INLYTA TABLETS 5MG

4.1 Therapeutic indications

INLYTA® is indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

4.3 Contraindications

None

4.2 Posology and method of administration

Posology

The recommended starting oral dose of INLYTA® is 5 mg twice daily. Administer INLYTA® doses approximately 12 hours apart with or without food (see Section 5.2 Pharmacokinetic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). INLYTA® should be swallowed whole with a glass of water.

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.

Over the course of treatment, patients who tolerate INLYTA® for at least two consecutive weeks with no adverse reactions >Grade 2 (according to the Common Toxicity Criteria for Adverse Events [CTCAE]), are normotensive, and are not receiving anti-hypertensive medication, may have their dose increased. When a dose increase from 5 mg twice daily is recommended, the INLYTA® dose may be increased to 7 mg twice daily, and further to 10 mg twice daily using the same criteria.

Over the course of treatment, management of some adverse drug reactions may require temporary interruption or permanent discontinuation and/or dose reduction of INLYTA® therapy (see Section 4.4 Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). If dose reduction from 5 mg twice daily is required, the recommended dose is 3 mg twice daily. If additional dose reduction is required, the recommended dose is 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

The concomitant use of strong CYP3A4/5 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole). Selection of an alternate concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. Although INLYTA® 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 INLYTA® by approximately half is recommended, as this dose reduction is predicted to adjust the axitinib area under the plasma concentration versus time curve (AUC) to the range observed without inhibitors. The subsequent doses can be increased or decreased based on individual safety and tolerability. If co-administration of the strong inhibitor is discontinued, the INLYTA® dose should be returned (after 3 – 5 half-lives of the inhibitor) to that used prior to initiation of the strong CYP3A4/5 inhibitor (see Sections 4.5 Interaction with other medicinal products and other forms of interaction, CYP3A4/5 inhibitors and 5.2 Pharmacokinetic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Concomitant strong CYP3A4/5 inducers

Co-administration of axitinib with strong CYP3A4/5 inducers (e.g., rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, and Hypericum perforatum [also known as St. John’s wort]) may decrease axitinib plasma concentrations. Selection of an alternate concomitant medication 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. If the dose of axitinib is increased, the patient should be monitored carefully 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.

Use in pediatrics

The safety and efficacy of INLYTA® in pediatric patients have not been studied.

Use in the elderly

No dosage adjustment is required in elderly patients (see Section 5.2 Pharmacokinetic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment

No starting dose adjustment is required when administering INLYTA® to patients with mild hepatic impairment (Child-Pugh class A). Based on the pharmacokinetic data, the INLYTA® starting dose should be reduced by approximately half in patients with baseline moderate hepatic impairment (Child-Pugh class B). The subsequent doses can be increased or decreased based on individual safety and tolerability. INLYTA® has not been studied in patients with severe hepatic impairment (Child-Pugh class C) (see Sections 4.4 Special warnings and precautions for use, Elevation of liver enzymes and 5.2 Pharmacokinetic properties, Special populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Renal impairment

No starting dose adjustment is needed for patients with pre-existing mild to severe renal impairment (see Section 5.2 Pharmacokinetic properties, Special populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).