Inlyta

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 1 mg film-coated tablets 
Inlyta 3 mg film-coated tablets 
Inlyta 5 mg film-coated tablets 
Inlyta 7 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Inlyta 1 mg film-coated tablets 
Each film-coated tablet contains 1 mg of axitinib. 
 
Inlyta 3 mg film-coated tablets 
Each film-coated tablet contains 3 mg of axitinib. 
 
Inlyta 5 mg film-coated tablets 
Each film-coated tablet contains 5 mg of axitinib. 
 
Inlyta 7 mg film-coated tablets 
Each film-coated tablet contains 7 mg of axitinib. 
 
 
Excipients with known effect 
 
Inlyta 1 mg film-coated tablet 
Each film-coated tablet contains 33.6 mg of lactose monohydrate. 
 
Inlyta 3 mg film-coated tablet 
Each film-coated tablet contains 35.3 mg of lactose monohydrate. 
 
Inlyta 5 mg film-coated tablet 
Each film-coated tablet contains 58.8 mg of lactose monohydrate. 
 
Inlyta 7 mg film-coated tablet 
Each film-coated tablet contains 82.3 mg of lactose monohydrate. 
 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Inlyta 1 mg film-coated tablets 
Red oval film-coated tablet debossed with “Pfizer” on one side and “1 XNB” on the other. 
 
Inlyta 3 mg film-coated tablets 
Red round film-coated tablet debossed with “Pfizer” on one side and “3 XNB” on the other. 
 
Inlyta 5 mg film-coated tablets 
Red triangular film-coated tablet debossed with “Pfizer” on one side and “5 XNB” on the other. 



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Inlyta 7 mg film-coated tablets 
Red diamond shaped film-coated tablet debossed with “Pfizer” on one side and “7 XNB” on the 
other. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Inlyta is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after 
failure of prior treatment with sunitinib or a cytokine. 
 
4.2 Posology and method of administration 
 
Treatment with Inlyta should be conducted by a physician experienced in the use of anticancer 
therapies. 
 
Posology 
 
The recommended dose of axitinib is 5 mg twice daily.  
 
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity 
occurs that cannot be managed by concomitant medicinal products or dose adjustments. 
 
If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed 
dose should be taken at the usual time. 
 
Dose adjustments 
 
Dose increase or reduction is recommended based on individual safety and tolerability. 
 
Patients who tolerate the axitinib starting dose of 5 mg twice daily with no adverse reactions 
> Grade 2 (i.e. without severe adverse reactions according to the Common Terminology Criteria for 
Adverse Events [CTCAE] version 3.0) for two consecutive weeks may have their dose increased to 
7 mg twice daily unless the patient’s blood pressure is > 150/90 mmHg or the patient is receiving 
antihypertensive treatment. Subsequently, using the same criteria, patients who tolerate an axitinib 
dose of 7 mg twice daily may have their dose increased to a maximum of 10 mg twice daily. 
 
Management of some adverse reactions may require temporary or permanent discontinuation and/or 
dose reduction of axitinib therapy (see section 4.4). When dose reduction is necessary, the axitinib 
dose may be reduced to 3 mg twice daily and further to 2 mg twice daily. 
 
Dose adjustment is not required on the basis of patient age, race, gender, or body weight. 
 
Concomitant strong CYP3A4/5 inhibitors 
Co-administration of axitinib with strong CYP3A4/5 inhibitors may increase axitinib plasma 
concentrations (see section 4.5). Selection of an alternate concomitant medicinal product with no or 
minimal CYP3A4/5 inhibition potential is recommended.  
 
Although axitinib dose adjustment has not been studied in patients receiving strong 
CYP3A4/5 inhibitors, if a strong CYP3A4/5 inhibitor must be co-administered, a dose decrease of 
axitinib to approximately half the dose (e.g. the starting dose should be reduced from 5 mg twice 



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daily to 2 mg twice daily) is recommended. Management of some adverse reactions may require 
temporary or permanent discontinuation of axitinib therapy (see section 4.4). If co-administration of 
the strong inhibitor is discontinued, a return to the axitinib dose used prior to initiation of the strong 
CYP3A4/5 inhibitor should be considered (see section 4.5). 
 
Concomitant strong CYP3A4/5 inducers 
Co-administration of axitinib with strong CYP3A4/5 inducers may decrease axitinib plasma 
concentrations (see section 4.5). Selection of an alternate concomitant medicinal product with no or 
minimal CYP3A4/5 induction potential is recommended.  
 
Although axitinib dose adjustment has not been studied in patients receiving strong 
CYP3A4/5 inducers, if a strong CYP3A4/5 inducer must be co-administered, a gradual dose 
increase of axitinib is recommended. Maximal induction with high-dose strong CYP3A4/5 inducers 
has been reported to occur within one week of treatment with the inducer. If the dose of axitinib is 
increased, the patient should be monitored carefully for toxicity. Management of some adverse 
reactions may require temporary or permanent discontinuation and/or dose reduction of axitinib 
therapy (see section 4.4). If co-administration of the strong inducer is discontinued, the axitinib 
dose should be immediately returned to the dose used prior to initiation of the strong CYP3A4/5 
inducer (see section 4.5). 
 
Special populations 
 
Elderly (≥ 65 years) 
No dose adjustment is required (see sections 4.4 and 5.2). 
 
Renal impairment 
No dose adjustment is required (see section 5.2). Virtually no data are available regarding axitinib 
treatment in patients with a creatinine clearance of < 15 mL/min. 
 
Hepatic impairment 
No dose adjustment is required when administering axitinib to patients with mild hepatic impairment 
(Child-Pugh class A). A dose decrease is recommended when administering axitinib to patients with 
moderate hepatic impairment (Child-Pugh class B) (e.g. the starting dose should be reduced from 
5 mg twice daily to 2 mg twice daily). Axitinib has not been studied in patients with severe hepatic 
impairment (Child-Pugh class C) and should not be used in this population (see sections 4.4 
and 5.2). 
 
Paediatric population 
The safety and efficacy of Inlyta in children and adolescents < 18 years have not been established. 
No data are available. 
 
Method of administration 
 
Axitinib is for oral use. The tablets should be taken orally twice daily approximately 12 hours apart 
with or without food (see section 5.2). They should be swallowed whole with a glass of water. 
 
4.3 Contraindications 
 
Hypersensitivity to axitinib or to any of the excipients listed in section 6.1. 
 



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4.4 Special warnings and precautions for use 
 
Specific safety events should be monitored before initiation of, and periodically throughout, 
treatment with axitinib as described below. 
 
Cardiac failure events 
In clinical studies with axitinib for the treatment of patients with RCC, cardiac failure events 
(including cardiac failure, cardiac failure congestive, cardiopulmonary failure, left ventricular 
dysfunction, ejection fraction decreased, and right ventricular failure) were reported (see section 
4.8).  
 
Signs or symptoms of cardiac failure should periodically be monitored throughout treatment with 
axitinib. Management of cardiac failure events may require temporary interruption or permanent 
discontinuation and/or dose reduction of axitinib therapy. 
 
Hypertension 
In clinical studies with axitinib for the treatment of patients with RCC, hypertension was very 
commonly reported (see section 4.8). 
 
In a controlled clinical study, the median onset time for hypertension (systolic blood pressure 
> 150 mmHg or diastolic blood pressure > 100 mmHg) was within the first month of the start of 
axitinib treatment and blood pressure increases have been observed as early as 4 days after starting 
axitinib.  
 
Blood pressure should be well-controlled prior to initiating axitinib. Patients should be monitored for 
hypertension and treated as needed with standard antihypertensive therapy. In the case of persistent 
hypertension, despite use of antihypertensive medicinal products, the axitinib dose should be 
reduced. For patients who develop severe hypertension, temporarily interrupt axitinib and restart at 
a lower dose once the patient is normotensive. If axitinib is interrupted, patients receiving 
antihypertensive medicinal products should be monitored for hypotension (see section 4.2). 
 
In case of severe or persistent arterial hypertension and symptoms suggestive of posterior reversible 
encephalopathy syndrome (PRES) (see below), a diagnostic brain magnetic resonance image (MRI) 
should be considered. 
 
Thyroid dysfunction 
In clinical studies with axitinib for the treatment of patients with RCC, events of hypothyroidism 
and, to a lesser extent, hyperthyroidism, were reported (see section 4.8).  
 
Thyroid function should be monitored before initiation of, and periodically throughout, treatment 
with axitinib. Hypothyroidism or hyperthyroidism should be treated according to standard medical 
practice to maintain euthyroid state. 
 
Arterial embolic and thrombotic events 
In clinical studies with axitinib, arterial embolic and thrombotic events (including transient ischemic 
attack, myocardial infarction, cerebrovascular accident and retinal artery occlusion) were reported 
(see section 4.8). 
 
