Tarceva

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Tarceva 25 mg film-coated tablets 
Tarceva 100 mg film-coated tablets 
Tarceva 150 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Tarceva 25 mg film coated tablets 
Each film-coated tablet contains 25 mg erlotinib (as erlotinib hydrochloride).  
 
Tarceva 100 mg film-coated tablets 
Each film-coated tablet contains 100 mg erlotinib (as erlotinib hydrochloride). 
 
Tarceva 150 mg film-coated tablets 
Each film-coated tablet contains 150 mg erlotinib (as erlotinib hydrochloride). 
 
Excipients with known effect  
 
Tarceva 25 mg film coated tablets 
Each 25 mg film-coated tablet contains 27.43 mg Lactose monohydrate.  
 
Tarceva 100 mg film-coated tablets 
Each 100 mg film-coated tablet contains 69.21 mg Lactose monohydrate. 
 
Tarceva 150 mg film-coated tablets 
Each 150 mg film-coated tablet contains 103.82 mg Lactose monohydrate. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Tarceva 25 mg film coated tablets 
White to yellowish, round, biconvex tablets with ‘T 25’ engraved on one side. 
 
Tarceva 100 mg film-coated tablets 
White to yellowish, round, biconvex tablets with ‘T 100’ engraved on one side. 
 
Tarceva 150 mg film-coated tablets 
White to yellowish, round, biconvex tablets with ‘T 150’ engraved on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Non-Small Cell Lung Cancer (NSCLC) 
Tarceva is indicated for the first-line treatment of patients with locally advanced or metastatic non-
small cell lung cancer (NSCLC) with EGFR activating mutations. 
 
Tarceva is also indicated for switch maintenance treatment in patients with locally advanced or 
metastatic NSCLC with EGFR activating mutations and stable disease after first-line chemotherapy. 
 



3 

Tarceva is also indicated for the treatment of patients with locally advanced or metastatic NSCLC 
after failure of at least one prior chemotherapy regimen. In patients with tumours without EGFR 
activating mutations, Tarceva is indicated when other treatment options are not considered suitable. 
 
When prescribing Tarceva, factors associated with prolonged survival should be taken into account. 
 
No survival benefit or other clinically relevant effects of the treatment have been demonstrated in 
patients with Epidermal Growth Factor Receptor (EGFR)-IHC negative tumours (see section 5.1). 
 
Pancreatic cancer 
Tarceva in combination with gemcitabine is indicated for the treatment of patients with metastatic 
pancreatic cancer. 
 
When prescribing Tarceva, factors associated with prolonged survival should be taken into account 
(see sections 4.2 and 5.1). 
 
No survival advantage could be shown for patients with locally advanced disease. 
 
4.2 Posology and method of administration 
 
Tarceva treatment should be supervised by a physician experienced in the use of anti-cancer therapies. 
 
Patients with Non-Small Cell Lung Cancer 
EGFR mutation testing should be performed in accordance with the approved indications (see section 
4.1). 
  
The recommended daily dose of Tarceva is 150 mg taken at least one hour before or two hours after 
the ingestion of food. 
 
Patients with pancreatic cancer 
The recommended daily dose of Tarceva is 100 mg taken at least one hour before or two hours after 
the ingestion of food, in combination with gemcitabine (see the summary of product characteristics of 
gemcitabine for the pancreatic cancer indication). In patients who do not develop rash within the first 
4 – 8 weeks of treatment, further Tarceva treatment should be re-assessed (see section 5.1). 
 
When dose adjustment is necessary, the dose should be reduced in 50 mg steps (see section 4.4). 
Tarceva is available in strengths of 25 mg, 100 mg and 150 mg. 
Concomitant use of CYP3A4 substrates and modulators may require dose adjustment (see section 4.5). 
 
Hepatic impairment  
Erlotinib is eliminated by hepatic metabolism and biliary excretion. Although erlotinib exposure was 
similar in patients with moderately impaired hepatic function (Child-Pugh score 7-9) compared with 
patients with adequate hepatic function, caution should be used when administering Tarceva to 
patients with hepatic impairment. Dose reduction or interruption of Tarceva should be considered if 
severe adverse reactions occur. The safety and efficacy of erlotinib has not been studied in patients 
with severe hepatic dysfunction (AST/SGOT and ALT/SGPT> 5 x ULN). Use of Tarceva in patients 
with severe hepatic dysfunction is not recommended (see section 5.2). 
 
Renal impairment  
The safety and efficacy of erlotinib has not been studied in patients with renal impairment (serum 
creatinine concentration >1.5 times the upper normal limit). Based on pharmacokinetic data no dose 
adjustments appear necessary in patients with mild or moderate renal impairment (see section 5.2). 
Use of Tarceva in patients with severe renal impairment is not recommended. 
 
Paediatric population  
The safety and efficacy of erlotinib in the approved indications has not been established in patients 
under the age of 18 years. Use of Tarceva in paediatric patients is not recommended. 



4 

 
Smokers  
Cigarette smoking has been shown to reduce erlotinib exposure by 50-60%. The maximum tolerated 
dose of Tarceva in NSCLC patients who currently smoke cigarettes was 300 mg. The 300 mg dose did 
not show improved efficacy in second line treatment after failure of chemotherapy compared to the 
recommended 150 mg dose in patients who continue to smoke cigarettes. Safety data were comparable 
between the 300 mg and 150 mg doses; however, there was a numerical increase in the incidence of 
rash, interstitial lung disease and diarrhoea, in patients receiving the higher dose of erlotinib. Current 
smokers should be advised to stop smoking (see sections 4.4, 4.5, 5.1 and 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to erlotinib or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Assessment of EGFR mutation status 
When considering the use of Tarceva as a first line or maintenance treatment for locally advanced or 
metastatic NSCLC, it is important that the EGFR mutation status of a patient is determined. 
 
A validated, robust, reliable and sensitive test with a prespecified positivity threshold and 
demonstrated utility for the determination of EGFR mutation status, using either tumor DNA derived 
from a tissue sample or circulating free DNA (cfDNA) obtained from a blood (plasma) sample, should 
be performed according to local medical practice.  
 
If a plasma-based cfDNA test is used and the result is negative for activating mutations, perform a 
tissue test wherever possible due to the potential for false negative results from a plasma-based test. 
 
Smokers 
Current smokers should be advised to stop smoking, as plasma concentrations of erlotinib in smokers 
as compared to non-smokers are reduced. The degree of reduction is likely to be clinically significant 
(see sections 4.2, 4.5, 5.1 and 5.2). 
 
Interstitial Lung Disease 
Cases of interstitial lung disease (ILD)-like events, including fatalities, have been reported 
uncommonly in patients receiving Tarceva for treatment of non-small cell lung cancer (NSCLC), 
pancreatic cancer or other advanced solid tumours. In the pivotal study BR.21 in NSCLC, the 
incidence of ILD (0.8%) was the same in both the placebo and Tarceva groups. In a meta-analysis of 
NSCLC randomised controlled clinical trials (excluding phase I and single-arm phase II studies due to 
lack of control groups), the incidence of ILD-like events was 0.9% on Tarceva compared to 0.4% in 
patients in the control arms. In the pancreatic cancer study in combination with gemcitabine, the 
incidence of ILD-like events was 2.5% in the Tarceva plus gemcitabine group versus 0.4% in the 
placebo plus gemcitabine treated group. Reported diagnoses in patients suspected of having ILD-like 
events included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial 
pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis, Acute Respiratory 
Distress Syndrome (ARDS), alveolitis, and lung infiltration. Symptoms started from a few days to 
several months after initiating Tarceva therapy. Confounding or contributing factors such as 
concomitant or prior chemotherapy, prior radiotherapy, pre-existing parenchymal lung disease, 
metastatic lung disease, or pulmonary infections were frequent. A higher incidence of ILD 
(approximately 5% with a mortality rate of 1.5%) is seen among patients in studies conducted in 
Japan. 
 
In patients who develop acute onset of new and/or progressive unexplained pulmonary symptoms such 
as dyspnoea, cough and fever, Tarceva therapy should be interrupted pending diagnostic evaluation. 
Patients treated concurrently with erlotinib and gemcitabine should be monitored carefully for the 
possibility to develop ILD-like toxicity. If ILD is diagnosed, Tarceva should be discontinued and 
appropriate treatment initiated as necessary (see section 4.8). 



5 

 
Diarrhoea, dehydration, electrolyte imbalance and renal failure 
Diarrhoea (including very rare cases with a fatal outcome) has occurred in approximately 50% of 
patients on Tarceva and moderate or severe diarrhoea should be treated with e.g. loperamide. In some 
cases dose reduction may be necessary. In the clinical studies doses were reduced by 50 mg steps. 
Dose reductions by 25 mg steps have not been investigated. In the event of severe or persistent 
diarrhoea, nausea, anorexia, or vomiting associated with dehydration, Tarceva therapy should be 
interrupted and appropriate measures should be taken to treat the dehydration (see section 4.8). There 
have been rare reports of hypokalaemia and renal failure (including fatalities). Some cases were 
secondary to severe dehydration due to diarrhoea, vomiting and/or anorexia, while others were 
confounded by concomitant chemotherapy. In more severe or persistent cases of diarrhoea, or cases 
leading to dehydration, particularly in groups of patients with aggravating risk factors (especially 
concomitant chemotherapy and other medications, symptoms or diseases or other predisposing 
conditions including advanced age), Tarceva therapy should be interrupted and appropriate measures 
should be taken to intensively rehydrate the patients intravenously. In addition, renal function and 
serum electrolytes including potassium should be monitored in patients at risk of dehydration. 
 
