Axitinib Tablets

Indications & Uses of Axitinib Tablets

• Advanced Renal Cell Carcinoma (RCC): Indicated as a single agent for the treatment of patients with advanced renal cell carcinoma after failure of one prior systemic therapy.
• First-Line Combination Therapy: Widely utilized in synergistic combination regimens (with immune checkpoint inhibitors such as pembrolizumab or avelumab) for treatment-naïve patients with advanced RCC.
• Second-Line & Subsequent Therapy: Serves as a vital targeted therapeutic option in refractory renal tumors that have progressed on prior cytokine or kinase inhibitor therapy.

Mechanism of Action (How Axitinib Works)

• Selective VEGFR Blockade: Potently inhibits vascular endothelial growth factor receptors VEGFR-1, VEGFR-2, and VEGFR-3 at sub-nanomolar concentrations.
• Anti-Angiogenesis: By blocking VEGF-mediated endothelial cell proliferation and survival, it halts the formation of new blood vessels (neovascularization) within the tumor microenvironment.
• Nutrient Starvation: The deprivation of oxygen and essential nutrients induces tumor starvation, inhibits cell proliferation, and reduces metastatic dissemination.

Side Effects of Axitinib

• Hypertension (elevated blood pressure, commonly emerging early in therapy)
• Gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain)
• Fatigue and generalized asthenia (weakness)
• Palmar-plantar erythrodysesthesia (hand-foot skin reaction)
• Decreased appetite, dysgeusia, and progressive weight loss
• Dysphonia (voice changes/hoarseness)
• Visual disturbances and skin/hair hypopigmentation

• Arterial and venous thromboembolic events (myocardial infarction, pulmonary embolism, stroke, deep vein thrombosis)
• Severe hemorrhagic complications (gastrointestinal bleeding, hemoptysis, intracranial hemorrhage)
• Gastrointestinal perforation and fistula formation
• Cardiac failure and left ventricular ejection fraction reduction
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS / PRES) characterized by headache, seizures, lethargy, and visual blindness
• Impaired wound healing and surgical wound dehiscence

Clinical Precautions with Axitinib

• Administration: Swallow tablets whole with water. Never crush, split, or chew the tablets.
• Antacid Timing: Avoid taking antacids within 2 hours before or 2 hours after administering Axitinib to prevent compromised oral absorption.
• Wound Management: Withhold Axitinib at least 24 to 48 hours prior to elective surgeries and dental procedures due to anti-angiogenic wound impairment.
• Pre-Existing Conditions: Exercise strict clinical caution in patients with uncontrolled hypertension, cardiovascular disease, hepatic impairment, bleeding diatheses, and thyroid dysfunction.

Warnings & Contraindications

• Pregnancy & Fetal Harm: Axitinib causes embryofetal lethality and severe teratogenicity. Effective non-hormonal contraception must be maintained by women of childbearing potential and male patients during therapy and for at least 1 week following discontinuation.
• Fertility: May impair male and female fertility; discuss reproductive preservation prior to initiation.
• Lactation: Breastfeeding must be discontinued during treatment and for 2 weeks after the last dose.
• Contraindications: Absolutely contraindicated in patients with known hypersensitivity to Axitinib or any inactive formulation ingredients.

Drug Interactions

• Strong CYP3A4/5 Inhibitors: Agents such as ketoconazole, itraconazole, clarithromycin, and atazanavir increase Axitinib plasma concentrations and toxicity. Dose adjustments are required.
• Strong CYP3A4/5 Inducers: Drugs like rifampin, carbamazepine, phenytoin, and St. John's Wort markedly reduce Axitinib efficacy and should be avoided.
• Theophylline: Concomitant administration increases theophylline plasma levels; monitor theophylline serum concentrations.
• Anticoagulants & NSAIDs: Concomitant use with aspirin, NSAIDs, or systemic anticoagulants (warfarin, heparin, DOACs) substantially elevates gastrointestinal bleeding risks.

Important Monitoring Parameters

• Blood pressure: Baseline measurement and weekly monitoring until stable, followed by ongoing assessment.
• Thyroid function: TSH, free T3, and free T4 monitoring for primary or secondary hypothyroidism.
• Liver function tests: ALT, AST, alkaline phosphatase, and total bilirubin prior to and during treatment.
• Urinalysis: Regular testing for proteinuria; evaluate 24-hour urine protein if dipstick shows 2+ or greater.
• Neurological status: Prompt evaluation for signs of RPLS in patients presenting with seizure, severe headache, or confusion.

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