Lamivudine Teva

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Lamivudine Teva 100 mg film-coated tablets  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 100 mg lamivudine  
For the full list of excipients see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet  
 
Orange, capsule shaped, biconvex film-coated tablet – engraved with “L 100” on one side and plain 
on the other. 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Lamivudine Teva is indicated for the treatment of chronic hepatitis B in adults with:  
 
• compensated liver disease with evidence of active viral replication, persistently elevated serum 

alanine aminotransferase (ALT) levels and histological evidence of active liver inflammation and 
/ or fibrosis. Initiation of lamivudine treatment should only be considered when the use of an 
alternative antiviral agent with a higher genetic barrier is not available or appropriate (see section 
5.1). 

 
4.2 Posology and method of administration 
 
Therapy with Lamivudine Teva should be initiated by a physician experienced in the management of 
chronic hepatitis B.  
 
Posology 
 
Adults  
The recommended dosage of Lamivudine Teva is 100 mg once daily. 
 
Duration of treatment  
The optimal duration of treatment is unknown. 
 
• In patients with HBeAg positive chronic hepatitis B (CHB) without cirrhosis, treatment should be 

administered for at least 6-12 months after HBeAg seroconversion (HBeAg and HBV DNA loss 
with HBeAb detection) is confirmed, to limit the risk of virological relapse, or until HBsAg 
seroconversion or there is loss of efficacy (see section 4.4). Serum ALT and HBV DNA levels 
should be followed regularly after treatment discontinuation to detect any late virological relapse.  

• In patients with HBeAg negative CHB (pre-core mutant) without cirrhosis, treatment should be 
administered at least until HBs seroconversion or there is evidence of loss of efficacy. With 
prolonged treatment, regular reassessment is recommended to confirm that continuation of the 
selected therapy remains appropriate for the patient.  

• In patients with cirrhosis and in liver transplant recipients, treatment cessation is not 
recommended (see section 5.1).  

 



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If lamivudine is discontinued, patients should be periodically monitored for evidence of recurrent 
hepatitis (see section 4.4).  
 
Clinical resistance  
In patients with either HBeAg positive or HBeAg negative CHB, the development of YMDD 
(tyrosine-methionine-aspartate-aspartate) mutant HBV may result in a diminished therapeutic 
response to lamivudine, indicated by a rise in HBV DNA and ALT from previous on-treatment levels. 
In order to reduce the risk of resistance in patients receiving lamivudine monotherapy, a switch to or 
addition of an alternative agent without cross-resistance to lamivudine based on therapeutic guidelines 
should be considered if serum HBV DNA remains detectable at or beyond 24 weeks of treatment (see 
section 5.1). 
 
For the treatment of patients who are co-infected with HIV and are currently receiving or plan to 
receive treatment with lamivudine or the combination lamivudine-zidovudine, the dose of lamivudine 
prescribed for HIV infection (usually 150 mg/twice daily in combination with other antiretrovirals) 
should be maintained. 
 
Special populations 
 
Renal impairment  
Lamivudine serum concentrations (AUC) are increased in patients with moderate to severe renal 
impairment due to decreased renal clearance. The dosage should therefore be reduced for patients 
with a creatinine clearance of < 50 ml/minute. Lamivudine Teva is not suitable for patients who 
require doses below 100 mg. 
 
Data available in patients undergoing intermittent haemodialysis (for less than or equal to 4 hrs 
dialysis 2-3 times weekly), indicate that following the initial dosage reduction of lamivudine to correct 
for the patient’s creatinine clearance, no further dosage adjustments are required while undergoing 
dialysis.  
 
Hepatic impairment 
Data obtained in patients with hepatic impairment, including those with end-stage liver disease 
awaiting transplant, show that lamivudine pharmacokinetics are not significantly affected by hepatic 
dysfunction. Based on these data, no dose adjustment is necessary in patients with hepatic impairment 
unless accompanied by renal impairment.  
 
Elderly 
In elderly patients, normal ageing with accompanying renal decline has no clinically significant effect 
on lamivudine exposure, except in patients with creatinine clearance of < 50 ml/min. 
 
Paediatric population 
The safety and efficacy of Lamivudine Teva in infants, children and adolescents aged below 18 years 
have not been established. Currently available data are described in sections 4.4 and 5.1 but no 
recommendation on a posology can be made. 
 
Method of administration 
Oral use.  
Lamivudine Teva can be taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
4.4 Special warnings and precautions for use 
 
Lactic acidosis and severe hepatomegaly with steatosis 



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Occurrences of lactic acidosis (in the absence of hypoxaemia), sometimes fatal, usually associated 
with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside 
analogues. As lamivudine is a nucleoside analogue, this risk cannot be excluded. Treatment with 
nucleoside analogues should be discontinued when rapidly elevating aminotransferase levels, 
progressive hepatomegaly or metabolic/lactic acidosis of unknown aetiology occur. Benign digestive 
symptoms, such as nausea, vomiting and abdominal pain, might be indicative of lactic acidosis 
development. Severe cases, sometimes with fatal outcome, were associated with pancreatitis, liver 
failure/hepatic steatosis, renal failure and higher levels of serum lactate. Caution should be exercised 
when prescribing nucleoside analogues 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 ribivirin may constitute a special risk. These patients should be followed closely. 
 
Exacerbations of hepatitis 
 
Exacerbations on treatment 
Spontaneous exacerbations in chronic hepatitis B are relatively common and are characterised by 
transient increases in serum ALT. After initiating antiviral therapy, serum ALT may increase in some 
patients as serum HBV DNA levels decline. In patients with compensated liver disease, these 
increases in serum ALT were generally not accompanied by an increase in serum bilirubin 
concentrations or signs of hepatic decompensation. 
 
HBV viral subpopulations with reduced susceptibility to lamivudine (YMDD mutant HBV) have been 
identified with extended therapy. In some patients the development of YMDD mutant HBV can lead 
to exacerbation of hepatitis, primarily detected by serum ALT elevations and re-emergence of HBV 
DNA (see section 4.2). In patients who have YMDD mutant HBV, a switch to or addition of an 
alternative agent without cross resistance to lamivudine based on therapeutic guidelines should be 
considered (see section 5.1). 
 
