Axitinib tablets are indicated for the management of advanced renal cell carcinoma (RCC) in patients whose disease has progressed following one prior systemic therapy.

Axitinib acts as an inhibitor of receptor tyrosine kinases, specifically targeting vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma levels. These receptors play a crucial role in abnormal angiogenesis, tumor development, and cancer progression. In vitro studies and animal models have demonstrated that axitinib suppresses VEGF-driven endothelial cell proliferation and survival. Additionally, axitinib has been shown to reduce tumor growth and inhibit VEGFR-2 phosphorylation in xenograft mouse models.

Recommended Dosing: The recommended starting oral dose of Axitinib is 5 mg twice daily. Administer Axitinib doses approximately 12 hours apart with or without food. Axitinib 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 Modification Guidelines: Dose increase or reduction is recommended based on individual safety and tolerability.

Over the course of treatment, patients who tolerate Axitinib for at least two consecutive weeks with no adverse reactions > Grade 2 (according to the Common Toxicity Criteria for Adverse Events), are normotensive, and are not receiving anti-hypertension medication, may have their dose increased. When a dose increase from 5 mg twice daily is recommended, the Axitinib 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 Axitinib therapy. 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.

In vitro studies suggest that axitinib is primarily metabolized by CYP3A4/5, with minor contributions from CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1.

CYP3A4/5 Inhibitors: Concurrent use of ketoconazole, a potent CYP3A4/5 inhibitor, has been shown to increase axitinib plasma levels in healthy individuals. Therefore, co-administration with strong CYP3A4/5 inhibitors should be avoided. Consumption of grapefruit or grapefruit juice may also elevate axitinib concentrations and should be avoided. It is advisable to select alternative medications with little or no CYP3A4/5 inhibitory effect. If unavoidable, the dose of axitinib should be reduced when used with strong inhibitors.

CYP3A4/5 Inducers: Co-administration with rifampin, a strong CYP3A4/5 inducer, has been shown to decrease axitinib plasma exposure in healthy subjects. Use of axitinib alongside strong CYP3A4/5 inducers (such as rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and St. John’s wort) should be avoided. Preferably, alternative drugs with minimal induction potential should be selected. Moderate CYP3A4/5 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) may also lower axitinib levels and should be avoided whenever possible.

No specific contraindications have been identified.

Adverse reactions reported in less than 10% of patients receiving axitinib include dizziness (9%), upper abdominal pain (8%), myalgia (7%), dehydration (6%), epistaxis (6%), anemia (4%), hemorrhoids (4%), hematuria (3%), tinnitus (3%), increased lipase (3%), glossodynia (3%), pulmonary embolism (2%), rectal hemorrhage (2%), hemoptysis (2%), deep vein thrombosis (1%), retinal vein occlusion/thrombosis (1%), polycythemia (1%), and transient ischemic attack (1%).

Pregnancy: Axitinib is classified as Pregnancy Category D and may cause fetal harm based on its mechanism of action. There are no adequate and well-controlled studies in pregnant women. Animal studies have demonstrated teratogenic, embryotoxic, and fetotoxic effects at exposures lower than those used clinically.

Women of reproductive potential should avoid pregnancy while taking axitinib. If pregnancy occurs during treatment, patients should be informed of the potential risks to the fetus.

Nursing Mothers: It is unknown whether axitinib is excreted in human breast milk. Due to the possibility of serious adverse reactions in nursing infants, a decision should be made to either discontinue breastfeeding or discontinue the drug, considering the importance of the treatment for the mother.

Hypertension, including severe hypertensive crisis, has been reported in patients receiving axitinib. Blood pressure should be adequately controlled before starting treatment. Regular monitoring is necessary, and antihypertensive therapy should be initiated when required. If hypertension persists despite treatment, the dose of axitinib should be reduced.

Both arterial and venous thromboembolic events have been observed and may be life-threatening. Axitinib should be used cautiously in patients with an increased risk of thrombosis.

Hemorrhagic events, including fatal cases, have been reported. Axitinib has not been evaluated in patients with untreated brain metastases or recent significant gastrointestinal bleeding and should be avoided in such cases.

Cardiac failure has been reported and may be fatal. Patients should be monitored for signs and symptoms of heart failure throughout therapy.

Gastrointestinal perforation and fistula formation, including fatal outcomes, have occurred. Use caution in patients at risk for these conditions.

Hypothyroidism requiring thyroid hormone replacement therapy has been reported. Thyroid function should be assessed before initiating treatment and monitored regularly during therapy.

Axitinib should be discontinued at least 24 hours prior to any planned surgical procedure.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been reported. If symptoms suggestive of RPLS develop, axitinib should be permanently discontinued.

Proteinuria has been observed during treatment. Urine protein levels should be monitored before and during therapy. In cases of moderate to severe proteinuria, dose reduction or temporary interruption of treatment is recommended.

Elevations in liver enzymes have been reported. Liver function tests, including ALT, AST, and bilirubin, should be checked before and periodically during treatment.

Dose adjustment is required in patients with moderate hepatic impairment. Axitinib has not been studied in patients with severe hepatic impairment.

Based on its mechanism of action, axitinib may cause fetal harm. Women of reproductive potential should be advised of the risks and should avoid pregnancy while receiving treatment.

Strong CYP3A4/5 Inhibitors: Concurrent use of strong CYP3A4/5 inhibitors (such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) should be avoided. It is recommended to select alternative medications with little or no CYP3A4/5 inhibitory activity. Although dose adjustment has not been formally studied, if co-administration is unavoidable, the axitinib dose should be reduced by approximately 50% to maintain plasma exposure within the expected range. Dose adjustments may then be made based on individual patient tolerability and safety. Once the strong inhibitor is discontinued, the axitinib dose should be returned to the previous level after approximately 3–5 half-lives of the inhibitor.

Hepatic Impairment: No initial dose adjustment is necessary for patients with mild hepatic impairment (Child-Pugh class A). However, in patients with moderate hepatic impairment (Child-Pugh class B), the starting dose should be reduced by about half based on pharmacokinetic data. Further dose adjustments may be made depending on patient response and tolerability. Axitinib has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C).

There is no specific antidote for axitinib overdose. In a controlled clinical trial, one patient accidentally received 20 mg twice daily for 4 days and experienced mild dizziness (Grade 1). In dose-escalation studies, higher doses (10 mg or 20 mg twice daily) were associated with adverse events such as hypertension, seizures related to hypertension, and fatal hemoptysis. In case of suspected overdose, treatment with axitinib should be stopped and supportive care should be provided.

Targeted anticancer agent.

Store below 25°C, protected from light and moisture. Keep out of the reach of children.