Trizivir

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 2 

1. NAME OF THE MEDICINAL PRODUCT 
 
TRIZIVIR 300 mg/150 mg/300 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 300 mg of abacavir (as sulfate), 150 mg lamivudine and 300 mg 
zidovudine. 
 
For the full list of excipients see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Blue-green capsule-shaped film-coated tablets engraved with “GX LL1” on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Trizivir is indicated for the treatment of Human Immunodeficiency Virus (HIV) infection in adults 
(see sections 4.4 and 5.1). This fixed combination replaces the three components (abacavir, 
lamivudine and zidovudine) used separately in similar doses. It is recommended that treatment is 
started with abacavir, lamivudine, and zidovudine separately for the first 6-8 weeks (see section 4.4). 
The choice of this fixed combination should be based not only on potential adherence criteria, but 
mainly on expected efficacy and risk related to the three nucleoside analogues.  
 
The demonstration of the benefit of Trizivir is mainly based on results of studies performed in 
treatment naive patients or moderately antiretroviral experienced patients with non-advanced disease. 
In patients with high viral load (> 100,000 copies/ml) choice of therapy needs special consideration 
(see section 5.1).  
 
Overall, the virologic suppression with this triple nucleoside regimen could be inferior to that 
obtained with other multitherapies notably including boosted Protease inhibitors or non nucleoside 
reverse transcriptase inhibitors, therefore the use of Trizivir should only be considered under special 
circumstances (e.g. co-infection with tuberculosis). 
 
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 
 
Posology 
 
Therapy should be prescribed by a physician experienced in the management of HIV infection. 
 
The recommended dose of Trizivir in adults (18 years and over) is one tablet twice daily. 
 
Trizivir can be taken with or without food. 
 



 3 

Where discontinuation of therapy with one of the active substances of Trizivir is indicated, or where 
dose reduction is necessary separate preparations of abacavir, lamivudine and zidovudine are 
available. 
 
Special populations 
 
Renal impairment 
 
 Whilst no dose adjustment of abacavir is necessary in patients with renal dysfunction, lamivudine and 
zidovudine concentrations are increased in patients with renal impairment due to decreased clearance. 
Therefore, as dose adjustments of these may be necessary, it is recommended that separate 
preparations of abacavir, lamivudine and zidovudine be administered to patients with reduced renal 
function (creatinine clearance ≤ 50 ml/min). Physicians should refer to the individual summary of 
product characteristics of these medicinal products. Trizivir should not be administered to patients 
with end-stage renal disease (see sections 4.3 and 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 Trizivir 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). 
 
Elderly 
 
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. 
 
Paediatric population 
 
The safety and efficacy of Trizivir in adolescents and children has not been established. No data are 
available. 
 
Dose adjustments in patients with haematological adverse reactions 
 
Dose adjustment of zidovudine may be necessary if the haemoglobin level falls below 9 g/dl or 
5.59 mmol/l or the neutrophil count falls below 1.0 x 109/l (see sections 4.3 and 4.4). As dose 
adjustment of Trizivir is not possible, separate preparations of abacavir, lamivudine and zidovudine 
should be used. Physicians should refer to the individual summary of product characteristics of these 
medicinal products. 
 
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 
 
Patients with end-stage renal disease. 
 
 
Due to the active substance zidovudine, Trizivir is contraindicated in patients with abnormally low 
neutrophil counts (< 0.75 x 109/l), or abnormally low haemoglobin levels (< 7.5 g/dl or 4.65 mmol/l) 
(see section 4.4). 
 
4.4 Special warnings and precautions for use 
 



 4 

The special warnings and precautions relevant to abacavir, lamivudine and zidovudine are included in 
this section. There are no additional precautions or warnings relevant to the combination Trizivir. 
 

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: 

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

• Trizivir 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. Kivexa, Ziagen, Triumeq)  

• Trizivir 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 Trizivir after the onset of 
hypersensitivity may result in a life-threatening reaction.  

• After stopping treatment with Trizivir for reasons of a suspected HSR, Trizivir or any other 
medicinal product containing abacavir (e.g. Kivexa, Ziagen, 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 Trizivir 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. 



 5 

 
Lactic acidosis  
Lactic acidosis, usually associated with hepatomegaly and hepatic steatosis, has been reported with the 
use of zidovudine .  Early symptoms (symptomatic hyperlactatemia) include benign digestive 
symptoms (nausea, vomiting and abdominal pain), non-specific malaise, loss of appetite, weight loss, 
respiratory symptoms (rapid and/or deep breathing) or neurological symptoms (including motor 
weakness). 
 
Lactic acidosis has a high mortality and may be associated with pancreatitis, liver failure, or renal 
failure. 
 
Lactic acidosis generally occurred after a few or several months of treatment. 
 
Treatment with zidovudine should be discontinued in the setting of symptomatic hyperlactatemia and 
metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels. 
 
Caution should be exercised when administering  zidovudine to any patient (particularly obese 
women) with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic 
steatosis (including certain medicinal products and alcohol). Patients co-infected with hepatitis C and 
treated with alpha interferon and ribavirin may constitute a special risk. 
 
Patients at increased risk should be followed closely.  
 
 
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 adverse 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. 
 
Lipoatrophy 
Treatment with zidovudine has been associated with loss of subcutaneous fat, which has been linked to 
mitochondrial toxicity. The incidence and severity of lipoatrophy are related to cumulative exposure. 
This fat loss, which is most evident in the face, limbs and buttocks, may not be reversible when 
switching to a zidovudine-free regimen. Patients should be regularly assessed for signs of lipoatrophy 
during therapy with zidovudine and zidovudine-containing products (Combivir and Trizivir). Therapy 
should be switched to an alternative regimen if there is suspicion of lipoatrophy development. 
 
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. 
 
 
 



 6 

Haematological adverse reactions 
 
Anaemia, neutropenia and leucopenia (usually secondary to neutropenia) can be expected to occur in 
patients receiving zidovudine. These occurred more frequently at higher zidovudine doses (1200-
1500 mg/day) and in patients with poor bone marrow reserve prior to treatment, particularly with 
advanced HIV disease. Haematological parameters should therefore be carefully monitored (see 
section 4.3) in patients receiving Trizivir. These haematological effects are not usually observed 
before four to six week’s therapy. For patients with advanced symptomatic HIV disease, it is generally 
recommended that blood tests are performed at least every two weeks for the first three months of 
therapy and at least monthly thereafter. 
 
In patients with early HIV disease haematological adverse reactions are infrequent. Depending on the 
overall condition of the patient, blood tests may be performed less often, for example every one to 
three months. Additionally, dose adjustment of zidovudine may be required if severe anaemia or 
myelosuppression occurs during treatment with Trizivir, or in patients with pre-existing bone marrow 
compromise e.g. haemoglobin < 9 g/dl (5.59 mmol/l) or neutrophil count < 1.0 x 109/l (see 
section 4.2). As dose adjustment of Trizivir is not possible separate preparations of zidovudine, 
abacavir and lamivudine should be used. Physicians should refer to the individual prescribing 
information for these medicinal products. 
 
Pancreatitis 
 
Cases of pancreatitis have occurred rarely in patients treated with abacavir, lamivudine and 
zidovudine. However, it is not clear whether these cases were due to treatment with these medicinal 
products or to the underlying HIV disease. Treatment with Trizivir should be stopped immediately if 
clinical signs, symptoms or laboratory abnormalities suggestive of pancreatitis occur. 
 