Exacerbations after treatment discontinuation 
Acute exacerbation of hepatitis has been observed in patients who have discontinued hepatitis B 
therapy and is usually detected by serum ALT elevations and re-emergence of HBV DNA. In the 
controlled Phase III trials with no-active-treatment follow-up, the incidence of post-treatment ALT 
elevations (more than 3 times baseline) was higher in lamivudine-treated patients (21%) compared 
with those receiving placebo (8%). However, the proportion of patients who had post-treatment 
elevations associated with bilirubin elevations was low and similar in both treatment arms (see Table 
3 in section 5.1). For lamivudine-treated patients, the majority of post-treatment ALT elevations 
occurred between 8 and 12 weeks post-treatment. Most events have been self-limiting, however some 
fatalities have been observed. If Lamivudine Teva is discontinued, patients should be periodically 
monitored both clinically and by assessment of serum liver function tests (ALT and bilirubin levels), 
for at least four months, and then as clinically indicated.  
 
Transplantation recipients are at greater risk from active viral replication. Due to the marginal liver 
function in these patients, hepatitis reactivation at discontinuation of lamivudine or loss of efficacy 
during treatment may induce severe and even fatal decompensation. These patients should be 
monitored for clinical, virological and serological parameters associated with hepatitis B, liver and 
renal function, and antiviral response during treatment (at least every month), and, if treatment is 
discontinued for any reason, for at least 6 months after treatment. Laboratory parameters to be 
monitored should include (as a minimum) serum ALT, bilirubin, albumin, blood urea nitrogen, 
creatinine, and virological status: HBV antigen/antibody, and serum HBV DNA concentrations when 
possible. Patients experiencing signs of hepatic insufficiency during or post-treatment should be 
monitored more frequently as appropriate. 
 
For patients who develop evidence of recurrent hepatitis post-treatment, there are insufficient data on 
the benefits of re-initiation of lamivudine treatment. 



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Mitochondrial dysfunction 
Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable 
degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in infants 
exposed in utero and/or post-natally to nucleoside analogues. The main adverse events reported are 
haematological disorders (anaemia, neutropenia), metabolic disorders (hyperlactatemia, 
hyperlipasemia). Some late-onset neurological disorders have been reported (hypertonia, convulsion, 
abnormal behaviour). The neurological disorders might be transient or permanent. Any child exposed 
in utero to nucleoside and nucleotide analogues, should have clinical and laboratory follow-up and 
should be fully investigated for possible mitochondrial dysfunction in cases which have relevant signs 
or symptoms. 
 
Paediatric patients 
Lamivudine has been administered to children (2 years and above) and adolescents with compensated 
chronic hepatitis B. However, due to limitations of the data, the administration of lamivudine to this 
patient population is not currently recommended (see section 5.1).  
 
Delta hepatitis or hepatitis C 
The efficacy of lamivudine in patients co-infected with Delta hepatitis or hepatitis C has not been 
established and caution is advised.  
 
Immunosuppressive treatments 
Data are limited on the use of lamivudine in HBeAg negative (pre-core mutant) patients and in those 
receiving concurrent immunosuppressive regimes, including cancer chemotherapy. Lamivudine 
should be used with caution in these patients. 
 
Monitoring 
During treatment with Lamivudine Teva patients should be monitored regularly. Serum ALT and 
HBV DNA levels should be monitored at 3 month intervals and in HBeAg positive patients HBeAg 
should be assessed every 6 months.  
 
HIV co-infection 
For the treatment of patients who are co-infected with HIV and are currently receiving or plan to 
receive treatment with lamivudine or the combination lamivudine-zidovudine, the dose of lamivudine 
prescribed for HIV infection (usually 150 mg/twice daily in combination with other antiretrovirals) 
should be maintained. For HIV co-infected patients not requiring anti-retroviral therapy, there is a risk 
of HIV mutation when using lamivudine alone for treating chronic hepatitis B. 
 
Transmission of hepatitis B  
There is no information available on maternal-foetal transmission of hepatitis B virus in pregnant 
women receiving treatment with lamivudine. The standard recommended procedures for hepatitis B 
virus immunisation in infants should be followed.  
 
Patients should be advised that therapy with lamivudine has not been proven to reduce the risk of 
transmission of hepatitis B virus to others and therefore, appropriate precautions should still be taken.  
 
Interactions with other medicinal products 
Lamivudine Teva should not be taken with any other medicinal products containing lamivudine or 
medicinal products containing emtricitabine (see section 4.5). 
 
The combination of lamivudine with cladribine is not recommended (see section 4.5). 
 
Excipient(s) 
 
Sodium 



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This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say 
essentially “sodium-free”. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults.  
 
The likelihood of metabolic interactions is low due to limited metabolism and plasma protein binding 
and almost complete renal elimination of unchanged substance.  
 
Lamivudine is predominantly eliminated by active organic cationic secretion. The possibility of 
interactions with other medicinal products administered concurrently should be considered, 
particularly when their main route of elimination is active renal secretion via the organic cationic 
transport system e.g. trimethoprim. Other medicinal products (e.g. ranitidine, cimetidine) are 
eliminated only in part by this mechanism and were shown not to interact with lamivudine.  
 
Substances shown to be predominately excreted either via the active organic anionic pathway, or by 
glomerular filtration are unlikely to yield clinically significant interactions with lamivudine.  
Administration of trimethoprim/sulphamethoxazole 160 mg/800 mg increased lamivudine exposure by 
about 40 %. Lamivudine had no effect on the pharmacokinetics of trimethoprim or 
sulphamethoxazole. However, unless the patient has renal impairment, no dosage adjustment of 
lamivudine is necessary.  
 
A modest increase in Cmax (28 %) was observed for zidovudine when administered with lamivudine, 
however overall exposure (AUC) was not significantly altered. Zidovudine had no effect on the 
pharmacokinetics of lamivudine (see section 5.2).  
 
Lamivudine has no pharmacokinetic interaction with alpha-interferon when the two medicinal 
products are concurrently administered. There were no observed clinically significant adverse 
interactions in patients taking lamivudine concurrently with commonly used immunosuppressant 
medicinal products (e.g. cyclosporin A). However, formal interaction studies have not been 
performed.  
 
Emtricitabine 
Due to similarities, Lamivudine Teva should not be administered concomitantly with other cytidine 
analogues, such as emtricitabine. Moreover, Lamivudine Teva should not be taken with any other 
medicinal products containing lamivudine (see section 4.4). 
 
