Axitinib

Axitinib is an anti-cancer medicine that was authorized by the US FDA in January 2012. It is an anti-cancer medicine that works by inhibiting the function of an aberrant protein that causes cancer cells to grow, hence preventing or spreading cancer cells. It is a second-generation tyrosine kinase inhibitor that preferentially targets vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3). This cancer typically originates in the kidney lining, which consists of tiny tubes known as tubules that filter waste from the blood and return required nutrients to circulation. This form of cancer is also known as renal cell carcinoma (RCC). It is used in conjunction with pembrolizumab as the first-line therapy for individuals with advanced renal cell carcinoma.

BRAND NAME : 

Inlyta - It is available in form of axitinib 1mg and 5mg tablets, and it is prescribed medication used in the treatment of the kidney cancer.

MECHANISM OF ACTION : 

Axitinib has been proven to inhibit receptor tyrosine kinases at therapeutic plasma receptor concentrations (VEGFR-1, VEGFR-2, and VEGFR-3).

PHARMACOKINETICS :

Absorption:

 A 5 mg dose reaches peak plasma levels between 2.5 to 4.1 hours. The plasma half-life remains steady for 2-3 days.

Distribution: 

It can be given with or without meals. It resulted in a 19% greater AUC for high-fat, high-calorie meals, while moderate-fat meals had a 10% lower AUC. The volume of distribution is 160L.

Metabolism: 

The time required for hepatic metabolism is 2.5–6.1 hours. In the liver, axitinib is metabolized by CYP3A4/5, CYP1A2, CYP2C19, and UGT1AI, in that order.

Excretion: 

A 5 mg dose of axitinib taken orally excretes approximately 41% unchanged, 12% via feces, and 23% via urine, all containing metabolites.

PHARMACODYNAMICS :

 It slows cancer progression by blocking angiogenesis and tumor growth.

DOSAGE AND ADMINISTRATION: 

The oral dosage of axitinib is 5 mg twice a day. Additionally, the dosage may be adjusted to the patient's tolerance. Whether administered with or without food, there should be a 12-hour interval between each dosage. It is not appropriate to give a patient another dosage if they miss it or throw up after taking it. Take the subsequent dosage at the scheduled time.

          The dose may change depending on the patient's health. A patient receiving a course must be observed for a minimum of two weeks. It is possible to raise the dosage from 7 mg twice a day to 10 mg if the patient can handle a 5 mg dose twice a day without experiencing any adverse effects, such as hypertension. Reduce the dosage to 1 mg or 3 mg twice a day if the medication is causing any negative health effects in the patient.

ADVERSE EFFECTS:

It may cause serious side effects, as mentioned below.

•   High blood pressure (hypertension): High blood pressure is common, and it can sometimes be severe. Therefore, blood pressure should be measured on a regular basis.

•   Thyroid gland: This can induce changes in the thyroid gland, leading in symptoms such as weight gain or loss, hair loss, muscular cramps, and fatigue. These are frequent symptoms, hence a thyroid gland function exam is recommended when using axitinib.

•  Blood clots: Blood clotting is a significant side effect that can lead to death. Symptoms include chest pain, pain in the back, neck, arms, and jaw, shortness of breath, headache, difficulty speaking, and changes in eyesight.

•    Bleeding: It is also a serious side effect that causes symptoms such as unusual gingival bleeding, pink or brown urine, uncontrollable bleeding, heavier menstrual flow than usual, bruises, and blood vomiting. This leads to the loss of blood.

•   Heart failure

•   Liver failure

•   Reversible posterior leukoencephalopathy syndrome

•   Risk of wound healing problems

•   Weakness

•   Decreased appetite

•   Proteinuria

•   Dry skin

DRUG INTERACTIONS:

Strong CYP3A4/5 inhibitor ketoconazole increased axitinib plasma exposure in healthy individuals. It is advised to choose concurrent medications with little to no CYP3A4/5 inhibitory potential.

In healthy participants, cyclosporin, a potent CYP3A4/5 inducer, was administered to lower axitinib plasma exposure. Axitinib and strong CYP3A4/5 inducers shouldn't be administered together. Avoiding moderate CYP3A4/5 inducers is advised as they may decrease the plasma exposure of axitinib.

FOOD INTERACTIONS:

The grapefruit and grape juice should be avoided. It may raise the serum levels of axitinib.

TOXICITY: 

Axitinib can induce toxicity, including gastrointestinal and cardiovascular issues.

STORAGE :

Store at temperatures ranging from 20℃ to 25℃ (68℉ to 77℉), but can be allowed to reach 15℃ to 30℃.