Gefitinib Mylan

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ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Gefitinib Mylan 250 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 250 mg of gefitinib. 
 
Excipient with known effect 
Each tablet contains 161.0 mg of lactose (as monohydrate).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Brown, round, biconvex film-coated tablets with approximately 11.1 mm x 5.6 mm of dimension and 
marked with “250” on one side and plain on the other. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Gefitinib Mylan is indicated as monotherapy for the treatment of adult patients with locally advanced 
or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR-TK 
(see section 4.4). 
 
4.2 Posology and method of administration 
 
Treatment with Gefitinib Mylan should be initiated and supervised by a physician experienced in the 
use of anticancer therapies. 
 
Posology 
The recommended posology of Gefitinib Mylan is one 250 mg tablet once a day. If a dose is missed, it 
should be taken as soon as the patient remembers. If it is less than 12 hours to the next dose, the 
patient should not take the missed dose. Patients should not take a double dose (two doses at the same 
time) to make up for a forgotten dose. 
 
Paediatric population 
The safety and efficacy of Gefitinib Mylan in children and adolescents aged less than 18 years have 
not been established. There is no relevant use of gefitinib in the paediatric population in the indication 
of NSCLC. 
 
Hepatic impairment 
Patients with moderate to severe hepatic impairment (Child-Pugh B or C) due to cirrhosis have 
increased plasma concentrations of gefitinib. These patients should be closely monitored for adverse 
events. Plasma concentrations were not increased in patients with elevated aspartate transaminase 
(AST), alkaline phosphatase or bilirubin due to liver metastases (see section 5.2). 
 
Renal impairment 
No dose adjustment is required in patients with impaired renal function at creatinine clearance 
> 20 ml/min. Only limited data are available in patients with creatinine clearance ≤ 20 ml/min and 
caution is advised in these patients (see section 5.2). 



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Elderly 
No dose adjustment is required on the basis of patient age (see section 5.2). 
 
CYP2D6 poor metabolisers 
No specific dose adjustment is recommended in patients with known CYP2D6 poor metaboliser 
genotype, but these patients should be closely monitored for adverse events (see section 5.2). 
 
Dose adjustment due to toxicity 
Patients with poorly tolerated diarrhoea or skin adverse reactions may be successfully managed by 
providing a brief (up to 14 days) therapy interruption followed by reinstatement of the 250 mg dose 
(see section 4.8). For patients unable to tolerate treatment after a therapy interruption, gefitinib should 
be discontinued and an alternative treatment should be considered. 
 
Method of administration  
Oral use. The tablet may be taken with or without food, at about the same time each day.  
The tablet can be swallowed whole with some water or if dosing of whole tablets is not possible, 
tablets may be administered as a dispersion in water (non-carbonated). No other liquids should be 
used.  
Without crushing it, the tablet should be dropped in half a glass of drinking water. The glass should be 
swirled occasionally, until the tablet is dispersed (this may take up to 20 minutes). The dispersion 
should be drunk immediately after dispersion is complete (i.e. within 60 minutes). The glass should be 
rinsed with half a glass of water, which should also be drunk. The dispersion can also be administered 
through a naso-gastric or gastrostomy tube. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
Breast-feeding (see section 4.6). 
 
4.4 Special warnings and precautions for use 
 
When considering the use of Gefitinib Mylan as a treatment for locally advanced or metastatic 
NSCLC, it is important that EGFR mutation assessment of the tumour tissue is attempted for all 
patients. If a tumour sample is not evaluable, then circulating tumour DNA (ctDNA) obtained from a 
blood (plasma) sample may be used. 
 
Only robust, reliable and sensitive test(s) with demonstrated utility for the determination of EGFR 
mutation status of tumours or ctDNA should be used to avoid false negative or false positive 
determinations (see section 5.1). 
 
Interstitial lung disease (ILD) 
Interstitial lung disease (ILD) which may be acute in onset, has been observed in 1.3% of patients 
receiving gefitinib, and some cases have been fatal (see section 4.8). If patients experience worsening 
of respiratory symptoms such as dyspnoea, cough and fever, Gefitinib Mylan should be interrupted 
and the patient should be promptly investigated. If ILD is confirmed, Gefitinib Mylan should be 
discontinued and the patient treated appropriately. 
In a Japanese pharmacoepidemiological case control study in 3,159 patients with NSCLC receiving 
gefitinib or chemotherapy who were followed up for 12 weeks, the following risk factors for 
developing ILD (irrespective of whether the patient received gefitinib or chemotherapy) were 
identified: smoking, poor performance status (PS≥ 2), CT scan evidence of reduced normal lung 
(≤ 50%), recent diagnosis of NSCLC (< 6 months), pre-existing ILD, older age (≥ 55 years old) and 
concurrent cardiac disease. An increased risk of ILD on gefitinib relative to chemotherapy was seen 
predominantly during the first 4 weeks of treatment (adjusted OR 3.8; 95% CI 1.9 to 7.7); thereafter 
the relative risk was lower (adjusted OR 2.5; 95% CI 1.1 to 5.8). Risk of mortality among patients who 
developed ILD on gefitinib or chemotherapy was higher in patients with the following risk factors: 



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smoking, CT scan evidence of reduced normal lung (≤ 50%), pre-existing ILD, older age (≥ 65 years 
old), and extensive areas adherent to pleura (≥ 50%). 
 
Hepatotoxicity and liver impairment 
Liver function test abnormalities (including increases in alanine aminotransferase, aspartate 
aminotransferase, bilirubin) have been observed, uncommonly presenting as hepatitis (see section 4.8). 
There have been isolated reports of hepatic failure which in some cases led to fatal outcomes. 
Therefore, periodic liver function testing is recommended. Gefitinib should be used cautiously in the 
presence of mild to moderate changes in liver function. Discontinuation should be considered if 
changes are severe. 
 
Impaired liver function due to cirrhosis has been shown to lead to increased plasma concentrations of 
gefitinib (see section 5.2). 
 
Interactions with other medicinal products 
CYP3A4 inducers may increase metabolism of gefitinib and decrease gefitinib plasma concentrations. 
Therefore, concomitant administration of CYP3A4 inducers (e.g. phenytoin, carbamazepine, 
rifampicin, barbiturates or herbal preparations containing St John’s wort/Hypericum perforatum) may 
reduce efficacy of the treatment and should be avoided (see section 4.5). 
 
In individual patients with CYP2D6 poor metaboliser genotype, treatment with a potent CYP3A4 
inhibitor might lead to increased plasma levels of gefitinib. At initiation of treatment with a CYP3A4 
inhibitor, patients should be closely monitored for gefitinib adverse reactions (see section 4.5). 
 
