Axitinib: Dose, Frequency, ROA, MOA, PK, PD, Usage & More

Axitinib is a tyrosine kinase inhibitor used primarily in the treatment of advanced renal cell carcinoma (RCC), a type of kidney cancer. It belongs to a class of medications known as vascular endothelial growth factor receptor (VEGFR) inhibitors, which work by blocking the activity of certain proteins involved in the growth and spread of cancer cells. Axitinib is available in tablet form and is typically used as a second-line or later treatment option for patients who have not responded to other therapies.

Recommended Dose and Dosage Regimen

The recommended dose of axitinib varies depending on the specific indication, the patient’s renal function, and other individual factors. For the treatment of advanced RCC, the typical starting dose is 5 mg orally twice daily, with dose adjustments made based on tolerability and response. The maximum recommended dose of axitinib is 10 mg twice daily. Patients should take axitinib consistently with or without food and swallow the tablets whole with a glass of water. It is essential to adhere to the prescribed dosing schedule and avoid missing doses to maintain therapeutic blood levels of axitinib.

Frequency of Administration

Axitinib tablets are typically administered orally twice daily, with approximately 12 hours between doses. Patients should take axitinib at the same times each day to maintain consistent blood levels of the medication. If a dose is missed, it should be taken as soon as remembered, unless it is almost time for the next scheduled dose. Patients should not double the dose to make up for a missed one and should resume the regular dosing schedule thereafter.

Route of Administration

Axitinib is administered orally as tablets and should be swallowed whole with a glass of water. Patients should not chew, crush, or break the tablets before swallowing. Axitinib can be taken with or without food, but patients should avoid consuming grapefruit or grapefruit juice during treatment, as it may increase the risk of side effects. Patients should also avoid consuming St. John’s wort, which may decrease the effectiveness of axitinib.

Mechanism of Action (MOA)

Axitinib exerts its pharmacological effects by selectively inhibiting the activity of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, which are involved in tumor angiogenesis and progression. By blocking the binding of vascular endothelial growth factor (VEGF) to its receptors, axitinib helps prevent the formation of new blood vessels that supply oxygen and nutrients to cancer cells, thereby slowing tumor growth and metastasis. Axitinib’s anti-angiogenic effects contribute to its therapeutic efficacy in the treatment of advanced RCC.

Pharmacokinetics (PK)

Following oral administration, axitinib is rapidly absorbed into the bloodstream, with peak plasma concentrations reached within 2-4 hours. The bioavailability of axitinib is approximately 58%, with food having a minimal effect on its absorption. Axitinib is extensively metabolized in the liver by cytochrome P450 enzymes, primarily CYP3A4, to form inactive metabolites. The elimination half-life of axitinib is approximately 2-6 hours, but the duration of pharmacological effects may be longer due to its potent inhibition of VEGFRs. Axitinib and its metabolites are predominantly eliminated in the feces and urine.

Pharmacodynamics (PD)

The pharmacodynamic effects of axitinib are primarily mediated by its inhibition of VEGFR signaling pathways, which are involved in tumor angiogenesis, proliferation, and metastasis. By blocking VEGFR 1, 2, and 3, axitinib disrupts the formation of new blood vessels that nourish cancerous tumors, leading to reduced tumor growth and metastatic spread. Axitinib’s anti-angiogenic effects contribute to its ability to prolong progression-free survival and overall survival in patients with advanced RCC.

Primary Indications

Axitinib is indicated for the treatment of advanced renal cell carcinoma (RCC) in patients who have failed prior systemic therapy. It may be used as monotherapy or in combination with other anticancer agents, depending on the individual patient’s disease characteristics and treatment history. Axitinib is typically reserved for patients with clear cell RCC, the most common subtype of RCC, who have experienced disease progression despite prior treatment with cytokine therapy or targeted agents such as sunitinib or sorafenib.