Cladribine  
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). 
 
Sorbitol 
Co-administration of sorbitol solution (3.2 g, 10.2 g, 13.4 g) with a single 300 mg dose (Adult HIV 
daily dose) of lamivudine oral solution resulted in dose-dependent decreases of 14%, 32%, and 36% 
in lamivudine exposure (AUC∞) and 28%, 52%, and 55% in the Cmax of lamivudine in adults. When 
possible, avoid chronic co-administration of Lamivudine Teva 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 HBV viral load when chronic co-
administration cannot be avoided.  
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 



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A large amount of data on pregnant women (more than 1000 exposed outcomes) indicate no 
malformative toxicity. Lamivudine Teva can be used during pregnancy if clinically needed.  
 
For patients who are being treated with lamivudine and subsequently become pregnant consideration 
should be given to the possibility of a recurrence of hepatitis on discontinuation of lamivudine. 
 
Breast-feeding 
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 ( less than 4% of maternal serum 
concentrations) and progressively decrease to undetectable levels when breastfed infants reach 24 
weeks of age. The total amount of lamivudine ingested by a breastfed infant is very low and is 
therefore likely to result in exposures exerting a sub-optimal antiviral effect. Maternal hepatitis B is 
not a contraindication to breast-feeding if the newborn is adequately managed for hepatitis B 
prevention at birth, and there is no evidence that the low concentration of lamivudine in human milk 
leads to adverse reactions in breastfed infants. Therefore breastfeeding may be considered in breast- 
feeding mothers being treated with lamivudine for HBV taking into account the benefit of breast 
feeding for the child and the benefit of therapy for the woman. Where there is maternal transmission 
of HBV, despite adequate prophylaxis, consideration should be given to discontinuing breastfeeding 
to reduce the risk of the emergence of lamivudine resistant mutants in the infant.  
 
Fertility 
Reproductive studies in animals have shown no effect on male or female fertility (see section 5.3). 
 
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 infants 
exposed in utero and/or post-natally to nucleoside analogues (see section 4.4). 
 
4.7 Effects on ability to drive and use machines 
 
Patients should be informed that malaise and fatigue have been reported during treatment with 
lamivudine. The clinical status of the patient and the adverse reaction profile of lamivudine should be 
borne in mind when considering the patient's ability to drive or operate machinery. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The incidence of adverse reactions and laboratory abnormalities (with the exception of elevations of 
ALT and CPK, see below) were similar between placebo and lamivudine treated patients). The most 
common adverse reactions reported were malaise and fatigue, respiratory tract infections, throat and 
tonsil discomfort, headache, abdominal discomfort and pain, nausea, vomiting and diarrhoea.  
 
Tabulated list of adverse reactions  
Adverse reactions are listed below by system organ class and frequency. Frequency categories are 
only assigned to those adverse reactions considered to be at least possibly causally related to 
lamivudine. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), 
uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000),very rare (< 1/10,000) and not known 
(cannot be estimated from the available data). 
 
The frequency categories assigned to the adverse reactions are mainly based on experience from 
clinical trials including a total of 1,171 patients with chronic hepatitis B receiving lamivudine at 
100 mg. 
 
Blood and lymphatic system disorders 
Not known Thrombocytopenia 
Immune system disorders: 



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Rare Angioedema 
Hepatobiliary disorders 
Very common ALT elevations (see section 4.4) 
Exacerbations of hepatitis, primarily detected by serum ALT elevations, have been reported ‘on-
treatment’ and following lamivudine withdrawal. Most events have been self-limited, however 
fatalities have been observed very rarely (see section 4.4). 
Skin and subcutaneous tissue disorders 
Common Rash, pruritus 
Musculoskeletal and connective tissue disorders 
Common Elevations of CPK 
 Common Muscle disorders, including myalgia and cramps*  

 
Not known Rhabdomyolysis 
* In Phase III studies frequency observed in the lamivudine treatment group was not greater than 
observed in the placebo group 
 
Paediatric population  
Based on limited data in children aged 2 to 17 years, there were no new safety issues identified 
compared to adults. 
 
Other special populations 
 
In patients with HIV infection, cases of pancreatitis and peripheral neuropathy (or paresthesia) have 
been reported. In patients with chronic hepatitis B there was no observed difference in incidence of 
these events between placebo and lamivudine treated patients.  
 
Cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic  
steatosis, have been reported with the use of combination nucleoside analogue therapy in patients with  
HIV. There have been rare reports of lactic acidosis in patients receiving lamivudine for hepatitis B.  
 
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 
 
Administration of lamivudine at very high dose levels in acute animal studies did not result in any 
organ toxicity. Limited data are available on the consequences of ingestion of acute overdoses in 
humans. No fatalities occurred, and the patients recovered. No specific signs or symptoms have been 
identified following such overdose.  
 
If overdose occurs the patient should be monitored and standard supportive treatment applied as 
required. Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of 
overdose, although this has not been studied.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group - Antivirals for systemic use, nucleoside and nucleotide reverse 
transcriptase inhibitors,ATC Code: J05AF05.  
 

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Lamivudine is an antiviral agent which is active against hepatitis B virus in all cell lines tested and in 
experimentally infected animals.  
 
Lamivudine is metabolised by both infected and uninfected cells to the triphosphate (TP) derivative 
which is the active form of the parent compound. The intracellular half life of the triphosphate in 
hepatocytes is 17-19 hours in vitro. Lamivudine-TP acts as a substrate for the HBV viral polymerase. 
 
The formation of further viral DNA is blocked by incorporation of lamivudine-TP into the chain and 
subsequent chain termination.  
Lamivudine-TP does not interfere with normal cellular deoxynucleotide metabolism. It is also only a 
weak inhibitor of mammalian DNA polymerases alpha and beta. Furthermore, lamivudine-TP has 
little effect on mammalian cell DNA content.  
 
In assays relating to potential substance effects on mitochondrial structure and DNA content and 
function, lamivudine lacked appreciable toxic effects. It has a very low potential to decrease 
mitochondrial DNA content, is not permanently incorporated into mitochondrial DNA, and does not 
act as an inhibitor of mitochondrial DNA polymerase gamma.  
 
