses of abacavir 300 mg 
twice a day there is no significant accumulation of abacavir. Elimination of abacavir is via hepatic 
metabolism with subsequent excretion of metabolites primarily in the urine. The metabolites and 
unchanged abacavir account for about 83% of the administered abacavir dose in the urine. The 
remainder is eliminated in the faeces. 
 
The observed lamivudine half-life of elimination is 5 to 7 hours. 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. Kivexa is not recommended for use in patients with a creatinine 
clearance < 50 ml/min as necessary dose adjustment cannot be made (see section 4.2).  
 
Intracellular pharmacokinetics 
 
In a study of 20 HIV-infected patients receiving abacavir 300 mg twice daily, with only one 300 mg 
dose taken prior to the 24 hour sampling period, the geometric mean terminal carbovir-TP intracellular 
half-life at steady-state was 20.6 hours, compared to the geometric mean abacavir plasma half-life in 



23 

this study of 2.6 hours. In a crossover study in 27 HIV-infected patients, intracellular carbovir-TP 
exposures were higher for the abacavir 600 mg once daily regimen (AUC24,ss  + 32%, Cmax24,ss + 99% 
and Ctrough + 18%) compared to the 300 mg twice daily regimen. For patients receiving lamivudine 
300 mg once daily, the terminal intracellular half-life of lamivudine-TP was prolonged to 16-19 hours, 
compared to the plasma lamivudine half-life of 5-7 hours. In a crossover study in 60 healthy volunteers, 
intracellular lamivudine-TP pharmacokinetic parameters were similar (AUC24,ss and Cmax24,ss) or lower 
(Ctrough – 24%) for the lamivudine 300 mg once daily regimen compared to the lamivudine 150 mg 
twice daily regimen. Overall, these data support the use of lamivudine 300 mg and abacavir 600 mg 
once daily for the treatment of HIV-infected patients. Additionally, the efficacy and safety of this 
combination given once daily has been demonstrated in a pivotal clinical study (CNA30021- See 
Clinical experience).  
 
Special  patient populations 
 
Hepatic impairment  
 
Pharmacokinetic data has been obtained for abacavir and lamivudine separately. 
 
Abacavir is metabolised primarily by the liver. The pharmacokinetics of abacavir have been studied in 
patients with mild hepatic impairment (Child-Pugh score 5-6) receiving a single 600 mg dose; the 
median (range) AUC value was 24.1 (10.4 to 54.8) ug.h/ml.The results showed that there was a mean 
(90%CI) increase of 1.89 fold [1.32; 2.70] in the abacavir AUC, and 1.58 [1.22; 2.04] fold in the 
elimination half-life. No definitive recommendation on dose reduction is possible in patients with mild 
hepatic impairment due to substantial variability of abacavir exposure.  
 
Data obtained in patients with moderate to severe hepatic impairment show that lamivudine 
pharmacokinetics are not significantly affected by hepatic dysfunction. 
 
Based on data obtained for abacavir, Kivexa is not recommended in patients with moderate or severe 
hepatic impairment. 
 
Renal impairment  
 
Pharmacokinetic data have been obtained for lamivudine and abacavir alone. Abacavir is primarily 
metabolised by the liver with approximately 2% of abacavir excreted unchanged in the urine. The 
pharmacokinetics of abacavir in patients with end-stage renal disease is similar to patients with normal 
renal function. Studies with lamivudine show that plasma concentrations (AUC) are increased in 
patients with renal dysfunction due to decreased clearance. Kivexa is not recommended for use in 
patients with a creatinine clearance < 50 ml/min as necessary dose adjustment cannot be made. 
 
Elderly  
 
No pharmacokinetic data are available in patients over 65 years of age. 
 
Children 
 
Abacavir is rapidly and well absorbed from oral formulations when administered to children.  
Paediatric pharmacokinetic studies have demonstrated that once daily dosing provides equivalent 
AUC24 to twice daily dosing of the same total daily dose for both oral solution and tablet formulations.  
 
The absolute bioavailability of lamivudine (approximately 58 to 66%) was lower and more variable in 
paediatric patients under 12 years of age.  However, paediatric pharmacokinetic studies with tablet 
formulations have demonstrated that once daily dosing provides equivalent AUC24 to twice daily 
dosing of the same total daily dose.  
 