Hepatitis, hepatic failure 
Rare cases of hepatic failure (including fatalities) have been reported during use of Tarceva. 
Confounding factors have included pre-existing liver disease or concomitant hepatotoxic medications. 
Therefore, in such patients, periodic liver function testing should be considered. Tarceva dosing 
should be interrupted if changes in liver function are severe (see section 4.8). Tarceva is not 
recommended for use in patients with severe hepatic dysfunction. 
 
Gastrointestinal perforation 
Patients receiving Tarceva are at increased risk of developing gastrointestinal perforation, which was 
observed uncommonly (including some cases with a fatal outcome). Patients receiving concomitant 
anti-angiogenic agents, corticosteroids, NSAIDs, and/or taxane based chemotherapy, or who have 
prior history of peptic ulceration or diverticular disease are at increased risk. Tarceva should be 
permanently discontinued in patients who develop gastrointestinal perforation (see section 4.8). 
 
Bullous and exfoliative skin disorders 
Bullous, blistering and exfoliative skin conditions have been reported, including very rare cases 
suggestive of Stevens-Johnson syndrome/Toxic epidermal necrolysis, which in some cases were fatal 
(see section 4.8). Tarceva treatment should be interrupted or discontinued if the patient develops 
severe bullous, blistering or exfoliating conditions. Patients with bullous and exfoliative skin disorders 
should be tested for skin infection and treated according to local management guidelines. 
 
Ocular disorders 
Patients presenting with signs and symptoms suggestive of keratitis such as acute or worsening: eye 
inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye should be referred 
promptly to an ophthalmology specialist. If a diagnosis of ulcerative keratitis is confirmed, treatment 
with Tarceva should be interrupted or discontinued. If keratitis is diagnosed, the benefits and risks of 
continuing treatment should be carefully considered. Tarceva should be used with caution in patients 
with a history of keratitis, ulcerative keratitis or severe dry eye. Contact lens use is also a risk factor 
for keratitis and ulceration.Very rare cases of corneal perforation or ulceration have been reported 
during use of Tarceva (see section 4.8). 
 
Interactions with other medicinal products 
Potent inducers of CYP3A4 may reduce the efficacy of erlotinib whereas potent inhibitors of CYP3A4 
may lead to increased toxicity. Concomitant treatment with these types of agents should be avoided 
(see section 4.5). 
 
Other forms of interactions 
Erlotinib is characterised by a decrease in solubility at pH above 5. Medicinal products that alter the 
pH of the upper Gastro-Intestinal (GI) tract, like proton pump inhibitors, H2 antagonists and antacids, 
may alter the solubility of erlotinib and hence its bioavailability. Increasing the dose of Tarceva when 



6 

co-administered with such agents is not likely to compensate for the loss of exposure. Combination of 
erlotinib with proton pump inhibitors should be avoided. The effects of concomitant administration of 
erlotinib with H2 antagonists and antacids are unknown; however, reduced bioavailability is likely. 
Therefore, concomitant administration of these combinations should be avoided (see section 4.5). If 
the use of antacids is considered necessary during treatment with Tarceva, they should be taken at 
least 4 hours before or 2 hours after the daily dose of Tarceva. 
 
The tablets contain lactose and should not be administered to patients with rare hereditary problems of 
galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Erlotinib and other CYP substrates 
Erlotinib is a potent inhibitor of CYP1A1, and a moderate inhibitor of CYP3A4 and CYP2C8, as well 
as a strong inhibitor of glucuronidation by UGT1A1 in vitro. 
The physiological relevance of the strong inhibition of CYP1A1 is unknown due to the very limited 
expression of CYP1A1 in human tissues.  
 
When erlotinib was co-administered with ciprofloxacin, a moderate CYP1A2 inhibitor, the erlotinib 
exposure [AUC] increased significantly by 39%, while no statistically significant change in Cmax was 
found. Similarly, the exposure to the active metabolite increased by about 60% and 48% for AUC and 
Cmax, respectively. The clinical relevance of this increase has not been established. Caution should be 
exercised when ciprofloxacin or potent CYP1A2 inhibitors (e.g. fluvoxamine) are combined with 
erlotinib. If adverse reactions related to erlotinib are observed, the dose of erlotinib may be reduced. 
 
Pre-treatment or co-administration of Tarceva did not alter the clearance of the prototypical CYP3A4 
substrates, midazolam and erythromycin, but did appear to decrease the oral bioavailability of 
midazolam by up to 24%. In another clinical study, erlotinib was shown not to affect pharmacokinetics 
of the concomitantly administered CYP3A4/2C8 substrate paclitaxel. Significant interactions with the 
clearance of other CYP3A4 substrates are therefore unlikely. 
 
The inhibition of glucuronidation may cause interactions with medicinal products which are substrates 
of UGT1A1 and exclusively cleared by this pathway. Patients with low expression levels of UGT1A1 
or genetic glucuronidation disorders (e.g. Gilbert’s disease) may exhibit increased serum 
concentrations of bilirubin and must be treated with caution. 
 
Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to 
a lesser extent by CYP1A2. Extrahepatic metabolism by CYP3A4 in intestine, CYP1A1 in lung, and 
CYP1B1 in tumour tissue also potentially contribute to the metabolic clearance of erlotinib. Potential 
interactions may occur with active substances which are metabolised by, or are inhibitors or inducers 
of, these enzymes. 
 
Potent inhibitors of CYP3A4 activity decrease erlotinib metabolism and increase erlotinib plasma 
concentrations. In a clinical study, the concomitant use of erlotinib with ketoconazole (200 mg orally 
twice daily for 5 days), a potent CYP3A4 inhibitor, resulted in an increase of erlotinib exposure (86% 
of AUC and 69% of Cmax). Therefore, caution should be used when erlotinib is combined with a potent 
CYP3A4 inhibitor, e.g. azole antifungals (i.e. ketoconazole, itraconazole, voriconazole), protease 
inhibitors, erythromycin or clarithromycin. If necessary the dose of erlotinib should be reduced, 
particularly if toxicity is observed. 
 
Potent inducers of CYP3A4 activity increase erlotinib metabolism and significantly decrease erlotinib 
plasma concentrations. In a clinical study, the concomitant use of erlotinib and rifampicin (600 mg 
orally once daily for 7 days), a potent CYP3A4 inducer, resulted in a 69% decrease in the median 
erlotinib AUC. Co-administration of rifampicin with a single 450 mg dose of Tarceva resulted in a 
mean erlotinib exposure (AUC) of 57.5% of that after a single 150 mg Tarceva dose in the absence of 



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rifampicin treatment. Co-administration of Tarceva with CYP3A4 inducers should therefore be 
avoided. For patients who require concomitant treatment with Tarceva and a potent CYP3A4 inducer 
such as rifampicin an increase in dose to 300 mg should be considered while their safety (including 
renal and liver functions and serum electrolytes) is closely monitored, and if well tolerated for more 
than 2 weeks, further increase to 450 mg could be considered with close safety monitoring. Reduced 
exposure may also occur with other inducers e.g. phenytoin, carbamazepine, barbiturates or St. John’s 
Wort (hypericum perforatum). Caution should be observed when these active substances are combined 
with erlotinib. Alternate treatments lacking potent CYP3A4 inducing activity should be considered 
when possible. 
 
Erlotinib and coumarin-derived anticoagulants 
Interaction with coumarin-derived anticoagulants including warfarin leading to increased International 
Normalized Ratio (INR) and bleeding events, which in some cases were fatal, have been reported in 
patients receiving Tarceva. Patients taking coumarin-derived anticoagulants should be monitored 
regularly for any changes in prothrombin time or INR. 
 
Erlotinib and statins 
The combination of Tarceva and a statin may increase the potential for statin-induced myopathy, 
including rhabdomyolysis, which was observed rarely. 
 
Erlotinib and smokers 
Results of a pharmacokinetic interaction study indicated a significant 2.8-, 1.5- and 9-fold reduced 
AUCinf, Cmax and plasma concentration at 24 hours, respectively, after administration of Tarceva in 
smokers as compared to non-smokers. Therefore, patients who are still smoking should be encouraged 
to stop smoking as early as possible before initiation of treatment with Tarceva, as plasma erlotinib 
concentrations are reduced otherwise. Based on the data from the CURRENTS study, no evidence was 
seen for any benefit of a higher erlotinib dose of 300 mg when compared with the recommended dose 
of 150 mg in active smokers. Safety data were comparable between the 300 mg and 150 mg doses; 
however, there was a numerical increase in the incidence of rash, interstitial lung disease and 
diarrhoea, in patients receiving the higher dose of erlotinib (see sections 4.2, 4.4, 5.1 and 5.2). 
 