Clinical experience  
 
Experience in patients with HBeAg positive CHB and compensated liver disease  
In controlled studies, 1 year of lamivudine therapy significantly suppressed HBV DNA replication 
[34-57 % of patients were below the assay detection limits (Abbott Genostics solution hybridization 
assay, LLOD < 1.6 pg/ml)}, normalised ALT level (40-72 % of patients), induced HBeAg 
seroconversion (HBeAg loss and HBeAb detection with HBV DNA loss [by conventional assay], 
16-18 % of patients), improved histology (38-52 % of patients had a ≥ 2 point decrease in the Knodell 
Histologic Activity Index [HAI]) and reduced progression of fibrosis (in 3-17 % of patients) and 
progression to cirrhosis. 
 
Continued lamivudine treatment for an additional 2 years in patients who had failed to achieve 
HBeAg seroconversion in the initial 1 year controlled studies resulted in further improvement in 
bridging fibrosis. In patients with YMDD mutant HBV, 41/82 (50 %) patients had improvement in 
liver inflammation and 40/56 (71 %) patients without YMDD mutant HBV had improvement. 
Improvement in bridging fibrosis occurred in 19/30 (63 %) patients without YMDD mutant and 22/44 
(50 %) patients with the mutant. Five percent (3/56) of patients without the YMDD mutant and 13 % 
(11/82) of patients with YMDD mutant showed worsening in liver inflammation compared to pre-
treatment. Progression to cirrhosis occurred in 4/68 (6 %) patients with the YMDD mutant, whereas 
no patients without the mutant progressed to cirrhosis.  
 
In an extended treatment study in Asian patients (NUCB3018) the HBeAg seroconversion rate and 
ALT normalisation rate at the end of the 5 year treatment period was 48 % (28/58) and 47 % (15/32), 
respectively. HBeAg seroconversion was increased in patients with elevated ALT levels; 77 % 
(20/26) of patients with pre-treatment ALT > 2 x ULN seroconverted. At the end of 5 years, all 
patients had HBV DNA levels that were undetectable or lower than pre-treatment levels.  
 
Further results from the trial by YMDD mutant status are summarised in Table 1.  
 
Table 1: Efficacy results 5 years by YMDD status (Asian Study) NUCB3018  
 

 Subjects, % (no.) 
YMDD mutant HBV status YMDD1 Non-YMDD1 

HBeAg seroconversion 
 

- All patients  
- Baseline ALT ≤ 1 x ULN2  

 
 
38  (15/40) 
9     (1/11) 

 
 
72    (13/18) 
33      (2/6) 



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- Baseline ALT > 2 x ULN 
 

Undetectable HBV DNA  
 

- Baseline3  
 

- Week 2604 
   negative  
   positive < baseline  
   positive > baseline 
 

ALT normalisation 
 
- Baseline  
  normal  
  above normal  
 
- Week 260  
  normal     
  above normal < baseline     
  above normal > baseline 
 

60   (9/15) 
 
 
 
5 (2/40) 
 
 
8       (2/25) 
92   (23/25) 
0 
 
 
 
 
28   (11/40) 
73   (29/40) 
 
 
46   (13/28) 
21    (6/28) 
32    (9/28) 

100  (11/11) 
 
 
 
6 (1/18) 
 
 
0 
100    (4/4) 
0 
 
 
 
 
33     (6/18) 
67    (12/18) 
 
 
50      (2/4) 
0 
50      (2/4) 

 
1 Patients designated as YMDD mutant were those with ≥5 % YMDD mutant HBV at any annual time-point during the 5-year period. 
Patients categorised as non-YMDD mutant were those with > 95 % wild-type HBV at all annual time-points during the 5-year study period  
2 Upper limit of normal  
3 Abbott Genostics solution hybridisation assay (LLOD < 1.6 pg/ml  
4 Chiron Quantiplex assay (LLOD 0.7 Meq/ml)  
 
Comparative data according to YMDD status were also available for histological assessment but only 
up to three years. In patients with YMDD mutant HBV, 18/39 (46 %) had improvements in 
necroinflammatory activity and 9/39 (23 %) had worsening. In patients without the mutant, 20/27 
(74 %) had improvements in necroinflammatory activity and 2/27 (7 %) had worsening.  
 
Following HBeAg seroconversion, serologic response and clinical remission are generally durable 
after stopping lamivudine. However, relapse following seroconversion can occur. In a long-term 
follow-up study of patients who had previously seroconverted and discontinued lamivudine, late 
virological relapse occurred in 39 % of the subjects. Therefore, following HBeAg seroconversion, 
patients should be periodically monitored to determine that serologic and clinical responses are being 
maintained. In patients who do not maintain a sustained serological response, consideration should be 
given to retreatment with either lamivudine or an alternative antiviral agent for resumption of clinical 
control of HBV.  
 
In patients followed for up to 16 weeks after discontinuation of treatment at one year, post-treatment 
ALT elevations were observed more frequently in patients who had received lamivudine than in 
patients who had received placebo. A comparison of post-treatment ALT elevations between weeks 52 
and 68 in patients who discontinued lamivudine at week 52 and patients in the same studies who 
received placebo throughout the treatment course is shown in Table 2. The proportion of patients who 
had post-treatment ALT elevations in association with an increase in bilirubin levels was low and 
similar in patients receiving either lamivudine or placebo.  
 
Table 2: Post-treatment ALT Elevations in 2 Placebo-Controlled Studies in Adults  
 

Abnormal Value  

Patients with ALT Elevation/  
Patients with Observations* 

Lamivudine Placebo 
ALT ≥ 2 x baseline value  37/137 (27 %) 22/116 (19 %)  



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ALT ≥ 3 x baseline value†  29/137 (21 %) 9/116 (8 %) 
ALT ≥ 2 x baseline value and absolute ALT > 500 
IU/l  21/137 (15 %) 8/116 (7 %) 
ALT ≥2 x baseline value; and bilirubin >2 x ULN 
and ≥2 x baseline value  1/137 (0.7 %) 1/116 (0.9 %) 
 
*Each patient may be represented in one or more category. †
Comparable to a Grade 3 toxicity in accordance with modified WHO criteria.  

ULN = Upper limit of normal.  
 