 



24 

5.3 Preclinical safety data 
 
With the exception of a negative in vivo rat micronucleus test, there are no data available on the effects 
of the combination of abacavir and lamivudine in animals.  
 
Mutagenicity and carcinogenicity 
 
Neither abacavir nor lamivudine were mutagenic in bacterial tests, but consistent with other nucleoside 
analogues, they inhibit cellular DNA replication in in vitro mammalian tests such as the mouse 
lymphoma assay. The results of an in vivo rat micronucleus test with abacavir and lamivudine in 
combination were negative.  
 
Lamivudine has not shown any genotoxic activity in the in vivo studies at doses that gave plasma 
concentrations up to 40-50 times higher than clinical plasma concentrations. Abacavir has a weak 
potential to cause chromosomal damage both in vitro and in vivo at high tested concentrations.  
 
The carcinogenic potential of a combination of abacavir and lamivudine has not been tested. In 
long-term oral carcinogenicity studies in rats and mice, lamivudine did not show any carcinogenic 
potential. Carcinogenicity studies with orally administered abacavir in mice and rats showed an 
increase in the incidence of malignant and non-malignant tumours. Malignant tumours occurred in the 
preputial gland of males and the clitoral gland of females of both species, and in rats in the thyroid 
gland of males and in the liver, urinary bladder, lymph nodes and the subcutis of females.  
 
The majority of these tumours occurred at the highest abacavir dose of 330 mg/kg/day in mice and 
600 mg/kg/day in rats. The exception was the preputial gland tumour which occurred at a dose of 
110 mg/kg in mice. The systemic exposure at the no effect level in mice and rats was equivalent to 3 
and 7 times the human systemic exposure during therapy. While the clinical relevance of these findings 
is unknown, these data suggest that a carcinogenic risk to humans is outweighed by the potential 
clinical benefit. 
 
Repeat-dose toxicity  
 
In toxicology studies abacavir was shown to increase liver weights in rats and monkeys. The clinical 
relevance of this is unknown. There is no evidence from clinical studies that abacavir is hepatotoxic. 
Additionally, autoinduction of abacavir metabolism or induction of the metabolism of other medicinal 
products hepatically metabolised has not been observed in man. 
 
Mild myocardial degeneration in the heart of mice and rats was observed following administration of 
abacavir for two years. The systemic exposures were equivalent to 7 to 24 times the expected systemic 
exposure in humans. The clinical relevance of this finding has not been determined. 
 
Reproductive toxicology 
 
In reproductive toxicity studies in animals, lamivudine and abacavir were shown to cross the placenta. 
 
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. 
 
Abacavir demonstrated toxicity to the developing embryo and foetus in rats, but not in rabbits. These 
findings included decreased foetal body weight, foetal oedema, and an increase in skeletal 
variations/malformations, early intra-uterine deaths and still births. No conclusion can be drawn with 
regard to the teratogenic potential of abacavir because of this embryo-foetal toxicity. 
 
A fertility study in rats has shown that abacavir and lamivudine had no effect on male or female 
fertility. 



25 

 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients   
 
Tablet Core 
magnesium stearate  
microcrystalline cellulose 
sodium starch glycollate 
 
Tablet Coating 
Opadry Orange YS-1-13065-A containing:  
hypromellose  
titanium dioxide   
macrogol 400  
polysorbate 80 
sunset yellow FCF (E110) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf-life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Do not store above 30ºC.  
 
6.5 Nature and contents of container 
 
30 tablets in opaque white (PVC/PVDCAluminium/Paper)  child-resistant blister packs Multipacks 
containing 90 (3 packs of 30) tablets in opaque white (PVC/PVDC-Aluminium/Paper) child-resistant 
blister packs.  
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
No special requirements for disposal. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/298/002 
EU/1/04/298/003 



26 

 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorization: 17 December 2004 
Date of latest renewal: 17 November 2014 
 
 
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/
http://www.ema.europa.eu/


27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

B.    CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 
 

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

 



28 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Glaxo Wellcome S.A., 
Avenida de 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, 4.2) 
  
 
C.       OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
 AUTHORISATION  
 
• Periodic Safety Update Reports 

 
The marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) provided for 
under Article 107c(7) of Directive 2001/83/EC and 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.  