Axitinib should be used with caution in patients who are at risk for, or who have a history of, these 
events. Axitinib has not been studied in patients who had an arterial embolic or thrombotic event 
within the previous 12 months.  
 



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Venous embolic and thrombotic events 
In clinical studies with axitinib, venous embolic and thrombotic events (including pulmonary 
embolism, deep vein thrombosis, and retinal vein occlusion/thrombosis) were reported (see 
section 4.8).  
 
Axitinib should be used with caution in patients who are at risk for, or who have a history of, these 
events. Axitinib has not been studied in patients who had a venous embolic or thrombotic event 
within the previous 6 months. 
 
Elevation of haemoglobin or haematocrit 
Increases in haemoglobin or haematocrit, reflective of increases in red blood cell mass, may occur 
during treatment with axitinib (see section 4.8, polycythaemia). An increase in red blood cell mass 
may increase the risk of embolic and thrombotic events. 
 
Haemoglobin or haematocrit should be monitored before initiation of, and periodically throughout, 
treatment with axitinib. If haemoglobin or haematocrit becomes elevated above the normal level, 
patients should be treated according to standard medical practice to decrease haemoglobin or 
haematocrit to an acceptable level. 
 
Haemorrhage 
In clinical studies with axitinib, haemorrhagic events were reported (see section 4.8).  
 
Axitinib has not been studied in patients who have evidence of untreated brain metastasis or recent 
active gastrointestinal bleeding, and should not be used in those patients. If any bleeding requires 
medical intervention, temporarily interrupt the axitinib dose.  
 
Aneurysms and artery dissections 
The use of VEGF pathway inhibitors in patients with or without hypertension may promote the 
formation of aneurysms and/or artery dissections. Before initiating Inlyta, this risk should be 
carefully considered in patients with risk factors such as hypertension or history of aneurysm. 
 
Gastrointestinal perforation and fistula formation 
In clinical studies with axitinib, events of gastrointestinal perforation and fistulas were reported (see 
section 4.8).  
 
Symptoms of gastrointestinal perforation or fistula should be periodically monitored for throughout 
treatment with axitinib. 
 
Wound healing complications 
No formal studies of the effect of axitinib on wound healing have been conducted.  
 
Treatment with axitinib should be stopped at least 24 hours prior to scheduled surgery. The decision 
to resume axitinib therapy after surgery should be based on clinical judgment of adequate wound 
healing. 
 
Posterior reversible encephalopathy syndrome (PRES) 
In clinical studies with axitinib, events of PRES were reported (see section 4.8).  
 
PRES is a neurological disorder which can present with headache, seizure, lethargy, confusion, 
blindness and other visual and neurologic disturbances. Mild to severe hypertension may be present. 
Magnetic resonance imaging is necessary to confirm the diagnosis of PRES. In patients with signs 
or symptoms of PRES, temporarily interrupt or permanently discontinue axitinib treatment. The 
safety of reinitiating axitinib therapy in patients previously experiencing PRES is not known. 



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Proteinuria 
In clinical studies with axitinib, proteinuria, including that of Grade 3 and 4 severity, was reported 
(see section 4.8).  
 
Monitoring for proteinuria before initiation of, and periodically throughout, treatment with axitinib is 
recommended. For patients who develop moderate to severe proteinuria, reduce the dose or 
temporarily interrupt axitinib treatment (see section 4.2). Axitinib should be discontinued if the 
patient develops nephrotic syndrome. 
 
Liver-related adverse reactions 
In a controlled clinical study with axitinib for the treatment of patients with RCC, liver-related 
adverse reactions were reported. The most commonly reported liver-related adverse reactions 
included increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood 
bilirubin (see section 4.8). No concurrent elevations of ALT (> 3 times the upper limit of normal 
[ULN]) and bilirubin (> 2 times the ULN) were observed. 
 
In a clinical dose-finding study, concurrent elevations of ALT (12 times the ULN) and bilirubin 
(2.3 times the ULN), considered to be drug-related hepatotoxicity, were observed in 1 patient who 
received axitinib at a starting dose of 20 mg twice daily (4 times the recommended starting dose). 
 
Liver function tests should be monitored before initiation of, and periodically throughout, treatment 
with axitinib. 
 
Hepatic impairment 
In clinical studies with axitinib, the systemic exposure to axitinib was approximately two-fold higher 
in subjects with moderate hepatic impairment (Child-Pugh class B) compared to subjects with 
normal hepatic function. A dose decrease is recommended when administering axitinib to patients 
with moderate hepatic impairment (Child-Pugh class B) (see section 4.2). 
 
Axitinib has not been studied in patients with severe hepatic impairment (Child-Pugh class C) and 
should not be used in this population.  
 
Elderly (≥ 65 years) and race 
In a controlled clinical study with axitinib for the treatment of patients with RCC, 34% of patients 
treated with axitinib were ≥ 65 years of age. The majority of patients were White (77%) or 
Asian (21%). Although greater sensitivity to develop adverse reactions in some older patients and 
Asian patients cannot be ruled out, overall, no major differences were observed in the safety and 
effectiveness of axitinib between patients who were ≥ 65 years of age and non-elderly, and between 
White patients and patients of other races. 
 
No dosage adjustment is required on the basis of patient age or race (see sections 4.2 and 5.2). 
 
Lactose 
This medicinal product contains lactose. Patients with rare hereditary problems of galactose 
intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
In vitro data indicate that axitinib is metabolised primarily by CYP3A4/5 and, to a lesser extent, 
CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1. 



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CYP3A4/5 inhibitors 
Ketoconazole, a strong inhibitor of CYP3A4/5, administered at a dose of 400 mg once daily for 
7 days, increased the mean area under the curve (AUC) 2-fold and Cmax 1.5-fold of a single 5-mg 
oral dose of axitinib in healthy volunteers. Co-administration of axitinib with strong CYP3A4/5 
inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, erythromycin, atazanavir, indinavir, 
nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin) may increase axitinib plasma 
concentrations. Grapefruit may also increase axitinib plasma concentrations. Selection of 
concomitant medicinal products with no or minimal CYP3A4/5 inhibition potential is recommended. 
If a strong CYP3A4/5 inhibitor must be co-administered, a dose adjustment of axitinib is 
recommended (see section 4.2). 
 
CYP1A2 and CYP2C19 inhibitors 
CYP1A2 and CYP2C19 constitute minor (< 10%) pathways in axitinib metabolism. The effect of 
strong inhibitors of these isozymes on axitinib pharmacokinetics has not been studied. Caution 
should be exercised due to the risk of increased axitinib plasma concentrations in patients taking 
strong inhibitors of these isozymes. 
 
CYP3A4/5 inducers 
Rifampicin, a strong inducer of CYP3A4/5, administered at a dose of 600 mg once daily for 9 days, 
reduced the mean AUC by 79% and Cmax by 71% of a single 5 mg dose of axitinib in healthy 
volunteers.  
 
Co-administration of axitinib with strong CYP3A4/5 inducers (e.g. rifampicin, dexamethasone, 
phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and Hypericum perforatum [St. 
John’s wort]) may decrease axitinib plasma concentrations. Selection of concomitant medicinal 
products with no or minimal CYP3A4/5 induction potential is recommended. If a strong CYP3A4/5 
inducer must be co-administered, a dose adjustment of axitinib is recommended (see section 4.2). 
 
In vitro studies of CYP and UGT inhibition and induction 
In vitro studies indicated that axitinib does not inhibit CYP2A6, CYP2C9, CYP2C19, CYP2D6, 
CYP2E1, CYP3A4/5, or UGT1A1 at therapeutic plasma concentrations.  
 
In vitro studies indicated that axitinib has a potential to inhibit CYP1A2. Therefore, co-
administration of axitinib with CYP1A2 substrates may result in increased plasma concentrations of 
CYP1A2 substrates (e.g. theophylline).  
 
In vitro studies also indicated that axitinib has the potential to inhibit CYP2C8. However, 
co-administration of axitinib with paclitaxel, a known CYP2C8 substrate, did not result in increased 
plasma concentrations of paclitaxel in patients with advanced cancer, indicating lack of clinical 
CYP2C8 inhibition.  
 
In vitro studies in human hepatocytes also indicated that axitinib does not induce CYP1A1, 
CYP1A2, or CYP3A4/5. Therefore co-administration of axitinib is not expected to reduce the 
plasma concentration of co-administered CYP1A1, CYP1A2, or CYP3A4/5 substrates in vivo. 
 
In vitro studies with P-glycoprotein 
In vitro studies indicated that axitinib inhibits P-glycoprotein. However, axitinib is not expected to 
inhibit P-glycoprotein at therapeutic plasma concentrations. Therefore, co-administration of axitinib 
is not expected to increase the plasma concentration of digoxin, or other P-glycoprotein substrates, 
in vivo. 
 



