INLYTA Ref.[4261] Active ingredients: Axitinib

Treatment with Inlyta should be conducted by a physician experienced in the use of anticancer therapies.

Posology

The recommended starting 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.

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).

n 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.

In cases of suspected overdose, axitinib should be withheld and supportive care instituted.

3 years.

This medicinal product does not require any special storage conditions.

1 mg, 3 mg, 5 mg, 7 mg film-coated tablets: Aluminium/aluminium blister containing 14 film-coated tablets. Each pack contains 28 or 56 film-coated tablets.

1 mg film-coated tablets: HDPE bottle with a silica gel desiccant and a polypropylene closure containing 180 film-coated tablets.

3 mg, 5 mg, 7 mg 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.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.