Experience in patients with HBeAg negative CHB:  
Initial data indicate the efficacy of lamivudine in patients with HBeAg negative CHB is similar to 
patients with HBeAg positive CHB, with 71 % of patients having HBV DNA suppressed below the 
detection limit of the assay, 67 % ALT normalisation and 38 % with improvement in HAI after one 
year of treatment. When lamivudine was discontinued, the majority of patients (70 %) had a return of 
viral replication. Data is available from an extended treatment study in HBeAg negative patients 
(NUCAB3017) treated with lamivudine. After two years of treatment in this study, ALT normalisation 
and undetectable HBV DNA occurred in 30/69 (43 %) and 32/68 (47 %) patients respectively and 
improvement in necroinflammatory score in 18/49 (37 %) patients. In patients without YMDD mutant 
HBV, 14/22 (64 %) showed improvement in necroinflammatory score and 1/22 (5 %) patients 
worsened compared to pre-treatment. In patients with the mutant, 4/26 (15 %) patients showed 
improvement in necroinflammatory score and 8/26 (31 %) patients worsened compared to pre-
treatment. No patients in either group progressed to cirrhosis.  
 
Frequency of emergence of YMDD mutant HBV and impact on the treatment response:  
Lamivudine monotherapy results in the selection of YMDD mutant HBV in approximately 24 % of 
patients following one year of therapy, increasing to 69 % following 5 years of therapy. Development 
of YMDD mutant HBV is associated with reduced treatment response in some patients, as evidenced 
by increased HBV DNA levels and ALT elevations from previous on-therapy levels, progression of 
signs and symptoms of hepatitis disease and/or worsening of hepatic necroinflammatory findings. 
Given the risk of YMDD mutant HBV, maintenance of lamivudine monotherapy is not appropriate in 
patients with detectable serum HBV DNA at or beyond 24 weeks of treatment (see section 4.4).  
 
In a retrospective study to determine the factors associated with HBV DNA breakthrough, 159 Asian 
HBeAg-positive patients were treated with lamivudine and followed up for a median period of almost 
30 months. Those with HBV DNA levels greater than 200 copies/mL at 6 months (24 weeks) of 
lamivudine therapy had a 60 % chance of developing the YMDD mutant compared with 8 % of those 
with HBV DNA levels less than 200 copies/mL at 24 weeks of lamivudine therapy. The risk for 
developing YMDD mutant was 63% versus 13% with a cut off of 1000 copies/ml (NUCB3009 and 
NUCB3018). 
 
Experience in patients with decompensated liver disease:  
Placebo controlled studies have been regarded as inappropriate in patients with decompensated liver 
disease, and have not been undertaken. In non-controlled studies, where lamivudine was administered 
prior to and during transplantation, effective HBV DNA suppression and ALT normalisation was 
demonstrated. When lamivudine therapy was continued post transplantation there was reduced graft 
re-infection by HBV, increased HBsAg loss and on one-year survival rate of 76-100 %.  
 
As anticipated due to the concomitant immunosuppression, the rate of emergence of YMDD mutant 
HBV after 52 weeks treatment was higher (36 %-64 %) in the liver transplant population than in the 
immunocompetent CHB patients (14 %-32 %). 
 
Experience in CHB patients with advanced fibrosis or cirrhosis:  
In a placebo-controlled study in 651 patients with clinically compensated chronic hepatitis B and 
histologically confirmed fibrosis or cirrhosis, lamivudine treatment (median duration 32 months) 



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significantly reduced the rate of overall disease progression (34/436, 7.8 % for lamivudine versus 
38/215, 17.7 % for placebo, p=0.001), demonstrated by a significant reduction in the proportion of 
patients having increased Child-Pugh scores (15/436, 3.4 % versus 19/215, 8.8 %, p=0.023) or 
developing hepatocellular carcinoma (17/436, 3.9 % versus 16/215, 7.4 %, p=0.047). The rate of 
overall disease progression in the lamivudine group was higher for subjects with detectable YMDD 
mutant HBV DNA (23/209, 11 %) compared to those without detectable YMDD mutant HBV 
(11/221, 5 %). However, disease progression in YMDD subjects in the lamivudine group was lower 
than the disease progression in the placebo group (23/209, 11 % versus 38/214, 18 % respectively). 
Confirmed HBeAg seroconversion occurred in 47 % (118/252) of subjects treated with lamivudine 
and 93 % (320/345) of subjects receiving lamivudine became HBV DNA negative (VERSANT 
[version 1], bDNA assay, LLOD < 0.7 MEq/ml) during the study.  
 
Experience in children and adolescents:  
Lamivudine has been administered to children and adolescents with compensated CHB in a placebo 
controlled study of 286 patients aged 2 to 17 years. This population primarily consisted of children 
with minimal hepatitis B. A dose of 3 mg/kg once daily (up to a maximum of 100 mg daily) was used 
in children aged 2 to 11 years and a dose of 100 mg once daily in adolescents aged 12 years and 
above. This dose needs to be further substantiated. The difference in the HBeAg seroconversion rates 
(HBeAg and HBV DNA loss with HBeAb detection) between placebo and lamivudine was not 
statistically significant in this population (rates after one year were 13 % (12/95) for placebo versus 
22 % (42/191) for lamivudine; p=0.057). The incidence of YMDD mutant HBV was similar to that 
observed in adults, ranging from 19 % at week 52 up to 45 % in patients treated continuously for 24 
months. 
 
5.2 Pharmacokinetic properties 
 
Absorption  
 
Lamivudine is well absorbed from the gastrointestinal tract, and the bioavailability of oral lamivudine 
in adults is normally between 80 and 85 %. Following oral administration, the mean time (tmax) to 
maximal serum concentrations (Cmax) is about an hour. At therapeutic dose levels i.e. 100 mg once 
daily, Cmax is in the order of 1.1-1.5 µg/ml and trough levels were 0.015-0.020 µg/ml.  
 
Co-administration of lamivudine with food resulted in a delay of tmax and a lower Cmax (decreased by 
up to 47 %). However, the extent (based on the AUC) of lamivudine absorbed was not influenced, 
therefore lamivudine can be administered with or without food.  
 
Distribution  
 
From intravenous studies the mean volume of distribution is 1.3 l/kg. Lamivudine exhibits linear 
pharmacokinetics over the therapeutic dose range and displays low plasma protein binding to albumin.  
Limited data shows lamivudine penetrates the central nervous system and reaches the cerebro-spinal 
fluid (CSF). The mean lamivudine CSF/serum concentration ratio 2-4 hours after oral administration 
was approximately 0.12.  
 
Biotransformation  
 
Lamivudine is predominately cleared by renal excretion of unchanged substance. The likelihood of 
metabolic substance interactions with lamivudine is low due to the small (5-10 %) extent of hepatic 
metabolism and the low plasma protein binding.  
 
Elimination  
 
The mean systemic clearance of lamivudine is approximately 0.3 l/h/kg. The observed half-life of 
elimination is 5 to 7 hours. The majority of lamivudine is excreted unchanged in the urine via 



13 

glomerular filtration and active secretion (organic cationic transport system). Renal clearance 
accounts for about 70 % of lamivudine elimination.  
 
Special populations 
 
Studies in patients with renal impairment show lamivudine elimination is affected by renal 
dysfunction. Dose reduction in patients with a creatinine clearance of < 50 ml/min is necessary (see 
section 4.2).  
 
The pharmacokinetics of lamivudine are unaffected by hepatic impairment. Limited data in patients 
undergoing liver transplantation show that impairment of hepatic function does not impact 
significantly on the pharmacokinetics of lamivudine unless accompanied by renal dysfunction.  
 
In elderly patients the pharmacokinetic profile of lamivudine suggests that normal ageing with 
accompanying renal decline has no clinically significant effect on lamivudine exposure, except in 
patients with creatinine clearance of < 50 ml/min (see section 4.2).  
 
5.3 Preclinical safety data 
 
Administration of lamivudine in animal toxicity studies at high doses was not associated with any 
major organ toxicity. At the highest dosage levels, minor effects on indicators of liver and kidney 
function were seen together with occasional reduction in liver weights. Reduction of erythrocytes and 
neutrophil counts were identified as the effects most likely to be of clinical relevance. These events 
were seen infrequently in clinical studies.  
 
Lamivudine was not mutagenic in bacterial tests but, like many nucleoside analogues showed activity 
in an in vitro cytogenetic assay and the mouse lymphoma assay. Lamivudine was not genotoxic in 
vivo at doses that gave plasma concentrations around 60-70 times higher than the anticipated clinical 
plasma levels. As the in vitro mutagenic activity of lamivudine could not be confirmed by in vivo 
tests, it is concluded that lamivudine should not represent a genotoxic hazard to patients undergoing 
treatment.  
 
Reproductive studies in animals have not shown evidence of teratogenicity and showed no effect on 
male or female fertility. Lamivudine induces early embryolethality when administered to pregnant 
rabbits at exposure levels comparable to those achieved in man, but not in the rat even at very high 
systemic exposures.  
 
The results of long term carcinogenicity studies with lamivudine in rats and mice did not shown any 
carcinogenic potential.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Microcrystalline cellulose 
Sodium starch glycolate (Type A) 
Magnesium stearate 
 
Tablet film coat 
Hypromellose 3cP 
Hypromellose 6cP 
Titanium dioxide  
Macrogol 400 
Polysorbate 80 



14 

Iron oxide yellow  
Iron oxide red  
 
6.2 Incompatibilities 
 
Not applicable 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
Blisters: 
 
White opaque PVC/PVdC – Aluminium blisters  
Pack sizes of 28, 30, 84 or 100 film-coated tablets 
 
Containers: 
 
White opaque HDPE tablet containers with white opaque polyethylene child resistent screw cap with 
induction seal  
Pack size of 60 film-coated tablets 
 
White opaque HDPE tablet containers with white opaque polypropylene child resistent, tamper-
evident screw cap with induction seal 
Pack size of 60 film-coated tablets 
 
Not all pack sizes may be marketed. 
 
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 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/566/001– 28 Tablets 
EU/1/09/566/002 – 30 Tablets 
EU/1/09/566/003 – 84 Tablets 
EU/1/09/566/004 – 100 Tablets 
EU/1/09/566/005 – 60 Tablets (bottle) 
EU/1/09/566/006 – 60 Tablets (bottle with tamper evident cap) 



15 

 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 23 October 2009 
Date of latest renewal: 09 September 2014  
 
 
10. DATE OF REVISION OF THE TEXT 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu  

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


16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 



17 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Teva Pharmaceutical Works Private Limited Company 
Pallagi út 13 
Debrecen H-4042 
Hungary 
 
TEVA UK Ltd 
Brampton Road 
Hampden Park 
Eastbourne, East Sussex 
BN22 9AG UK 
 
Pharmachemie B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
Teva Operations Poland Sp.z o. o. 
Mogilska 80 Str. 
31-546 Kraków 
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 Report 
The requirements for submission of periodic safety update reports for this medicinal products are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
Not applicable. 
 



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



20 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lamivudine Teva 100 mg film-coated tablets  
Lamivudine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 100 mg of lamivudine 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Blisters: 
28 film-coated tablets 
30 film-coated tablets 
84 film-coated tablets 
100 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
 
Oral use  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



21 

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 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/566/001– 28 Tablets 
EU/1/09/566/002 – 30 Tablets 
EU/1/09/566/003 – 84 Tablets 
EU/1/09/566/004 – 100 Tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Lamivudine Teva 100 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.  
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
PC: 
SN: 
NN: 
 



22 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Immediate packaging (blister foil) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lamivudine Teva 100 mg film-coated tablets  
Lamivudine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
TEVA B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



23 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
Tablet container 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lamivudine Teva 100 mg film-coated tablets  
Lamivudine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 100 mg of lamivudine 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablet container: 
60 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use  
 
Oral use  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 



24 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/566/005 
EU/1/09/566/006  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Outer packaging (carton): 
Lamivudine Teva 100 mg 
 
Immediate packaging (bottle label): 
In case no outer packaging is used 
Lamivudine Teva 100 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Outer packaging (carton): 
2D barcode carrying the unique identifier included.  
 
Immediate packaging (bottle label): 
In case no outer packaging is used 
<2D barcode carrying the unique identifier included.> 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
Outer packaging (carton): 
PC: 
SN: 
NN: 
 



25 

Immediate packaging (bottle label): 
In case no outer packaging is used 
<PC: 
SN: 
NN:> 
 
 



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



27 

Package leaflet: Information for the patient 
 

Lamivudine Teva 100 mg film-coated tablets 
lamivudine 

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

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

side effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet:  
1. What Lamivudine Teva is and what it is used for 
2. What you need to know before you take Lamivudine Teva 
3. How to take Lamivudine Teva 
4. Possible side effects 
5. How to store Lamivudine Teva 
6. Contents of the pack and other information 
 
 
1. What Lamivudine Teva is and what it is used for 
 
The active ingredient in Lamivudine Teva is lamivudine. 
 
Lamivudine Teva is used to treat long term (chronic) hepatitis B infection in adults. 
 
Lamivudine Teva is an antiviral medicine that suppresses the hepatitis B virus and belongs to a group 
of medicines called nucleoside analogue reverse transcriptase inhibitors (NRTIs). 
 
Hepatitis B is a virus that infects the liver causes long term (chronic) infection, and can lead to liver 
damage. Lamivudine Teva can be used in people whose liver is damaged but still functions normally 
(compensated liver disease). 
 
Treatment with Lamivudine Teva can reduce the amount of hepatitis B virus in your body. This should 
lead to a reduction in liver damage and an improvement in your liver function. Not everyone responds 
to treatment with Lamivudine Teva in the same way. Your doctor will monitor the effectiveness of 
your treatment with regular blood tests. 
 
 
2. What you need to know before you take Lamivudine Teva 
 
Do not take Lamivudine Teva 
 
• if you are allergic to lamivudine or any of the other ingredients of this medicine (listed in Section 

6). 
 Check with your doctor if you think this applies to you. 
 
Warnings and precautions 



28 

Some people taking Lamivudine Teva or other similar medicines are more at risk of serious side 
effects. You need to be aware of the extra risks: 
• if you have ever had other types of liver disease, such as hepatitis C. 
• if you are seriously overweight (especially if you are a woman). 
 Talk to your doctor if any of these apply to you. You may need extra check-ups, including 

blood tests, while you are taking your medication. See Section 4 for more information about the 
risks.  

 
Do not stop taking Lamivudine Teva without your doctor’s advice, as there is a risk of your hepatitis 
getting worse. When you stop taking Lamivudine Teva your doctor will monitor you for at least four 
months to check for any problems. This will mean taking blood samples to check for any raised liver 
enzyme levels, which may indicate liver damage. See section 3 for more information about how to take 
Lamivudine Teva. 

Look out for important symptoms 
Some people taking medicines for hepatitis B infection develop other conditions, which can be 
serious. You need to know about important signs and symptoms to look out for while you are taking 
Lamivudine Teva. 
 Read the information ‘Other possible side effects of therapy for Hepatitis B’ in Section 4 of this 

leaflet. 

Protect other people 
Hepatitis B infection is spread by sexual contact with someone who has the infection, or by transfer of 
infected blood (for example, by sharing injection needles). Lamivudine Teva will not stop you passing 
hepatitis B infection on to other people. To protect other people from becoming infected with hepatitis 
B: 
 Use a condom when you have oral or penetrative sex. 
 Do not risk blood transfer — for example, do not share needles. 
 
Other medicines and Lamivudine Teva 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, 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 
Lamivudine Teva. 
 
These medicines should not be used with Lamivudine Teva: 
• medicines (usually liquids) containing sorbitol and other sugar alcohols (such as xylitol, 

mannitol, lactitol or maltitol), if taken regularly 
• other medicines containing lamivudine, used to treat HIV infection (sometimes called the AIDS 

virus) 
• emtricitabine (used to treat HIV or hepatitis B infection) 
• cladribine, used to treat hairy cell leukaemia 
 Tell your doctor if you are being treated with any of these. 
 
Pregnancy  
If you are pregnant, think you may be pregnant, or are planning to have a baby: 
 Talk to your doctor about the risks and benefits of taking Lamivudine Teva during your 

pregnancy. 
Do not stop treatment with Lamivudine Teva without your doctor’s advice. 
 
Breast-feeding  
Lamivudine Teva can pass into breast-milk. If you are breast-feeding, or thinking about breast-
feeding: 



29 

 Talk to your doctor before you take Lamivudine Teva. 
 
Driving and using machines 
Lamivudine Teva may make you feel tired, which could affect your ability to drive or use machines.  
 Don’t drive or use machines unless you are sure you’re not affected. 
 
Lamivudine Teva contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say 
essentially “sodium-free”. 
 
3. How to take Lamivudine Teva  
 
Always take this medicine exactly as your doctor has told you to. Check with your doctor or 
pharmacist if you are not sure.  

Stay in regular contact with your doctor 
Lamivudine Teva helps to control your hepatitis B infection. You need to keep taking it every day to 
control your infection and stop your illness getting worse. 
 Keep in touch with your doctor, and do not stop taking Lamivudine Teva without your 

doctor’s advice. 

How much to take 
The usual dose of Lamivudine Teva is one tablet (100 mg lamivudine) once a day.  
 
Your doctor may prescribe a lower dose if you have problems with your kidneys. An oral solution of 
Lamivudine is available for people who need a lower than usual dose, or who can’t take tablets. 
 
 Talk to your doctor if this applies to you. 
 
If you are already taking another medicine that contains lamivudine for HIV infection, your doctor 
will continue to treat you with the higher dose, (usually 150 mg twice a day), because the dose of 
lamivudine in Lamivudine Teva (100 mg) is not enough to treat HIV infection. If you are planning to 
change your HIV treatment, discuss this change with your doctor first. 
 
Swallow the tablet whole, with some water. Lamivudine Teva can be taken with or without food. 
 
If you take more Lamivudine Teva than you should 
Accidentally taking too much Lamivudine Teva is unlikely to cause any serious problems. If you 
accidentally take too much, tell your doctor or pharmacist, or contact your nearest hospital emergency 
department for further advice. 
 
If you forget to take Lamivudine Teva 
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 missed dose. 
 
Do not stop taking Lamivudine Teva 
You must not stop taking Lamivudine Teva without consulting your doctor. There is a risk of your 
hepatitis getting worse (see section 2). When you stop taking Lamivudine Teva your doctor will 
monitor you for at least four months to check for any problems. This will mean taking blood samples 
to check for any raised liver enzyme levels, which may indicate liver damage. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, but not everyone gets them.  



30 

 
As well as the side effects listed below for Lamivudine Teva, other conditions can develop during 
therapy for hepatitis B.  
 It is important to read the information under ‘Other possible side effects of therapy for hepatitis 

B’. 
 
Side effects that were commonly reported in Lamivudine clinical trials were tiredness, respiratory 
tract infections, throat discomfort, headache, stomach discomfort and pain, nausea, vomiting and 
diarrhoea, increases in liver enzymes and enzymes produced in the muscles (see below).  
 
Allergic reaction  
These are rare (may affect up to 1 in 1,000 people). Signs include: 
• swelling of eyelids, face or lips 
• difficulty swallowing or breathing 
 Contact a doctor immediately if you get these symptoms. Stop taking Lamivudine Teva. 
 
Side effects thought to be caused by Lamivudine Teva 
 
A very common side effect (these may affect more than 1 in 10 people) which may show up in 
blood tests is: 
• an increase in the level of some liver enzymes (transaminases), which may be a sign of 

inflammation or damage in the liver. 
 
A common side effect (these may affect up to 1 in 10 people) is: 
• cramps and muscle pains  
• skin rash or ‘hives’ anywhere on the body. 
 
A common side effect which may show up in blood tests is: 
• an increase in the level of an enzyme produced in the muscles (creatine phosphokinase) which 

may be a sign that body tissue is damaged. 
 
Other side effects  
Other side effects have occurred in a very small number of people but their exact frequency is 
unknown 
• breakdown of muscle tissue 
• a worsening of liver disease after Lamivudine Teva is stopped or during treatment if the hepatitis 

B virus becomes resistant to Lamivudine Teva. This can be fatal in some people. 
• lactic acidosis (see the next section, ‘Other possible side effects of therapy for Hepatitis B’). 

 
A side effect which may show up in blood tests is: 
• a decrease in the number of cells involved in blood clotting (thrombocytopenia). 

If you get any side effects 
 Talk to your doctor or pharmacist. This includes any possible side effects not listed in this 

leaflet.  
 
Other possible side effects of therapy for Hepatitis B 
Lamivudine Teva and related medicines (NRTIs) may cause other conditions to develop during 
hepatitis B treatment. 
 
Lactic acidosis is a rare but serious side effect 
Some people taking Lamivudine Teva, or other medicines like it (NRTIs), develop a condition called 
lactic acidosis, together with an enlarged liver.  
 



31 

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: 
• deep, rapid, difficult breathing 
• drowsiness 
• numbness or weakness in the limbs 
• feeling sick (nausea), being sick (vomiting)  
• stomach pain. 
 
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. 
 
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 Lamivudine Teva 
 
Keep this medicine out of the sight and reach of children. 
 
Do not take this medicine after the expiry date shown on the container or carton and blister pack after 
EXP. The expiry date refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions 
 
Do not use Lamivudine Teva if you notice any change in the appearance of the tablet. 
 
Do not throw away any medicines in your wastewater or household waste. Ask your pharmacist how 
to throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Lamivudine Teva contains 
 
- The active substance is lamivudine. Each film-coated tablet contains 100 mg of lamivudine. 
- The other ingredients are;  

Tablet core: Microcrystalline cellulose, sodium starch glycolate, magnesium stearate. Tablet 
film coat: Hypromellose, titanium dioxide (E171), macrogol, polysorbate 80, iron oxide yellow 
(E172), iron oxide red (E172). 

 
What Lamivudine Teva looks like and contents of the pack 
 
Orange, capsule shaped, biconvex film-coated tablet – engraved with “L100” on one side and plain on 
the other 
 

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


32 

Lamivudine Teva is available in aluminium blisters containing 28, 30, 84 or 100 tablets or HDPE 
containers containing 60 tablets. 
 
Not all pack sizes may beavailable in your country . 
 
 
Marketing Authorisation Holder 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
Netherlands 
 
Manufacturer 
 
Teva Pharmaceutical Works Private Limited Company 
Pallagi út 13 
Debrecen H-4042 
Hungary 
 
TEVA UK Ltd 
Brampton Road 
Hampden Park 
Eastbourne, East Sussex 
BN22 9AG UK 
 
Pharmachemie B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
Teva Operations Poland Sp.z o. o. 
Mogilska 80 Str. 
31-546 Kraków 
Poland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 38207373  
 

Lietuva 
UAB Teva Baltics 
Tel: +370 52660203 
 

България  
Актавис ЕАД 
Teл.: +359 24899585 
 

Luxembourg/Luxemburg  
ratiopharm GmbH 
Allemagne/ Deutschland 
Tél/Tel: +49 73140202  
 

Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251007111 
 

Magyarország  
Teva Gyógyszergyár Zrt.  
Tel.: +36 12886400  
 



33 

Danmark  
Teva Denmark A/S  
Tlf: +45 44985511 
  

Malta  
Teva Pharmaceuticals Ireland 
L-Irlanda 
Tel: +353 19127700 
 

Deutschland 
Teva GmbH 
Tel: +49 73140208 
 

Nederland  
Teva Nederland B.V. 
Tel: +31 8000228400  
 

Eesti 
UAB Teva Baltics Eesti filiaal 
Tel: +372 6610801 
 

Norge 
Teva Norway AS 
Tlf: +47 66775590 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 2118805000 
 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1970070 
 

España 
Teva Pharma, S.L.U. 
Tél: +34 913873280 
 

Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48223459300 
 

France 
Teva Santé 
Tél: +33 155917800 
 

Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 214767550 
 

Hrvatska 
Pliva Hrvatska d.o.o. 
Tel: +385 13720000 
 

România 
Teva Pharmaceuticals S.R.L 
Tel: +40 212306524 
 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 19127700  
 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 15890390 
 

Ísland 
Teva Finland Oy 
Finnland 
Simi: +358 201805900  
 

Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 257267911 
 

Italia 
Teva Italia S.r.l. 
Tel: +39 028917981 
 

Suomi/Finland 
Teva Finland Oy 
Puh/Tel: +358 201805900 
 

Κύπρος 
Teva Ελλάς Α.Ε. 
Ελλάδα 
Τηλ: +30 2118805000 
 

Sverige 
Teva Sweden AB 
Tel: +46 42121100 
 

Latvija 
UAB Teva Baltics filiāle Latvijā 
Tel: +371 67323666 
 

United Kingdom 
Teva UK Limited 
Tel: +44 1977628500 
 

 
This leaflet was last revised in {MM/YYYY}. 
 
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/

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