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 

 

  



29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
  



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 

 
 



31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON BLISTER PACK  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kivexa 600 mg/300 mg film-coated tablets  
abacavir/lamivudine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 600 mg abacavir (as sulfate) and 300 mg lamivudine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sunset yellow (E110), see leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



32 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/298/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 

16.     INFORMATION IN BRAILLE 
 
kivexa  
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC: 
SN: 
NN:  
 



33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer label of 90 (3 packs of 30 film-coated tablets) (with Blue Box) wrapped in clear plastic foil 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kivexa 600 mg/300 mg film-coated tablets  
abacavir/lamivudine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains abacavir 600 mg abacavir (as sulfate) and 300 mg lamivudine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sunset yellow (E110), see package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack containing 90 (3 packs of 30) film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



34 

Do not store above 30°C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/298/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 

16.     INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC: 
SN: 
NN:  
 



35 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Multipacks of 90 (3 packs of 30 film-coated tablets) – without blue box –  
OUTER CARTON BLISTER PACK  
30 TABLETS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kivexa 600 mg/300 mg film-coated tablets  
abacavir/lamivudine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 600 mg abacavir (as sulfate) and 300 mg lamivudine 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sunset yellow (E110), see package leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
Component of a multipack, not to be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



36 

 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 

16.     INFORMATION IN BRAILLE 
 
kivexa  
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
  



37 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kivexa 600 mg/300 mg tablets. 
abacavir/lamivudine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV  
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 

5.       OTHER 
 
 
  



38 

KIVEXA TABLETS ALERT CARD  
 
SIDE 1 

 
IMPORTANT  -  ALERT CARD 

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

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

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



39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 

 
 



40 

  Package leaflet: Information for the user  
 

Kivexa 600 mg/300 mg film-coated tablets 
abacavir/lamivudine 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions ask your doctor or pharmacist. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 
even if their signs of illness are the same as yours. 

- If you get any side effects talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 
IMPORTANT — Hypersensitivity reactions 

Kivexa contains abacavir (which is also an active substance in medicines such as Trizivir, Triumeq 
and Ziagen). Some people who take abacavir may develop a hypersensitivity reaction (a serious 
allergic reaction), which can be life-threatening if they continue to take abacavir containing products. 
You must carefully read all the information under ‘Hypersensitivity reactions’ in the panel in 
Section 4. 

The Kivexa pack includes an Alert Card, to remind you and medical staff about abacavir 
hypersensitivity. Detach this card and keep it with you at all times. 
 
What is in this leaflet  

1. What Kivexa is and what it is used for 
2. What you need to know before you take Kivexa 
3. How to take Kivexa 
4. Possible side effects 
5. How to store Kivexa  
6. Contents of the pack and other information 
 

1. What  Kivexa is and what it is used for 
 
Kivexa is used to treat HIV (human immunodeficiency virus) infection in adults, adolescents and 
in children weighing at least 25 kg.  
 
Kivexa contains two active ingredients that are used to treat HIV infection: abacavir and lamivudine.  
These belong to a group of anti-retroviral medicines called nucleoside analogue reverse transcriptase 
inhibitors (NRTIs). 
 
Kivexa does not completely cure HIV infection; it reduces the amount of virus in your body, and keeps 
it at a low level. It also increases the CD4 cell count 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 Kivexa in the same way. Your doctor will monitor the 
effectiveness of your treatment. 
 



41 

2. What you need to know before you take Kivexa  

  
Do not take Kivexa: 
• if you are allergic (hypersensitive) to abacavir (or any other medicine containing abacavir — (e.g. 

Trizivir, Triumeq or Ziagen), lamivudine or any of the other ingredients of this medicine (listed 
in Section 6) 
Carefully read all the information about hypersensitivity reactions in Section 4. 
Check with your doctor if you think this applies to you. Do not take Kivexa 

Take special care with Kivexa 

Some people taking Kivexa or other combination treatments for HIV are more at risk of serious side 
effects. You need to be aware of the extra risks: 
• if you have  moderate or severe liver disease 
• if you have ever had liver disease, including hepatitis B or C  (if you have hepatitis B infection, do 

not stop Kivexa without your doctor’s advice, as your hepatitis may come back) 
• if you are seriously overweight (especially if you are a woman) 
• if you have a kidney problem  

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

 
Abacavir hypersensitivity reactions 

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

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

 
Risk of heart attack 
It cannot be excluded that abacavir may increase the risk of having a heart attack. 