Contraindications

Contraindications to the use of axitinib include hypersensitivity to axitinib or any component of the formulation. Axitinib should not be used concomitantly with strong CYP3A4 inhibitors or inducers, as this may alter its systemic exposure and increase the risk of adverse effects. Axitinib is also contraindicated in patients with uncontrolled hypertension, as it may exacerbate hypertension and increase the risk of cardiovascular events. Patients with a history of hemorrhagic events or gastrointestinal perforation should use axitinib with caution.

Purpose of Taking Medication

The purpose of using axitinib is to slow the progression of advanced renal cell carcinoma (RCC) and improve progression-free survival and overall survival in patients who have failed prior systemic therapy. By inhibiting vascular endothelial growth factor receptors (VEGFR), axitinib helps disrupt tumor angiogenesis and reduce the growth and spread of cancer cells in the kidneys. Regular use of axitinib as prescribed by the healthcare provider is important for achieving and maintaining therapeutic efficacy and improving quality of life.

Usage Instructions

Patients should follow the instructions provided by their healthcare provider for the proper administration of axitinib tablets. The tablets should be swallowed whole with a glass of water and taken consistently at the same times each day. Patients should avoid consuming grapefruit or grapefruit juice during treatment, as it may increase the risk of side effects. Axitinib can be taken with or without food, but patients should maintain a consistent dosing schedule to ensure optimal drug levels in the bloodstream.

Precautions and Care

Patients taking axitinib should be closely monitored for signs of hypertension, proteinuria, bleeding, thromboembolic events, and gastrointestinal perforation, particularly during the initial weeks of treatment or following dose adjustments. Regular follow-up appointments with the healthcare provider are important for assessing therapeutic response, monitoring for adverse effects, and making necessary adjustments to the treatment plan. Patients should be educated about the potential risks and benefits of axitinib and instructed to seek medical attention if they experience any concerning symptoms.

Dietary Considerations

There are no specific dietary restrictions associated with the use of axitinib. However, patients should maintain a balanced diet and adequate hydration to support overall health and well-being during treatment. Patients should be cautious when consuming alcohol or other central nervous system depressants while taking axitinib, as this may increase the risk of side effects such as dizziness or drowsiness. Additionally, patients should avoid activities that require mental alertness or coordination until they know how axitinib affects them.

Possible Side Effects

Common side effects of axitinib may include hypertension, fatigue, diarrhea, nausea, dysphonia (hoarseness), and hand-foot syndrome (palmar-plantar erythrodysesthesia). Less common but more serious side effects may include proteinuria, bleeding, thromboembolic events, gastrointestinal perforation, and hepatic toxicity. Patients should be advised to report any new or worsening symptoms to their healthcare provider promptly. Dose modifications or temporary interruptions may be necessary to manage side effects and maintain treatment tolerability.

Storage and Disposal

Axitinib tablets should be stored at room temperature away from moisture, heat, and light. The tablets should be kept in their original blister packaging until ready to use to protect them from moisture and contamination. Patients should check the expiration date on the label and discard any expired medication properly according to local regulations or guidelines for medication disposal. Unused or partially used tablets should not be shared with others to avoid the risk of contamination or infection.

Conclusion

Axitinib is a tyrosine kinase inhibitor used in the treatment of advanced renal cell carcinoma (RCC) that has progressed despite prior systemic therapy. By selectively inhibiting vascular endothelial growth factor receptors (VEGFR), axitinib helps disrupt tumor angiogenesis and slow the progression of RCC. Patients should follow the prescribed dosing schedule, adhere to dietary recommendations, and promptly report any new or worsening symptoms to their healthcare provider. Close monitoring and regular follow-up are essential for optimizing therapeutic outcomes and minimizing the risk of adverse effects during axitinib treatment.

Important Note: Always consult with a healthcare professional for personalized medical advice and guidance regarding the use of given drug, especially regarding dosing, administration, and potential side effects. Your healthcare provider can provide tailored recommendations based on your individual medical history, current medications, and specific treatment needs. Never self-adjust your given drug regimen or discontinue treatment without first consulting your healthcare provider. If you have any questions or concerns about given drug or its use, talk to your doctor or pharmacist for further information and assistance.