Liver disease 
 
If lamivudine is being used concomitantly for the treatment of HIV and HBV, additional information 
relating to the use of lamivudine in the treatment of hepatitis B infection is available in the Zeffix 
SmPC. 
 
The safety and efficacy of Trizivir has not been established in patients with significant underlying 
liver disorders. Trizivir is not recommended in patients with moderate or severe hepatic impairment 
(see sections 4.2 and 5.2).  
 
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 Trizivir is discontinued in patients co-infected with hepatitis B virus, periodic monitoring of both 
liver function tests and markers of HBV replication is recommended, as withdrawal of lamivudine 
may result in an acute exacerbation of hepatitis (see Zeffix SmPC). 
 
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 hepatitis  B or C virus 
 
The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of 
anaemia (see section 4.5). 
  
Children and adolescents 



 7 

 
Because insufficient data are available, the use of Trizivir in children or adolescents is not 
recommended. In this patient population, hypersensitivity reactions are particularly difficult to 
identify. 
 
Immune Reactivation Syndrome 
 
In HIV-infected patients with severe immune deficiency at the time of institution of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, 
such reactions have been observed within the first few weeks or months of initiation of CART. 
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterium infections, 
and Pneumocystis jirovecii pneumonia. 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 can occur many months after initiation of treatment. 
 
Osteonecrosis 
 
Although the aetiology 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 combination 
antiretroviral therapy (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 Trizivir 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 Trizivir, action should be taken to try to minimize all 
modifiable risk factors (e.g. smoking, hypertension, and hyperlipidaemia). 
 
Transmission 
 
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.  
 
Drug Interactions: 
 
To date there are insufficient data on the efficacy and safety of Trizivir given concomitantly with 
NNRTIs or PIs (see section 5.1).  
 
Trizivir should not be taken with any other medicinal products containing lamivudine or medicinal 
products containing emtricitabine.    
 



 8 

The concomitant use of stavudine with zidovudine should be avoided (see section 4.5). 
 
The combination of lamivudine with cladribine is not-recommended (see section 4.5). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Trizivir contains abacavir, lamivudine and zidovudine, therefore any interactions identified for these 
individually are relevant to Trizivir. Clinical studies have shown that there are no clinically significant 
interactions between abacavir, lamivudine and zidovudine. 
 
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.  Zidovudine is primarily metabolised by UGT 
enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine 
exposure. Lamivudine is cleared renally. Active renal 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, lamivudine and zidovudine 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. 
 
Interaction studies have only been performed in adults. 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. 
Didanosine/Zidovudine Interaction not studied. 
Stavudine/Abacavir Interaction not studied. Combination not 

recommended. Stavudine/Lamivudine Interaction not studied. 
Stavudine/Zidovudine In vitro antagonism of anti-HIV 

activity between stavudine and 
zidovudine could result in 
decreased efficacy of both 
drugs. 

ANTI-INFECTIVE PRODUCTS 
Atovaquone/Abacavir Interaction not studied. As only limited data available 

the clinical significance is 
unknown. 

Atovaquone/Lamivudine Interaction not studied. 
Atovaquone/Zidovudine 
 (750 mg twice daily with 
food/200 mg thrice daily) 

Zidovudine AUC ↑33% 
Atovaquone AUC ↔ 

Clarithromycin/Abacavir Interaction not studied. Separate administration of  
Trizivir and clarithromycin by 
at least 2 hours 

Clarithromycin/Lamivudine Interaction not studied. 
Clarithromycin/Zidovudine 
(500 mg twice daily/100 mg 
every 4 hours) 

Zidovudine AUC ↓12% 

Trimethoprim/sulfamethoxazole 
(Co-trimoxazole)/Abacavir 

Interaction not studied. No Trizivir dosage adjustment 
necessary, unless patient has 

Trimethoprim/sulfamethoxazole Lamivudine: AUC ↑40% 



 9 

 
 

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

 
Trimethoprim: AUC ↔ 
Sulfamethoxazole: AUC ↔ 
 
(organic cation transporter 
inhibition) 

renal impairment (See Section 
4.2). 
 
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)/Zidovudine 

Interaction not studied. 

   
ANTIFUNGALS 
Fluconazole/Abacavir Interaction not studied. As only limited data are 

available the clinical 
significance is not known.  
Monitor for signs of 
zidovudine toxicity (see 
section 4.8). 

Fluconazole/Lamivudine Interaction not studied. 
Fluconazole/Zidovudine 
(400 mg once daily/200 mg 
thrice daily) 

Zidovudine AUC ↑74% 
 
(UGT inhibition) 

ANTIMYCOBACTERIALS 
Rifampicin/Abacavir Interaction not studied. 

 
Potential to slightly decrease 
abacavir plasma concentrations 
through UGT induction. 

Insufficient data to 
recommend dosage 
adjustment. 

Drugs by Therapeutic Area Interaction 
Geometric mean change 
(%) 
(Possible mechanism) 

Recommendation 
concerning co-
administration 

Rifampicin/Lamivudine Interaction not studied. Insufficient data to 
recommend dosage 
adjustment. 

Rifampicin/Zidovudine  
(600mg once daily/200 mg 
thrice daily) 

Zidovudine AUC ↓48% 
 
(UGT induction) 

ANTICONVULSANTS 
Phenobarbital/Abacavir Interaction not studied. 

 
Potential to slightly decrease 
abacavir plasma concentrations 
through UGT induction. 

Insufficient data to 
recommend dosage 
adjustment. 

Phenobarbital/Lamivudine Interaction not studied. 
Phenobarbital/Zidovudine Interaction not studied. 

 
Potential to slightly decrease 
zidovudine plasma 
concentrations through UGT 
induction. 
 

Phenytoin/Abacavir Interaction not studied. 
 



 10 

 

Potential to slightly decrease 
abacavir plasma concentrations 
through UGT induction. 

Insufficient data to 
recommend dosage 
adjustment. 
 
Monitor phenytoin 
concentrations. 

Phenytoin/Lamivudine Interaction not studied. 
Phenytoin/Zidovudine Phenytoin AUC ↑↓  

Valproic acid/Abacavir Interaction not studied. As only limited data are 
available the clinical 
significance is not known.  
Monitor for signs of 
zidovudine toxicity (see 
section 4.8). 

Valproic acid/Lamivudine Interaction not studied. 
Valproic acid/Zidovudine 
(250 mg or 500 mg thrice 
daily/100 mg thrice daily) 

Zidovudine AUC ↑80% 
 
(UGT inhibition) 

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. 

Ranitidine/Zidovudine Interaction not studied 
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. 

Cimetidine/Zidovudine Interaction not studied. 



 11 

Drugs by Therapeutic Area Interaction 
Geometric mean change 
(%) 
(Possible mechanism) 

Recommendation 
concerning co-
administration 

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% 

As only limited data are 
available the clinical 
significance is not known.  
Monitor for signs of 
zidovudine toxicity (see 
section 4.8). 
 
Methadone dosage adjustment 
unlikely in majority of 
patients; occasionally 
methadone re-titration may be 
required. 