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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no data regarding the use of axitinib in pregnant women. Based on the pharmacological 
properties of axitinib, it may cause foetal harm when administered to a pregnant woman. Studies in 
animals have shown reproductive toxicity including malformations (see section 5.3). Axitinib should 
not be used during pregnancy unless the clinical condition of the woman requires treatment with 
this medicinal product. 
 
Women of childbearing potential must use effective contraception during and up to 1 week after 
treatment. 
 
Breast-feeding 
It is unknown whether axitinib is excreted in human milk. A risk to the suckling child cannot be 
excluded. Axitinib should not be used during breast-feeding.  
 
Fertility 
Based on non-clinical findings, axitinib has the potential to impair reproductive function and fertility 
in humans (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Axitinib has minor influence on the ability to drive and use machines. Patients should be advised that 
they may experience events such as dizziness and/or fatigue during treatment with axitinib. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The following risks, including appropriate action to be taken, are discussed in greater detail in 
section 4.4: cardiac failure events, hypertension, thyroid dysfunction, arterial thromboembolic 
events, venous thromboembolic events, elevation of haemoglobin or haematocrit, haemorrhage, 
gastrointestinal perforation and fistula formation, wound healing complications, PRES, proteinuria, 
and elevation of liver enzymes. 
 
The most common (≥ 20%) adverse reactions observed following treatment with axitinib were 
diarrhoea, hypertension, fatigue, decreased appetite, nausea, weight decreased, dysphonia, 
palmar-plantar erythrodysaesthesia (hand-foot) syndrome, haemorrhage, hypothyroidism, vomiting, 
proteinuria, cough, and constipation. 
 
Tabulated list of adverse reactions 
Table 1 presents adverse reactions reported in a pooled dataset of 672 patients who received axitinib 
in clinical studies for the treatment of patients with RCC (see section 5.1). Post-marketing adverse 
reactions identified in clinical studies are also included. 
 
The adverse reactions are listed by system organ class, frequency category and grade of severity. 
Frequency categories 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), and not 
known (cannot be estimated from the available data). The current safety database for axitinib is too 
small to detect rare and very rare adverse reactions. 
 
Categories have been assigned based on absolute frequencies in the pooled clinical studies data. 
Within each system organ class, adverse reactions with the same frequency are presented in order 
of decreasing seriousness. 



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Table 1. Adverse reactions reported in RCC studies in patients who received axitinib 

(N = 672) 

System organ 
class 

Frequency 
category Adverse reactions

a 
All 

Gradesb 
% 

Grade 3b 
% 

Grade 4b 
% 

Blood and 
lymphatic system 
disorders  

Common Anaemia 6.3 1.2 0.4 
Thrombocytopenia 1.6 0.1 0 
Polycythaemiac 1.5 0.1 0 

Uncommon Neutropaenia 0.3 0.1 0 
Leukopaenia 0.4 0 0 

Endocrine 
disorders  

Very common Hypothyroidismc 24.6 0.3 0 
Common Hyperthyroidismc 1.6 0.1 0.1 

Metabolism and 
nutrition disorders  

Very common Decreased appetite 39.0 3.6 0.3 
Common Dehydration 6.7 3.1 0.3 

Hyperkalaemia 2.7 1.2 0.1 
Hypercalcaemia 2.2 0.1 0.3 

Nervous system 
disorders 

Very common Headache 16.2 0.7 0 

  Dysgeusia 11.5 0 0 
Common Dizziness 9.1 0.6 0 
Uncommon Posterior reversible 

encephalopathy 
syndromee 

0.3 
 

0.1 0 

Ear and labyrinth 
disorders  

Common Tinnitus 3.1 0 0 

Cardiac disorders Common Cardiac failure 
eventsc,d,f 

1.8 0.3 0.7 



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System organ 
class 

Frequency 
category Adverse reactions

a 
All 

Gradesb 
% 

Grade 3b 
% 

Grade 4b 
% 

Vascular disorders  Very common Hypertensiong 51.2 22.0 1.0 
Haemorrhagec,d,h 25.7 3.0 1.0 

Common Venous embolic and 
thrombotic eventsc,d,i 

2.8 0.9 
 

1.2 

Arterial embolic and 
thrombotic eventsc,d,j 

2.8 1.2 1.3 

Not known Aneurysms and artery 
dissectionsd 

- - - 

Respiratory, 
thoracic and 
mediastinal 
disorders  

Very common Dyspnoead 17.1 3.6 0.6 
Cough 20.4 0.6 0 
Dysphonia 32.7 0 0.1 

Common Oropharyngeal pain 7.4 0 0 
Gastrointestinal 
disorders  

Very common 
 

Diarrhoea 55.4 10.1 0.1 
Vomiting 23.7 2.7 0.1 
Nausea 33.0 2.2 0.1 
Abdominal pain 14.7 2.5 0.3 
Constipation 20.2 1.0 0 
Stomatitis 15.5 1.8 0 

  Dyspepsia 11.2 0.1 0 
 Common Upper abdominal pain 9.4 0.9 0 

Flatulence 4.5 0 0 
Haemorrhoids 3.3 0 0 
Glossodynia 2.8 0 0 
Gastrointestinal 
perforation and 
fistulac,k 

1.9 0.9 0.3 

Hepatobiliary 
disorders 

Common Hyperbilirubinaemia 1.3 0.1 0.1 
Cholecystitisn 1.0 0.6 0.1 

Skin and 
subcutaneous 
tissue disorders  

Very common Palmar-plantar 
erythrodysaesthesia 
(hand-foot syndrome) 

32.1 7.6 0 

Rash 14.3 0.1 0 
Dry skin 10.1 0.1 0 

Common Pruritus 6.0 0 0 
Erythema 3.7 0 0 
Alopecia 5.7 0 0 

Musculoskeletal 
and connective 
tissue disorders  

Very common Arthralgia 17.7 1.9 0.3 
Pain in extremity 14.1 1.0 0.3 

Common Myalgia 8.2 0.6 0.1 
Renal and urinary 
disorders  

Very common Proteinurial 21.1 4.8 0.1 
Common Renal failurem 1.6 0.9 0.1 

General disorders 
and administration 
site conditions  

Very common Fatigue 45.1 10.6 0.3 
Asthaeniad 13.8 2.8 0.3 
Mucosal inflammation 13.7 1.0 0 

Investigations  Very common Weight decreased 32.7 4.9 0 
Common Lipase increased 3.7 0.7 0.7 



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System organ 
class 

Frequency 
category Adverse reactions

a 
All 

Gradesb 
% 

Grade 3b 
% 

Grade 4b 
% 

 Alanine 
aminotransferase 
increased 

6.5 1.2 0 

Amylase increased 3.4 0.6 0.4 
Aspartate 
aminotransferase 
increased 

6.1 1.0 0 

Alkaline phosphatase 
increased 

4.8 0.3 0 

Creatinine increased 5.7 0.4 0 
Thyroid stimulating 
hormone increased 

7.9 
 

0 
 

0 
 

a Adverse reactions are according to treatment-emergent, all causality frequency. 
b National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 
c See Description of selected adverse reactions section. 
d Fatal (Grade 5) cases were reported. 
e Including Leukoencephalopathy.  
f Including cardiac failure, cardiac failure congestive, cardiopulmonary failure, ejection fraction decreased, 

left ventricular dysfunction and right ventricular failure.  
g Including accelerated hypertension, blood pressure increased, hypertension and hypertensive crisis. 
h Including activated partial thromboplastin time prolonged, anal haemorrhage, arterial haemorrhage, blood 

urine present, central nervous system haemorrhage, cerebral haemorrhage, coagulation time prolonged, 
conjunctival haemorrhage, contusion, diarrhea haemorrhagic, dysfunctional uterine bleeding, epistaxis, 
gastric haemorrhage, gastrointestinal haemorrhage, gingival bleeding, haematemesis, haematochezia, 
haematocrit decreased, haematoma, haematuria, haemoglobin decreased, haemoptysis, haemorrhage, 
haemorrhage coronary artery, haemorrhage urinary tract, haemorrhoidal haemorrhage, haemostasis, 
increased tendency to bruise, international normalized ratio increased, lower gastrointestinal 
haemorrhage, melaena, petechiae, pharyngeal haemorrhage, prothrombin time prolonged, pulmonary 
haemorrhage, purpura, rectal haemorrhage, red blood cell count decreased, renal haemorrhage, scleral 
haemorrhage, scrotal haematocoele, splenic haemotoma, splinter haemorrhage, subarachnoid 
haemorrhage, tongue haemorrhage, upper gastrointestinal haemorrhage and vaginal haemorrhage.  

i Including Budd-Chiari syndrome, deep vein thrombosis, jugular vein thrombosis, pelvic venous 
thrombosis, pulmonary embolism, retinal vein occlusion, retinal vein thrombosis, subclavian vein 
thrombosis, venous thrombosis, and venous thrombosis limb. 

j Including acute myocardial infarction, embolism, myocardial infarction, retinal artery occlusion and 
transient ischaemic attack.  

k Gastrointestinal perforation and fistula includes the following preferred terms: abdominal abscess, anal 
abscess, anal fistula, fistula, gastrointestinal anastomotic leak, gastrointestinal perforation, large 
intestine perforation, oesophagobronchial fistula and peritonitis. 

l Proteinuria includes the following preferred terms: protein urine, protein urine present and proteinuria.  
m Including acute renal failure  
n Cholecystitis includes Cholecystitis acute, Cholecystitis, Cholecystitis infective. 
 
