You are here: Urology Textbook > Drugs in Urology > Axitinib

Axitinib: Indications, Adverse Effects, Contraindications and Dosage

Mechanism of Action of Axitinib

Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3). By blocking VEGFR-mediated signaling, axitinib suppresses pathologic angiogenesis and tumor vascular permeability. Treatment will also lead to apoptosis of tumor cells.

Urological Indications for Axitinib

Axitinib is indicated for advanced or metastatic renal cell carcinoma. Clinicians use axitinib as monotherapy after disease progression on one prior systemic therapy and, in contemporary practice, as a first-line combination partner with avelumab or pembrolizumab.

As second-line monotherapy: A randomized phase 3 trial (AXIS, Rini et al., 2011) demonstrated improved progression-free survival with axitinib versus sorafenib (6.7 vs. 4.7 months).

Pharmacokinetics of Axitinib

Administer axitinib orally. Hepatic metabolism (mainly CYP3A4/5). The terminal elimination half-life is approximately 2.5–6 hours.

Adverse Effects of Axitinib

The most common side effects include diarrhea, hypertension, fatigue, dysphonia, nausea, decreased appetite, and palmar–plantar erythrodysesthesia (hand–foot syndrome). Where available, grade ≥3 incidence appears in parentheses.

Gastrointestinal tract:

Diarrhea (10%), vomiting (1–2%).

Skin:

Hand-foot syndrome (5%), mucositis (1–2%).

Cardiovascular:

Hypertension (15%), arterial or venous thromboembolism (2–3%).

Other adverse effects:

Hypothyroidism, lack of appetite (3%), dehydration (2–3%), fatigue (10%).

Drug Interactions with Axitinib

Avoid concomitant use with strong CYP3A4/5 inhibitors (e.g., clarithromycin, ketoconazole, grapefruit) or strong inducers (e.g., rifampin), as they can significantly alter axitinib exposure.

Contraindications of Axitinib

• Severe hepatic impairment (Child-Pugh C)
• Pregnancy and lactation
• Discontinue axitinib for persistent or recurrent grade 3–4 toxicity despite dose modifications

Dosage of Axitinib

Start at 5 mg by mouth twice daily (approximately every 12 hours) with or without food. If tolerated, titrate at 1–2-week intervals to 7 mg twice daily and then 10 mg twice daily. For adverse reactions, reduce stepwise to 3 mg twice daily and then 2 mg twice daily, or interrupt therapy according to labeling.

Clinical Controls During Therapy:

Measure blood pressure at baseline and regularly thereafter. Periodically obtain a complete blood count, electrolytes, liver function tests, thyroid function, serum creatinine and blood glucose. Examine the skin and oral mucosa as clinically indicated.

Supportive Therapy:

Treat diarrhea with loperamide. Use gentle mouth rinses for mucositis. Manage hand–foot skin reaction by reducing friction and pressure, and consider keratolytics or low- to mid-potency topical corticosteroids. Treat hypertension with standard antihypertensive therapy. Replace thyroid hormone for hypothyroidism. If toxicity persists, reduce the dose or interrupt therapy.

References

Rini, B. I.; Escudier, B.; Tomczak, P.; Kaprin, A.; Szczylik, C.; Hutson, T. E.; Michaelson, M. D.; Gorbunova, V. A.; Gore, M. E.; Rusakov, I. G.; Negrier, S.; Ou, Y.; Castellano, D.; Lim, H. Y.; Uemura, H.; Tarazi, J.; Cella, D.; Chen, C.; Rosbrook, B.; Kim, S. & Motzer, R. J. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.
Lancet, 2011, 378, 1931-1939.

  Deutsche Version: Axitinib

Urology-Textbook.com – Choose the Ad-Free, Professional Resource

This website is designed for physicians and medical professionals. It presents diseases of the genital organs through detailed text and images. Some content may not be suitable for children or sensitive readers. Many illustrations are available exclusively to Steady members. Are you a physician and interested in supporting this project? Join Steady to unlock full access to all images and enjoy an ad-free experience. Try it free for 7 days—no obligation.

New release: The first edition of the Urology Textbook as an e-book—ideal for offline reading and quick reference. With over 1300 pages and hundreds of illustrations, it’s the perfect companion for residents and medical students. After your 7-day trial has ended, you will receive a download link for your exclusive e-book.