Indications:

Axinix  5 mg is prescribed for the treatment of advanced renal cell carcinoma (RCC) after the failure of one prior systemic therapy.

Pharmacology:

Axitinib functions by inhibiting receptor tyrosine kinases, particularly vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3, at therapeutic plasma concentrations. These receptors play vital roles in pathologic angiogenesis, tumor growth, and cancer progression. Axitinib has been demonstrated to impede VEGF-mediated endothelial cell proliferation and survival in both laboratory experiments and mouse models, leading to inhibited tumor growth and reduced phosphorylation of VEGFR-2 in tumor xenograft mouse models.

Dosage & Administration:

Recommended Dosing: The initial oral dose of Axitinib is typically 5 mg taken twice daily. Axitinib doses should be administered approximately 12 hours apart, with or without food, and swallowed whole with water. Patients should not take an additional dose if they vomit or miss a scheduled dose; instead, they should resume with the next prescribed dose at the usual time.

Dose Modification Guidelines: Adjustments to the dose, either an increase or reduction, should be made based on individual safety and tolerability.

In cases where patients tolerate Axitinib for at least two consecutive weeks without experiencing adverse reactions greater than Grade 2, maintaining normal blood pressure and not requiring antihypertensive medication, dose escalation may be considered. The dose may be increased to 7 mg twice daily and further to 10 mg twice daily using the same criteria.

Throughout treatment, some adverse drug reactions may necessitate temporary interruption, permanent discontinuation, and/or dose reduction of Axitinib therapy. If dose reduction is warranted from the initial 5 mg twice daily dose, the recommended dose is 3 mg twice daily. Further dose reduction may be considered, with the recommended dose being 2 mg twice daily.

Interaction:

Axitinib is primarily metabolized by CYP3A4/5, with minor contributions from CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1.

CYP3A4/5 Inhibitors: Co-administration of strong CYP3A4/5 inhibitors, such as ketoconazole, can increase the plasma exposure of Axitinib. Therefore, concurrent use of Axitinib with strong CYP3A4/5 inhibitors should be avoided. Grapefruit or grapefruit juice may also elevate Axitinib plasma concentrations and should be avoided. Selecting concomitant medication with minimal or no inhibition potential for CYP3A4/5 is advised. If co-administration with a strong CYP3A4/5 inhibitor is necessary, Axitinib dosage should be reduced.

CYP3A4/5 Inducers: Strong inducers of CYP3A4/5, such as rifampin, can decrease the plasma exposure of Axitinib. Thus, combining Axitinib with strong CYP3A4/5 inducers should be avoided. Moderate CYP3A4/5 inducers may also reduce Axitinib plasma levels and should be avoided if possible.

Contraindications:

There are no contraindications for Axitinib use.

Side Effects:

Adverse reactions reported in less than 10% of patients treated with Axitinib include dizziness, upper abdominal pain, myalgia, dehydration, epistaxis, anemia, hemorrhoids, hematuria, tinnitus, lipase increased, glossodynia, pulmonary embolism, rectal hemorrhage, hemoptysis, deep vein thrombosis, retinal-vein occlusion/thrombosis, polycythemia, and transient ischemic attack.

Pregnancy & Lactation:

Axitinib is classified as Pregnancy Category D and can cause fetal harm if administered to pregnant women. There are inadequate studies on pregnant women using Axitinib, but developmental toxicity studies in mice have shown teratogenic, embryotoxic, and fetotoxic effects at maternal exposures lower than those seen with the recommended clinical dose. Women of childbearing potential should avoid pregnancy during Axitinib treatment. If pregnancy occurs during treatment, the patient should be informed of the potential risk to the fetus.

It is unknown whether Axitinib is excreted in human milk. Considering the potential for serious adverse reactions in nursing infants from Axitinib, nursing mothers should decide whether to discontinue breastfeeding or discontinue the drug, weighing the importance of the drug to the mother.

Precautions & Warnings:

Axitinib should be used cautiously in patients with hypertension, cardiac disease, a history of or risk for thrombosis, those taking strong CYP3A4 inhibitors, and those with moderate hepatic impairment (Child-Pugh Class B). Treatment should be withheld at least 24 hours before scheduled surgery.

Use in Special Populations:

No dosage adjustments are necessary in elderly patients.

Overdose Effects:

There is no specific treatment for Axitinib overdose. In cases of suspected overdose, Axitinib should be withheld, and supportive care instituted.

Therapeutic Class:

Axitinib belongs to the class of targeted cancer therapy drugs.

Storage Conditions:

Axitinib should be stored at temperatures between 20°C to 25°C.