Erlotinib and P-glycoprotein inhibitors 
Erlotinib is a substrate for the P-glycoprotein active substance transporter. Concomitant administration 
of inhibitors of Pgp, e.g. cyclosporine and verapamil, may lead to altered distribution and/or altered 
elimination of erlotinib. The consequences of this interaction for e.g. CNS toxicity have not been 
established. Caution should be exercised in such situations. 
 
Erlotinib and medicinal products altering pH 
Erlotinib is characterised by a decrease in solubility at pH above 5. Medicinal products that alter the 
pH of the upper Gastro-Intestinal (GI) tract may alter the solubility of erlotinib and hence its 
bioavailability. Co-administration of erlotinib with omeprazole, a proton pump inhibitor (PPI), 
decreased the erlotinib exposure [AUC] and maximum concentration [Cmax] by 46% and 61%, 
respectively. There was no change to Tmax or half-life. Concomitant administration of Tarceva with 
300 mg ranitidine, an H2-receptor antagonist, decreased erlotinib exposure [AUC] and maximum 
concentrations [Cmax] by 33% and 54%, respectively. Increasing the dose of Tarceva when co-
administered with such agents is not likely to compensate for this loss of exposure. However, when 
Tarceva was dosed in a staggered manner 2 hours before or 10 hours after ranitidine 150 mg b.i.d., 
erlotinib exposure [AUC] and maximum concentrations [Cmax] decreased only by 15% and 17%, 
respectively. The effect of antacids on the absorption of erlotinib has not been investigated but 
absorption may be impaired, leading to lower plasma levels. In summary, the combination of erlotinib 
with proton pump inhibitors should be avoided. If the use of antacids is considered necessary during 
treatment with Tarceva, they should be taken at least 4 hours before or 2 hours after the daily dose of 
Tarceva. If the use of ranitidine is considered, it should be used in a staggered manner; i.e. Tarceva 
must be taken at least 2 hours before or 10 hours after ranitidine dosing. 
 



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Erlotinib and Gemcitabine 
In a Phase Ib study, there were no significant effects of gemcitabine on the pharmacokinetics of 
erlotinib nor were there significant effects of erlotinib on the pharmacokinetics of gemcitabine. 
 
Erlotinib and Carboplatin/Paclitaxel 
Erlotinib increases platinum concentrations. In a clinical study, the concomitant use of erlotinib with 
carboplatin and paclitaxel led to an increase of total platinum AUC0-48 of 10.6%. Although statistically 
significant, the magnitude of this difference is not considered to be clinically relevant. In clinical 
practice, there may be other co-factors leading to an increased exposure to carboplatin like renal 
impairment. There were no significant effects of carboplatin or paclitaxel on the pharmacokinetics of 
erlotinib. 
 
Erlotinib and Capecitabine 
Capecitabine may increase erlotinib concentrations. When erlotinib was given in combination with 
capecitabine, there was a statistically significant increase in erlotinib AUC and a borderline increase in 
Cmax when compared with values observed in another study in which erlotinib was given as single 
agent. There were no significant effects of erlotinib on the pharmacokinetics of capecitabine.  
 
Erlotinib and proteasome inhibitors 
Due to the working mechanism, proteasome inhibitors including bortezomib may be expected to 
influence the effect of EGFR inhibitors including erlotinib. Such influence is supported by limited 
clinical data and preclinical studies showing EGFR degradation through the proteasome. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data for the use of erlotinib in pregnant women. Studies in animals have shown 
no evidence of teratogenicity or abnormal parturition. However, an adverse effect on the pregnancy 
can not be excluded as rat and rabbit studies have shown increased embryo/foetal lethality (see 
section 5.3). The potential risk for humans is unknown.  
 
Women of childbearing potential 
Women of childbearing potential must be advised to avoid pregnancy while on Tarceva. Adequate 
contraceptive methods should be used during therapy, and for at least 2 weeks after completing 
therapy. Treatment should only be continued in pregnant women if the potential benefit to the mother 
outweighs the risk to the foetus. 
 
Breast-feeding 
It is not known whether erlotinib is excreted in human milk. No studies have been conducted to assess 
the impact of Tarceva on milk production or its presence in breast milk. As the potential for harm to 
the nursing infant is unknown, mothers should be advised against breast-feeding while receiving 
Tarceva and for at least 2 weeks after the final dose. 
 
Fertility 
Studies in animals have shown no evidence of impaired fertility. However, an adverse effect on the 
fertility can not be excluded as animal studies have shown effects on reproductive parameters (see 
section 5.3). The potential risk for humans is unknown.  
 
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; however 
erlotinib is not associated with impairment of mental ability. 
 



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4.8 Undesirable effects 
 
Safety evaluation of Tarceva is based on the data from more than 1500 patients treated with at least 
one 150 mg dose of Tarceva monotherapy and more than 300 patients who received Tarceva 100 or 
150 mg in combination with gemcitabine. 
 
The incidence of adverse drug reactions (ADRs) from clinical trials reported with Tarceva alone or in 
combination with chemotherapy are summarised by National Cancer Institute-Common Toxicity 
Criteria (NCI-CTC) Grade in Table 1. The listed ADRs were those reported in at least 10% (in the 
Tarceva group) of patients and occurred more frequently (≥3%) in patients treated with Tarceva than 
in the comparator arm. Other ADRs including those from other studies are summarized in Table 2. 
 
Adverse drug reactions from clinical trials (Table 1) are listed by MedDRA system organ class. The 
corresponding frequency category for each adverse drug reaction is based on the following 
convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare 
(≥1/10,000 to <1/1,000), very rare (<1/10,000). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
Non-small cell lung cancer (Tarceva administered as monotherapy) 
 
First-Line Treatment of Patients with EGFR Mutations 
 
In an open-label, randomised phase III study, ML20650 conducted in 154 patients, the safety of 
Tarceva for first-line treatment of NSCLC patients with EGFR activating mutations was assessed in 75 
patients; no new safety signals were observed in these patients. 
 
The most frequent ADRs seen in patients treated with Tarceva in study ML20650 were rash and 
diarrhoea (any Grade 80% and 57%, respectively), most were Grade 1/2 in severity and manageable 
without intervention. Grade 3 rash and diarrhoea occurred in 9% and 4% of patients, respectively. No 
Grade 4 rash or diarrhoea was observed. Both rash and diarrhoea resulted in discontinuation of 
Tarceva in 1% of patients. Dose modifications (interruptions or reductions) for rash and diarrhoea 
were needed in 11% and 7% of patients, respectively. 
 
Maintenance treatment 
 
In two other double-blind, randomised, placebo-controlled Phase III studies BO18192 (SATURN) and 
BO25460 (IUNO); Tarceva was administered as maintenance after first-line chemotherapy. These 
studies were conducted in a total of 1532 patients with advanced, recurrent or metastatic NSCLC 
following first-line standard platinum-based chemotherapy, no new safety signals were identified.  
 
The most frequent ADRs seen in patients treated with Tarceva in studies BO18192 and BO25460 were 
rash (BO18192: all grades 49.2%, grade 3: 6.0%; BO25460: all grades 39.4%, grade 3: 5.0%) and 
diarrhoea (BO18192: all grades 20.3%, grade 3: 1.8%; BO25460: all grades 24.2%, grade 3: 2.5%). 
No Grade 4 rash or diarrhoea was observed in either study. Rash and diarrhoea resulted in 
discontinuation of Tarceva in 1% and <1% of patients, respectively, in study BO18192, while no 
patients discontinued for rash or diarrhoea in BO25460. Dose modifications (interruptions or 
reductions) for rash and diarrhoea were needed in 8.3% and 3% of patients, respectively, in study 
BO18192 and 5.6% and 2.8% of patients, respectively, in study BO25460. 
 
Second and Further Line Treatment  
 
In a randomised double-blind study (BR.21; Tarceva administered as second line therapy), rash (75%) 
and diarrhoea (54%) were the most commonly reported adverse drug reactions (ADRs). Most were 
Grade 1/2 in severity and manageable without intervention. Grade 3/4 rash and diarrhoea occurred in 
9% and 6%, respectively in Tarceva-treated patients and each resulted in study discontinuation in 1% 
of patients. Dose reduction for rash and diarrhoea was needed in 6% and 1% of patients, respectively. 



10 

In study BR.21, the median time to onset of rash was 8 days, and the median time to onset of diarrhoea 
was 12 days. 
 
In general, rash manifests as a mild or moderate erythematous and papulopustular rash, which may 
occur or worsen in sun exposed areas. For patients who are exposed to sun, protective clothing, and/or 
use of sunscreen (e.g. mineral-containing) may be advisable. 
 