Methadone/Lamivudine Interaction not studied. 
Methadone/Zidovudine 
(30 to 90 mg once daily/200 mg 
every 4 hours) 

Zidovudine AUC ↑43% 
Methadone AUC ↔ 

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. 

Retinoid compounds  
(e.g. isotretinoin)/Zidovudine 

Interaction not studied. 

URICOSURIC 
Probenecid/Abacavir Interaction not studied. As only limited data are 

available the clinical 
significance is not known.  
Monitor for signs of 
zidovudine toxicity (see 
section 4.8). 

Probenecid/Lamivudine Interaction not studied. 
Probenecid/Zidovudine 
(500 mg four times 
daily/2mg/kg thrice daily) 

Zidovudine AUC ↑106% 
 
(UGT inhibition) 

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

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

No dosage adjustment 
necessary. 

Ethanol/Lamivudine Interaction not studied. 



 12 

Abbreviations: ↑ = Increase; ↓=decrease; ↔= no significant change; AUC=area under the 
concentration versus time curve; Cmax=maximum observed concentration; CL/F=apparent oral 
clearance 
Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen 
used to treat HIV although the exact mechanism remains to be elucidated. The concomitant use of 
ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.4). 
Consideration should be given to replacing zidovudine in a combination ART regimen if this is 
already established. This would be particularly important in patients with a known history of 
zidovudine induced anaemia. 
 
Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive 
medicinal products (e.g. systemic pentamidine, dapsone, pyrimethamine, co-trimoxazole, 
amphotericin, flucytosine, ganciclovir, interferon, vincristine, vinblastine and doxorubicin) may also 
increase the risk of adverse reactions to zidovudine (see section 4.8). If concomitant therapy with 
Trizivir and any of these medicinal products is necessary then extra care should be taken in monitoring 
renal function and haematological parameters and, if required, the dosage of one or more agents 
should be reduced. 
 
Limited data from clinical trials do not indicate a significantly increased risk of adverse reactions to 
zidovudine with cotrimoxazole (see interaction information above relating to lamivudine and co-
trimoxazole), aerosolised pentamidine, pyrimethamine and acyclovir at doses used in prophylaxis. 
 
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. In 
the present case, the use in pregnant women of zidovudine, with subsequent treatment of the newborn 
infants, has been shown to reduce the rate of maternal-foetal transmission of HIV. There are no data 
on the use of Trizivir in pregnancy. A moderate amount of data on pregnant women taking the 
individual actives abacavir, lamivudine and zidovudine in combination indicates no malformative 
toxicity (more than 300 outcomes from first trimester exposures). A large amount of data on pregnant 
women taking lamivudine or zidovudine indicate no malformative toxicity (more than 3000 outcomes 
from first trimester exposure each, of which over 2000 outcomes involved exposure to both 
lamivudine and zidovudine). Moderate amount of data (more than 600 outcomes from first trimester) 

Ethanol/Zidovudine 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 Trizivir 
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. 



 13 

indicates no malformative toxicity for abacavir. The malformative risk is unlikely in humans based on 
the mentioned moderate amount of data. 
 
The active ingredients of Trizivir may inhibit cellular DNA replication, zidovudine has been shown to 
be transplacental carcinogen in one animal study and abacavir has been shown to be carcinogenic in 
animal models (see section 5.3). The clinical relevance of these findings is unknown. 
 
For patients co-infected with hepatitis who are being treated with a lamivudine containing medicinal 
product such as Trizivir and subsequently become pregnant, consideration should be given to the 
possibility of a recurrence of hepatitis on discontinuation of lamivudine. 
 
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.  
 
After administration of a single dose of 200 mg zidovudine to HIV-infected women, the mean 
concentration of zidovudine was similar in human milk and serum. 
 
It is recommended that mothers infected by HIV 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 nor zidovudine had any effect on 
fertility (see section 5.3). Zidovudine has been shown not to affect the number of sperm, sperm 
morphology and motility in man. 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. The clinical 
status of the patient and the adverse event profile of Trizivir 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 
 
Adverse reactions have been reported with abacavir, lamivudine and zidovudine used separately or in 
combination for therapy of HIV disease. Because Trizivir contains abacavir, lamivudine and 
zidovudine, the adverse reactions associated with these compounds may be expected.   
 
Tabulated list of adverse reactions reported with the individual substances 
 
The adverse reactions reported with abacavir, lamivudine and zidovudine are presented in Table 2. 
They are listed by body system, organ class and absolute frequency. Frequencies are defined as very 



 14 

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).  Care must be taken to eliminate the possibility of a hypersensitivity 
reaction if any of these symptoms occur. 
 
Table 1: Adverse reactions reported with the individual components of Trizivir 
 

Abacavir Lamivudine Zidovudine 

IMPORTANT: for information on abacavir hypersensitivity  see the information  below,  
under the  Description of selected adverse reactions 

Abacavir hypersensitivity 

Blood and lymphatic system disorders 

 Uncommon: neutropenia, 
anaemia (both occasionally 
severe), thrombocytopenia  
Very rare: pure red cell aplasia 

Common: anaemia, neutropenia 
and leucopenia  
Uncommon: thrombocytopenia 
and pancytopenia with marrow 
hypoplasia 
Rare: pure red cell aplasia  
Very rare: aplastic anaemia 

Immune system disorders 

Common: hypersensitivity   

Metabolism and nutrition disorders 

Common: anorexia 

Very Rare : lactic acidosis 

 

Very Rare : lactic acidosis 

 
Rare: anorexia, lactic acidosis 
in the absence of hypoxaemia  

Psychiatric disorders 

  Rare: anxiety, depression 

Nervous system disorders 

Common: headache Common: headache, insomnia Very rare: peripheral 
neuropathy (paraesthesiae) 

Very common: headache 
Common: dizziness  
Rare: insomnia, paraesthesia, 
somnolence, loss of mental 
acuity, convulsions 

Cardiac disorders 

  Rare: cardiomyopathy 

Respiratory, thoracic and mediastinal disorders 

 Common: cough, nasal 
symptoms 

Uncommon: dyspnoea 
Rare: cough 

 



 15 

Abacavir Lamivudine Zidovudine 

Gastrointestinal disorders 

Common: nausea, vomiting, 
diarrhoea  
Rare: pancreatitis 

Common: nausea, vomiting, 
abdominal pain, diarrhoea 
Rare: rises in serum amylase, 
pancreatitis 

Very common: Nausea  
Common: vomiting, abdominal 
pain, and diarrhoea 
Uncommon: flatulence 
Rare: oral mucosa 
pigmentation, taste disturbance 
dyspepsia, pancreatitis 

Hepatobiliary disorders 

 Uncommon: transient rises in liver enzymes (AST, ALT) 
Rare: hepatitis 

Common: raised blood levels 
of liver enzymes and bilirubin 
Rare: liver disorders such as 
severe hepatomegaly with 
steatosis, 

Skin and subcutaneous tissue disorders 

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

Common: rash, alopecia Uncommon: rash and pruritus 
Rare:  nail and skin 
pigmentation, urticaria and 
sweating 

Musculoskeletal and connective tissue disorders 

 Common: arthralgia, muscle 
disorders  
Rare: rhabdomyolysis 

Common: myalgia 
Uncommon: myopathy 

Renal and urinary disorders 

  Rare: urinary frequency 

Reproductive system and breast disorders 

  Rare: gynaecomastia 

General disorders and administration site conditions 

Common: fever, lethargy, 
fatigue 

Common: fatigue, malaise, 
fever 

Common: malaise 
Uncommon: fever, generalised 
pain and asthenia 
Rare: chills, chest pain, and 
influenza-like syndrome 

Many of the adverse reactions listed in the table  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 



 16 

have been reported where abacavir hypersensitivity could not be ruled out. In such cases medicinal 
products containing abacavir should be permanently discontinued. 
 