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

 
Look out for important symptoms 
Some people taking medicines for HIV infection develop other conditions, which can be serious. You 
need to know about important signs and symptoms to look out for while you are taking Kivexa. 

Read the information ‘Other possible side effects of combination therapy for HIV’ in 
Section 4 of this leaflet. 

 
Protect other people 
HIV infection is spread by sexual contact with someone who has the infection, or by transfer of 
infected blood (for example, by sharing injection needles). You can still pass on HIV when taking this 
medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your doctor the 
precautions needed to avoid infecting other people. 
 
Other medicines and Kivexa 
Tell your doctor or pharmacist if you are taking any other medicines, or if you have taken any 
recently, including herbal medicines or other medicines you bought without a prescription.  

Remember to tell your doctor or pharmacist if you begin taking a new medicine while you are taking 
Kivexa. 
 
These medicines should not be used with Kivexa: 
• Emtricitabine, to treat HIV infection 
• other medicinal products containing lamivudine, used to treat HIV infection or hepatitis B 

infection 



42 

• high doses of trimethoprim/sulfamethoxazole, an antibiotic 
• cladribine, used to treat hairy cell leukaemia 

Tell your doctor if you are being treated with any of these. 
 
 
Some medicines interact with Kivexa 
These include: 
 
• phenytoin, for treating epilepsy.   

Tell your doctor if you are taking phenytoin. Your doctor may need to monitor you while 
you are taking Kivexa. 

 
• methadone, used as a heroin substitute. Abacavir increases the rate at which methadone is 

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

Tell your doctor if you are taking methadone. 
 

• medicines (usually liquids) containing sorbitol and other sugar alcohols (such as xylitol, mannitol, 
lactitol or maltitol), if taken regularly.                                                                                                
Tell your doctor or pharmacist if you are taking any of these. 

 
Pregnancy 
Kivexa is not recommended for use during pregnancy. Kivexa and similar medicines may cause 
side effects in unborn babies.  
If you have taken Kivexa  during your pregnancy, your doctor may request regular blood tests and 
other diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs 
during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects. 
 
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 Kivexa 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 
Kivexa may cause side effects which could affect your ability to drive or use machines.  

       Talk to your doctor about your ability to drive or operate machines while taking    
            Kivexa.  
 

Important information about some of the other ingredients of Kivexa tablets 
Kivexa contains a colouring called sunset yellow (E110), this may cause allergic reactions in some 
people. 
 
3. How to take Kivexa  
 
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 Kivexa for adults, adolescents and children weighing 25 kg or more 
is one tablet once a day.  

Swallow the tablets whole, with some water. Kivexa can be taken with or without food. 

Stay in regular contact with your doctor 
Kivexa helps to control your condition. You need to keep taking it every day to stop your illness 
getting worse. You may still develop other infections and illnesses linked to HIV infection. 

Keep in touch with your doctor, and do not stop taking Kivexa without your doctor’s advice. 



43 

If you take more Kivexa than you should 

If you accidentally take too much Kivexa, tell your doctor or your pharmacist, or contact your nearest 
hospital emergency department for further advice. 
 
If you forget to take Kivexa 
If you forget to take a dose, take it as soon as you remember. Then continue your treatment as before.  
Do not take a double dose to make up for a forgotten dose.  
 
It is important to take Kivexa regularly, because if you take it at irregular intervals, you may be more 
likely to have a hypersensitivity reaction. 
 
If you have stopped taking Kivexa 
If you have stopped taking Kivexa for any reason — especially because you think you are having side 
effects, or because you have other illness: 

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

 
If your doctor advises that you can start taking Kivexa again, you may be asked to take your first doses 
in a place where you will have ready access to medical care if you need it. 
 
 
4. Possible side effects 

 
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.  

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

Even patients who don’t have the HLA-B*5701 gene may still develop a hypersensitivity reaction 
(a serious allergic reaction), described in this leaflet in the panel headed ‘Hypersensitivity 
reactions’.  

 
 It is very important that you read and understand the information about this serious 
reaction. 
 