 
Description of selected adverse reactions 
 
Cardiac failure events (see section 4.4) 
In a controlled clinical study with axitinib (N = 359) for the treatment of patients with RCC, cardiac 
failure events were reported in 1.7 % patients receiving axitinib, including cardiac failure (0.6%), 
cardiopulmonary failure (0.6%), left ventricular dysfunction (0.3%), and right ventricular failure 



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(0.3%). Grade 4 cardiac failure adverse reactions were reported in 0.6 % of patients receiving 
axitinib. Fatal cardiac failure was reported in 0.6 % of patients receiving axitinib.  
 
In monotherapy studies with axitinib (N = 672) for the treatment of patients with RCC, cardiac 
failure events (including cardiac failure, cardiac failure congestive, cardiopulmonary failure, left 
ventricular dysfunction, ejection fraction decreased, and right ventricular failure) were reported in 
1.8% patients receiving axitinib. Grade 3/4 cardiac failure events were reported in 1.0% patients and 
fatal cardiac failure events were reported in 0.3% patients receiving axitinib.  
 
Thyroid dysfunction (see section 4.4) 
In a controlled clinical study with axitinib for the treatment of patients with RCC, hypothyroidism 
was reported in 20.9% of patients and hyperthyroidism was reported in 1.1% of patients. Thyroid 
stimulating hormone (TSH) increased was reported as an adverse reaction in 5.3% of patients 
receiving axitinib. During routine laboratory assessments, in patients who had TSH < 5 μU/mL 
before treatment, elevations of TSH to ≥ 10 μU/mL occurred in 32.2% of patients receiving axitinib.  
 
In pooled clinical studies with axitinib (N = 672) for the treatment of patients with RCC, 
hypothyroidism was reported in 24.6% of patients receiving axitinib. Hyperthyroidism was reported 
in 1.6% of patients receiving axitinib. 
 
Venous embolic and thrombotic events (see section 4.4) 
In a controlled clinical study with axitinib for the treatment of patients with RCC, venous embolic 
and thrombotic adverse reactions were reported in 3.9% of patients receiving axitinib, including 
pulmonary embolism (2.2%), retinal vein occlusion/thrombosis (0.6%) and deep vein 
thrombosis (0.6%). Grade 3/4 venous embolic and thrombotic adverse reactions were reported in 
3.1% of patients receiving axitinib. Fatal pulmonary embolism was reported in one patient (0.3%) 
receiving axitinib. 
 
In pooled clinical studies with axitinib (N = 672) for the treatment of patients with RCC, venous 
embolic and thrombotic events were reported in 2.8% of patients receiving axitinib. Grade 3 venous 
embolic and thrombotic events were reported in 0.9% of patients. Grade 4 venous embolic and 
thrombotic events were reported in 1.2% of patients. Fatal venous embolic and thrombotic events 
were reported 0.1% patients receiving axitinib. 
 
Arterial embolic and thrombotic events (see section 4.4) 
In a controlled clinical study with axitinib for the treatment of patients with RCC, arterial embolic 
and thrombotic adverse reactions were reported in 4.7% of patients receiving axitinib, including 
myocardial infarction (1.4%), transient ischemic attack (0.8%) and cerebrovascular accident 
(0.6%). Grade 3/4 arterial embolic and thrombotic adverse reactions were reported in 3.3% of 
patients receiving axitinib. A fatal acute myocardial infarction and cerebrovascular accident was 
reported in one patient each (0.3%). In monotherapy studies with axitinib (N = 850), arterial 
embolic and thrombotic adverse reactions (including transient ischemic attack, myocardial 
infarction, and cerebrovascular accident) were reported in 5.3% of patients receiving axitinib. 
 
In pooled clinical studies with axitinib (N = 672) for the treatment of patients with RCC, arterial 
embolic and thrombotic events were reported in 2.8% of patients receiving axitinib. Grade 3 arterial 
embolic and thrombotic events were reported in 1.2% of patients. Grade 4 arterial embolic and 
thrombotic events were reported in 1.3% of patients. Fatal arterial embolic and thrombotic events 
were reported in 0.3% patients receiving axitinib. 
 
Polycythaemia (see Elevation of haemoglobin or haematocrit in section 4.4) 
In a controlled clinical study with axitinib for the treatment of patients with RCC, polycythaemia 
was reported in 1.4% of patients receiving axitinib. Routine laboratory assessments detected 



14 

elevated haemoglobin above ULN in 9.7% of patients receiving axitinib. In four clinical studies with 
axitinib for the treatment of patients with RCC (N = 537), elevated haemoglobin above ULN was 
observed in 13.6% receiving axitinib. 
 
In pooled clinical studies with axitinib (N = 672) for the treatment of patients with RCC, 
polycythaemia was reported in 1.5% of patients receiving axitinib. 
 
Haemorrhage (see section 4.4) 
In a controlled clinical study with axitinib for the treatment of patients with RCC that excluded 
patients with untreated brain metastasis, haemorrhagic adverse reactions were reported in 21.4% of 
patients receiving axitinib. The haemorrhagic adverse reactions in patients treated with axitinib 
included epistaxis (7.8%), haematuria (3.6%), haemoptysis (2.5%), rectal haemorrhage (2.2%), 
gingival bleeding (1.1%), gastric haemorrhage (0.6%), cerebral haemorrhage (0.3%) and lower 
gastrointestinal haemorrhage (0.3%). Grade > 3 haemorrhagic adverse reactions were reported in 
3.1% of patients receiving axitinib (including cerebral haemorrhage, gastric haemorrhage, lower 
gastrointestinal haemorrhage and haemoptysis). Fatal haemorrhage was reported in one patient 
(0.3%) receiving axitinib (gastric haemorrhage). In monotherapy studies with axitinib (N = 850), 
haemoptysis was reported in 3.9% of patients; Grade > 3 haemoptysis was reported in 0.5% of 
patients. 
 
In pooled clinical studies with axitinib (N = 672) for the treatment of patients with RCC, 
haemorrhagic events were reported in 25.7% of patients receiving axitinib. Grade 3 haemorrhagic 
adverse reactions were reported in 3% of patients. Grade 4 haemorrhagic adverse reactions were 
reported in 1% of patients and fatal haemorrhage were reported in 0.4% of patients receiving 
axitinib. 
 
Gastrointestinal perforation and fistula formation (see section 4.4) 
In a controlled clinical study with axitinib for the treatment of patients with RCC, gastrointestinal 
perforation-type events were reported in 1.7% of patients receiving axitinib, including anal 
fistula (0.6%), fistula (0.3%) and gastrointestinal perforation (0.3%).In monotherapy studies with 
axitinib (N = 850), gastrointestinal perforation-type events were reported in 1.9% of patients and 
fatal gastrointestinal perforation was reported in one patient (0.1%). 
 
In pooled clinical studies with axitinib (N = 672) for the treatment of patients with RCC, 
gastrointestinal perforation and fistula were reported in 1.9% of patients receiving axitinib. 
 
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 for axitinib overdose.  
 
In a controlled clinical study with axitinib for the treatment of patients with RCC, one patient 
inadvertently received a dose of 20 mg twice daily for 4 days and experienced dizziness (Grade 1).  
 
In a clinical dose finding study with axitinib, subjects who received starting doses of 10 mg twice 
daily or 20 mg twice daily experienced adverse reactions which included hypertension, seizures 
associated with hypertension, and fatal haemoptysis. 
 

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


15 

In cases of suspected overdose, axitinib should be withheld and supportive care instituted. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01XE17 
 
Mechanism of action 
Axitinib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor 
receptors (VEGFR)-1, VEGFR-2 and VEGFR-3. These receptors are implicated in pathologic 
angiogenesis, tumour growth, and metastatic progression of cancer. Axitinib has been shown to 
potently inhibit VEGF-mediated endothelial cell proliferation and survival. Axitinib inhibited the 
phosphorylation of VEGFR-2 in xenograft tumour vasculature that expressed the target in vivo and 
produced tumour growth delay, regression, and inhibition of metastases in many experimental 
models of cancer. 
 
Effect on QTc interval 
In a randomised, 2-way crossover study, 35 healthy subjects were administered a single oral dose 
of axitinib (5 mg) in the absence and presence of 400 mg ketoconazole for 7 days. Results of this 
study indicated that axitinib plasma exposures up to two-fold greater than therapeutic levels 
expected following a 5 mg dose, did not produce clinically-significant QT interval prolongation. 
 
Clinical efficacy and safety 
The safety and efficacy of axitinib were evaluated in a randomised, open-label, multicenter Phase 3 
study. Patients (N = 723) with advanced RCC whose disease had progressed on or after treatment 
with one prior systemic therapy, including sunitinib-, bevacizumab-, temsirolimus-, or cytokine-
containing regimens were randomised (1:1) to receive axitinib (N = 361) or sorafenib (N = 362). 
The primary endpoint, progression-free survival (PFS), was assessed using a blinded independent 
central review. Secondary endpoints included objective response rate (ORR) and overall survival 
(OS).  
 
Of the patients enrolled in this study, 389 patients (53.8%) had received one prior sunitinib-based 
therapy, 251 patients (34.7%) had received one prior cytokine-based therapy (interleukin-2 or 
interferon-alpha), 59 patients (8.2%) had received one prior bevacizumab-based therapy, and 
24 patients (3.3%) had received one prior temsirolimus-based therapy. The baseline demographic 
and disease characteristics were similar between the axitinib and sorafenib groups with regard to 
age, gender, race, Eastern Cooperative Oncology Group (ECOG) performance status, geographic 
region, and prior treatment. 
 
In the overall patient population and the two main subgroups (prior sunitinib treatment and prior 
cytokine treatment), there was a statistically significant advantage for axitinib over sorafenib for the 
primary endpoint of PFS (see Table 2 and Figures 1, 2 and 3). The magnitude of median PFS effect 
was different in the subgroups by prior therapy. Two of the subgroups were too small to give 
reliable results (prior temsirolimus treatment or prior bevacizumab treatment). There were no 
statistically significant differences between the arms in OS in the overall population or in the 
subgroups by prior therapy. 
 



16 

Table 2. Efficacy results 
Endpoint / study population axitinib  sorafenib HR (95% CI) p-value 
Overall ITT N = 361 N = 362   

Median PFS a,b in months  
(95% CI) 

6.8 (6.4, 8.3) 4.7 (4.6, 6.3) 0.67 (0.56, 0.81) < 0.0001c 

Median OS d in months  
(95% CI) 

20.1 (16.7, 23.4) 19.2 (17.5, 22.3) 0.97 (0.80, 1.17) NS 

ORR b,e % (95% CI) 19.4 (15.4, 23.9) 9.4 (6.6, 12.9) 2.06f (1.41, 3.00) 0.0001g 
Prior sunitinib treatment N = 194 N = 195   

Median PFS a,b in months  
(95% CI) 

4.8 (4.5, 6.5) 3.4 (2.8, 4.7) 0.74 (0.58, 0.94) 0.0063h 

Median OS d in months  
(95% CI) 

15.2 (12.8, 18.3) 16.5 (13.7, 19.2) 1.00 (0.78, 1.27) NS 

ORR b,e % (95% CI) 11.3 (7.2, 16.7) 7.7 (4.4, 12.4) 1.48f (0.79, 2.75) NS 
Prior cytokine treatment N = 126 N = 125   

Median PFS a,b in months  
(95% CI) 

12.0 (10.1, 13.9) 6.6 (6.4, 8.3) 0.52 (0.38, 0.72) < 0.0001h 

Median OS d in months  
(95% CI) 

29.4 (24.5, NE) 27.8 (23.1, 34.5) 0.81 (0.56, 1.19) NS 

ORR b,e % (95% CI) 32.5 (24.5, 41.5) 13.6 (8.1, 20.9) 2.39f (1.43-3.99) 0.0002i 
CI = Confidence interval, HR = Hazard ratio (axitinib/sorafenib); ITT: Intent-to-treat; NE: not estimable; NS: 
not statistically significant; ORR: Objective response rate; OS: Overall survival; PFS: Progression-free 
survival. 
a Time from randomisation to progression or death due to any cause, whichever occurs first. Cutoff 

date: 03 June 2011. 
b Assessed by independent radiology review according to Response Evaluation Criteria in Solid 

Tumours (RECIST).  
c One-sided p-value from a log-rank test of treatment stratified by ECOG performance status and prior 

therapy. 
d Cutoff date: 01 November 2011. 
e Cutoff date: 31 August 2010. 
f Risk ratio is used for ORR. A risk ratio > 1 indicated a higher likelihood of responding in the axitinib 

arm; a risk ratio < 1 indicated a higher likelihood of responding in the sorafenib arm. 
g One-sided p-value from Cochran-Mantel-Haenszel test of treatment stratified by ECOG performance 

status and prior therapy. 
h One-sided p-value from a log-rank test of treatment stratified by ECOG performance status. 
i One-sided p-value from Cochran-Mantel-Haenszel test of treatment stratified by ECOG performance 
status. 
 



17 

Figure 1. Kaplan-Meier curve of progression-free survival by independent assessment for 
the overall population 

 
 
Figure 2. Kaplan-Meier curve of progression-free survival by independent assessment for 
the prior sunitinib subgroup 

 



18 

Figure 3. Kaplan-Meier curve of progression-free survival by independent assessment for 
the prior cytokine subgroup 

 
 
Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
axitinib in all subsets of the paediatric population for treatment of kidney and renal pelvis carcinoma 
(excluding nephroblastoma, nephroblastomatosis, clear cell sarcoma, mesoblastic nephroma, renal 
medullary carcinoma and rhabdoid tumour of the kidney) (see section 4.2 for information on 
paediatric use). 
 
5.2 Pharmacokinetic properties 
 
After oral administration of axitinib tablets, the mean absolute bioavailability is 58% compared to 
intravenous administration. The plasma half life of axitinib ranges from 2.5 to 6.1 hours. Dosing of 
axitinib at 5 mg twice daily resulted in less than two-fold accumulation compared to administration 
of a single dose. Based on the short half-life of axitinib, steady state is expected within 2 to 3 days 
of the initial dose. 
 
Absorption and distribution 
Peak axitinib concentrations in plasma are generally reached within 4 hours following oral 
administration of axitinib with median Tmax ranging from 2.5 to 4.1 hours. Administration of axitinib 
with a moderate fat meal resulted in 10% lower exposure compared to overnight fasting. A high fat, 
high-calorie meal resulted in 19% higher exposure compared to overnight fasting. Axitinib may be 
administered with or without food (see section 4.2). 
 
The average Cmax and AUC increased proportionally over an axitinib dosing range of 5 to 10 mg. 
In vitro binding of axitinib to human plasma proteins is > 99% with preferential binding to albumin 
and moderate binding to α1-acid glycoprotein. At the 5 mg twice daily dose in the fed state, the 
geometric mean peak plasma concentration and 24-hour AUC were 27.8 ng/mL and 265 ng.h/mL, 
respectively, in patients with advanced RCC. The geometric mean oral clearance and apparent 
volume of distribution were 38 L/h and 160 L, respectively. 
 
Biotransformation and elimination 
Axitinib is metabolised primarily in the liver by CYP3A4/5 and to a lesser extent by CYP1A2, 
CYP2C19, and UGT1A1. 



19 

 
Following oral administration of a 5 mg radioactive dose of axitinib, 30-60% of the radioactivity 
was recovered in faeces and 23% of the radioactivity was recovered in urine. Unchanged axitinib, 
accounting for 12% of the dose, was the major component identified in faeces. Unchanged axitinib 
was not detected in urine; the carboxylic acid and sulfoxide metabolites accounted for the majority 
of radioactivity in urine. In plasma, the N-glucuronide metabolite represented the predominant 
radioactive component (50% of circulating radioactivity) and unchanged axitinib and the sulfoxide 
metabolite each accounted for approximately 20% of the circulating radioactivity. 
 
The sulfoxide and N-glucuronide metabolites show approximately 400-fold and 8000-fold less in 
vitro potency, respectively, against VEGFR-2 compared to axitinib. 
 
Special populations 
 
Elderly, gender, and race 
Population pharmacokinetic analyses in patients with advanced cancer (including advanced RCC) 
and healthy volunteers indicate that there are no clinically relevant effects of age, gender, body 
weight, race, renal function, UGT1A1 genotype, or CYP2C19 genotype. 
 
Paediatric population 
Axitinib has not been studied in patients < 18 years of age.  
 
Hepatic impairment 
In vitro and in vivo data indicate that axitinib is primarily metabolised by the liver. 
 
Compared to subjects with normal hepatic function, systemic exposure following a single dose of 
axitinib was similar in subjects with mild hepatic impairment (Child-Pugh class A) and higher 
(approximately two-fold) in subjects with moderate hepatic impairment (Child-Pugh class B). 
Axitinib has not been studied in subjects with severe hepatic impairment (Child-Pugh class C) and 
should not be used in this population (see section 4.2 for dose adjustment recommendations). 
 
Renal impairment 
Unchanged axitinib is not detected in the urine.  
 
Axitinib has not been studied in subjects with renal impairment. In clinical studies with axitinib for 
the treatment of patients with RCC, patients with serum creatinine > 1.5 times the ULN or 
calculated creatinine clearance < 60 mL/min were excluded. Population pharmacokinetic analyses 
have shown that axitinib clearance was not altered in subjects with renal impairment and no dose 
adjustment of axitinib is required. 
 
5.3 Preclinical safety data 
 
Repeat dose toxicity 
Major toxicity findings in mice and dogs following repeated dosing for up to 9 months were the 
gastrointestinal, haematopoietic, reproductive, skeletal and dental systems, with No Observed 
Adverse Effect Levels (NOAEL) approximately equivalent to or below expected human exposure at 
the recommended clinical starting dose (based on AUC levels). 
 
Carcinogenicity 
Carcinogenicity studies have not been performed with axitinib. 
 



20 

Genotoxicity 
Axitinib was not mutagenic or clastogenic in conventional genotoxicity assays in vitro. A significant 
increase in polyploidy was observed in vitro at concentrations > 0.22 µg/mL, and an elevation in 
micronucleated polychromatic erythrocytes was observed in vivo with No Observed Effect Level 
(NOEL) 69-fold the expected human exposure. Genotoxicity findings are not considered clinically 
relevant at exposure levels observed in humans. 
 
Reproduction toxicity 
Axitinib-related findings in the testes and epididymis included decreased organ weight, atrophy or 
degeneration, decreased numbers of germinal cells, hypospermia or abnormal sperm forms, and 
reduced sperm density and count. These findings were observed in mice at exposure levels 
approximately 12-fold the expected human exposure, and in dogs at exposure levels below the 
expected human exposure. There was no effect on mating or fertility in male mice at exposure 
levels approximately 57-fold the expected human exposure. Findings in females included signs of 
delayed sexual maturity, reduced or absent corpora lutea, decreased uterine weights and uterine 
atrophy at exposures approximately equivalent to the expected human exposure. Reduced fertility 
and embryonic viability were observed in female mice at all doses tested, with exposure levels at the 
lowest dose approximately 10-fold the expected human exposure. 
 
Pregnant mice exposed to axitinib showed an increased occurrence of cleft palate malformations 
and skeletal variations, including delayed ossification, at exposure levels below the expected human 
exposure. Perinatal and postnatal developmental toxicity studies have not been conducted.  
 
Toxicity findings in immature animals 
Reversible physeal dysplasia was observed in mice and dogs given axitinib for at least 1 month at 
exposure levels approximately six-fold higher than the expected human exposure. Partially reversible 
dental caries were observed in mice treated for more than 1 month at exposure levels similar to the 
expected human exposure. Other toxicities of potential concern to paediatric patients have not been 
evaluated in juvenile animals. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Microcrystalline cellulose 
Lactose monohydrate 
Croscarmellose sodium 
Magnesium stearate 
 
Tablet film-coating 
Hypromellose 2910 (15 mPa·s) 
Titanium dioxide (E171) 
Lactose monohydrate 
Triacetin (E1518) 
Iron oxide red (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 



21 

6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
Inlyta 1 mg film-coated tablet 
Aluminium/aluminium blister containing 14 film-coated tablets. Each pack contains 28 or 
56 film-coated tablets. 
 
HDPE bottle with a silica gel desiccant and a polypropylene closure containing 180 film-coated 
tablets. 
 
Inlyta 3 mg film-coated tablet 
Aluminium/aluminium blister containing 14 film-coated tablets. Each pack contains 28 or 
56 film-coated tablets. 
 
HDPE bottle with a silica gel desiccant and a polypropylene closure containing 60 film-coated 
tablets. 
 
Inlyta 5 mg film-coated tablet 
Aluminium/aluminium blister containing 14 film-coated tablets. Each pack contains 28 or 
56 film-coated tablets. 
 
HDPE bottle with a silica gel desiccant and a polypropylene closure containing 60 film-coated 
tablets. 
 
Inlyta 7 mg film-coated tablet 
Aluminium/aluminium blister containing 14 film-coated tablets. Each pack contains 28 or 
56 film-coated tablets. 
 
HDPE bottle with a silica gel desiccant and a polypropylene closure containing 60 film-coated 
tablets. 
 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 



22 

7. MARKETING AUTHORISATION HOLDER 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Inlyta 1 mg film-coated tablets 
EU/1/12/777/001 
EU/1/12/777/002 
EU/1/12/777/003 
 
Inlyta 3 mg film-coated tablets 
EU/1/12/777/007 
EU/1/12/777/008 
EU/1/12/777/009 
 
Inlyta 5 mg film-coated tablets 
EU/1/12/777/004 
EU/1/12/777/005 
EU/1/12/777/006 
 
Inlyta 7 mg film-coated tablets 
EU/1/12/777/010 
EU/1/12/777/011 
EU/1/12/777/012 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 3 September 2012 
Date of latest renewal: 22 May 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

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


23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 
 
 



24 

A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Pfizer Manufacturing Deutschland GmbH 
Betriebsstätte Freiburg 
Mooswaldallee 1 
D-79090 Freiburg 
Germany 
 
 
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 (PSURs) 

 
The requirements for submission of PSURs 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 marketing authorisation holder (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. 

 
 



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 1 mg film-coated tablets  
axitinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 1 mg axitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 tablets 
56 tablets 
 
 
5. METHOD AND ROUTE 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 
 
 



28 

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 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/777/001  28 tablets 
EU/1/12/777/002  56 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Inlyta 1 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN 
NN  



29 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  
 
BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 1 mg film-coated tablets  
axitinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 1 mg axitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
180 tablets 
 
 
5. METHOD AND ROUTE 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 
 
 



30 

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 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/777/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Inlyta 1 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 
 
BLISTER  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 1 mg film-coated tablets  
axitinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pfizer 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 3 mg film-coated tablets  
axitinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 3 mg axitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 tablets 
56 tablets 
 
 
5. METHOD AND ROUTE 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 
 
 



33 

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 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/777/007  28 tablets 
EU/1/12/777/008  56 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Inlyta 3 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN  
NN  
 



34 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  
 
BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 3 mg film-coated tablets  
axitinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 3 mg axitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 tablets 
 
 
5. METHOD AND ROUTE 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 
 
 



35 

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 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/777/009 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Inlyta 3 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN  
NN  
 



36 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 3 mg film-coated tablets  
axitinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pfizer 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 5 mg film-coated tablets  
axitinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 5 mg axitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 tablets 
56 tablets 
 
 
5. METHOD AND ROUTE 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 
 
 



38 

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 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/777/004  28 tablets 
EU/1/12/777/005  56 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Inlyta 5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN  
NN  
 



39 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 5 mg film-coated tablets  
axitinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 5 mg axitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 tablets 
 
 
5. METHOD AND ROUTE 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 
 
 



40 

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 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/777/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Inlyta 5 mg 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN  
NN  
 



41 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 5 mg film-coated tablets  
axitinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pfizer 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



42 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 7 mg film-coated tablets  
axitinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 7 mg axitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 tablets 
56 tablets 
 
 
5. METHOD AND ROUTE 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 
 
 



43 

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 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/777/010  28 tablets 
EU/1/12/777/011  56 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Inlyta 7 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN  
NN  
 



44 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING  
 
BOTTLE  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 7 mg film-coated tablets  
axitinib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 7 mg axitinib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 tablets 
 
 
5. METHOD AND ROUTE 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 
 
 



45 

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 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/12/777/012 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Inlyta 7 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN  
NN  
 



46 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Inlyta 7 mg film-coated tablets  
axitinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pfizer 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



47 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



48 

Package leaflet: Information for the patient 
 

Inlyta 1 mg film-coated tablets 
Inlyta 3 mg film-coated tablets 
Inlyta 5 mg film-coated tablets 
Inlyta 7 mg film-coated tablets 

axitinib 
 
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 Inlyta is and what it is used for 
2. What you need to know before you take Inlyta 
3. How to take Inlyta 
4. Possible side effects 
5. How to store Inlyta 
6. Contents of the pack and other information 
 
 
1. What Inlyta is and what it is used for 
 
Inlyta is a medicine containing the active substance axitinib. Axitinib reduces the blood supply to the 
tumour and slows down the growth of cancer. 
 
Inlyta is indicated for the treatment of advanced kidney cancer (advanced renal cell carcinoma) in 
adults, when another medicine (called sunitinib or a cytokine) is no longer stopping disease from 
progressing. 
 
If you have any questions about how this medicine works or why this medicine has been prescribed 
for you, ask your doctor. 
 
 
2. What you need to know before you take Inlyta 
 
Do not take Inlyta: 
If you are allergic to axitinib or any of the other ingredients of this medicine (listed in section 6). 
If you think you may be allergic, ask your doctor for advice. 
 
Warnings and precautions 
 
Talk to your doctor or nurse before taking Inlyta 
 
• If you have high blood pressure. 

Inlyta can raise your blood pressure. It is important to check your blood pressure before you 



49 

take this medicine, and regularly while you are taking it. If you have high blood pressure 
(hypertension) you may be treated with medicines to reduce the blood pressure. Your doctor 
should make sure that your blood pressure is under control before starting Inlyta treatment, 
and while on treatment with this medicine. 

 
• If you have thyroid gland problems. 

Inlyta can cause thyroid gland problems. Tell your doctor if you get tired more easily, 
generally feel colder than other people, or your voice deepens whilst taking this medicine. 
Your thyroid function should be checked before you take Inlyta and regularly while you are 
taking it. If your thyroid gland is not producing enough thyroid hormone before, or while on 
treatment with this medicine, you should be treated with thyroid hormone replacement. 

 
• If you have had a recent problem with blood clots in your veins and arteries (types of 

blood vessels), including stroke, heart attack, embolism, or thrombosis.  
Get emergency help right away and call your doctor if you get symptoms such as chest pain 
or pressure; pain in your arms, back, neck or jaw; shortness of breath; numbness or 
weakness on one side of your body; trouble talking; headache; vision changes; or dizziness 
while on treatment with this medicine. 

 
• If you suffer from bleeding problems. 

Inlyta may increase your chance of bleeding. Tell your doctor if you have any bleeding, 
coughing up of blood or bloody sputum while on treatment with this medicine.   

 
• If you have or have had an aneurysm (enlargement and weakening of a blood vessel 

wall) or a tear in a blood vessel wall. 
 

• If during treatment with this medicine you get severe stomach (abdominal) pain or 
stomach pain that does not go away. 
Inlyta may increase the risk of developing a hole in the stomach or intestine or formation of 
fistula (abnormal tube-like passage from one normal body cavity to another body cavity or the 
skin). 
Tell your doctor if you have severe abdominal pain while on treatment with this medicine. 
 

• If you are going to have an operation or if you have an unhealed wound. 
Your doctor should stop Inlyta at least 24 hours before your operation as it may affect wound 
healing. Your treatment with this medicine should be restarted when the wound has 
adequately healed. 
 

• If during treatment with this medicine, you get symptoms such as headache, 
confusion, seizures (fits), or changes in vision with or without high blood pressure. 
Get emergency help right away and call your doctor. This could be a rare neurological side 
effect named posterior reversible encephalopathy syndrome.  

 
• If you have liver problems. 

Your doctor should do blood tests to check your liver function before and during treatment 
with Inlyta. 
 

• If during treatment with this medicine, you get symptoms such as excessive tiredness, 
swelling of the abdomen, legs or ankles, shortness of breath, or protruding neck 
veins. 
Inlyta may increase the risk of developing heart failure events. Your doctor should monitor 
for signs or symptoms of heart failure events periodically throughout treatment with axitinib. 



50 

 
Use in children and adolescents 
Inlyta is not recommended for people aged under 18. This medicine has not been studied in children 
and adolescents. 
 
Other medicines and Inlyta 
Some medicines may affect Inlyta, or be affected by it. Please tell your doctor, pharmacist or nurse 
about all the medicines you have recently taken, are currently taking, or plan to take, including 
medicines obtained without a prescription, vitamins, and herbal medicines. The medicines listed in 
this leaflet may not be the only ones that could interact with Inlyta. 
 
The following medicines may increase the risk of side effects with Inlyta: 
• ketoconazole or itraconazole, used to treat fungal infections; 
• clarithromycin, erythromycin or telithromycin, antibiotics used to treat bacterial infections; 
• atazanavir, indinavir, nelfinavir, ritonavir or saquinavir, used to treat HIV infections/AIDS; 
• nefazodone, used to treat depression. 
 
The following medicines may reduce the effectiveness of Inlyta: 
• rifampicin, rifabutin or rifapentin, used to treat tuberculosis (TB); 
• dexamethasone, a steroid medicine prescribed for many different conditions, including serious 

illnesses; 
• phenytoin, carbamazepine or phenobarbital, anti-epileptics used to stop seizures or fits; 
• St. John’s wort (Hypericum perforatum), a herbal product used to treat depression. 
 
You should not take these medicines during your treatment with Inlyta. If you are taking any of 
them, tell your doctor, pharmacist or nurse. Your doctor may change the dose of these medicines, 
change the dose of Inlyta, or switch you to a different medicine. 
 
Inlyta may increase side effects associated with theophylline, used to treat asthma or other lung 
diseases.  
 
Inlyta with food and drink 
 
Do not take this medicine with grapefruit or grapefruit juice, as it may increase the chance of side 
effects. 
 
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, pharmacist or nurse for advice before taking this medicine. 
 
• Inlyta could harm an unborn baby or breast-fed baby.  
 
• Do not take this medicine during pregnancy. Talk to your doctor before taking it if you are 

pregnant or might become pregnant.  
 
• Use a reliable method of contraception while you are taking Inlyta and up to 1 week after the 

last dose of this medicine, to prevent pregnancy. 
 
• Do not breast-feed during treatment with Inlyta. If you are breast-feeding, your doctor should 

discuss with you whether to discontinue breast-feeding or discontinue Inlyta treatment. 
 
 



51 

Driving and using machines 
If you experience dizziness and/or feel tired while on treatment with Inlyta, take special care when 
driving or using machines. 
 
Inlyta contains lactose (milk sugar) 
If you have been told by your doctor that you have an intolerance to some sugars, contact your 
doctor before taking this medicine. 
 
 
3. How to take Inlyta 
 
Always take this medicine exactly as your doctor has told you. You should check with your doctor, 
pharmacist or nurse if you are not sure. 
 
The recommended dose is 5 mg twice a day. Your doctor may subsequently increase or decrease 
your dose depending on how you tolerate treatment with Inlyta. 
 
Swallow the tablets whole with water, with or without food. Take the Inlyta doses approximately 
12 hours apart. 
 
If you take more Inlyta than you should 
If you accidentally take too many tablets or a higher dose than you need, contact a doctor for 
advice right away. If possible, show the doctor the pack, or this leaflet. You may require medical 
attention. 
 
If you forget to take Inlyta 
Take your next dose at your regular time. Do not take a double dose to make up for the forgotten 
tablets. 
 
If you vomit while taking Inlyta 
If you vomit, an additional dose should not be taken. The next prescribed dose should be taken at 
the usual time. 
 
If you stop taking Inlyta 
If you are not able to take this medicine as your doctor prescribed or you feel you do not need it 
anymore, contact your doctor right away.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Some side effects could be serious. You must immediately contact your doctor if you 
experience any of those following serious side effects (see also section 2 “What you need to 
know before you take Inlyta”): 
 
• Heart failure events. Tell your doctor if you experience excessive tiredness, swelling of the 

abdomen, legs, or ankles, shortness of breath, or protruding neck veins. 
 



52 

• Blood clots in your veins and arteries (types of blood vessels), including stroke, heart 
attack, embolism, or thrombosis. Get emergency help right away and call your doctor if 
you get symptoms such as chest pain or pressure; pain in your arms, back, neck or jaw; 
shortness of breath; numbness or weakness on one side of your body; trouble talking; 
headache; vision changes: or dizziness. 
 

• Bleeding. Tell your doctor right away if you have any of these symptoms or a serious 
bleeding problem during treatment with Inlyta: black tarry stools, coughing up of blood or 
bloody sputum, or change in your mental status.  

 
• Hole in the stomach or intestine or formation of fistula (abnormal tube-like passage 

from one normal body cavity to another body cavity or the skin). Tell your doctor if you 
have severe abdominal pain. 

 
• Severe increase in blood pressure (hypertensive crisis). Tell your doctor if you have a 

very high blood pressure, severe headache, or severe chest pain. 
 

• Reversible swelling of the brain (posterior reversible encephalopathy syndrome). Get 
emergency help right away and call your doctor if you get symptoms such as headache, 
confusion, seizures (fits), or changes in vision with or without high blood pressure. 

 
Other side effects with Inlyta may include: 

 
Very common: may affect more than 1 in 10 people 
• High blood pressure, or increases in blood pressure 
• Diarrhoea, feeling or being sick (nausea or vomiting), stomach ache, indigestion, soreness of 

the mouth, tongue or throat, constipation  
• Shortness of breath, cough, hoarseness 
• Lack of energy, feeling weak or tired 
• Under-active thyroid gland (may show in your blood tests) 
• Redness and swelling of the palms of the hands or soles of the feet (hand-foot syndrome), 

skin rash, dryness of the skin 
• Joint pain, pain in hands or feet 
• Loss of appetite 
• Protein in the urine (may show in your urine tests) 
• Weight loss 
• Headache, taste disturbance or loss of taste 

 
Common: may affect up to 1 in 10 people 
• Dehydration (loss of body fluids) 
• Kidney failure 
• Flatulence (wind), haemorrhoids, bleeding from gums, bleeding from the rectum, a burning 

or stinging sensation in the mouth 
• Hyper-active thyroid gland (may show in your blood tests) 
• Sore throat or nose and throat irritation 
• Muscle pain 
• Nose bleeding 
• Skin itching, redness of the skin, hair loss 
• Ringing/sound in the ears (tinnitus) 
• Reduction in the number of red blood cells (may show in your blood tests) 
• Reduction in the number of blood platelets (cells that help blood to clot) (may show in your 

blood tests) 
• Presence of red blood cells in the urine (may show in your urine tests) 



53 

• Changes in the levels of different chemicals/enzymes in the blood (may show in your blood 
tests) 

• Increase in the number of red blood cells (may show in your blood tests) 
• Swelling of the abdomen, legs, or ankles, protruding neck veins, excessive tiredness, 

shortness of breath (signs of heart failure events) 
• Fistula (abnormal tube like passage from one normal body cavity to another body cavity or 

the skin) 
• Dizziness  
• Inflammation of the gall bladder 
 
Uncommon: may affect up to 1 in 100 people 
• Reduction in the number of white blood cells (may show in your blood tests) 
 
Not known: frequency cannot be estimated from the available data 
• An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall 

(aneurysms and artery dissections). 
 
 
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 Inlyta 
 
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 carton and on the blister foil or 
bottle after “EXP”. The expiry date refers to the last day of the month. 
 
This medicine does not require any special storage conditions. 
 
Do not use any pack that is damaged or shows signs of tampering. 
 
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 Inlyta contains  
• The active substance is axitinib. Inlyta film-coated tablets come in different strengths. 

Inlyta 1 mg: each tablet contains 1 mg axitinib 
Inlyta 3 mg: each tablet contains 3 mg axitinib 
Inlyta 5 mg: each tablet contains 5 mg axitinib 
Inlyta 7 mg: each tablet contains 7 mg axitinib 

 
• The other ingredients are microcrystalline cellulose, lactose monohydrate, croscarmellose 

sodium, magnesium stearate, hypromellose 2910 (15 mPa·s), titanium dioxide (E171), 
triacetin (E1518), iron oxide red (E172) (see section 2 Inlyta contains lactose (milk sugar)). 

 

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


54 

What Inlyta looks like and contents of the pack 
 
Inlyta 1 mg film-coated tablets are red, oval and debossed with “Pfizer” on one side and “1 XNB” 
on the other. Inlyta 1 mg is available in bottles of 180 tablets and blisters of 14 tablets. Each blister 
pack contains 28 tablets or 56 tablets. 
 
Inlyta 3 mg film-coated tablets are red, round and debossed with “Pfizer” on one side and “3 XNB” 
on the other. Inlyta 3 mg is available in bottles of 60 tablets and blisters of 14 tablets. Each blister 
pack contains 28 tablets or 56 tablets. 
 
Inlyta 5 mg film-coated tablets are red, triangular and debossed with “Pfizer” on one side and 
“5 XNB” on the other. Inlyta 5 mg is available in bottles of 60 tablets and blisters of 14 tablets. Each 
blister pack contains 28 tablets or 56 tablets. 
 
Inlyta 7 mg film-coated tablets are red, diamond shaped and debossed with “Pfizer” on one side and 
“7 XNB” on the other. Inlyta 7 mg is available in bottles of 60 tablets and blisters of 14 tablets. Each 
blister pack contains 28 tablets or 56 tablets. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
 
Pfizer Europe MA EEIG 
Boulevard de la Plaine 17 
1050 Bruxelles 
Belgium 
 
Manufacturer  
 
Pfizer Manufacturing Deutschland GmbH 
Betriebsstätte Freiburg 
Mooswaldallee 1 
79090 Freiburg 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
 
Belgique/ België /Belgien 
Pfizer S.A. / N.V. 
Tél/Tel: +32 (0)2 554 62 11 

Lietuva 
Pfizer Luxembourg SARL filialas Lietuvoje 
Tel. + 370 52 51 4000 
 

България 
Пфайзер Люксембург САРЛ, Клон България 
Тел.: +359 2 970 4333 

Luxembourg/Luxemburg 
Pfizer S.A. 
Tél/Tel: +32 (0)2 554 62 11 
 

Česká republika 
Pfizer PFE, spol. s r.o. 
Tel: +420 283 004 111 

Magyarország 
Pfizer Kft. 
Tel.: +36-1-488-37-00 



55 

Danmark 
Pfizer ApS 
Tlf: +45 44 20 11 00 
 

Malta 
Vivian Corporation Ltd. 
Tel: +356 21344610 

Deutschland 
Pfizer Pharma GmbH 
Tel: +49 (0)30 550055 51000 
  

Nederland 
Pfizer BV 
Tel: +31 (0)10 406 43 01 
 

Eesti 
Pfizer Luxembourg SARL Eesti filiaal  
Tel.: +372 666 7500 

Norge 
Pfizer Norge AS 
Tlf: +47 67 52 61 00 
 

Ελλάδα 
Pfizer Ελλάς A.E. 
Τηλ: +30 210 6785 800 

Österreich 
Pfizer Corporation Austria Ges.m.b.H. 
Tel: +43 (0)1 521 15-0 
 

España 
Pfizer S.L. 
Tél: +34 91 490 99 00 

Polska 
Pfizer Polska Sp. z o.o. 
Tel.:+48 22 335 61 00 
 

France 
Pfizer  
Tél: +33 (0)1 58 07 34 40 

Portugal 
Pfizer Biofarmacêutica, Sociedade 
Unipessoal Lda 
Tel: +351 21 423 5500 
 

Hrvatska  
Pfizer Croatia d.o.o. 
Tel: + 385 1 3908 777 

România 
Pfizer Romania S.R.L. 
Tel: +40 (0) 21 207 28 00 
 

Ireland 
Pfizer Healthcare Ireland 
Tel: 1800 633 363 (toll free) 
+44 (0)1304 616161 

Slovenija 
Pfizer Luxembourg SARL 
Pfizer, podružnica za svetovanje s področja 
farmacevtske dejavnosti, Ljubljana 
Tel.: + 386 (0)1 52 11 400 
 

Ísland 
Icepharma hf. 
Sími: +354 540 8000 
 

Slovenská republika 
Pfizer Luxembourg SARL, organizačná zložka  
Tel.: + 421 2 3355 5500 

Italia 
Pfizer S.r.l. 
Tel: +39 06 33 18 21 

Suomi/Finland 
Pfizer Oy 
Puh./Tel: +358 (0)9 43 00 40 

Kύπρος 
Pfizer Ελλάς Α.Ε. (Cyprus Branch)  
Τηλ: +357 22 817690 
 

Sverige  
Pfizer Innovations AB 
Tel: +46 (0)8 550 520 00 
 

Latvija 
Pfizer Luxembourg SARL filiāle Latvijā 
Tel.: + 371 670 35 775 
 

United Kingdom 
Pfizer Limited 
Tel: +44 (0) 1304 616161 

 



56 

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/. 

http://www.ema.europa.eu/
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57 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 

 
 
 
 
 

 



58 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for axitinib, the scientific 
conclusions of CHMP are as follows:  
 
Based on the review of the data submitted in the PSUR procedure, including case reports and one 
literature article, and considering that a plausible biological mechanism exists, there is at least a 
reasonable possibility that axitinib may cause cholecystitis. Therefore, the product information 
should be updated to include cholecystitis as an ADR in section 4.8 of the SmPC and section 4 of 
the PL, with frequency ‘common’.  
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
 
On the basis of the scientific conclusions for axitinib the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing axitinib is unchanged subject to the 
proposed changes to the product information. 
 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 


	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
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)