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.  
 
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). 
 
 
Haematological adverse reactions with zidovudine 
 
Anaemia, neutropenia and leucopenia occurred more frequently at higher doses (1,200-1,500 mg/day) 
and in patients with advanced HIV disease (especially when there is poor bone marrow reserve prior to 
treatment) and particularly in patients with CD4 cell counts less than 100/mm3. Dose reduction or 
cessation of therapy may become necessary (see section 4.4).  The anaemia may necessitate 
transfusions. 
 
The incidence of neutropenia was also increased in those patients whose neutrophil counts, 
haemoglobin levels and serum vitamin B12 levels were low at the start of zidovudine therapy. 



 17 

 
Lactic acidosis 
 
Treatment with  zidovudine has been associated with cases of lactic acidosis, sometimes fatal, usually 
associated with severe hepatomegaly and hepatic steatosis, (see section 4.4). 
 
Lipoatrophy 
Treatment with zidovudine has been associated with loss of subcutaneous fat which is most evident in 
the face, limbs and buttocks.  Patients receiving Trizivir  should be frequently examined and 
questioned for signs of lipoatrophy. When such development is found, treatment with Trizivir should 
not be continued (see section 4.4). 
 
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 (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
infections may arise. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have 
also been reported 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 (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 combination antiretroviral therapy (CART). 
The frequency of this is unknown (see section 4.4). 
 
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 
 
There is no experience of overdose with Trizivir. No specific symptoms or signs have been identified 
following acute overdose with zidovudine or lamivudine apart from those listed as adverse reactions. 
No fatalities occurred, and all patients recovered. Single doses up to 1,200 mg and daily doses up to 
1,800 mg of abacavir have been administered to patients in clinical studies. No unexpected adverse 
reactions were reported. The effects of higher doses are not known. 
 
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. 
Haemodialysis and peritoneal dialysis appear to have a limited effect on elimination of zidovudine, but 
enhance the elimination of the glucuronide metabolite. It is not known whether abacavir can be 
removed by peritoneal dialysis or haemodialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 

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


 18 

Pharmacotherapeutic group 
Antivirals for systemic use, antivirals for treatment of HIV infections, combinations. ATC Code: 
J05AR04.  
 
Mechanism of action 
Abacavir, lamivudine and zidovudine are all NRTIs, and are potent selective inhibitors of HIV-1 and 
HIV-2.All three medicinal products are metabolised sequentially by intracellular kinases to the 
respective 5′-triphosphate (TP). Lamivudine-TP, carbovir-TP (the active triphosphate form of 
abacavir) and zidovudine-TP 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, lamivudine and zidovudine 
triphosphates show significantly less affinity for host cell DNA polymerases. 
 
 No antagonistic effects in vitro were seen with lamivudine and other antiretrovirals (tested agents: 
abacavir, didanosine and nevirapine). No antagonistic effects in vitro were seen with zidovudine and 
other antiretrovirals (tested agents: didanosine and interferon-alpha). The antiviral activity of abacavir 
in cell culture was not antagonized when combined with the nucleoside reverse transcriptase inhibitors 
(NRTIs) didanosine, emtricitabine, stavudine  or tenofovir,  the non-nucleoside reverse transcriptase 
inhibitor (NNRTI) nevirapine, or the protease inhibitor (PI) amprenavir.  
 
In vitro resistance 
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. 
 
Abacavir-resistant isolates of HIV-1 have been selected in vitro and are associated with specific 
genotypic changes in the RT codon region (codons M184V, K65R, L74V and Y115F). Viral 
resistance to abacavir develops relatively slowly in vitro, requiring multiple mutations for a clinically 
relevant increase in EC50 over wild-type virus.  
 
In vivo resistance (therapy naïve patients) 
The M184V or M184I variants arise in HIV-1 infected patients treated with lamivudine-containing 
antiretroviral therapy. Most patients experiencing virological failure with a regimen containing 
abacavir in a pivotal clinical trial with Combivir (fixed dose combination of lamivudine and 
zidovudine) showed either no NRTI-related changes from baseline (15 %) or only M184V or M184I 
selection (78 %). The overall selection frequency for M184V or M184I was high (85 %), and selection 
of L74V, K65R and Y115F was not observed (see Table). Thymidine analogue mutations (TAMs) 
which are selected by zidovudine (ZDV) were also found (8%).  
 

Therapy Abacavir + Combivir  

Number of Subjects 282 

Number of Virological Failures 43 

Number of On-Therapy  Genotypes 40 (100 %) 

K65R 0 

L74V 0 
Y115F 0 

M184V/I 34 (85 %) 
TAMs1 3 (8 %) 

1. Number of subjects with ≥1 TAM. 
 
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 



 19 

(22/86, 26 %).  In addition, the selection of L74V and K65R was reduced when co-administered with 
ZDV (K65R: without ZDV: 13/127, 10 %; with ZDV: 1/86, 1 %; L74V: without ZDV: 51/127, 40 %; 
with ZDV: 2/86, 2 %). 
 
In vivo resistance (Therapy experienced patients) 
The M184V or M184I variants arise in HIV-1 infected patients treated with lamivudine-containing 
antiretroviral therapy and confers 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. Similarly, the presence of TAMs gives rise to resistance to ZDV. 
 
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 abacavir 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-1 RNA [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, 
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. Appropriate use of abacavir can be 
guided using currently recommended resistance algorithms. 
 
Cross-resistance between abacavir, lamivudine or zidovudine and antiretrovirals from other classes 
e.g. PIs or NNRTIs is unlikely. 



 20 

 
Clinical efficacy and safety  
 
One randomised, double blind, placebo controlled clinical study has compared the combination of 
abacavir, lamivudine and zidovudine to the combination of indinavir, lamivudine and zidovudine in 
treatment naive patients. Due to the high proportion of premature discontinuation (42 % of patients 
discontinued randomised treatment by week 48), no definitive conclusion can be drawn regarding the 
equivalence between the treatment regimens at week 48. Although a similar antiviral effect was 
observed between the abacavir and indinavir containing regimens in terms of proportion of patients 
with undetectable viral load (≤ 400 copies/ml; intention to treat analysis (ITT), 47 % versus 49 %; as 
treated analysis (AT), 86 % versus 94 % for abacavir and indinavir combinations respectively), results 
favoured the indinavir combination, particularly in the subset of patients with high viral load 
(> 100,000 copies/ml at baseline; ITT, 46 % versus 55 %; AT, 84 % versus 93 % for abacavir and 
indinavir respectively). 
 
ACTG5095 was a randomised (1:1:1), double-blind, placebo-controlled trial performed in 1147 
antiretroviral naïve HIV-1 infected adults, comparing 3 regimens: zidovudine (ZDV), lamivudine 
(3TC), abacavir (ABC), efavirenz (EFV) vs ZDV/3TC/EFV vs ZDV/3TC/ABC. After a median 
follow-up of 32 weeks, the tritherapy with the three nucleosides ZDV/3TC/ABC was shown to be 
virologically inferior to the two other arms regardless of baseline viral load (< or > 100 000 copies/ml) 
with 26 % of subjects on the ZDV/3TC/ABC arm, 16 % on the ZDV/3TC/EFV arm and 13 % on the 4 
drug arm categorised as having virological failure (HIV RNA >200 copies/ml). At week 48 the 
proportion of subjects with HIV RNA <50 copies/ml were 63 %, 80 % and 86 % for the 
ZDV/3TC/ABC, ZDV/3TC/EFV and ZDV/3TC/ABC/EFV arms, respectively. The study Data Safety 
Monitoring Board stopped the ZDV/3TC/ABC arm at this time based on the higher proportion of 
patients with virologic failure. The remaining arms were continued in a blinded fashion. After a 
median follow-up of 144 weeks, 25 % of subjects on the ZDV/3TC/ABC/EFV arm and 26 % on the 
ZDV/3TC/EFV arm were categorised as having virological failure. There was no significant 
difference in the time to first virologic failure (p=0.73, log-rank test) between the 2 arms. In this study, 
addition of ABC to ZDV/3TC/EFV did not significantly improve efficacy. 
 

  ZDV/3TC/ABC ZDV/3TC/EFV ZDV/3TC/ABC/EFV 
Virologic failure (HIV 
RNA >200 copies/ml) 

32 weeks 26 % 16 % 13 % 
144 weeks - 26 % 25 % 

Virologic success (48 
weeks HIV RNA < 50 
copies/ml) 

 63 % 80 % 86 % 

 
In antiretroviral-naive patients treated with a combination of abacavir, lamivudine, zidovudine and 
efavirenz in a small, ongoing, open label pilot study, the proportion of patients with undetectable viral 
load (< 400 copies/ml) was approximately 90 % with 80 % having < 50 copies/ml after 24 weeks of 
treatment. 
 
Currently there are no data on the use of Trizivir in heavily pre-treated patients, patients failing on 
other therapies or patients with advanced disease (CD4 cells < 50 cells/mm3).  
 
The degree of benefit of this nucleoside combination in heavily pre-treated patients will depend on the 
nature and duration of prior therapy that may have selected for HIV-1 variants with cross-resistance to 
abacavir, lamivudine or zidovudine. 
 
To date there are insufficient data on the efficacy and safety of Trizivir given concomitantly with 
NNRTIs or PIs. 
 



 21 

5.2 Pharmacokinetic properties 
 
Absorption 
 
Abacavir, lamivudine and zidovudine are rapidly and well absorbed from the gastro-intestinal tract 
following oral administration. The absolute bioavailability of oral abacavir, lamivudine and 
zidovudine in adults is about 83 %, 80 - 85 % and 60 - 70 % respectively. 
 
In a pharmacokinetic study in HIV-1 infected patients, the steady state pharmacokinetic parameters of 
abacavir, lamivudine and zidovudine were similar when either Trizivir alone or the combination tablet 
lamivudine/zidovudine and abacavir in combination were administered, and also similar to the values 
obtained in the bioequivalence study of Trizivir in healthy volunteers. 
 
A bioequivalence study compared Trizivir with abacavir 300 mg, lamivudine 150 mg and zidovudine 
300 mg taken together. The effect of food on the rate and extent of absorption was also studied. 
Trizivir was shown to be bioequivalent to abacavir 300 mg, lamivudine 150 mg and zidovudine 
300 mg given as separate tablets for AUC0-∞ and Cmax. Food decreased the rate of absorption of 
Trizivir (slight decrease Cmax (mean 18 - 32 %) and increase tmax (approximately 1 hour), but not the 
extent of absorption (AUC0-∞). These changes are not considered clinically relevant and no food 
restrictions are recommended for administration of Trizivir. 
 
At a therapeutic dose (one Trizivir tablet twice daily) in patients, the mean (CV) steady-state Cmax of 
abacavir, lamivudine and zidovudine in plasma are 3.49 µg/ml (45 %), 1.33 µg/ml (33 %) and 
1.56 µg/ml (83 %), respectively.  Corresponding values for Cmin could not be established for abacavir 
and are 0.14 µg/ml (70 %) for lamivudine and 0.01 µg/ml (64 %) for zidovudine. The mean (CV) 
AUCs for abacavir, lamivudine and zidovudine over a dosing interval of 12 hours are 6.39 µg.h/ml 
(31 %), 5.73 µg.h/ml (31 %) and 1.50 µg.h/ml (47 %), respectively. 
 
A modest increase in Cmax (28 %) was observed for zidovudine when administered with lamivudine, 
however overall exposure (AUC) was not significantly altered. Zidovudine has no effect on the 
pharmacokinetics of lamivudine. An effect of abacavir is observed on zidovudine (Cmax reduced with 
20 %) and on lamivudine (Cmax reduced with 35 %). 
 
Distribution 
 
Intravenous studies with abacavir, lamivudine and zidovudine showed that the mean apparent volume 
of distribution is 0.8, 1.3 and 1.6 l/kg respectively. Lamivudine exhibits linear pharmacokinetics over 
the therapeutic dose range and displays limited binding to the major plasma protein albumin (< 36 % 
serum albumin in vitro). Zidovudine plasma protein binding is 34 % to 38 %. Plasma protein binding 
studies in vitro indicate that abacavir binds only low to moderately (~ 49 %) to human plasma proteins 
at therapeutic concentrations. This indicates a low likelihood for interactions with other medicinal 
products through plasma protein binding displacement. 
 
Interactions involving binding site displacement are not anticipated with Trizivir. 
 
Data show that abacavir, lamivudine and zidovudine penetrate the central nervous system (CNS) and 
reach the cerebrospinal fluid (CSF). The mean ratios of CSF/serum lamivudine and zidovudine 
concentrations 2 - 4 hours after oral administration were approximately 0.12 and 0.5 respectively. The 
true extent of CNS penetration of lamivudine and its relationship with any clinical efficacy is 
unknown.  
 
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.  
 
 



 22 

 
Biotransformation 
 
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 %) and low plasma binding. 
 
The 5’-glucuronide of zidovudine is the major metabolite in both plasma and urine, accounting for 
approximately 50 - 80 % of the administered dose eliminated by renal excretion. 3’-amino-3’-
deoxythymidine (AMT) has been identified as a metabolite of zidovudine following intravenous 
dosing. 
 
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 dose excreted in the urine. 
 
Elimination 
 
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, with predominantly renal clearance (> 70 %) via the organic 
cationic transport system. Studies in patients with renal impairment show lamivudine elimination is 
affected by renal dysfunction. Dose reduction is required for patients with creatinine clearance 
≤ 50 ml/min (see section 4.2).  
 
From studies with intravenous zidovudine, the mean terminal plasma half-life was 1.1 hours and the 
mean systemic clearance was 1.6 l/h/kg. Renal clearance of zidovudine is estimated to be 0.34 l/h/kg, 
indicating glomerular filtration and active tubular secretion by the kidneys. Zidovudine concentrations 
are increased in patients with advanced renal failure. 
 
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. 
 