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

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

  



44 

Hypersensitivity reactions 

Kivexa contains abacavir (which is also an active substance in medicines such as Trizivir, Triumeq 
and Ziagen). Abacavir can cause a serious allergic reaction known as a hypersensitivity reaction.   
These hypersensitivity reactions have been seen more frequently in people taking medicines that 
contain abacavir.  
 
 
Who gets these reactions? 
Anyone taking Kivexa could develop a hypersensitivity reaction to abacavir, which could be life 
threatening if they continue to take Kivexa. 

You are more likely to develop this reaction if you have a gene called HLA-B*5701 (but you can get a 
reaction even if you do not have this gene). You should have been tested for this gene before Kivexa 
was prescribed for you. If you know you have this gene, tell your doctor before you take Kivexa. 
 
About 3 to 4 in every 100 patients treated with abacavir in a clinical trial who did not have the HLA-
B*5701 gene developed a hypersensitivity reaction. 
 
What are the symptoms? 
The most common symptoms are: 
• fever (high temperature) and skin rash. 
 
Other common symptoms are: 
• nausea (feeling sick), vomiting (being sick), diarrhoea, abdominal (stomach) pain, severe  
 tiredness. 
 
Other symptoms include: 
 
Pains in the joints or muscles, swelling of the neck, shortness of breath, sore throat, cough, occasional 
headaches, inflammation of the eye (conjunctivitis), mouth ulcers, low blood pressure, tingling or 
numbness of the hands or feet. 
 
 
When do these reactions happen? 
 
Hypersensitivity reactions can start at any time during treatment with Kivexa, but are more likely 
during the first 6 weeks of treatment. 
 
 
Contact your doctor immediately: 
1 if you get a skin rash, OR 
2 if you get symptoms from at least 2 of the following groups: 
 - fever  
 - shortness of breath, sore throat or cough 
 - nausea or vomiting, diarrhoea or abdominal pain 
 - severe tiredness or achiness, or generally feeling ill. 
 
Your doctor may advise you to stop taking Kivexa. 
 



45 

If you have stopped taking Kivexa 

If you have stopped taking Kivexa because of a hypersensitivity reaction, you must NEVER AGAIN 
take Kivexa, or any other medicine containing abacavir (e.g. Trizivir, Triumeq or Ziagen). If you 
do, within hours, your blood pressure could fall dangerously low, which could result in death. 

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

Talk to your doctor before you start again. Your doctor will check whether your symptoms were 
related to a hypersensitivity reaction. If the doctor thinks they may have been, you will then be told 
never again to take Kivexa, or any other medicine containing abacavir (e.g. Trizivir,  Triumeq or 
Ziagen). It is important that you follow this advice. 
 
Occasionally hypersensitivity reactions have developed in people who start taking abacavir containing 
products again, but who had only one symptom on the Alert Card before they stopped taking it. 

Very rarely patients who have taken medicines containing abacavir in the past without any symptoms 
of hypersensitivity have developed a hypersensitivity reaction when they start taking these medicines 
again. 

 
If your doctor advises that you can start taking Kivexa again, you may be asked to take your first doses 
in a place where you will have ready access to medical care if you need it. 
 
If you are hypersensitive to Kivexa, return all your unused Kivexa tablets for safe disposal. Ask 
your doctor or pharmacist for advice. 

The Kivexa pack includes an Alert Card, to remind you and medical staff about hypersensitivity 
reactions. Detach this card and keep it with you at all times. 

 

 
Common side effects 
These may affect up to 1 in 10 people: 
• hypersensitivity reaction  
• headache 
• being sick (vomiting) 
• feeling sick (nausea) 
• diarrhoea 
• stomach pains 
• loss of appetite 
• tiredness, lack of energy 
• fever (high temperature) 
• general feeling of being unwell 
• difficulty in sleeping (insomnia) 
• muscle pain and discomfort 
• joint pain 
• cough 
• irritated or runny nose 
• skin rash  
• hair loss 

Uncommon side effects  
These may affect up to 1 in 100 people and may show up in blood tests: 
• a low red blood cell count (anaemia) or low white blood cell count (neutropenia) 
• an increase in the level of liver enzymes 
• a decrease in the number of cells involved in blood clotting (thrombocytopenia). 