International normalised ratio (INR) elevations and/or bleeding events have been reported in some 
patients taking warfarin together with gefitinib (see section 4.5). Patients taking warfarin and gefitinib 
concomitantly should be monitored regularly for changes in prothrombin time (PT) or INR. 
 
Medicinal products that cause significant sustained elevation in gastric pH, such as proton-pump 
inhibitors and h2-antagonists may reduce bioavailability and plasma concentrations of gefitinib and, 
therefore, may reduce efficacy. Antacids if taken regularly close in time to administration of gefitinib 
may have a similar effect (see sections 4.5 and 5.2). 
 
Data from phase II clinical trials, where gefitinib and vinorelbine have been used concomitantly, 
indicate that gefitinib may exacerbate the neutropenic effect of vinorelbine. 
 
Lactose  
Gefitinib Mylan contains lactose. Patients with rare hereditary problems of galactose intolerance, total 
lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 
 
Sodium 
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
Further precautions for use 
Patients should be advised to seek medical advice immediately if they experience severe or persistent 
diarrhoea, nausea, vomiting or anorexia as these may indirectly lead to dehydration. These symptoms 
should be managed as clinically indicated (see section 4.8). 
 
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 gefitinib should be interrupted, and if 
symptoms do not resolve, or if symptoms recur on reintroduction of gefitinib, permanent 
discontinuation should be considered. 



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In a phase I/II trial studying the use of gefitinib and radiation in paediatric patients, with newly 
diagnosed brain stem glioma or incompletely resected supratentorial malignant glioma, 4 cases 
(1 fatal) of Central Nervous System (CNS) haemorrhages were reported from 45 patients enrolled. A 
further case of CNS haemorrhage has been reported in a child with an ependymoma from a trial with 
gefitinib alone. An increased risk of cerebral haemorrhage in adult patients with NSCLC receiving 
gefitinib has not been established. 
 
Gastrointestinal perforation has been reported in patients taking gefitinib. In most cases this is 
associated with other known risk factors, including concomitant medicinal products such as steroids or 
NSAIDS, underlying history of GI ulceration, age, smoking or bowel metastases at sites of 
perforation. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
The metabolism of gefitinib is via the cytochrome P450 isoenzyme CYP3A4 (predominantly) and via 
CYP2D6. 
 
Active substances that may increase gefitinib plasma concentrations 
In vitro studies have shown that gefitinib is a substrate of p-glycoprotein (Pgp). Available data do not 
suggest any clinical consequences to this in vitro finding. 
 
Substances that inhibit CYP3A4 may decrease the clearance of gefitinib. Concomitant administration 
with potent inhibitors of CYP3A4 activity (e.g. ketoconazole, posaconazole, voriconazole, protease 
inhibitors, clarithromycin, telithromycin) may increase gefitinib plasma concentrations. The increase 
may be clinically relevant since adverse reactions are related to dose and exposure. The increase might 
be higher in individual patients with CYP2D6 poor metaboliser genotype. Pre-treatment with 
itraconazole (a potent CYP3A4 inhibitor) resulted in an 80% increase in the mean AUC of gefitinib in 
healthy volunteers. In situations of concomitant treatment with potent inhibitors of CYP3A4 the 
patient should be closely monitored for gefitinib adverse reactions. 
 
There are no data on concomitant treatment with an inhibitor of CYP2D6 but potent inhibitors of this 
enzyme might cause increased plasma concentrations of gefitinib in CYP2D6 extensive metabolisers 
by about 2-fold (see section 5.2). If concomitant treatment with a potent CYP2D6 inhibitor is initiated, 
the patient should be closely monitored for adverse reactions. 
 
Active substances that may reduce gefitinib plasma concentrations 
Substances that are inducers of CYP3A4 activity may increase metabolism and decrease gefitinib 
plasma concentrations and thereby reduce the efficacy of gefitinib. Concomitant medicinal products 
that induce CYP3A4 (e.g. phenytoin, carbamazepine, rifampicin, barbiturates or St John’s wort, 
Hypericum perforatum) should be avoided. Pre-treatment with rifampicin (a potent CYP3A4 inducer) 
in healthy volunteers reduced mean gefitinib AUC by 83% (see section 4.4). 
 
Substances that cause significant sustained elevation in gastric pH may reduce gefitinib plasma 
concentrations and thereby reduce the efficacy of gefitinib. High doses of short-acting antacids may 
have a similar effect if taken regularly close in time to administration of gefitinib. Concomitant 
administration of gefitinib with ranitidine at a dose that caused sustained elevations in gastric pH ≥ 5 
resulted in a reduced mean gefitinib AUC by 47% in healthy volunteers (see section 4.4 and 5.2). 
 
Active substances that may have their plasma concentrations altered by gefitinib 
In vitro studies have shown that gefitinib has limited potential to inhibit CYP2D6. In a clinical trial in 
patients, gefitinib was co-administered with metoprolol (a CYP2D6 substrate). This resulted in a 35% 
increase in exposure to metoprolol. Such an increase might potentially be relevant for CYP2D6 
substrates with narrow therapeutic index. When the use of CYP2D6 substrates are considered in 
combination with gefitinib, a dose modification of the CYP2D6 substrate should be considered 
especially for products with a narrow therapeutic window. 
 



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Gefitinib inhibits the transporter protein BCRP in vitro, but the clinical relevance of this finding is 
unknown. 
 
Other potential interactions 
INR elevations and/or bleeding events have been reported in some patients concomitantly taking 
warfarin (see section 4.4). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
Women of childbearing potential must be advised not to get pregnant during therapy. 
 
Pregnancy 
There are no data from the use of gefitinib in pregnant women. Studies in animals have shown 
reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Gefitinib Mylan 
should not be used during pregnancy unless clearly necessary. 
 
Breast-feeding 
It is not known whether gefitinib is secreted in human milk. Gefitinib and metabolites of gefitinib 
accumulated in milk of lactating rats (see section 5.3). Gefitinib is contraindicated during 
breast-feeding and therefore breast-feeding must be discontinued while receiving gefitinib therapy (see 
section 4.3). 
 
4.7 Effects on ability to drive and use machines 
 
During treatment with gefitinib, asthenia has been reported. Therefore, patients who experience this 
symptom should be cautious when driving or using machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
In the pooled dataset from the ISEL, INTEREST and IPASS phase III clinical trials (2462 
gefitinib-treated patients), the most frequently reported adverse drug reactions (ADRs), occurring in 
more than 20% of the patients, are diarrhoea and skin reactions (including rash, acne, dry skin and 
pruritus). ADRs usually occur within the first month of therapy and are generally reversible. 
Approximately 8% of patients had a severe ADR (common toxicity criteria, (CTC) grade 3 or 4). 
Approximately 3% of patients stopped therapy due to an ADR. 
 