 
Special patient populations 
 
Hepatic impairment 
. 
Pharmacokinetic data has been obtained for abacavir, lamivudine and zidovudine separately. Limited 
data in patients with cirrhosis suggest that accumulation of zidovudine may occur in patients with 
hepatic impairment because of decreased glucuronidation. Data obtained in patients with moderate to 
severe hepatic impairment show that lamivudine pharmacokinetics are not significantly affected by 
hepatic dysfunction.  
 
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 in this patient population.  
Based on data obtained for abacavir, Trizivir is not recommended in patients with moderate or severe 
hepatic impairment. 
 



 23 

Renal impairment 
 
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, with predominantly renal clearance (> 70 %) via the organic 
cationic transport system. Studies in patients with renal impairment show lamivudine elimination is 
affected by renal dysfunction. 
 
From studies with intravenous zidovudine, the mean terminal plasma half-life was 1.1 hours and the 
mean systemic clearance was 1.6 l/h/kg. Renal clearance of zidovudine is estimated to be 0.34 l/h/kg, 
indicating glomerular filtration and active tubular secretion by the kidneys. Zidovudine concentrations 
are increased in patients with advanced renal failure. 
 
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, and, therefore, no dose reduction is required in patients 
with renal impairment. 
 
As dose adjustments of lamivudine and zidovudine may be necessary it is recommended that separate 
preparations of abacavir, lamivudine and zidovudine be administered to patients with reduced renal 
function (creatinine clearance ≤ 50 ml/min). Trizivir is contraindicated in patients with end-stage renal 
disease (see section 4.3). 
 
Elderly 
 
No pharmacokinetic data are available in patients over 65 years of age. 
 
5.3 Preclinical safety data 
 
There are no data available on treatment with the combination of abacavir, lamivudine and zidovudine 
in animals. The clinically relevant toxicological effects of these three medicinal products are anaemia, 
neutropenia and leucopenia. 
 
Mutagenicity and carcinogenicity 
 
Neither abacavir, lamivudine nor zidovudine is 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.  
 
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 levels. Zidovudine showed clastogenic 
effects in oral repeated dose micronucleus tests in mice and rats. Peripheral blood lymphocytes from 
AIDS patients receiving zidovudine treatment have also been observed to contain higher numbers of 
chromosome breakages.  
 
A pilot study has demonstrated that zidovudine is incorporated into leukocyte nuclear DNA of adults, 
including pregnant women, taking zidovudine as treatment for HIV-1 infection, or for the prevention 
of mother to child viral transmission.  Zidovudine was also incorporated into DNA from cord blood 
leukocytes of infants from zidovudine-treated mothers.  A transplacental genotoxicity study conducted 
in monkeys compared zidovudine alone with the combination of zidovudine and lamivudine at human-
equivalent exposures.  The study demonstrated that foetuses exposed in utero to the combination 
sustained a higher level of nucleoside analogue-DNA incorporation into multiple foetal organs, and 
showed evidence of more telomere shortening than in those exposed to zidovudine alone. The clinical 
significance of these findings is unknown.  
 



 24 

Abacavir has a weak potential to cause chromosomal damage both in vitro and in vivo at high test 
concentrations and therefore any potential risk to man must be balanced against the expected benefits 
of treatment.  
 
The carcinogenic potential of a combination of abacavir, lamivudine and zidovudine has not been 
tested. In long-term oral carcinogenicity studies in rats and mice, lamivudine did not show any 
carcinogenic potential. In oral carcinogenicity studies with zidovudine in mice and rats, late appearing 
vaginal epithelial tumours were observed.  A subsequent intravaginal carcinogenicity study confirmed 
the hypothesis that the vaginal tumours were the result of long term local exposure of the rodent 
vaginal epithelium to high concentrations of unmetabolised zidovudine in urine. There were no other  
zidovudine-related tumours observed in either sex of either species. 
 
In addition, two transplacental carcinogenicity studies have been conducted in mice. In one study, by 
the US National Cancer Institute, zidovudine was administered at maximum tolerated doses to 
pregnant mice from day 12 to 18 of gestation. One year postnatally, there was an increase in the 
incidence of tumours in the lung, liver and female reproductive tract of offspring exposed to the 
highest dose level (420 mg/kg term body weight). 
 
In a second study, mice were administered zidovudine at doses up to 40 mg/kg for 24 months, with 
exposure beginning prenatally on gestation day 10. Treatment related findings were limited to late-
occurring vaginal epithelial tumours, which were seen with a similar incidence and time of onset as in 
the standard oral carcinogenicity study. The second study thus provided no evidence that zidovudine 
acts as a transplacental carcinogen. 
 
It is concluded that as the increase in incidence of tumours in the first transplacental carcinogenicity 
study represents a hypothetical risk, this should be balanced against the proven therapeutic benefit. 
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 
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 
 
Lamivudine was not teratogenic in animal studies but there were indications of an increase in early 
embryonic deaths in the rabbit 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. 
 



 25 

Zidovudine had a similar effect in both species, but only at very high systemic exposures. At 
maternally toxic doses, zidovudine given to rats during organogenesis resulted in an increased 
incidence of malformations, but no evidence of foetal abnormalities was observed at lower doses. 
 
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 the rat has shown that abacavir had no effect on male or female fertility. Likewise, 
neither lamivudine nor zidovudine had any effect on fertility. Zidovudine has not been shown to affect 
the number of sperm, sperm morphology and motility in man. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet Core:  
microcrystalline cellulose,  
sodium starch glycollate (type A),  
magnesium stearate. 
 
Tablet Coating:  
Opadry Green 03B11434 containing: hypromellose, titanium dioxide, polyethylene glycol, indigo 
carmine aluminium lake, iron oxide yellow. 
 
6.2 Incompatibilities 
 
Not applicable 
 
6.3 Shelf-life 
 
2 years 
 
6.4 Special precautions for storage 
 
Do not store above 30°C  
 
6.5 Nature and contents of container 
 
Trizivir tablets are available in opaque white PCTFE/PVC-Al blister packs or child-resistant foil 
PVC/PCTFE/PVC-Al/Paper blister packs containing 60 tablets, or child resistant HDPE bottles 
containing 60 tablets. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 



 26 

Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/00/156/002 – opaque white PCTFE/PVC-Al Blister pack (60 Tablets) 
EU/1/00/156/003 -Bottle pack (60 Tablets) 
EU/1/00/156/004 - child-resistant foil PVC/PCTFE/PVC-Al/Paper Blister pack (60 Tablets) 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  2 January 2001 
 
Date of latest renewal: 2 January 2011 
 
 
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 Operations UK Ltd (trading as Glaxo Wellcome Operations),  
Priory Street,  
Ware,  
Hertfordshire, SG 12 0DJ, UK 
 
Or 
 
GlaxoSmithKline Pharmaceuticals S.A. 
ul. Grunwaldzka 189  
60-322 Poznan  
Poland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 

 
The 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 RESTRICTIONSWITH REGARD TO THE SAFE ANDEFFECTIVE 

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 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 
 
BLISTER CARTON x 60 FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trizivir 300 mg/150 mg/300 mg film-coated tablets 
abacavir/lamivudine/zidovudine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains: 
abacavir 300 mg (as sulfate) 
lamivudine 150 mg 
zidovudine 300 mg 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
 
Read the package leaflet before 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” (with Alert card attached) 
 
