axitinib

Contraindicated in:

Untreated brain metastases;
Recent active GI bleeding;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Hypertension (must be well controlled prior to/during therapy);
Moderate hepatic impairment (↓ dose);
Surgery (discontinue 24 hr prior if possible);
End-stage renal disease (CCr <15 mL/min);
Rep: Woman of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, AORTIC ANEURYSM, ARTERIAL/VENOUS THROMBOEMBOLIC EVENTS, CARDIAC DEATH (WITH AVELUMAB), MI (WITH AVELUMAB), HF

Derm: dry skin, rash, palmar-plantar erythrodysesthesia (hand-foot syndrome), alopecia, erythema, wound healing impairment, pruritus

EENT: dysphonia

Endo: hypothyroidism

F and E: ↓bicarbonate, hyperglycemia, hyperkalemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hyponatremia, hypophosphatemia, hypercalcemia

GI: ↑liver enzymes, abdominal pain, altered taste, constipation, diarrhea, hepatotoxicity, nausea, stomatitis, burning mouth, GI PERFORATION/FISTULA

GU: ↑serum creatinine, proteinuria

Hemat: anemia, neutropenia, thrombocytopenia, BLEEDING

Metab: ↓appetite, weight loss

MS: arthralgia, extremity pain

Neuro: dysphoria, fatigue, headache, REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME (RPLS)

Resp: cough

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4/5 inhibitors, including atazanavir, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, and voriconazole, may ↑ levels and risk of toxicity; avoid concurrent use, if possible; if concurrent use unavoidable, select alternative agent. If none is acceptable, ↓ axitinib dose by 50%.
Strong CYP3A4/5 inducers, including carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentin, as well as moderate CYP3A4/5 inducers, including bosentan, efavirenz, etravirine, modafanil, and nafcillin, may ↓ levels and effectiveness; avoid concurrent use, if possible.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit/grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent used.

Availability ⬆ ⬇

Tablets : 1 mg; 5 mg

Route/Dosage ⬆ ⬇

First-Line Treatment of Advanced Renal Cell Carcinoma

PO (Adults ): In combination with avelumab: 5 mg twice daily, approximately 12 hr apart initially; after tolerating therapy for ≥2 consecutive wk (i.e., no adverse reactions Grade >2, remaining normotensive, and not receiving antihypertensive medications), may ↑ to 7 mg twice daily; after tolerating adjusted dose for ≥2 consecutive wk (using same criteria), may ↑ to 10 mg twice daily. Continue treatment until unacceptable toxicity or disease progression. In combination with pembrolizumab: 5 mg twice daily, approximately 12 hr apart initially; after tolerating therapy for ≥6 wk (i.e., no adverse reactions Grade >2, remaining normotensive, and not receiving antihypertensive medications), may ↑ to 7 mg twice daily; after tolerating adjusted dose for ≥6 consecutive wk (using same criteria), may ↑ to 10 mg twice daily. Continue treatment until unacceptable toxicity or disease progression. Concurrent use of strong CYP3A4/5 inhibitors: ↓dose by 50%.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: ↓dose by 50%.

Second-Line Treatment of Advanced Renal Cell Carcinoma

PO (Adults ): 5 mg twice daily, approximately 12 hr apart initially; after tolerating therapy for ≥2 consecutive wk (i.e., no adverse reactions Grade >2, remaining normotensive, and not receiving antihypertensive medications), may ↑ to 7 mg twice daily; after tolerating adjusted dose for ≥2 consecutive wk (using same criteria), may ↑ to 10 mg twice daily. Continue treatment until unacceptable toxicity or disease progression. Concurrent use of strong CYP3A4/5 inhibitors: ↓dose by approximately 50%.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: ↓dose by 50%.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits tyrosine kinases on various receptors, including vascular endothelial growth factor receptors that may be involved in tumor angiogenesis/growth and cancer progression.

Therapeutic effects:

Inhibited tumor growth with decreased disease progression.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed (58%) following oral administration.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Mostly metabolized by the CYP3A4/5 isoenzymes, with some metabolism by CYP2C19 and UGT1A1 systems. 41% eliminated in feces (12% as unchanged drug); 23% eliminated in urine as metabolites.

Half-Life: 2.5–6.1 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION‡
PO	unknown	2.5–4.1 hr	12 hr

‡↓progression of disease may last up to 18 mo.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Instruct patient that if a dose is vomited or missed, omit dose and take next dose at regular time; do not double doses. Advise patient to read Patient Information before starting therapy.
Advise patient to avoid drinking grapefruit juice or eating grapefruit during axitinib therapy.
Advise patient to notify health care professional of therapy prior to treatment, dental procedure, or surgery.
Advise patient to notify health care professional immediately if unexpected bleeding; bleeding of gums; heavier than normal menses; severe or uncontrollable bleeding; pink or brown urine; red or black stools; bloody or dark coffee-ground looking vomit; unexpected pain, swelling, or joint pain; headaches; feeling dizzy; or weakness occur.
Advise patient to notify health care professional immediately with signs and symptoms of venous or arterial clots (chest pain or pressure; pain in arms, back, neck, or jaw; shortness of breath; numbness or weakness on one side of body; confusion; difficulty talking; headache; or vision changes) occur.
May cause stomach or intestinal wall perforation. Caution patient to notify health care professional if severe abdominal pain, vomiting blood, or red or black stools occur.
Advise patient to notify health care professional promptly if signs and symptoms of RPLS (headache, seizures, weakness, confusion, high BP, blindness or change in vision, problems thinking), thyroid problems (worsening or persistent tiredness, feeling hot or cold, voice deepening, weight gain or loss, hair loss, muscle cramps and aches), or HF (tiredness, swelling abdomen, legs or ankles, shortness of breath, protruding neck veins) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Rep: May cause fetal harm. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during therapy and for 1 wk after last dose. Advise female patients to avoid breastfeeding during therapy and for 2 wk after last dose. May impair fertility in male and female patients.

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Indications ⬇

Contraind./Precautions ⬆ ⬇