Interstitial lung disease (ILD) has occurred in 1.3% of patients, often severe (CTC grade 3-4). Cases 
with fatal outcomes have been reported. 
 
Tabulated list of adverse reactions 
The safety profile presented in Table 1 is based on the gefitinib clinical development programme and 
post-marketed experience. Adverse reactions have been assigned to the frequency categories in Table 
1 where possible based on the incidence of comparable adverse reactions reports in a pooled dataset 
from the ISEL, INTEREST and IPASS phase III clinical trials (2462 gefitinib-treated patients). 
 
Frequencies of occurrence of undesirable effects are defined as: very common (≥ 1/10); common 
(≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare 
(< 1/10,000), not known (cannot be estimated from the available data). 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 



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Table 1 Adverse reactions 
Adverse reactions by system organ class and frequency 
Metabolism and nutrition 
disorders 

Very common Anorexia mild or moderate (CTC grade 1 or 2). 

Eye disorders Common Conjunctivitis, blepharitis, and dry eye*, mainly 
mild (CTC grade 1). 

Uncommon Corneal erosion, reversible and sometimes in 
association with aberrant eyelash growth. 
Keratitis (0.12%)

Vascular disorders Common Haemorrhage, such as epistaxis and haematuria.
Respiratory, thoracic and 
mediastinal disorders 

Common Interstitial lung disease (1.3%), often severe (CTC 
grade 3-4). Cases with fatal outcomes have been 
reported. 

Gastrointestinal disorders Very common Diarrhoea, mainly mild or moderate (CTC grade 1 
or 2). 
Vomiting, mainly mild or moderate (CTC grade 1 
or 2). 
Nausea, mainly mild (CTC grade 1). 

Stomatitis, predominantly mild in nature (CTC 
grade 1). 

Common Dehydration, secondary to diarrhoea, nausea, 
vomiting or anorexia. 
Dry mouth*, predominantly mild (CTC grade 1). 

Uncommon Pancreatitis 
Gastrointestinal perforation 

Hepatobiliary disorders Very common Elevations in alanine aminotransferase, mainly 
mild to moderate. 

Common Elevations in aspartate aminotransferase, mainly 
mild to moderate.
Elevations in total bilirubin, mainly mild to 
moderate. 

Uncommon Hepatitis** 
Skin and subcutaneous tissue 
disorders 

Very common Skin reactions, mainly a mild or moderate (CTC 
grade 1 or 2) pustular rash, sometimes itchy with 
dry skin, including skin fissures, on an 
erythematous base.

Common Nail disorder 
Alopecia 
Allergic reactions (1.1%), including angioedema 
and urticaria. 

Rare Bullous conditions including Toxic epidermal 
necrolysis, Stevens Johnson syndrome and 
erythema multiforme.
Cutaneous vasculitis 

Renal and urinary disorders Common Asymptomatic laboratory elevations in blood 
creatinine. 
Proteinuria 
Cystitis 

Rare Haemorrhagic cystitis 
General disorders and 
administration site conditions 

Very common Asthenia, predominantly mild (CTC grade 1). 
Common Pyrexia



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The frequency of adverse drug reactions relating to abnormal laboratory values is based on patients with a change 
from baseline of 2 or more CTC grades in the relevant laboratory parameters. 
*This adverse reaction can occur in association with other dry conditions (mainly skin reactions) seen with 
gefitinib. 
**This includes isolated reports of hepatic failure which in some cases led to fatal outcomes. 
 
Interstitial lung disease (ILD) 
In the INTEREST trial, the incidence of ILD type events was 1.4% (10) patients in the gefitinib group 
versus 1.1% (8) patients in the docetaxel group. One ILD-type event was fatal, and this occurred in a 
patient receiving gefitinib. 
 
In the ISEL trial, the incidence of ILD-type events in the overall population was approximately 1% in 
both treatment arms. The majority of ILD-type events reported was from patients of Asian ethnicity 
and the ILD incidence among patients of Asian ethnicity receiving gefitinib therapy and placebo was 
approximately 3% and 4% respectively. One ILD-type event was fatal, and this occurred in a patient 
receiving placebo. 
 
In a post-marketing surveillance study in Japan (3350 patients) the reported rate of ILD-type events in 
patients receiving gefitinib was 5.8%. The proportion of ILD-type events with a fatal outcome was 
38.6%. 
 
In a phase III open-label clinical trial (IPASS) in 1217 patients comparing gefitinib to 
carboplatin/paclitaxel doublet chemotherapy as first-line treatment in selected patients with advanced 
NSCLC in Asia, the incidence of ILD-type events was 2.6% on the gefitinib treatment arm versus 
1.4% on the carboplatin/paclitaxel treatment arm. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no specific treatment in the event of overdose of gefitinib. However, in phase I clinical trials, 
a limited number of patients were treated with daily doses of up to 1000 mg. An increase of frequency 
and severity of some adverse reactions was observed, mainly diarrhoea and skin rash. Adverse 
reactions associated with overdose should be treated symptomatically; in particular severe diarrhoea 
should be managed as clinically indicated. In one study a limited number of patients were treated 
weekly with doses from 1500 mg to 3500 mg. In this study gefitinib exposure did not increase with 
increasing dose, adverse events were mostly mild to moderate in severity, and were consistent with the 
known safety profile of gefitinib. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antineoplastic agents, protein kinase inhibitors; ATC code: L01XE02 
 
Mechanism of action and pharmacodynamic effects 
The epidermal growth factor (EGF) and its receptor (EGFR [HER1; ErbB1]) have been identified as 
key drivers in the process of cell growth and proliferation for normal and cancer cells. EGFR 
activating mutation within a cancer cell is an important factor in promotion of tumour cell growth, 
blocking of apoptosis, increasing the production of angiogenic factors and facilitating the processes of 
metastasis. 
 



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Gefitinib is a selective small molecule inhibitor of the epidermal growth factor receptor tyrosine 
kinase and is an effective treatment for patients with tumours with activating mutations of the EGFR 
tyrosine kinase domain regardless of line of therapy. No clinically relevant activity has been shown in 
patients with known EGFR mutation-negative tumours. 
 
The common EGFR activating mutations (Exon 19 deletions; L858R) have robust response data 
supporting sensitivity to gefitinib; for example a progression free survival HR (95% CI) of 
0.489 (0.336, 0.710) for gefitinib vs. doublet chemotherapy [WJTOG3405]. Gefitinib response data is 
more sparse in patients whose tumours contain the less common mutations; the available data indicates 
that G719X, L861Q and S7681 are sensitising mutations; and T790M alone or exon 20 insertions 
alone are resistance mechanisms. 
 
Resistance 
Most NSCLC tumours with sensitising EGFR kinase mutations eventually develop resistance to 
gefitinib treatment, with a median time to disease progression of 1 year. In about 60% of cases, 
resistance is associated with a secondary T790M mutation for which T790M targeted EGFR TKIs may 
be considered as a next line treatment option. Other potential mechanisms of resistance that have been 
reported following treatment with EGFR signal blocking agents include: bypass signalling such as 
HER2 and MET gene amplification and PIK3CA mutations. Phenotypic switch to small cell lung 
cancer has also been reported in 5-10% of cases. 
 
Circulating Tumour DNA (ctDNA) 
In the IFUM trial, mutation status was assessed in tumour and ctDNA samples derived from plasma, 
using the Therascreen EGFR RGQ PCR kit (Qiagen). Both ctDNA and tumour samples were 
evaluable for 652 patients out of 1060 screened. The objective response rate (ORR) in those patients 
who were tumour and ctDNA mutation positive was 77% (95% CI: 66% to 86%) and in those who 
were tumour only mutation positive 60% (95% CI: 44% to 74%). 
 
Table 2 - Summary of baseline mutation status for tumour and ctDNA samples in all screened 
patients evaluable for both samples 

Measure Definition IFUM rate  
% (CI) 

IFUM 
N 

Sensitivity Proportion of tumour M+ that are 
M+ by ctDNA 

65.7 (55.8, 74.7) 105 

Specificity Proportion of tumour M- that are 
M- by ctDNA) 

99.8 (99.0, 100.0) 547 

 
These data are consistent with the pre-planned exploratory Japanese subgroup analysis in IPASS 
(Goto 2012). In that study ctDNA derived from serum, not plasma was used for EGFR mutation 
analysis using the EGFR Mutation Test Kit (DxS) (N= 86). In that study, sensitivity was 43.1%, 
specificity was 100%. 
 
Clinical efficacy and safety 
First line treatment 
The randomised phase III first line IPASS study was conducted in patients in Asia1 with advanced 
(stage IIIB or IV) NSCLC of adenocarcinoma histology who were ex-light smokers (ceased smoking 
≥ 15 years ago and smoked ≤ 10 pack years) or never smokers (see Table 3). 
 
1China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, Taiwan and Thailand. 
 



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Table 3 - Efficacy outcomes for gefitinib versus carboplatin/paclitaxel from the IPASS study 
Population N Objective response 

rates and 95% CI 
for difference 

between treatmentsa 

Primary endpoint 
Progression free 
survival (PFS) a,b 

Overall 
survivala,b 

Overall 1217 43.0% vs 32.2% 
[5.3%, 16.1%] 

HR 0.74 
[0.65, 0.85] 

5.7 m vs 5.8 m 
p<0.0001

HR 0.90 
[0.79, 1.02] 

18.8 m vs 17.4 m 
p=0.1087

EGFR 
mutation-positive 

261 71.2% vs 47.3% 
[12.0%, 34.9%] 

HR 0.48 
[0.36, 0.64] 

9.5 m vs 6.3 m 
p<0.0001

HR 1.00 
[0.76, 1.33] 

21.6 m vs 21.9 m 

EGFR 
mutation-negative 

176 1.1% vs 23.5% 
[-32.5%, -13.3%] 

HR 2.85 
[2.05, 3.98] 

1.5 m vs 5.5 m 
p<0.0001

HR 1.18 
[0.86, 1.63] 

11.2 m vs 12.7 m 

EGFR 
mutation-unknown 

780 43.3% vs 29.2% 
[7.3%, 20.6%] 

HR 0.68 
[0.58 to 0.81] 

6.6 m vs 5.8 m 
p<0.0001

HR 0.82 
[0.70 to 0.96] 

18.9 m vs. 17.2 
m 

a 
b 
N 
HR 

Values presented are for gefitinib versus carboplatin/paclitaxel. 
“m” is medians in months. Numbers in square brackets are 95% confidence intervals for HR 
Number of patients randomised. 
Hazard ratio (hazard ratios <1 favour gefitinib)

 
Quality of life outcomes differed according to EGFR mutation status. In EGFR mutation-positive 
patients, significantly more gefitinib-treated patients experienced an improvement in quality of life 
and lung cancer symptoms vs carboplatin/paclitaxel (see Table 4). 
 
Table 4 - Quality of life outcomes for gefitinib versus carboplatin/paclitaxel from the IPASS 
study 

Population N FACT-L QoL 
improvement ratea  

% 

LCS symptom 
improvement ratea  

% 
Overall 1151 (48.0% vs 40.8%) 

p=0.0148
(51.5% vs 48.5%) 

p=0.3037 
EGFR 

mutation-positive 
259 (70.2% vs 44.5%) 

p<0.0001
(75.6% vs 53.9%) 

p=0.0003 
EGFR 

mutation-negative 
169 (14.6% vs 36.3%) 

p=0.0021
(20.2% vs 47.5%) 

p=0.0002 
Trial outcome index results were supportive of FACT-L and LCS results
a Values presented are for gefitinib versus carboplatin/paclitaxel.
N Number of patients evaluable for quality of life analyses.
QoL Quality of life. 
FACT-L  Functional assessment of cancer therapy-lung.
LSC Lung cancer subscale. 

 
In the IPASS trial, gefitinib demonstrated superior PFS, ORR, QoL and symptom relief with no 
significant difference in overall survival compared to carboplatin/paclitaxel in previously untreated 
patients, with locally advanced or metastatic NSCLC, whose tumours harboured activating mutations 
of the EGFR tyrosine kinase. 
 
Pre-treated patients 
The randomised phase III INTEREST study was conducted in patients with locally advanced or 
metastatic NSCLC who had previously received platinum-based chemotherapy. In the overall 



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population, no statistically significant difference between gefitinib and docetaxel (75 mg/m2) was 
observed for overall survival, progression free survival and objective response rates (see Table 5). 
 
Table 5 - Efficacy outcomes for gefitinib versus docetaxel from the INTEREST study 

Population N Objective response 
rates and 95% CI 

for difference 
between treatmentsa

Progression free 
survivala,b 

Primary 
endpoint overall 

survivala,b 

Overall 1466 9.1% vs 7.6% 
[-1.5%, 4.5%] 

HR 1.04 
[0.93,1.18] 

2.2 m vs 2.7 m 
p=0.4658

HR 1.020 
[0.905, 1.150]c 
7.6 m vs 8.0 m 

p=0.7332
EGFR 

mutation-positive 
44 42.1% vs 21.1% 

[-8.2%, 46.0%] 
HR 0.16 

[0.05, 0.49] 
7.0 m vs 4.1 m 

p=0.0012

HR 0.83 
[0.41, 1.67] 

14.2 m vs 16.6 m 
p=0.6043

EGFR 
mutation-negative 

253 6.6% vs 9.8% 
[-10.5%, 4.4%] 

HR 1.24 
[0.94,1.64] 

1.7 m vs 2.6 m 
p=0.1353

HR 1.02 
[0.78, 1.33] 

6.4 m vs 6.0 m 
p=0.9131

Asiansc 323 19.7% vs 8.7% 
[3.1%, 19.2%] 

HR 0.83 
[0.64,1.08] 

2.9 m vs 2.8 m 
p=0.1746

HR 1.04 
[0.80, 1.35] 

10.4 m vs 12.2 m 
p=0.7711

Non-Asians 1143 6.2% vs 7.3% 
[-4.3%, 2.0%] 

HR 1.12 
[0.98, 1.28] 

2.0 m vs 2.7 m 
p=0.1041 

HR 1.01 
[0.89, 1.14] 

6.9 m vs 6.9 m 
p=0.9259 

a Values presented are for gefitinib versus docetaxel.
b “m” is medians in months. Numbers in square brackets are 96% confidence interval for overall survival 

HR in the overall population, or otherwise 95% confidence intervals for HR
c Confidence interval entirely below non-inferiority margin of 1.154
N Number of patients randomised. 
HR Hazard ratio (hazard ratios <1 favour gefitinib) 

 



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Figures 1 and 2 - Efficacy outcomes in subgroups of non-Asian patients in the INTEREST study 
(N patients = Number of patients randomised) 

 
 

 
 
The randomised phase III ISEL study was conducted in patients with advanced NSCLC who had 
received 1 or 2 prior chemotherapy regimens and were refractory or intolerant to their most recent 
regimen. Gefitinib plus best supportive care was compared to placebo plus best supportive care. 
Gefitinib did not prolong survival in the overall population. Survival outcomes differed by smoking 
status and ethnicity (see Table 6). 
 



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Table 6 Efficacy outcomes for gefitinib versus placebo from the ISEL study 
Population N Objective response 

rates and 95% CI for 
difference between 
treatmentsa 

Time to treatment 
failurea,b 

Primary 
endpoint overall 
survivala,b,c 

Overall 1692 8.0% vs 1.3% 
[4.7%, 8.8%] 

HR 0.82 
[0.73, 0.92] 
3.0 m vs 2.6 m 
p=0.0006

HR 0.89 
[0.77,1.02] 
5.6 m vs 5.1 m 
p=0.0871 

EGFR 
mutation-positive 

26 37.5% vs 0% 
[-15.1%, 61.4%] 

HR 0.79 
[0.20, 3.12] 
10.8 m vs 3.8 m 
p=0.7382

HR NC 
 
NR vs 4.3 m 

EGFR  
mutation-negative 

189 2.6% vs 0% 
[-5.6%, 7.3%] 

HR 1.10 
[0.78, 1.56] 
2.0 m vs 2.6 m 
p=0.5771

HR 1.16 
[0.79, 1.72] 
3.7 m vs 5.9 m 
p=0.4449 

Never smoker 375 18.1% vs 0% 
[12.3%, 24.0%] 

HR 0.55 
[0.42, 0.72] 
5.6 m vs 2.8 m 
p<0.0001

HR 0.67 
[0.49, 0.92] 
8.9 m vs 6.1 m 
p=0.0124 

Ever smoker 1317 5.3% vs 1.6% 
[1.4%, 5.7%] 

HR 0.89 
[0.78, 1.01] 
2.7 m vs 2.6 m 
p=0.0707

HR 0.92 
[0.79, 1.06] 
5.0 m vs 4.9 m 
p=0.2420 

Asiansd 342 12.4% vs 2.1% 
[4.0%, 15.8%] 

HR 0.69 
[0.52, 0.91] 
4.4 m vs 2.2 m 
p=0.0084

HR 0.66 
[0.48, 0.91] 
9.5 m vs 5.5 m 
p=0.0100 

Non-Asians 1350 6.8% vs 1.0% 
[3.5%, 7.9%] 

HR 0.86 
[0.76, 0.98] 
2.9 m vs 2.7 m 
p=0.0197

HR 0.92 
[0.80, 1.07] 
5.2 m vs 5.1 m 
p=0.2942 

a Values presented are for gefitinib versus placebo.
b “m” is medians in months. Numbers in square brackets are 95% confidence intervals for HR. 
c Stratified log-rank test for overall; otherwise cox proportional hazards model.
d Asian ethnicity excludes patients of Indian origin and refers to the racial origin of a patient group and 

not necessarily their place of birth. 
N Number of patients randomised. 
NC Not calculated for overall survival HR as the number of events is too few.
NR Not reached. 
HR Hazard ratio (hazard ratios <1 favour gefitinib).

 
The IFUM study was a single-arm, multicentre study conducted in Caucasian patients (n=106) with 
activating, sensitizing EGFR mutation positive NSCLC to confirm that the activity of gefitinib is 
similar in Caucasian and Asian populations. The ORR according to investigator review was 70% and 
the median PFS was 9.7 months. These data are similar to those reported in the IPASS study. 
 
EGFR mutation status and clinical characteristics 
Clinical characteristics of never smoker, adenocarcinoma histology, and female gender have been 
shown to be independent predictors of positive EGFR mutation status in a multivariate analysis of 
786 Caucasian patients from gefitinib studies* (see Table 7). Asian patients also have a higher 
incidence of EGFR mutation-positive tumours. 
 



14 

Table 7 - Summary of multivariate logistic regression analysis to identify factors that 
independently predicted for the presence of EGFR mutations in 786 Caucasian patients* 

Factors that 
predicted for 
presence of 

EGFR mutation 

p-value Odds of EGFR 
mutation 

Positive predictive value (9.5% of 
the overall population are EGFR 

mutation-positive (M+)) 

Smoking status <0.0001 6.5 times higher in never 
smokers than 
ever-smokers

28/70 (40%) of never smokers are M+. 
47/716 (7%) of ever smokers are M+. 

Histology <0.0001 4.4 times higher in 
adenocarcinoma than in 

non-adenocarcinoma 

63/396 (16%) of patients with 
adenocarcinoma histology are M+. 

12/390 (3%) of patients with 
non-adenocarcinoma histology are 

M+. 
Gender 0.0397 1.7 times higher in 

females than males
40/235 (17%) of females are M+. 

35/551 (6%) of males are M+.
*from the following studies: INTEREST, ISEL, INTACT 1&2, IDEAL 1&2, INVITE 

 
5.2 Pharmacokinetic properties 
 
Absorption 
Following oral administration of gefitinib, absorption is moderately slow and peak plasma 
concentrations of gefitinib typically occur at 3 to 7 hours after administration. Mean absolute 
bioavailability is 59% in cancer patients. Exposure to gefitinib is not significantly altered by food. In a 
trial in healthy volunteers where gastric pH was maintained above pH 5, gefitinib exposure was 
reduced by 47%, likely due to impaired solubility of gefitinib in the stomach (see sections 4.4 and 4.5). 
 
Distribution 
Gefitinib has a mean steady-state volume of distribution of 1400 L indicating extensive distribution 
into tissue. Plasma protein binding is approximately 90%. Gefitinib binds to serum albumin and alpha 
1-acid glycoprotein. 
 
In vitro data indicate that gefitinib is a substrate for the membrane transport protein P-gp. 
 
Biotransformation 
In vitro data indicate that CYP3A4 and CYP2D6 are the major P450 isozyme involved in the oxidative 
metabolism of gefitinib. 
 
In vitro studies have shown that gefitinib has limited potential to inhibit CYP2D6. Gefitinib shows no 
enzyme induction effects in animal studies and no significant inhibition (in vitro) of any other 
cytochrome P450 enzyme. 
 
Gefitinib is extensively metabolised in humans. Five metabolites have been fully identified in excreta 
and 8 metabolites in plasma. The major metabolite identified was O-desmethyl gefitinib, which is 
14-fold less potent than gefitinib at inhibiting EGFR stimulated cell growth and has no inhibitory 
effect on tumour cell growth in mice. It is therefore considered unlikely that it contributes to the 
clinical activity of gefitinib. 
 
The formation of O-desmethyl gefitinib has been shown, in vitro, to be via CYP2D6. The role of 
CYP2D6 in the metabolic clearance of gefitinib has been evaluated in a clinical trial in healthy 
volunteers genotyped for CYP2D6 status. In poor metabolisers no measurable levels of O-desmethyl 
gefitinib were produced. The levels of exposure to gefitinib achieved in both the extensive and the 
poor metaboliser groups were wide and overlapping but the mean exposure to gefitinib was 2-fold 
higher in the poor metaboliser group. The higher average exposures that could be achieved by 
individuals with no active CYP2D6 may be clinically relevant since adverse effects are related to dose 
and exposure. 
 



15 

Elimination 
Gefitinib is excreted mainly as metabolites via the faeces, with renal elimination of gefitinib and 
metabolites accounting for less than 4% of the administered dose. 
 
Gefitinib total plasma clearance is approximately 500 ml/min and the mean terminal half-life is 
41 hours in cancer patients. Administration of gefitinib once daily results in 2- to 8-fold accumulation, 
with steady state exposures achieved after 7 to 10 doses. At steady state, circulating plasma 
concentrations are typically maintained within a 2- to 3-fold range over the 24-hour dosing interval. 
 
Special populations 
From analyses of population pharmacokinetic data in cancer patients, no relationships were identified 
between predicted steady-state trough concentration and patient age, body weight, gender, ethnicity or 
creatinine clearance (above 20 ml/min). 
 
Hepatic impairment 
In a phase I open-label study of single dose gefitinib 250 mg in patients with mild, moderate or severe 
hepatic impairment due to cirrhosis (according to Child-Pugh classification), there was an increase in 
exposure in all groups compared with healthy controls. An average 3.1-fold increase in exposure to 
gefitinib in patients with moderate and severe hepatic impairment was observed. None of the patients 
had cancer, all had cirrhosis and some had hepatitis. This increase in exposure may be of clinical 
relevance since adverse experiences are related to dose and exposure to gefitinib. 
 
Gefitinib has been evaluated in a clinical trial conducted in 41 patients with solid tumours and normal 
hepatic function, or moderate or severe hepatic impairment (classified according to baseline Common 
Toxicity Criteria grades for AST, alkaline phosphatase and bilirubin) due to liver metastases. It was 
shown that following daily administration of 250 mg gefitinib, time to steady-state, total plasma 
clearance (CmaxSS) and steady-state exposure (AUC24SS) were similar for the groups with normal and 
moderately impaired hepatic function. Data from 4 patients with severe hepatic impairment due to 
liver metastases suggested that steady-state exposures in these patients are also similar to those in 
patients with normal hepatic function. 
 
5.3 Preclinical safety data 
 
Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to the 
clinical exposure levels and with possible relevance to clinical use were as follows: 
-  Corneal epithelia atrophy and corneal translucencies 
-  Renal papillary necrosis 
-  Hepatocellular necrosis and eosinophilic sinusoidal macrophage infiltration. 
 
Data from non-clinical (in vitro) studies indicate that gefitinib has the potential to inhibit the cardiac 
action potential repolarization process (e.g. QT interval). Clinical experience has not shown a causal 
association between QT prolongation and gefitinib. 
 
A reduction in female fertility was observed in the rat at a dose of 20 mg/kg/day. 
 
Published studies have shown that genetically modified mice, lacking expression of EGFR, exhibit 
developmental defects, related to epithelial immaturity in a variety of organs including the skin, 
gastrointestinal tract and lung. When gefitinib was administered to rats during organogenesis, there 
were no effects on embryofoetal development at the highest dose (30 mg/kg/day). However, in the 
rabbit, there were reduced foetal weights at 20 mg/kg/day and above. There were no 
compound-induced malformations in either species. When administered to the rat throughout gestation 
and parturition, there was a reduction in pup survival at a dose of 20 mg/kg/day. 
 
Following oral administration of C-14 labelled gefitinib to lactating rats 14 days post-partum, 
concentrations of radioactivity in milk were 11-19 fold higher than in blood. 
 



16 

Gefitinib showed no genotoxic potential. 
 
A 2-year carcinogenicity study in rats resulted in a small but statistically significant increased 
incidence of hepatocellular adenomas in both male and female rats and mesenteric lymph node 
haemangiosarcomas in female rats at the highest dose (10 mg/kg/day) only. The hepatocellular 
adenomas were also seen in a 2-year carcinogenicity study in mice, which demonstrated a small 
increased incidence of this finding in male mice at the mid dose, and in both male and female mice at 
the highest dose. The effects reached statistical significance for the female mice, but not for the males. 
At no-effect levels in both mice and rats there was no margin in clinical exposure. The clinical 
relevance of these findings is unknown. 
 
The results of an in vitro phototoxicity study demonstrated that gefitinib may have phototoxicity 
potential. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Lactose monohydrate 
Microcrystalline cellulose (101) 
Crospovidone (Type A) 
Povidone (K30) 
Sodium laurilsulfate 
Magnesium stearate 
 
Tablet coating 
Polyvinyl alcohol (E1203) 
Macrogol 4000 (E1521) 
Talc (E553b) 
Titanium dioxide (E171) 
Red iron oxide (E172) 
Yellow iron oxide (E172) 
 
6.2 Incompatibilities 
 
Not applicable 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
6.5 Nature and contents of container  
 
PVC/PVDC/Aluminium blister in cartons containing 30 film-coated tablets. 
PVC/PVDC/Aluminium perforated unit dose blister in cartons containing 30x1 film-coated tablets. 
 
The blisters may be packed into aluminium pouches. 
 
Not all pack sizes may be marketed. 
 



17 

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 
 
Mylan S.A.S. 
117 Allée des Parcs  
69800 Saint-Priest 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1321/001 
EU/1/18/1321/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
 
 
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.  
  



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 

 



19 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer responsible for batch release 

Idifarma Desarrollo Farmacéutico, S.L.  
Polígono Mocholí  
C/ Noáin, Nº 1  
31110 Noáin (Navarra)  
Spain 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

 Periodic safety update reports  
 

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

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

 Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed  subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 
 
 
 
 
 
 
 
 
 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



22 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON  
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Gefitinib Mylan 250 mg film-coated tablets  
gefitinib  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 250 mg of gefitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See package leaflet for further information.  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablet 
 
30 film-coated tablets 
30x1 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 
 
Do not store above 30°C. 
 
 



23 

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 
 
Mylan S.A.S. 
117 Allée des Parcs  
69800 Saint-Priest 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1321/001 
EU/1/18/1321/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
gefitinib mylan 250 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
  



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
POUCH 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Gefitinib Mylan 250 mg film-coated tablets  
gefitinib  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Mylan S.A.S. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
  



25 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Gefitinib Mylan 250 mg film-coated tablets  
gefitinib  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Mylan S.A.S. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



26 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PERFORATED UNIT DOSE BLISTER 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Gefitinib Mylan 250 mg tablets  
gefitinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Mylan S.A.S. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
  



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



28 

Package leaflet: Information for the patient 
 

Gefitinib Mylan 250 mg film-coated tablets 
gefitinib 

 
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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Gefitinib Mylan is and what it is used for  
2. What you need to know before you take Gefitinib Mylan 
3. How to take Gefitinib Mylan 
4. Possible side effects  
5. How to store Gefitinib Mylan 
6. Contents of the pack and other information 
 
 
1. What Gefitinib Mylan is and what it is used for 
 
Gefitinib Mylan contains the active substance gefitinib which blocks a protein called ‘epidermal 
growth factor receptor’ (EGFR). This protein is involved in the growth and spread of cancer cells. 
 
Gefitinib Mylan is used to treat adults with non-small cell lung cancer. This cancer is a disease in 
which malignant (cancer) cells form in the tissues of the lung. 
 
 
2. What you need to know before you take Gefitinib Mylan 
 
Do not take Gefitinib Mylan: 
- if you are allergic to gefitinib or any of the other ingredients of this medicine (listed in 

section 6). 
- if you are breast-feeding. 
 
Warnings and precautions  
Talk to your doctor or pharmacist before taking Gefitinib Mylan 
- if you have ever had any other lung problems. Some lung problems may get worse during 

treatment with Gefitinib Mylan. 
- if you have ever had problems with your liver. 
 
Children and adolescents 
Gefitinib Mylan is not indicated in children and adolescents under 18 years. 
 
Other medicines and Gefitinib Mylan 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
In particular, tell your doctor or pharmacist if you are taking any of the following medicines: 
- Phenytoin or carbamazepine (for epilepsy). 
- Rifampicin (for tuberculosis). 
- Itraconazole (for fungal infections). 



29 

- Barbiturates (a type of medicine used for sleeping problems). 
- Herbal remedies containing St John’s wort (Hypericum perforatum, used for depression and 

anxiety). 
- Proton-pump inhibitors, H2-antagonists and antacids (for ulcers, indigestion, heartburn and to 

reduce acids in the stomach). 
These medicines may affect the way this medicine works. 
- Warfarin (a so-called oral anticoagulant, to prevent blood clots). If you are taking a medicine 

containing this active substance, your doctor may need to do blood tests more often. 
If any of the above applies to you, or if you are not sure, check with your doctor or pharmacist before 
taking Gefitinib Mylan. 
 
Pregnancy and breast-feeding 
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. 
 
It is recommended that you avoid becoming pregnant during treatment with this medicine because 
Gefitinib Mylan could harm your baby. 
 
Do not take Gefitinib Mylan if you are breast-feeding for the safety of your baby. 
 
Driving and using machines 
If you feel weak whilst taking this medicine, take care driving or using tools or machines. 
 
Gefitinib Mylan contains lactose  
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
Gefitinib Mylan contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘ 
sodium-free’. 
 
 
3. How to take Gefitinib Mylan 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
 The recommended dose is one 250 mg tablet per day. 
 Take the tablet at about the same time each day. 
 You can take the tablet with or without food. 
 Do not take antacids (to reduce the acid level of your stomach) 2 hours before or 1 hour after 

taking Gefitinib Mylan. 
 
If you have trouble swallowing the tablet, dissolve it in half a glass of still (non-fizzy) water. Do not 
use any other liquids. Do not crush the tablet. Swirl the water until the tablet has dissolved. This may 
take up to 20 minutes. Drink the liquid straight away.  
To make sure that you have drunk all of the medicine, rinse the glass very well with half a glass of 
water and drink it. 
 
If you take more Gefitinib Mylan than you should 
If you have taken more tablets than you should, talk to a doctor or pharmacist straight away. 
 
If you forget to take Gefitinib Mylan 
What to do if you forget to take a tablet depends on how long it is until your next dose. 
 If it is 12 hours or more until your next dose: take the missed tablet as soon as you remember. 

Then take the next dose as usual. 



30 

 If it is less than 12 hours until your next dose: skip the missed tablet. Then take the next tablet at 
the usual time. 

Do not take a double dose (two tablets at the same time) to make up for a forgotten dose. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor immediately if you notice any of the following side effects - you may need urgent 
medical treatment: 
 Allergic reaction (common), particularly if symptoms include swollen face, lips, tongue or 

throat, difficulty to swallow, hives, nettle rash and difficulty breathing. 
 Serious breathlessness, or sudden worsening breathlessness, possibly with a cough or fever. This 

may mean that you have an inflammation of the lungs called ‘interstitial lung disease’. This may 
affect about 1 in 100 patients taking gefitinib and can be life-threatening. 

 Severe skin reactions (rare) affecting large areas of your body. The signs may include redness, 
pain, ulcers, blisters, and shedding of the skin. The lips, nose, eyes and genitals may also be 
affected. 

 Dehydration (common) caused by long term or severe diarrhoea, vomiting (being sick), nausea 
(feeling sick) or loss of appetite. 

 Eye problems (uncommon), such as pain, redness, watery eyes, light sensitivity, changes in 
vision or ingrowing eyelashes. This may mean that you have an ulcer on the surface of the eye 
(cornea). 

 
Tell your doctor as soon as possible if you notice any of the following side effects: 
 
Very common (may affect more than 1 in 10 people): 
 Diarrhoea. 
 Vomiting. 
 Nausea. 
 Skin reactions such as an acne-like rash, which is sometimes itchy with dry and/or cracked skin. 
 Loss of appetite. 
 Weakness. 
 Red or sore mouth. 
 Increase of a liver enzyme known as alanine aminotransferase in a blood test; if too high, your 

doctor may tell you to stop taking this medicine. 
 
Common (may affect up to 1 in 10 people): 
 Dry mouth. 
 Dry, red or itchy eyes. 
 Red and sore eyelids. 
 Nail problems. 
 Hair loss. 
 Fever. 
 Bleeding (such as nose bleed or blood in your urine). 
 Protein in your urine (shown in a urine test). 
 Increase of bilirubin and the other liver enzyme known as aspartate aminotransferase in a blood 

test; if too high, your doctor may tell you to stop taking Gefitinib Mylan. 
 Increase of creatinine levels in a blood test (related to kidney function). 
 Cystitis (burning sensations during urination and frequent, urgent need to urinate). 
 



31 

Uncommon (may affect up to 1 in 100 people): 
 Inflammation of the pancreas. The signs include very severe pain in the upper part of the 

stomach area and severe nausea and vomiting. 
 Inflammation of the liver. Symptoms may include a general feeling of being unwell, with or 

without possible jaundice (yellowing of the skin and eyes). This side effect is uncommon; 
however, some patients have died from this. 

 Gastrointestinal perforation. 
 
Rare (may affect up to 1 in 1,000 people): 
 Inflammation of the blood vessels in the skin. This may give the appearance of bruising or 

patches of non-blanching rash on the skin. 
 Haemorrhagic cystitis (burning sensations during urination and frequent, urgent need to urinate 

with blood in the urine). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 Gefitinib Mylan 
 
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 carton or pouch after 
EXP. The expiry date refers to the last day of that month. 
 
Do not store above 30°C. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Gefitinib Mylan contains  
- The active substance is gefitinib. Each film-coated tablet contains 250 mg of gefitinib.  
- The other ingredients are lactose monohydrate, microcrystalline cellulose (101), crospovidone 

(type A), povidone (K30), sodium laurilsulfate, magnesium stearate in the tablet core. The tablet 
coating contains polyvinyl alcohol (E1203), macrogol 4000 (E1521), talc (E553b), titanium dioxide 
(E171), red iron oxide (E172), yellow iron oxide (E172). 

 
What Gefitinib Mylan looks like and contents of the pack 
Gefitinib Mylan tablets are brown, round, biconvex film-coated tablets with approximately 11.1 mm x 
5.6 mm of dimension and marked with “250” on one side and plain on the other. 
It comes in PVC/PVDC/Aluminium blisters in packs of 30 film-coated tablets or in 
PVC/PVDC/Aluminium perforated unit dose blisters in packs of 30x1 film-coated tablets. The blisters 
may be packed into aluminium pouches. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
Mylan S.A.S. 
117 Allée des Parcs  
69800 Saint-Priest 



32 

France 
 
Manufacturer 
Idifarma Desarrollo Farmacéutico, S.L.  
Polígono Mocholí  
C/ Noáin, Nº 1  
31110 Noáin (Navarra)  
Spain 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Mylan bvba/sprl 
Tél/Tel: + 32 (0)2 658 61 00 
 

Lietuva 
BGP Products UAB  
Tel: +370 5 205 1288 
 

България 
Майлан ЕООД 
Тел: +359 2 44 55 400 
 

Luxembourg/Luxemburg 
Mylan bvba/sprl 
Tel: + 32 (0)2 658 61 00 
(Belgique/Belgien) 
 

Česká republika 
Mylan Pharmaceuticals.s.r.o. 
Tel: + 420 222 004 400 

Magyarország 
Mylan EPD Kft 
Tel: + 36 1 465 2100 
 

Danmark 
Mylan AB 
Tlf: + 46 855 522 750  
(Sverige) 
 

Malta 
V.J. Salomone Pharma Ltd 
Tel: + 356 21 22 01 74 
 

Deutschland 
Mylan dura GmbH  
Tel: + 49-(0) 6172 888 01 
 

Nederland 
Mylan BV 
Tel: + 31 (0)20 426 3300 

Eesti 
BGP Products Switzerland GmbH Eesti 
filiaal  
Tel: + 372 6363 052 
 

Norge 
Mylan AB 
Tel: + 46 855 522 750 
(Sverige) 
 

Ελλάδα  
Generics Pharma Hellas ΕΠΕ  
Τηλ:  +30 210 993 6410  
 

Österreich 
Arcana Arzneimittel GmbH 
Tel: +43 1 416 2418 
 

España 
Mylan Pharmaceuticals, S.L 
Tel: + 34 900 102 712 
 

Polska 
Mylan Healthcare Sp. z.o.o. 
Tel: + 48 22 546 64 00 
 



33 

France 
Mylan S.A.S 
Tel: +33 4 37 25 75 00 
 

Portugal 
Mylan, Lda. 
Tel: + 351 21 412 72 56 
 

Hrvatska 
Mylan Hrvatska d.o.o.   
Tel: +385 1 23 50 599 
 

România 
BGP Products SRL 
Tel: +40 372 579 000 
 

Ireland 
Mylan Ireland Limited 
Tel: +353 (0) 87 1694982 
 

Slovenija 
GSP Proizvodi d.o.o. 
Tel: + 386 1 236 31 85 
 

Ísland 
Mylan AB 
Tel: + 46 855 522 750 
(Svíþjóð) 
 

Slovenská republika 
Mylan s.r.o. 
Tel: +421 2 32 199 100 
 

Italia 
Mylan S.p.A 
Tel: + 39 02 612 46921 
 

Suomi/Finland 
Mylan OY 
Puh/Tel: +358 20 720 9555 
 

Κύπρος 
Pharmaceutical Trading Co. Ltd. 
Τηλ: + 357 99403969 
 

Sverige 
Mylan AB  
Tel: + 46 855 522 750 
 

Latvija 
BGP Products SIA  
Tel: +371 676 055 80 
 

United Kingdom 
Generics [UK] Ltd 
Tel: +44 1707 853000 

 
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
This leaflet is available in all EU/EEA languages on the European Medicines Agency website. 


	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 MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET