Prescribing information for INLYTA® (axitinib)

PRESCRIBING INFORMATION

Inlyta (axitinib) Film-Coated Tablets Please refer to the Summary of Product Characteristics (SmPC) before prescribing Inlyta 1 mg or 5 mg film-coated tablets.

Presentation: Each 1 mg and 5 mg film-coated tablet contains 1 mg and 5 mg of axitinib, respectively.

Indications: For the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine.

Dosage: Treatment should be initiated by a physician experienced in the use of anticancer therapies. The recommended oral dose is 5 mg twice daily (approximately 12 hours apart) taken with or without food. Dose increase or reduction is recommended based on individual safety and tolerability. Patients who tolerate the starting dose of 5 mg twice daily with no adverse reactions > Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) for two consecutive weeks may have their dose increased to 7 mg twice daily unless BP > 150/90 mmHg or patient is receiving anti-hypertensive medication. Subsequently, using the same criteria, patients who tolerate a dose of 7 mg twice daily, may have their dose increased to a maximum of 10 mg twice daily. Management of some adverse drug reactions may require temporary or permanent discontinuation and/or dose reduction. When dose reduction is necessary, the dose may be reduced to 3 mg twice daily and further to 2 mg twice daily. Co-administration with strong CYP3A4/5 inhibitors or inducers may increase or decrease axitinib plasma concentrations respectively. Selection of an alternative concomitant medicine with no or minimal CYP3A4/5 inhibition or induction potential is recommended. If a strong CYP3A4/5 inhibitor must be co-administered, a dose decrease of axitinib to approximately half the dose (e.g. from a starting dose of 5 mg twice daily to a reduced dose of 2 mg twice daily) is recommended. If co-administration of the strong inhibitor is discontinued, a return to the axitinib dose used prior to initiation of the CYP3A4/5 inhibitor should be considered. If a strong CYP3A4/5 inducer must be co-administered, a gradual dose increase is recommended with careful monitoring for toxicity. 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. No dose adjustment is required in elderly patients or patients with renal impairment or with mild hepatic impairment (Child Pugh class A). A dose decrease is recommended in 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. Dose adjustment is not required on the basis of patient age, race, gender, or body weight. The safety and efficacy of axitinib in children (<18 years) have not been established.

Contra-indications: Hypersensitivity to axitinib or to any of the excipients.

Special warnings and precautions for use: Signs or symptoms of cardiac failure should periodically be monitored throughout treatment. Management of cardiac failure events may require temporary interruption or permanent discontinuation and/or dose reduction of axitinib therapy. Blood pressure should be well-controlled prior to initiation. 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 therapy should be monitored for hypotension. In case of severe or persistent arterial hypertension and symptoms suggestive of posterior reversible encephalopathy syndrome (PRES), a diagnostic brain MRI should be considered. Thyroid function should be monitored before initiation of, and periodically throughout, treatment. Hypothyroidism and, to a lesser extent, hyperthyroidism were reported in clinical studies and should be treated as per standard medical practice to maintain a euthyroid state. Arterial embolic and thrombotic events (including transient ischaemic attack, myocardial infarction, cerebrovascular accident and retinal artery occlusion) and venous embolic and thrombotic events (including pulmonary embolism, deep vein thrombosis, and retinal vein occlusion/thrombosis) were reported in clinical studies and axitinib should be used with caution in patients at risk of or who have a history of these events. Increases in haemoglobin or haematocrit, reflective of increase in red blood cell mass may occur during treatment and should be monitored before initiation of, and periodically throughout, treatment and treated as per standard medical practice. An increase in red blood cell mass may increase the risk of embolic and thrombotic events. Haemorrhagic events (most commonly epistaxis, haematuria, rectal haemorrhage and gingival bleeding) were reported in clinical studies. 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. Temporarily interrupt treatment if any bleeding requires medical intervention. The use of VEGF pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections. Before initiating axitinib, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm. Events of gastrointestinal perforation and fistulas were reported in clinical studies and symptoms for these should be monitored periodically throughout treatment. Treatment with axitinib should be stopped at least 24 hours prior to scheduled surgery and the decision to resume therapy after surgery should be based on clinical judgment of adequate wound healing. Events of PRES (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) were reported in clinical studies. MRI is necessary to confirm diagnosis. In patients with signs or symptoms of PRES, temporarily interrupt or permanently discontinue axitinib treatment. The safety of reinitiating therapy in patients previously experiencing PRES is not known. Proteinuria, including that of Grade 3 and 4 severity, was reported in clinical studies. Monitoring for proteinuria before initiation of, and periodically throughout, treatment with axitinib is recommended. In moderate to severe proteinuria reduce the dose or temporarily interrupt treatment. Axitinib should be discontinued if the patient develops nephrotic syndrome. Increases in ALT, AST and bilirubin have been reported. Liver function tests should be monitored before initiation of, and periodically throughout, treatment. 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. In these patients dose decrease is recommended (see Dosage section). Axitinib has not been studied in patients with severe hepatic impairment (Child Pugh class C) and should not be used in these patients. Contains lactose and patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Other interactions: Axitinib is metabolised primarily by CYP3A4/5 and, to a lesser extent, CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1. If a strong CYP3A4/5 inhibitor (e.g. itraconazole, clarithromycin, erythromycin) or inducer (rifampicin, dexamethasone phenytoin, and Hypericum perforatum [St. John’s wort]) must be co-administered, a dose adjustment of axitinib is recommended (see Dosage section). In patients taking strong inhibitors of CYP1A2 and CYP2C19 caution should be exercised due to the risk of increased axitinib plasma concentrations.

Fertility, pregnancy and lactation: Axitinib may cause foetal harm when administered to a pregnant woman. Studies in animals have shown reproductive toxicity including foetal malformations. Axitinib should not be used during pregnancy unless the clinical condition of the woman requires treatment. Axitinib should not be used during breast-feeding and women of childbearing potential must use effective contraception during and up to 1 week after treatment. Fertility may be impaired during treatment.

Driving and operating machinery: Axitinib has a minor influence on the ability to drive and use machines. Advise patients that they may experience dizziness and/or fatigue during treatment.

Undesirable effects: The most important serious adverse reactions reported in patients receiving axitinib were 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. Very common (³ 1/10) adverse events are hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, haemorrhage, dyspnoea, cough, dysphonia, diarrhoea, vomiting, nausea, abdominal pain, stomatitis, constipation, dyspepsia, palmar-plantar erythrodysaesthesia (hand-foot syndrome), rash, dry skin, arthralgia, pain in extremity, proteinuria, fatigue, asthaenia, mucosal inflammation, weight decreased. Common (³ 1/100 to < 1/10) reported adverse events are anaemia, thrombocytopenia, polycythaemia, hyperthyroidism, dehydration, hyperkalaemia, hypercalcaemia, dizziness, tinnitus, cardiac failure events, venous and arterial embolic and thrombotic events, oropharyngeal pain, upper abdominal pain, flatulence, haemorrhoids, glossodynia, gastrointestinal perforation and fistula, hyperbilirubinaemia, cholecystitis, pruritus, erythema, alopecia, myalgia, renal failure, thyroid stimulating hormone increased, lipase increased, and ALT, AST, alkaline phosphatase, creatinine and amylase increased. Refer to SmPC for information on other adverse effects.

Legal Category: S1A

Marketing Authorisation Number: EU/1/12/777/002 - 1 mg (56 tablets); EU/1/12/777/005 - 5 mg (56 tablets).

Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at [email protected]. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500.

Last revised: November 2019

Ref: IL 11_1

PP-INL-IRL-0060 April 2020