 
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/1/00/156/002 PCTFE/PVC-Al  
EU/1/00/156/004 PVC/PCTFE/PVC-Al/Paper 
 
 
13. BATCH NUMBER 
 
LOT 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
trizivir       
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC: 
SN: 
NN:  
 
                                                                                                                                                                                     



 33 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER x 60 FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trizivir 300 mg/150 mg/300 mg tablets 
abacavir/lamivudine/zidovudine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV Netherlands 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
LOT 
 
 

5. OTHER 
 
  



 34 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
BOTTLE CARTON x 60 FILM COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trizivir 300 mg/150 mg/300 mg film-coated tablets 
abacavir/lamivudine/zidovudine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains: 
abacavir 300 mg (as sulfate) 
lamivudine 150 mg 
zidovudine 300 mg 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
 
Read the package leaflet before 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” (with Alert card attached) 
 
 
8. EXPIRY DATE 
 
EXP  
 



 35 

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/1/00/156/003 
 
 
13. BATCH NUMBER 
 
LOT 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
trizivir  
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
PC: 
SN: 
NN:  
 



 36 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL x 60 FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trizivir 300 mg/150 mg/300 mg film-coated tablets 
abacavir/lamivudine/zidovudine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains: 
abacavir 300 mg (as sulfate) 
lamivudine 150 mg 
zidovudine 300 mg 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
 
Read the package leaflet before use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACHOF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C 
 
 



 37 

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/1/00/156/003 
 
 
13. BATCH NUMBER 
 
LOT 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA  
 
 



 38 

TRIZIVIR TABLETS ALERT CARD (blister and bottle pack) 
 
SIDE 1 
 

IMPORTANT  -  ALERT CARD 
TRIZIVIR (abacavir sulfate / lamivudine / zidovudine) Tablets 

Carry this card with you at all times 
 
Since Trizivir contains abacavir  some patients taking Trizivir may develop a hypersensitivity reaction 
(serious allergic reaction) which can be life-threatening if treatment with Trizivir is continued. 
CONTACT YOUR DOCTOR IMMEDIATELY for advice on whether you should stop taking 
Trizivir 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 Trizivir due to this reaction, YOU MUST NEVER TAKE Trizivir, or any 
medicine containing abacavir (Kivexa, Ziagen or Triumeq) 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 
Trizivir.  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 Trizivir information enquiries, contact (local company name and telephone number inserted 
here) 
 
  



 39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 



 40 

Package leaflet: Information for the user 
 

Trizivir 300 mg/150 mg/300 mg film-coated tablets 
abacavir/lamivudine/zidovudine 

 
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 immediately. This includes 
any possible side effects not listed in this leaflet. See section 4. 

 
IMPORTANT — Hypersensitivity reactions 

Trizivir contains abacavir (which is also an active substance in medicines such as Kivexa, 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 Trizivir 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 Trizivir is and what it is used for 
2. What you need to know before you take Trizivir 
3. How to take Trizivir 
4. Possible side effects 
5. How to store Trizivir  
6. Contents of the pack and other information 
 
1. What Trizivir is and what it is used for 

Trizivir is used to treat HIV (human immunodeficiency virus) infection in adults. 
 
Trizivir contains three active ingredients that are used to treat HIV infection: abacavir, lamivudine and 
zidovudine. All of these belong to a group of anti-retroviral medicines called nucleoside analogue 
reverse transcriptase inhibitors (NRTIs). 
 
Trizivir helps to control your condition. Trizivir does not cure HIV infection; it reduces the amount of 
virus in your body, and keeps it at a low level. This helps your body to increase  the CD4 cell count in 
your blood. CD4 cells are a type of white blood cell that are important in helping your body to fight 
infection. 
  
Not everyone responds to treatment with Trizivir in the same way. Your doctor will monitor the 
effectiveness of your treatment. 
 
 



 41 

2. What you need to know before you take Trizivir  
 
Do not take Trizivir: 
• if you are allergic (hypersensitive) to abacavir (or any other medicine containing abacavir — 

Kivexa, Triumeq  or Ziagen), lamivudine or zidovudine, or any of the other ingredients of this 
medicine (listed in Section 6) 

Carefully read all the information about hypersensitivity reactions in Section 4. 
• if you have severe kidney problems 
• if you have a very low red blood cell count (anaemia) or a very low white blood cell count 

(neutropenia) 
Check with your doctor if you think any of these apply to you. 

 
Take special care with Trizivir 

Some people taking Trizivir 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 Trizivir without your doctor’s advice, as your hepatitis may come back) 
• if you are seriously overweight (especially if you are a woman) 

Talk to your doctor if any of these apply to you before using Trizivir. 
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 
Trizivir unless your doctor advises you to do so. 

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

Read the information ‘Other possible side effects of Trizivir’ 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 Trizivir 
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 
Trizivir. 
 
 
These medicines should not be used with Trizivir: 
• stavudine or emtricitabine, to treat HIV infection 



 42 

• other medicinal products containing lamivudine, used to treat HIV infection or hepatitis B 
infection 

• ribavirin or injections of ganciclovir to treat viral infections 
• high doses of co-trimoxazole, an antibiotic 
• cladribine, used to treat hairy cell leukaemia 

Tell your doctor if you are being treated with any of these. 
 
Some medicines can make it more likely that you will have side effects, or make side 
effects worse  

These include: 
• sodium valproate, to treat epilepsy 
• interferon, to treat viral infections 
• pyrimethamine, to treat malaria and other parasitic infections 
• dapsone, to prevent pneumonia and treat skin infections 
• fluconazole or flucytosine, to treat fungal infections such as candida 
• pentamidine or atovaquone, to treat parasitic infections such as  Pneumocystis  jirovecii 

pneumonia (often referred to as PCP)  
• amphotericin or co-trimoxazole, to treat fungal and bacterial infections 
• probenecid, to treat gout and similar conditions, and given with some antibiotics to make them 

more effective 
• methadone, used as a heroin substitute 
• vincristine, vinblastine or doxorubicin, to treat cancer 

Tell your doctor if you’re taking any of these. 
 
Some medicines interact with Trizivir 
These include: 
• clarithromycin, an antibiotic 

If you are taking clarithromycin, take your dose at least 2 hours before or after you take your 
Trizivir. 

• phenytoin, for treating epilepsy 
Tell your doctor if you are taking phenytoin. Your doctor may need to monitor you while you 
are taking Trizivir. 
 

•  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. 
 
Methadone and Trizivir 
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.  
 
Pregnancy 
If you are pregnant, if you become pregnant or if you are planning to become pregnant, talk to 
your doctor about the risks and benefits to you and your baby of taking Trizivir during your 
pregnancy.  
Trizivir and similar medicines may cause side effects in unborn babies.  
If you have taken Trizivir  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 Trizivir can also pass into your breast milk. 



 43 

If you are breast-feeding, or thinking about breast-feeding: 
Talk to your doctor immediately. 

 
Driving and using machines 
Trizivir can make you dizzy and have other side effects that make you less alert. 
Don’t drive or operate machines unless you’re feeling well. 
 
3. How to take Trizivir  
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or 
pharmacist if you are not sure. 

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

How much to take 
The usual dose of Trizivir for adults is one tablet twice a day.  

Take the tablets at regular times, leaving approximately 12 hours between each tablet. 
 
Swallow the tablets whole, with some water. Trizivir can be taken with or without food. 
 
If you take more Trizivir than you should 
If you accidentally take too much Trizivir, tell your doctor or your pharmacist, or contact your nearest 
hospital emergency department for further advice. 
 
If you forget to take Trizivir 
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 Trizivir regularly, because if you take it at irregular intervals it may not continue 
to work against the HIV infection, and you may be more likely to have a hypersensitivity reaction. 
 
If you have stopped taking Trizivir 
If you have stopped taking Trizivir 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 Trizivir, or any other medicine containing 
abacavir (Kivexa,Triumeq or Ziagen). It is important that you follow this advice. 

 
If your doctor advises that you can start taking Trizivir 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.  

 

Treatment with Trizivir often causes a loss of fat from legs, arms and face (lipoatrophy). This loss of 
body fat has been shown to be not fully reversible after discontinuation of zidovudine. Your doctor 
should monitor for signs of lipoatrophy. Tell your doctor if you notice any loss of fat from your legs, 
arms, and face. When these signs occur, Trizivir should be stopped and your HIV treatment changed. 



 44 

 
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 
Trizivir or other medicines you are taking, or an effect of the HIV infection 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 Trizivir, other conditions can develop during treatment.  

It is important to read the information on the other side of this leaflet under ‘Other possible side 
effects of Trizivir’. 
 
 

Hypersensitivity reactions 

Trizivir contains abacavir (which is also an active substance in Kivexa, 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 Trizivir could develop a hypersensitivity reaction to abacavir, which could be life 
threatening if they continue to take Trizivir. 

You are more likely to develop such a 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 
Trizivir was prescribed for you. If you know you have this gene, tell your doctor before you take 
Trizivir. 
 
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 Trizivir, 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 



 45 

Your doctor may advise you to stop taking Trizivir. 
 

If you have stopped taking Trizivir 

      If you have stopped taking Trizivir because of a hypersensitivity reaction, you must NEVER 
AGAIN take Trizivir, or any other medicine containing abacavir (Kivexa, 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 Trizivir 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 Trizivir, or any other medicine containing abacavir (Kivexa, 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 Trizivir 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 Trizivir, return all your unused Trizivir tablets for safe disposal. 
Ask your doctor or pharmacist for advice. 

The Trizivir 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. 
 

 
Very common side effects 
These may affect more than 1 in 10 people: 
• headache 
• feeling sick (nausea) 
 
Common side effects 
These may affect up to 1 in 10 people: 
• hypersensitivity reaction  
• being sick (vomiting) 
• diarrhoea 
• stomach pains 
• loss of appetite 
• feeling dizzy 
• 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 



 46 

• hair loss 
Common side effects that may show up in blood tests are: 
• a low red blood cell count (anaemia) or low white blood cell count (neutropenia or leucopenia) 
• an increase in the level of liver enzymes 
• an increased amount in the blood of bilirubin (a substance produced in the liver) which may make 

your skin appear yellow 
 
Uncommon side effects 
These may affect up to 1 in 100 people: 
• feeling breathless 
• wind (flatulence) 
• itching 
• muscle weakness 
An uncommon side effect that may show up in blood tests is: 
• a decrease in the number of cells involved in blood clotting (thrombocytopenia), or in all kinds of 

blood cells (pancytopenia) 
 
Rare side effects 
These may affect up to 1 in 1000 people: 
• liver disorders, such as jaundice, enlarged liver or fatty liver, inflammation (hepatitis) 
• lactic acidosis (excess lactic acid in the blood ; see the next section, ‘Other possible side effects of 

Trizivir’) 
• inflammation of the pancreas (pancreatitis) 
• chest pain; disease of the heart muscle (cardiomyopathy) 
• fits (convulsions) 
• feeling depressed or anxious, not being able to concentrate, feeling drowsy 
• indigestion, taste disturbance 
• changes in the colour of your nails, your skin, or the skin inside your mouth 
• a flu-like feeling — chills and sweating 
• tingly feelings in the skin (pins and needles) 
• sensation of weakness in the limbs 
• breakdown of muscle tissue 
• numbness 
• passing urine more often 
• enlarged breasts in men 
Rare side effects that may show up in blood tests are: 
• increase in an enzyme called amylase 
• a failure of the bone marrow to produce new red blood cells (pure red cell aplasia) 
 
Very rare side effects 
These may affect up to 1 in 10,000 people: 
• 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) 

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

A very rare side effect that may show up in blood tests is: 
 a failure of the bone marrow to produce new red or white blood cells (aplastic anaemia) 
 
 

If you get side effects 



 47 

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 Trizivir 

Trizivir 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). When these people start treatment, they may find 
that old, hidden infections flare up, causing signs and symptoms of inflammation. These symptoms are 
probably caused by the body’s immune system becoming stronger, so that the body starts to fight these 
infections. 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 while you’re taking Trizivir: 

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

 
Lactic acidosis is a rare but serious side effect 

Some people taking Trizivir develop a condition called lactic acidosis, together with an enlarged liver.  
 
Lactic acidosis is caused by a build-up of lactic acid in the body. It is rare; if it happens, it usually 
develops after a few months of treatment. It can be life-threatening, causing failure of internal organs. 
 
Lactic acidosis is more likely to develop in people who have liver disease, or in obese (very 
overweight) people, especially women. 

Signs of lactic acidosis include: 
• feeling sick (nausea), being sick (vomiting) 
• stomach pain 
• generally feeling unwell 
• loss of appetite, weight loss 
• deep, rapid, difficult breathing 
• numbness or weakness in the limbs 
During your treatment, your doctor will monitor you for signs of lactic acidosis. If you have any of the 
symptoms listed above or any other symptoms that worry you: 

See your doctor as soon as possible. 
 
You may have problems with your bones 



 48 

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. 
 
Other effects may show up in blood tests 

Trizivir can also cause: 
• increased levels of lactic acid in the blood, which on rare occasions can lead to lactic acidosis 
 
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 Trizivir  
 
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 help protect the environment. 
 
 
6. Contents of the pack and other information  
 
What Trizivir contains 
The active substances in each Trizivir film-coated tablet are 300 mg of abacavir (as sulfate), 150 mg 
lamivudine and 300 mg zidovudine. 
 
The other ingredients are microcrystalline cellulose, sodium starch glycollate and magnesium stearate 
in the core of the tablet. The tablet coating contains hypromellose, titanium dioxide, polyethylene 
glycol, indigo carmine aluminium lake, iron oxide yellow. 
 
What Trizivir looks like and contents of the pack 
Trizivir film-coated tablets are engraved with ‘GX LL1’ on one side. They are blue/green and capsule-
shaped and are provided in blister packs containing 60 tablets or bottles containing 60 tablets with 
child-resistant tops. 
 
Marketing Authorisation Holder 

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


 49 

ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
Manufacturer 
Glaxo Operations UK Ltd (trading as Glaxo Wellcome Operations), Priory Street, Ware, 
Hertfordshire, SG 12 0DJ, United Kingdom. 
 
or 
 
GlaxoSmithKline Pharmaceuticals S.A., ul. Grunwaldzka 189 , 60-322 Poznan, Poland 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

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

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

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

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

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

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

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

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

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

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

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

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

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

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

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


 50 

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 RESTRICTIONSWITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET