Inlyta 1 mg film-coated tablets

Inlyta 3 mg film-coated tablets

Inlyta 5 mg film-coated tablets

Inlyta 7 mg film-coated tablets

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 tablets

Each film-coated tablet contains 33.6 mg of lactose monohydrate.

Inlyta 3 mg film-coated tablets

Each film-coated tablet contains 35.3 mg of lactose monohydrate.

Inlyta 5 mg film-coated tablets

Each film-coated tablet contains 58.8 mg of lactose monohydrate.

Inlyta 7 mg film-coated tablets

Each film-coated tablet contains 82.3 mg of lactose monohydrate.

For the full list of excipients, see section 6.1.

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

Inlyta 7 mg film-coated tablets

Red diamond shaped film-coated tablet debossed with “Pfizer” on one side and “7 XNB” on the other

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.

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 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

Older people (≥ 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 axitinib in children and adolescents < 18 years have not been established. No data are available.

Method of administration

Axitinib should be taken orally twice daily approximately 12 hours apart with or without food (see section 5.2). Axitinib tablets should be swallowed whole with a glass of water.

Hypersensitivity to axitinib or to any of the excipients listed in section 6.1.

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.

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.

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.

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.

Older people (≥ 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.