Pancreatic cancer (Tarceva administered concurrently with gemcitabine) 
 
The most common adverse reactions in pivotal study PA.3 in pancreatic cancer patients receiving 
Tarceva 100 mg plus gemcitabine were fatigue, rash and diarrhoea. In the Tarceva plus gemcitabine 
arm, Grade 3/4 rash and diarrhoea were each reported in 5% of patients. The median time to onset of 
rash and diarrhoea was 10 days and 15 days, respectively. Rash and diarrhoea each resulted in dose 
reductions in 2% of patients, and resulted in study discontinuation in up to 1% of patients receiving 
Tarceva plus gemcitabine.  
 
 
 



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Table 1: ADRs occurring in ≥ 10% of patients in BR.21 (treated with Tarceva) and PA.3 (treated 
with Tarceva plus gemcitabine) studies and ADRs occurring more frequently (≥ 3%) than placebo in 
BR.21 (treated with Tarceva) and PA.3 (treated with Tarceva plus gemcitabine) studies   
 

 
Tarceva (BR.21) 

N = 485 
Tarceva (PA.3) 

N = 259  
Frequency 
category of 

highest 
incidence NCI-CTC Grade 

Any 
Grade 3 4 

Any 
Grade 3 4    

MedDRA Preferred Term % % % % % %    

           

Infections and infestations 
 Infection* 24 4 0 

 
31 

 
3 

 
<1    

 
very common 

Metabolism and nutrition 
disorders 
 Anorexia 
 Weight decreased 

52 
- 

8 
- 

1 
- 

 
 
- 

39 

 
 
- 
2 

 
 
- 
0 

 
 

 
 

 
 

 
 

very common 
very common 

Eye disorders 
 Keratoconjunctivitis sicca 

Conjunctivitis 

 
12 
12 

0 
<1 

 
0 
0 

 
- 
- 

 
- 
- 

 
- 
-    

 
very common 
very common 

Psychiatric disorders 
 Depression 

 
- 

 
- 

 
- 

 
19 

 
2 

 
0    

 
very common 

Nervous system disorders 
 Neuropathy 
 Headache 

 
- 
- 

 
- 
- 

 
- 
- 

 
13 
15 

 
1 

<1 

 
<1 
0    

 
very common 
very common 

Respiratory, thoracic and 
mediastinal disorders 
 Dyspnoea 
 Cough 

41 
33 

17 
4 

11 
0 

 
 
- 

16 

 
 
- 
0 

 
 
- 
0    

 
 

very common 
very common 

Gastrointestinal disorders 
 Diarrhoea** 
 Nausea 
 Vomiting 
 Stomatitis 
 Abdominal pain 
 Dyspepsia 
 Flatulence 

54 
33 
23 
17 
11 
- 
- 

6 
3 
2 

<1 
2 
- 
- 

<1 
0 

<1 
0 

<1 
- 
- 

 
48 
- 
- 

22 
- 

17 
13 

 
5 
- 
- 

<1 
- 

<1 
0 

 
<1 
- 
- 
0 
- 
0 
0 

 
 
 

 
 
 

 
 
 

 
very common 
very common 
very common 
very common 
very common 
very common 
very common 

Skin and subcutaneous tissue 
disorders 
 Rash*** 
 Pruritus 
 Dry skin 
 Alopecia 

75 
13 
12 
- 

8 
<1 
0 
- 

<1 
0 
0 
- 

 
 

69 
- 
- 

14 

 
 

5 
- 
- 
0 

 
 
0 
- 
- 
0 

 
 

 
 

 
 

 
 

very common 
very common 
very common 
very common 

General disorders and 
administration site conditions 
 Fatigue 
 Pyrexia 
 Rigors 

52 
- 
- 

14 
- 
- 

4 
- 
- 

 
 

73 
36 
12 

 
 

14 
3 
0 

 
 
2 
0 
0 

 
 
 

 
 
 

 
 
 

 
 

very common 
very common 
very common 

* Severe infections, with or without neutropenia, have included pneumonia, sepsis, and cellulitis. 



12 

** Can lead to dehydration, hypokalemia and renal failure. 
*** Rash included dermatitis acneiform. 
- corresponds to percentage below threshold. 
 
 
Table 2: Summary of ADRs per frequency category: 
 
Body System Very 

common 
(≥1/10) 

Common 
(≥1/100 to 
<1/10) 

Uncommon 
(≥1/1,000 to 
<1/100) 

Rare 
(≥1/10,000  
to 
<1/1,000) 

Very rare 
(<1/10,000) 

Eye disorders  -Keratitis 
-Conjunctivitis1 

-Eyelash 
changes 2 

 -Corneal 
perforations 
-Corneal 
ulcerations  
-Uveitis 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 -Epistaxis -Interstitial 
lung disease 
(ILD)3 

  

Gastro-
intestinal 
disorders 

-Diarrhoea7 -Gastro-
intestinal 
bleeding4, 7 

-Gastro-
intestinal 
perforations7 

  

Hepato biliary 
disorders 

-Liver 
function test 
abnormalities 
5 

  -Hepatic 
failure 6 

 

Skin and 
subcutaneous 
tissue disorders 

-Rash -Alopecia 
-Dry skin1 
-Paronychia  
-Folliculitis 
-Acne/ 
Dermatitis 
acneiform  
-Skin fissures 
 

-Hirsutism 
-Eyebrow 
changes  
-Brittle and 
Loose nails 
-Mild skin 
reactions 
such as 
hyperpigmen
tation 

-Palmar 
plantar 
erythrodys-
aesthesia 
syndrome 
 

-Stevens-Johnson 
syndrome/Toxic 
epidermal 
necrolysis7 

Renal and 
urinary 
disorders 

 -Renal 
insufficiency1 

-Nephritis1 
-Proteinuria1 

  

1 In clinical study PA.3. 
2 Including in-growing eyelashes, excessive growth and thickening of the eyelashes. 
3 Including fatalities, in patients receiving Tarceva for treatment of NSCLC or other advanced solid tumours (see 
section 4.4). A higher incidence has been observed in patients in Japan (see section 4.4). 
4 In clinical studies, some cases have been associated with concomitant warfarin administration and some with 
concomitant NSAID administration (see section 4.5). 
5 Including increased alanine aminotransferase [ALT], aspartate aminotransferase [AST] and bilirubin. These 
were very common in clinical study PA.3 and common in clinical study BR.21. Cases were mainly mild to 
moderate in severity, transient in nature or associated with liver metastases.  
6 Including fatalities. Confounding factors included pre-existing liver disease or concomitant hepatotoxic 
medications (see section 4.4). 
7 Including fatalities (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. 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


13 

 
4.9 Overdose 
 
Symptoms 
Single oral doses of Tarceva up to 1000 mg erlotinib in healthy subjects, and up to 1600 mg in cancer 
patients have been tolerated. Repeated twice daily doses of 200 mg in healthy subjects were poorly 
tolerated after only a few days of dosing. Based on the data from these studies, severe adverse 
reactions such as diarrhoea, rash and possibly increased activity of liver aminotransferases may occur 
above the recommended dose. 
 
Management 
In case of suspected overdose, Tarceva should be withheld and symptomatic treatment initiated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: antineoplastic agent protein kinase inhibitor, ATC code: L01XE03 
 
Mechanism of action 
Erlotinib is an epidermal growth factor receptor/human epidermal growth factor receptor type 1 
(EGFR also known as HER1) tyrosine kinase inhibitor. Erlotinib potently inhibits the intracellular 
phosphorylation of EGFR. EGFR is expressed on the cell surface of normal cells and cancer cells. In 
non-clinical models, inhibition of EGFR phosphotyrosine results in cell stasis and/or death. 
 
EGFR mutations may lead to constitutive activation of anti-apoptotic and proliferation signaling 
pathways. The potent effectiveness of erlotinib in blocking EGFR-mediated signalling in these EGFR 
mutation positive tumours is attributed to the tight binding of erlotinib to the ATP-binding site in the 
mutated kinase domain of the EGFR. Due to the blocking of downstream-signaling, the proliferation 
of cells is stopped, and cell death is induced through the intrinsic apoptotic pathway. Tumour 
regression is observed in mouse models of enforced expression of these EGFR activating mutations. 
 
Clinical efficacy 
 
- First-line Non-Small Cell Lung Cancer (NSCLC) therapy for patients with EGFR activating 
mutations (Tarceva administered as monotherapy)  
 
The efficacy of Tarceva in first-line treatment of patients with EGFR activating mutations in NSCLC 
was demonstrated in a phase III, randomised, open-label trial (ML20650, EURTAC). This study was 
conducted in Caucasian patients with metastatic or locally advanced NSCLC (stage IIIB and IV) who 
have not received previous chemotherapy or any systemic antitumour therapy for their advanced 
disease and who present mutations in the tyrosine kinase domain of the EGFR (exon 19 deletion or 
exon 21 mutation). Patients were randomised 1:1 to receive Tarceva 150 mg daily or up to 4 cycles of 
platinum based doublet chemotherapy.  
The primary endpoint was investigator assessed PFS. The efficacy results are summarized in Table 3. 



14 

Figure 1: Kaplan-Meier curve for investigator assessed PFS in trial ML20650 (EURTAC) (April 2012 
cut-off) 
 

 
 
Table 3: Efficacy results of Tarceva versus chemotherapy in trial ML20650 (EURTAC)  
 
  Tarceva Chemo-

therapy 
Hazard Ratio 

(95% CI) 
p-value 

Pre-planned 
Interim 
Analysis 
(35% OS 
maturity) 
(n=153) 
 
Cut-off date: Aug 2010 

 n=77 n=76   
Primary endpoint: 
Progression Free Survival 
(PFS, median in months)* 
Investigator Assessed ** 
 
Independent Review ** 
 

 
 
 

9.4 
 

10.4 
 

 
 
 

5.2 
 

5.4 
 

 
 
 

0.42 
[0.27-0.64] 

0.47 
[0.27-0.78] 

 
 
 

p<0.0001 
 

p=0.003 
 

Best Overall Response Rate 
(CR/PR) 54.5% 10.5%  p<0.0001 

Overall Survival (OS) 
(months) 

22.9 18.8 0.80 
[0.47-1.37] p=0.4170 

Exploratory 
Analysis  
(40% OS 
maturity) 
(n=173) 
 
Cut-off date: Jan 2011 

 n=86 n=87   

PFS (median in months), 
Investigator assessed 9.7 5.2 

0.37 
[0.27-0.54] p<0.0001 

Best Overall Response Rate 
(CR/PR) 58.1% 14.9%  p<0.0001 

OS (months) 19.3 19.5 1.04 [0.65-1.68] p=0.8702 

Updated 
Analysis  
(62% OS 
maturity) 
(n=173) 
 
Cut-off date: April 2012 

 

 n=86 n=87   

PFS (median in months) 10.4 5.1 0.34 [0.23-0.49] p<0.0001 

OS*** (months) 22.9 20.8 0.93 [0.64-1.36] p=0.7149 

CR=complete response; PR=partial response 
*     A 58% reduction in the risk of disease progression or death was observed 
**   Overall concordance rate between investigator and IRC assessment was 70% 
*** A high crossover was observed with 82% of the patients in the chemotherapy arm receiving subsequent therapy with an 
EGFR tyrosine kinase inhibitor and all but 2 of those patients had subsequent Tarceva. 

 



15 

- Maintenance NSCLC therapy after first-line chemotherapy (Tarceva administered as monotherapy) 
  
The efficacy and safety of Tarceva as maintenance after first-line chemotherapy for NSCLC was 
investigated in a randomised, double-blind, placebo-controlled trial (BO18192, SATURN). This study 
was conducted in 889 patients with locally advanced or metastatic NSCLC who did not progress after 
4 cycles of platinum-based doublet chemotherapy. Patients were randomised 1:1 to receive Tarceva 
150 mg or placebo orally once daily until disease progression. The primary endpoint of the study 
included progression free survival (PFS) in all patients. Baseline demographic and disease 
characteristics were well balanced between the two treatment arms. Patients with ECOG PS>1, 
significant hepatic or renal co-morbidities were not included in the study. 
 
In this study, the overall population showed a benefit for the primary PFS end-point (HR= 0.71 
p< 0.0001) and the secondary OS end-point (HR= 0.81 p=0.0088). However the largest benefit was 
observed in a predefined exploratory analysis in patients with EGFR activating mutations (n= 49) 
demonstrating a substantial PFS benefit (HR=0.10, 95% CI, 0.04 to 0.25; p<0.0001) and an overall 
survival HR of 0.83 (95% CI, 0.34 to 2.02). 67% of placebo patients in the EGFR mutation positive 
subgroup received second or further line treatment with EGFR-TKIs. 
 
The BO25460 (IUNO) study was conducted in 643 patients with advanced NSCLC whose tumors did 
not harbor an EGFR-activating mutation (exon 19 deletion or exon 21 L858R mutation) and who had 
not experienced disease progression after four cycles of platinum-based chemotherapy.  
 
The objective of the study was to compare the overall survival of first line maintenance therapy with 
erlotinib versus erlotinib administered at the time of disease progression. The study did not meet its 
primary endpoint. OS of Tarceva in first line maintenance was not superior to Tarceva as second line 
treatment in patients whose tumor did not harbor an EGFR-activating mutation (HR= 1.02, 95% CI, 
0.85 to 1.22, p=0.82). The secondary endpoint of PFS showed no difference between Tarceva and 
placebo in maintenance treatment (HR=0.94, 95 % CI, 0.80 to 1.11; p=0.48).  
 
Based on the data from the BO25460 (IUNO) study, Tarceva use is not recommended for first-line 
maintenance treatment in patients without an EGFR activating mutation. 
  
- NSCLC treatment after failure of at least one prior chemotherapy regimen (Tarceva administered as 
monotherapy)  
 
The efficacy and safety of Tarceva as second/third-line therapy was demonstrated in a randomised, 
double-blind, placebo-controlled trial (BR.21), in 731 patients with locally advanced or metastatic 
NSCLC after failure of at least one chemotherapy regimen. Patients were randomised 2:1 to receive 
Tarceva 150 mg or placebo orally once daily. Study endpoints included overall survival, 
progression-free survival (PFS), response rate, duration of response, time to deterioration of lung 
cancer-related symptoms (cough, dyspnoea and pain), and safety. The primary endpoint was survival. 
 
Demographic characteristics were well balanced between the two treatment groups. About two-thirds 
of the patients were male and approximately one-third had a baseline ECOG performance status (PS) 
of 2, and 9% had a baseline ECOG PS of 3. Ninety-three percent and 92% of all patients in the 
Tarceva and placebo groups, respectively, had received a prior platinum-containing regimen and 36% 
and 37% of all patients, respectively, had received a prior taxane therapy.  
 
The adjusted hazard ratio (HR) for death in the Tarceva group relative to the placebo group was 0.73 
(95% CI, 0.60 to 0.87) (p = 0.001). The percent of patients alive at 12 months was 31.2% and 21.5%, 
for the Tarceva and placebo groups, respectively. The median overall survival was 6.7 months in the 
Tarceva group (95% CI, 5.5 to 7.8 months) compared with 4.7 months in the placebo group (95% CI, 
4.1 to 6.3 months). 
 
The effect on overall survival was explored across different patient subsets. The effect of Tarceva on 
overall survival was similar in patients with a baseline performance status (ECOG) of 2-3 (HR = 0.77, 
95% CI 0.6-1.0) or 0-1 (HR = 0.73, 95% CI 0.6-0.9), male (HR = 0.76, 95% CI 0.6-0.9) or female 



16 

patients (HR = 0.80, 95% CI 0.6-1.1), patients < 65 years of age (HR = 0.75, 95% CI 0.6-0.9) or older 
patients (HR = 0.79, 95% CI 0.6-1.0), patients with one prior regimen (HR = 0.76, 95% CI 0.6-1.0) or 
more than one prior regimen (HR = 0.75, 95% CI 0.6-1.0), Caucasian (HR = 0.79, 95% CI 0.6-1.0) or 
Asian patients (HR = 0.61, 95% CI 0.4-1.0), patients with adenocarcinoma (HR = 0.71, 95% 
CI 0.6-0.9) or squamous cell carcinoma (HR = 0.67, 95% CI 0.5-0.9), but not in patients with other 
histologies (HR 1.04, 95% CI 0.7-1.5), patients with stage IV disease at diagnosis (HR = 0.92, 95% 
CI 0.7-1.2) or < stage IV disease at diagnosis (HR = 0.65, 95% CI 0.5-0.8). Patients who never 
smoked had a much greater benefit from erlotinib (survival HR = 0.42, 95% CI 0.28-0.64) compared 
with current or ex-smokers (HR = 0.87, 95% CI 0.71-1.05).  
In the 45% of patients with known EGFR-expression status, the hazard ratio was 0.68 (95% 
CI 0.49-0.94) for patients with EGFR-positive tumours and 0.93 (95% CI 0.63-1.36) for patients with 
EGFR-negative tumours (defined by IHC using EGFR pharmDx kit and defining EGFR-negative as 
less than 10% tumour cells staining). In the remaining 55% of patients with unknown 
EGFR-expression status, the hazard ratio was 0.77 (95% CI 0.61-0.98).  
 
The median PFS was 9.7 weeks in the Tarceva group (95% CI, 8.4 to 12.4 weeks) compared with 
8.0 weeks in the placebo group (95% CI, 7.9 to 8.1 weeks). 
 
The objective response rate by RECIST in the Tarceva group was 8.9% (95% CI, 6.4 to 12.0).  
The first 330 patients were centrally assessed (response rate 6.2%); 401 patients were investigator-
assessed (response rate 11.2%).  
The median duration of response was 34.3 weeks, ranging from 9.7 to 57.6+ weeks. The proportion of 
patients who experienced complete response, partial response or stable disease was 44.0% and 27.5%, 
respectively, for the Tarceva and placebo groups (p = 0.004). 
 
A survival benefit of Tarceva was also observed in patients who did not achieve an objective tumour 
response (by RECIST). This was evidenced by a hazard ratio for death of 0.82 (95% CI, 0.68 to 0.99) 
among patients whose best response was stable disease or progressive disease. 
 
Tarceva resulted in symptom benefits by significantly prolonging time to deterioration in cough, 
dyspnoea and pain, versus placebo.  
 
In a double-blind, randomised phase III study (MO22162, CURRENTS) comparing two doses of 
Tarceva (300 mg versus 150 mg) in current smokers (mean of 38 pack years) with locally advanced or 
metastatic NSCLC in the second-line setting after failure on chemotherapy, the 300 mg dose of 
Tarceva demonstrated no PFS benefit over the recommended dose (7.00 vs 6.86 weeks, respectively).  
 
Secondary efficacy endpoints were all consistent with the primary endpoint and no difference was 
detected for OS between patients treated with erlotinib 300 mg and 150 mg daily (HR 1.03, 95% CI 
0.80 to 1.32). Safety data were comparable between the 300 mg and 150 mg doses; however, there 
was a numerical increase in the incidence of rash, interstitial lung disease and diarrhoea, in patients 
receiving the higher dose of erlotinib. Based on the data from the CURRENTS study, no evidence was 
seen for any benefit of a higher erlotinib dose of 300 mg when compared with the recommended dose 
of 150 mg in active smokers. 
 
Patients in this study were not selected based on EGFR mutation status. See sections 4.2, 4.4, 4.5, and 
5.2. 
 
-Pancreatic cancer (Tarceva administered concurrently with gemcitabine in study PA.3) 
 
The efficacy and safety of Tarceva in combination with gemcitabine as a first-line treatment was 
assessed in a randomised, double-blind, placebo-controlled trial in patients with locally advanced, 
unresectable or metastatic pancreatic cancer. Patients were randomised to receive Tarceva or placebo 
once daily on a continuous schedule plus gemcitabine IV (1000 mg/m2, Cycle 1 - Days 1, 8, 15, 22, 
29, 36 and 43 of an 8 week cycle; Cycle 2 and subsequent cycles - Days 1, 8 and 15 of a 4 week cycle 
[approved dose and schedule for pancreatic cancer, see the gemcitabine SPC]). Tarceva or placebo 



17 

was taken orally once daily until disease progression or unacceptable toxicity. The primary endpoint 
was overall survival.  
 
Baseline demographic and disease characteristics of the patients were similar between the 2 treatment 
groups, 100 mg Tarceva plus gemcitabine or placebo plus gemcitabine, except for a slightly larger 
proportion of females in the erlotinib/gemcitabine arm compared with the placebo/gemcitabine arm: 
 

Baseline  Tarceva Placebo 
Females 51% 44% 
Baseline ECOG performance status (PS) = 0 31% 32% 
Baseline ECOG performance status (PS) = 1 51% 51% 
Baseline ECOG performance status (PS) = 2 17% 17% 
Metastatic disease at baseline 77% 76% 

 
Survival was evaluated in the intent-to-treat population based on follow-up survival data. Results are 
shown in the table below (results for the group of metastatic and locally advanced patients are derived 
from exploratory subgroup analysis). 
 

Outcome 
Tarceva 
(months) 

Placebo 
(months) 

∆ 
(months) CI of ∆ HR 

CI of 
HR 

P- 
value 

Overall Population 
Median overall survival 6.4 6.0 0.41 -0.54-1.64 

0.82 0.69-0.98 0.028 
Mean overall survival 8.8 7.6 1.16 -0.05-2.34 

Metastatic Population 
Median overall survival 5.9 5.1 0.87 -0.26-1.56 

0.80 0.66-0.98 0.029 
Mean overall survival 8.1 6.7 1.43 0.17-2.66 

Locally Advanced Population 
Median overall survival 8.5 8.2 0.36 -2.43-2.96 

0.93 0.65-1.35 0.713 
Mean overall survival 10.7 10.5 0.19 -2.43-2.69 

 

 
 



18 

 
In a post-hoc analysis, patients with favourable clinical status at baseline (low pain intensity, good 
QoL and good PS) may derive more benefit from Tarceva. The benefit is mostly driven by the 
presence of a low pain intensity score.  
 
In a post-hoc analysis, patients on Tarceva who developed a rash had a longer overall survival 
compared to patients who did not develop rash (median OS 7.2 months vs 5 months, HR:0.61).  
90% of patients on Tarceva developed rash within the first 44 days. The median time to onset of rash 
was 10 days. 
 
Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Tarceva in all subsets of the paediatric population in Non Small Cell Lung Cancer and Pancreatic 
cancer indications (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption  
After oral administration, erlotinib peak plasma levels are obtained in approximately 4 hours after oral 
dosing. A study in normal healthy volunteers provided an estimate of the absolute bioavailability of 
59%. The exposure after an oral dose may be increased by food. 
 
Distribution  
Erlotinib has a mean apparent volume of distribution of 232 l and distributes into tumour tissue of 
humans. In a study of 4 patients (3 with non-small cell lung cancer [NSCLC], and 1 with laryngeal 
cancer) receiving 150 mg daily oral doses of Tarceva, tumour samples from surgical excisions 
on Day 9 of treatment revealed tumour concentrations of erlotinib that averaged 1185 ng/g of tissue. 
This corresponded to an overall average of 63% (range 5-161%) of the steady state observed peak 
plasma concentrations. The primary active metabolites were present in tumour at concentrations 
averaging 160 ng/g tissue, which corresponded to an overall average of 113% (range 88-130%) of the 
observed steady state peak plasma concentrations. Plasma protein binding is approximately 95%. 
Erlotinib binds to serum albumin and alpha-1 acid glycoprotein (AAG). 
 
Biotransformation  
Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to 
a lesser extent by CYP1A2. Extrahepatic metabolism by CYP3A4 in intestine, CYP1A1 in lung, and 
1B1 in tumour tissue potentially contribute to the metabolic clearance of erlotinib. 



19 

 
There are three main metabolic pathways identified: 1) O-demethylation of either side chain or both, 
followed by oxidation to the carboxylic acids; 2) oxidation of the acetylene moiety followed by 
hydrolysis to the aryl carboxylic acid; and 3) aromatic hydroxylation of the phenyl-acetylene moiety. 
The primary metabolites OSI-420 and OSI-413 of erlotinib produced by O-demethylation of either 
side chain have comparable potency to erlotinib in non-clinical in vitro assays and in vivo tumour 
models. They are present in plasma at levels that are <10% of erlotinib and display similar 
pharmacokinetics as erlotinib. 
 
Elimination  
Erlotinib is excreted predominantly as metabolites via the faeces (>90%) with renal elimination 
accounting for only a small amount (approximately 9%) of an oral dose. Less than 2% of the orally 
administered dose is excreted as parent substance. A population pharmacokinetic analysis in 
591 patients receiving single agent Tarceva shows a mean apparent clearance of 4.47 l/hour with a 
median half-life of 36.2 hours. Therefore, the time to reach steady state plasma concentration would be 
expected to occur in approximately 7-8 days. 
 
Pharmacokinetics in special populations 
 
Based on population pharmacokinetic analysis, no clinically significant relationship between predicted 
apparent clearance and patient age, bodyweight, gender and ethnicity were observed. Patient factors, 
which correlated with erlotinib pharmacokinetics, were serum total bilirubin, AAG and current 
smoking. Increased serum concentrations of total bilirubin and AAG concentrations were associated 
with a reduced erlotinib clearance. The clinical relevance of these differences is unclear. However, 
smokers had an increased rate of erlotinib clearance. This was confirmed in a pharmacokinetic study 
in non-smoking and currently cigarette smoking healthy subjects receiving a single oral dose of 
150 mg erlotinib. The geometric mean of the Cmax was 1056 ng/mL in the non-smokers and 689 ng/mL 
in the smokers with a mean ratio for smokers to non-smokers of 65.2% (95% CI: 44.3 to 95.9, 
p = 0.031). The geometric mean of the AUC0-inf was 18726 ng•h/mL in the non-smokers and 6718 
ng•h/mL in the smokers with a mean ratio of 35.9% (95% CI: 23.7 to 54.3, p < 0.0001). The geometric 
mean of the C24h was 288 ng/mL in the non-smokers and 34.8 ng/mL in the smokers with a mean ratio 
of 12.1% (95% CI: 4.82 to 30.2, p = 0.0001). In the pivotal Phase III NSCLC trial, current smokers 
achieved erlotinib steady state trough plasma concentration of 0.65 µg/mL (n=16) which was 
approximately 2-fold less than the former smokers or patients who had never smoked (1.28 µg/mL, 
n=108). This effect was accompanied by a 24% increase in apparent erlotinib plasma clearance. In a 
phase I dose escalation study in NSCLC patients who were current smokers, pharmacokinetic analyses 
at steady-state indicated a dose proportional increase in erlotinib exposure when the Tarceva dose was 
increased from 150 mg to the maximum tolerated dose of 300 mg. Steady-state trough plasma 
concentrations at a 300 mg dose in current smokers in this study was 1.22 µg/mL (n=17). See 
sections 4.2, 4.4, 4.5 and 5.1. 
 
Based on the results of pharmacokinetic studies, current smokers should be advised to stop smoking 
while taking Tarceva, as plasma concentrations could be reduced otherwise. 
 
Based on population pharmacokinetic analysis, the presence of an opioid appeared to increase 
exposure by about 11%. 
 
A second population pharmacokinetic analysis was conducted that incorporated erlotinib data from 
204 pancreatic cancer patients who received erlotinib plus gemcitabine. This analysis demonstrated 
that covariants affecting erlotinib clearance in patients from the pancreatic study were very similar to 
those seen in the prior single agent pharmacokinetic analysis. No new covariate effects were 
identified. Co-administration of gemcitabine had no effect on erlotinib plasma clearance. 
 
Paediatric population  
There have been no specific studies in paediatric patients. 
 



20 

Elderly population  
There have been no specific studies in elderly patients. 
 
Hepatic impairment  
Erlotinib is primarily cleared by the liver. In patients with solid tumours and with moderately impaired 
hepatic function (Child-Pugh score 7-9), geometric mean erlotinib AUC0-t and Cmax was 27000 
ng•h/mL and 805 ng/mL, respectively, as compared to 29300 ng•h/mL and 1090 ng/mL in patients 
with adequate hepatic function including patients with primary liver cancer or hepatic metastases. 
Although the Cmax was statistically significant lower in moderately hepatic impaired patients, this 
difference is not considered clinically relevant. No data are available regarding the influence of severe 
hepatic dysfunction on the pharmacokinetics of erlotinib. In population pharmacokinetic analysis, 
increased serum concentrations of total bilirubin were associated with a slower rate of erlotinib 
clearance. 
 
Renal impairment  
Erlotinib and its metabolites are not significantly excreted by the kidney, as less than 9% of a single 
dose is excreted in the urine. In population pharmacokinetic analysis, no clinically significant 
relationship was observed between erlotinib clearance and creatinine clearance, but there are no data 
available for patients with creatinine clearance <15 ml/min. 
 
5.3 Preclinical safety data 
 
Chronic dosing effects observed in at least one animal species or study included effects on the cornea 
(atrophy, ulceration), skin (follicular degeneration and inflammation, redness, and alopecia), ovary 
(atrophy), liver (liver necrosis), kidney (renal papillary necrosis and tubular dilatation), and 
gastrointestinal tract (delayed gastric emptying and diarrhoea). Red blood cell parameters were 
decreased and white blood cells, primarily neutrophils, were increased. There were treatment-related 
increases in ALT, AST and bilirubin. These findings were observed at exposures well below clinically 
relevant exposures. 
 
Based on the mode of action, erlotinib has the potential to be a teratogen. Data from reproductive 
toxicology tests in rats and rabbits at doses near the maximum tolerated dose and/or maternally toxic 
doses showed reproductive (embryotoxicity in rats, embryo resorption and foetotoxicity in rabbits) and 
developmental (decrease in pup growth and survival in rats) toxicity, but was not teratogenic and did 
not impair fertility. These findings were observed at clinically relevant exposures. 
 
Erlotinib tested negative in conventional genotoxicity studies. Two-year carcinogenicity studies with 
erlotinib conducted in rats and mice were negative up to exposures exceeding human therapeutic 
exposure (up to 2-fold and 10-fold higher, respectively, based on Cmax and/or AUC).  
 
A mild phototoxic skin reaction was observed in rats after UV irradiation. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Lactose monohydrate 
Cellulose, microcrystalline (E460) 
Sodium starch glycolate Type A 
Sodium laurilsulfate 
Magnesium stearate (E470 b) 
 
Tablet coat 
Hydroxypropyl cellulose (E463) 
Titanium dioxide (E171) 



21 

Macrogol 
Hypromellose (E464) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
PVC blister sealed with aluminium foil containing 30 tablets. 
 
6.6 Special precautions for disposal  
 
No special requirements for disposal. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/05/311/001 
EU/1/05/311/002 
EU/1/05/311/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorization: 19 September 2005 
Date of latest renewal: 2 July 2010 
 
 
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 



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



23 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Roche Pharma AG 
Emil-Barell-Strasse 1 
D-79639 Grenzach-Wyhlen 
Germany 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

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

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk Management Plan (RMP) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.  
 
An updated RMP should be submitted: 

● At the request of the European Medicines Agency 
● Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile 
or as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

 
 



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



26 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tarceva 25 mg film-coated tablets 
Erlotinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 25 mg of erlotinib (as erlotinib hydrochloride). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For 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 
 
 
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 

 
 



27 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/05/311/001 
 
 
13. BATCH NUMBER 
 
Batch  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
tarceva 25 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



28 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tarceva 25 mg film-coated tablets 
Erlotinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



29 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tarceva 100 mg film-coated tablets 
Erlotinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 100 mg of erlotinib (as erlotinib hydrochloride). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For 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 
 
 
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 

 
 



30 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/05/311/002 
 
 
13. BATCH NUMBER 
 
Batch  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
tarceva 100 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



31 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tarceva 100 mg film-coated tablets 
Erlotinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



32 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tarceva 150 mg film-coated tablets 
Erlotinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 150 mg of erlotinib (as erlotinib hydrochloride). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For 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 
 
 
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 

 
 



33 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/05/311/003  
 
 
13. BATCH NUMBER 
 
Batch  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
tarceva 150 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



34 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tarceva 150 mg film-coated tablets 
Erlotinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



35 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



36 

 
Package leaflet: Information for the user 

 
Tarceva 25 mg film-coated tablets 

Tarceva 100 mg film-coated tablets 
Tarceva 150 mg film-coated tablets 

Erlotinib 
 

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 further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

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

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Tarceva is and what it is used for 
2. What you need to know before you take Tarceva 
3. How to take Tarceva 
4. Possible side effects 
5. How to store Tarceva 
6. Contents of the pack and other information 
 
 
1. What Tarceva is and what it is used for 
 
Tarceva contains the active substance erlotinib. Tarceva is a medicine used to treat cancer by 
preventing the activity of a protein called epidermal growth factor receptor (EGFR). This protein is 
known to be involved in the growth and spread of cancer cells. 
 
Tarceva is indicated for adults. This medicine can be prescribed to you if you have non-small cell lung 
cancer at an advanced stage. It can be prescribed as initial therapy or as therapy if your disease 
remains largely unchanged after initial chemotherapy, provided your cancer cells have specific EGFR 
mutations. It can also be prescribed if previous chemotherapy has not helped to stop your disease. 
 
This medicine can also be prescribed to you in combination with another treatment called gemcitabine 
if you have cancer of the pancreas at a metastatic stage. 
 
 
2. What you need to know before you take Tarceva  
 
Do not take Tarceva: 
• if you are allergic to erlotinib or any of the ingredients of this medicine (listed in section 6). 
 
Warnings and precautions: 
• if you are taking other medicines that may increase or decrease the amount of erlotinib in your 

blood or influence its effect (for example antifungals like ketoconazole, protease inhibitors, 
erythromycin, clarithromycin, phenytoin, carbamazepine, barbiturates, rifampicin, 
ciprofloxacin, omeprazole, ranitidine, St. John’s Wort or proteasome inhibitors), talk to your 
doctor. In some cases these medicines may reduce the efficacy or increase the side effects of 
Tarceva and your doctor may need to adjust your treatment. Your doctor might avoid treating 
you with these medicines while you are receiving Tarceva. 



37 

• if you are taking anticoagulants (a medicine which helps to prevent thrombosis or blood clotting 
e.g. warfarin), Tarceva may increase your tendency to bleed. Talk to your doctor, he will need 
to regularly monitor you with some blood tests. 

• if you are taking statins (medicines to lower your blood cholesterol), Tarceva may increase the 
risk of statin related muscle problems, which on rare occasions can lead to serious muscle 
breakdown (rhabdomyolysis) resulting in kidney damage, talk to your doctor. 

• if you use contact lenses and/or have a history of eye problems such as severe dry eyes, 
inflammation of the front part of the eye (cornea) or ulcers involving the front part of the eye, 
tell your doctor. 

 
See also below “Other medicines and Tarceva” 
 
You should tell your doctor: 
• if you have sudden difficulty in breathing associated with cough or fever because your doctor 

may need to treat you with other medicines and interrupt your Tarceva treatment; 
• if you have diarrhoea because your doctor may need to treat you with anti-diarrhoeal (for 

example loperamide); 
• immediately, if you have severe or persistent diarrhoea, nausea, loss of appetite, or vomiting 

because your doctor may need to interrupt your Tarceva treatment and may need to treat you in 
the hospital; 

• if you have severe pain in the abdomen, severe blistering or peeling of skin. Your doctor may 
need to interrupt or stop your treatment; 

• if you develop acute or worsening redness and pain in the eye, increased eye watering, blurred 
vision and/or sensitivity to light, please tell your doctor or nurse immediately as you may need 
urgent treatment (see Possible Side Effects below). 

• if you are also taking a statin and experience unexplained muscle pain, tenderness, weakness or 
cramps. Your doctor may need to interrupt or stop your treatment. 

 
See also section 4 “Possible side effects”. 
 
Liver or kidney disease 
It is not known whether Tarceva has a different effect if your liver or kidneys are not functioning 
normally. The treatment with this medicine is not recommended if you have a severe liver disease or 
severe kidney disease. 
 
Glucuronidation disorder like Gilbert’s syndrome 
Your doctor must treat you with caution if you have a glucuronidation disorder like Gilbert’s 
syndrome. 
 
Smoking 
You are advised to stop smoking if you are treated with Tarceva as smoking could decrease the 
amount of your medicine in the blood. 
 
Children and adolescents 
Tarceva has not been studied in patients under the age of 18 years. The treatment with this medicine is 
not recommended for children and adolescents. 
 
Other medicines and Tarceva 
Tell your doctor or pharmacist if you are taking, have recently taken any other medicines or might take 
any other medicines. 
 
Tarceva with food and drink 
Do not take Tarceva with food. See also section 3 ‘How to take Tarceva’ 
 
Pregnancy and breast-feeding 
Avoid pregnancy while being treated with Tarceva. If you could become pregnant, use adequate 
contraception during treatment, and for at least 2 weeks after taking the last tablet.  



38 

If you become pregnant while you are being treated with Tarceva, immediately inform your doctor 
who will decide if the treatment should be continued. 
Do not breast-feed if you are being treated with Tarceva, and for at least 2 weeks after taking the last 
tablet. 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
Tarceva has not been studied for its possible effects on the ability to drive and use machines but it is 
very unlikely that your treatment will affect this ability. 
 
Hypersensitivity 
Tarceva contains a sugar called lactose monohydrate. 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking Tarceva. 
 
 
3. How to take Tarceva 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
The tablet should be taken at least one hour before or two hours after the ingestion of food. 
 
The usual dose is one tablet of Tarceva 150 mg each day if you have non-small cell lung cancer. 
 
The usual dose is one tablet of Tarceva 100 mg each day if you have metastatic pancreatic cancer. 
Tarceva is given in combination with gemcitabine treatment. 
 
Your doctor may adjust your dose in 50 mg steps. For the different dose regimens Tarceva is available 
in strengths of 25 mg, 100 mg or 150 mg. 
 
If you take more Tarceva than you should 
Contact your doctor or pharmacist immediately. 
You may have increased side effects and your doctor may interrupt your treatment. 
 
If you forget to take Tarceva 
If you miss one or more doses of Tarceva, contact your doctor or pharmacist as soon as possible.  
Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking Tarceva 
It is important to keep taking Tarceva every day, as long as your doctor prescribes it for you.  
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 



39 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Contact your doctor as soon as possible if you suffer from any of the below side effects. In some cases 
your doctor may need to reduce your dose of Tarceva or interrupt treatment: 
 

• Diarrhoea and vomiting (very common: may affect more than 1 out of 10 people). 
Persistent and severe diarrhoea may lead to low blood potassium and impairment of your 
kidney function, particularly if you receive other chemotherapy treatments at the same 
time. If you experience more severe or persistent diarrhoea contact your doctor 
immediately as your doctor may need to treat you in the hospital. 

 
• Eye irritation due to conjunctivitis/keratoconjunctivitis (very common: may affect more 

than 1 out of 10 people) and keratitis (common: may affect up to 1 in 10 people). 
 
• Form of lung irritation called interstitial lung disease (uncommon in European patients; 

common in Japanese patients: may affect up to 1 in 100 people in Europe and up to 1 in 
10 in Japan). This disease can also be linked to the natural progression of your medical 
condition and can have a fatal outcome in some cases. If you develop symptoms such as 
sudden difficulty in breathing associated with cough or fever contact your doctor 
immediately as you could suffer from this disease. Your doctor may decide to 
permanently stop your treatment with Tarceva. 

 
• Gastrointestinal perforations have been observed (uncommon: may affect up to 1 in 100 

people). Tell your doctor if you have severe pain in your abdomen. Also, tell your doctor 
if you had peptic ulcers or diverticular disease in the past, as this may increase this risk.   

 
• In rare cases liver failure was observed (rare: may affect up to 1 in 1,000 people). If your 

blood tests indicate severe changes in your liver function, your doctor may need to 
interrupt your treatment. 

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

• Rash which may occur or worsen in sun exposed areas. If you are exposed to sun, 
protective clothing, and/or use of sunscreen (e.g. mineral-containing) may be advisable 

• Infection 
• Loss of appetite, decreased weight 
• Depression 
• Headache, altered skin sensation or numbness in the extremities 
• Difficulty in breathing, cough 
• Nausea 
• Mouth irritation 
• Stomach pain, indigestion and flatulence 
• Abnormal blood tests for the liver function 
• Itching, dry skin and loss of hair 
• Tiredness, fever, rigors 

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

• Bleeding from the nose 
• Bleeding from the stomach or the intestines 
• Inflammatory reactions around the fingernail 
• Infection of hair follicles   
• Acne 
• Cracked skin (skin fissures) 



40 

• Reduced kidney function (when given outside the approved indications in combination with 
chemotherapy) 

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

• Eyelash changes  
• Excess body and facial hair of a male distribution pattern  
• Eyebrow changes 
• Brittle and loose nails  

 
Rare side effects (may affect up to 1 in 1,000 people): 

•    Flushed or painful palms or soles (Palmar plantar erythrodysaesthesia syndrome) 
 
Very rare side effects (may affect up to 1 in 10,000 people): 

• Cases of perforation or ulceration of the cornea 
• Severe blistering or peeling of skin (suggestive of Stevens-Johnson syndrome) 
• Inflammation of the coloured part of the eye 

 
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 Tarceva 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the blister and the carton after EXP. 
The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Tarceva contains: 
• The active substance of Tarceva is erlotinib. Each film-coated tablet contains 25 mg, 100 mg 

or 150 mg of erlotinib (as erlotinib hydrochloride) depending on the strength. 
• The other ingredients are:  

Tablet core: lactose monohydrate, cellulose microcrystalline, sodium starch glycolate type A, 
sodium laurilsulfate, magnesium stearate (see also section 2 for lactose monohydrate). 
Tablet coat: hypromellose, hydroxypropyl cellulose, titanium dioxide, macrogol. 

 
What Tarceva looks like and contents of the pack: 
Tarceva 25 mg is supplied as a white to yellowish, round, film-coated tablet with ‘T 25’ engraved on 
one side and is available in pack sizes of 30 tablets. 
Tarceva 100 mg is supplied as a white to yellowish, round, film-coated tablet with ‘T 100’ engraved 
on one side and is available in pack sizes of 30 tablets. 
Tarceva 150 mg is supplied as a white to yellowish, round, film-coated tablet with ‘T 150’ engraved 
on one side and is available in pack sizes of 30 tablets. 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


41 

Marketing Authorisation Holder 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
Manufacturer 
Roche Pharma AG 
Emil-Barell-Strasse 1 
D-79639 Grenzach-Wyhlen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A. 
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva 
UAB “Roche Lietuva” 
Tel: +370 5 2546799 
 

България 
Рош България ЕООД 
Тел: +359 2 818 44 44 
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. o. 
Tel: +420 - 2 20382111 
 

Magyarország 
Roche (Magyarország) Kft. 
Tel: +36 - 23 446 800 
 

Danmark 
Roche a/s 
Tlf: +45 - 36 39 99 99 
 

Malta 
(See Ireland)  

Deutschland 
Roche Pharma AG 
Tel: +49 (0) 7624 140 
 

Nederland 
Roche Nederland B.V. 
Tel: +31 (0) 348 438050 
 

Eesti 
Roche Eesti OÜ 
Tel: + 372 - 6 177 380 
 

Norge 
Roche Norge AS 
Tlf: +47 - 22 78 90 00 
 

Ελλάδα 
Roche (Hellas) A.E.  
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH 
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A. 
Tel: +34 - 91 324 81 00 
 

Polska 
Roche Polska Sp.z o.o. 
Tel: +48 - 22 345 18 88 
 

France 
Roche 
Tél: +33 (0) 1 47 61 40 00 
 

Portugal 
Roche Farmacêutica Química, Lda 
Tel: +351 - 21 425 70 00 
 

Hrvatska 
Roche d.o.o. 
Tel: +385 1 4722 333 
 

România 
Roche România S.R.L. 
Tel: +40 21 206 47 01 
 



42 

Ireland 
Roche Products (Ireland) Ltd. 
Tel: +353 (0) 1 469 0700 
 

Slovenija 
Roche farmacevtska družba d.o.o. 
Tel: +386 - 1 360 26 00 
 

Ísland  
Roche a/s 
c/o Icepharma hf 
Sími: +354 540 8000 
 

Slovenská republika  
Roche Slovensko, s.r.o. 
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A. 
Tel: +39 - 039 2471 
 

Suomi/Finland 
Roche Oy  
Puh/Tel: +358 (0) 10 554 500 
 

Kύπρος  
Γ.Α.Σταμάτης & Σια Λτδ. 
Τηλ: +357 - 22 76 62 76 
 

Sverige 
Roche AB 
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA 
Tel: +371 - 6 7 039831 
 

United Kingdom 
Roche Products Ltd. 
Tel: +44 (0) 1707 366000 
 

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

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

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