46 

 
Rare side effects 
These may affect up to 1 in 1000 people: 
• liver disorders, such as jaundice, enlarged liver or fatty liver, inflammation (hepatitis) 
• 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: 
• numbness, tingly feelings in the skin (pins and needles) 
• sensation of weakness in the limbs 
• skin rash, which may form blisters and  looks like small targets (central dark spots surrounded by a 

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

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

• lactic acidosis (excess lactic acid in the blood) 
 
 

If you notice any of these symptoms contact a doctor urgently. 

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

Tell your doctor or pharmacist if any of the side effects gets severe or troublesome, or if you 
notice any side effects not listed in this leaflet. 

 
Other possible side effects of combination therapy for HIV 

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

Old infections may flare up 

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

• headache 
• stomach ache 
• difficulty breathing 

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

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

 
If you get any symptoms of infection and inflammation or if you notice any of the symptoms above: 

Tell your doctor immediately. Do not take other medicines for the infection without your doctor’s 
advice. 



47 

 
 
 
You may have problems with your bones 
 
Some people taking combination therapy for HIV develop a condition called osteonecrosis. With this 
condition, parts of the bone tissue die because of reduced blood supply to the bone. People may be 
more likely to get this condition: 
• if they have been taking combination therapy for a long time 
• if they are also taking anti-inflammatory medicines called corticosteroids 
• if they drink alcohol 
• if their immune systems are very weak 
• if they are overweight. 

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

Tell your doctor. 
 

 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in 
Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine. 
 
 
5. How to store Kivexa  
 
Keep this medicine out of the sight and reach of children. 
 
Do not take this medicine after the expiry date shown on the carton. The expiry date refers to the last 
day of that month. 
 
Do not store above 30°C. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other  information  
 
What Kivexa contains 
The active substances in each Kivexa film-coated tablet are 600 mg of abacavir (as sulfate) and 300 mg 
of lamivudine. 
 
The other ingredients are microcrystalline cellulose, sodium starch glycollate and magnesium stearate 
in the core of the tablet. The tablet coating contains Opadry Orange YS-1-13065-A containing 
hypromellose, titanium dioxide, macrogol 400, polysorbate 80 and sunset yellow FCF (E110). 

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


48 

 
What Kivexa looks like and contents of the pack 
Kivexa film-coated tablets are engraved with ‘GS FC2’ on one side. They are orange  and capsule-
shaped and are provided in blister packs containing 30 tablets and multipack blister packs containing 
90(3 x 30) tablets. 
 
Marketing Authorisation Holder  
ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands 
 
Manufacturer  
 
Glaxo Wellcome S.A., Avenida de 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 
dk-info@gsk.com 
 

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

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

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

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 
 

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

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

mailto:info.lt@gsk.com
mailto:info.lt@gsk.com
mailto:cz.info@gsk.com
mailto:cz.info@gsk.com
mailto:dk-info@gsk.com
mailto:dk-info@gsk.com
mailto:viiv.med.info@viivhealthcare.com
mailto:viiv.med.info@viivhealthcare.com
mailto:estonia@gsk.com
mailto:estonia@gsk.com
mailto:at.info@gsk.com
mailto:at.info@gsk.com


49 

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 6969 
Infomed@viivhealthcare.com 
 
Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: + 385 1 6051 999 
 

Portugal 
VIIVHIV HEALTHCARE, 
UNIPESSOAL, LDA  
Tel: + 351 21 094 08 01 
viiv.fi.pt@viivhealthcare.com 
 
România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 
 

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

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

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

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

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

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

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

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

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

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

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

mailto:es-ci@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com
mailto:medical.x.si@gsk.com
mailto:medical.x.si@gsk.com
mailto:recepcia.sk@gsk.com
mailto:recepcia.sk@gsk.com
mailto:Finland.tuoteinfo@gsk.com
mailto:Finland.tuoteinfo@gsk.com
mailto:gskcyprus@gsk.com
mailto:gskcyprus@gsk.com
mailto:info.produkt@gsk.com
mailto:info.produkt@gsk.com
mailto:lv-epasts@gsk.com
mailto:lv-epasts@gsk.com
mailto:customercontactuk@gsk.com
mailto:customercontactuk@gsk.com
http://www.ema.europa.eu/
http://www.ema.europa.eu/

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