INLYTA- axitinib tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

AXITINIB (UNII: C9LVQ0YUXG) (AXITINIB - UNII:C9LVQ0YUXG)

Available from:

Pfizer Laboratories Div Pfizer Inc

INN (International Name):

AXITINIB

Composition:

AXITINIB 1 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

INLYTA in combination with avelumab is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). INLYTA in combination with pembrolizumab is indicated for the first-line treatment of patients with advanced RCC. INLYTA as a single agent is indicated for the treatment of advanced RCC after failure of one prior systemic therapy. None. Risk Summary Based on findings in animal studies and its mechanism of action, INLYTA can cause fetal harm when administered to a pregnant woman. There are no available human data to inform the drug-associated risk. In developmental toxicity studies, axitinib was teratogenic, embryotoxic and fetotoxic in mice at exposures lower than human exposures at the recommended starting dose (see Data) . Advise females of reproductive potential of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the United States (U.S.) general population of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies. When INLYTA is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for pregnancy information. Data Animal Data Oral axitinib administered twice daily to female mice prior to mating and through the first week of pregnancy caused an increase in post-implantation loss at all doses tested (≥15 mg/kg/dose, approximately 10 times the systemic exposure (AUC) in patients at the recommended starting dose). In an embryo-fetal developmental toxicity study, pregnant mice received oral doses of 0.15, 0.5 and 1.5 mg/kg/dose axitinib twice daily during the period of organogenesis. Embryo-fetal toxicities observed in the absence of maternal toxicity included malformation (cleft palate) at 1.5 mg/kg/dose (approximately 0.5 times the AUC in patients at the recommended starting dose) and variation in skeletal ossification at ≥0.5 mg/kg/dose (approximately 0.15 times the AUC in patients at the recommended starting dose). Risk Summary There are no data on the presence of axitinib in human milk, or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child from INLYTA, advise lactating women not to breastfeed during treatment and for 2 weeks after the last dose. When INLYTA is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for lactation information. Based on findings in animal studies, INLYTA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. When INLYTA is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for contraception information. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating treatment with INLYTA. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with INLYTA and for 1 week after the last dose. Males Based on findings in animal studies, advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. Infertility Females and Males Based on findings in animals, INLYTA may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1)] . The safety and efficacy of INLYTA in pediatric patients have not been studied. Juvenile Animal Toxicity Data Toxicities in bone and teeth were observed in immature mice and dogs administered oral axitinib twice daily for 1 month or longer. Effects in bone consisted of thickened growth plates in mice and dogs at ≥15 mg/kg/dose (approximately 6 and 15 times, respectively, the systemic exposure (AUC) in patients at the recommended starting dose). Abnormalities in growing incisor teeth (including dental caries, malocclusions and broken and/or missing teeth) were observed in mice administered oral axitinib twice daily at ≥5 mg/kg/dose (approximately 1.5 times the AUC in patients at the recommended starting dose). Other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals. In a controlled clinical study with INLYTA for the treatment of patients with RCC, 123/359 patients (34%) treated with INLYTA were ≥65 years of age. Although greater sensitivity in some older individuals cannot be ruled out, no overall differences were observed in the safety and effectiveness of INLYTA between patients who were ≥65 years of age and younger. Of the 434 patients randomized to INLYTA 5 mg twice daily administered in combination with avelumab 10 mg/kg in the JAVELIN Renal 101 trial, 38% were 65 years or older and 8% were 75 years or older. No overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger. Of the 432 patients randomized to INLYTA 5 mg twice daily administered in combination with pembrolizumab 200 mg in the KEYNOTE-426 trial, 40% were 65 years or older. No overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger. No dosage adjustment is required in elderly patients [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)] . In a dedicated hepatic impairment trial, compared to subjects with normal hepatic function, systemic exposure following a single dose of INLYTA was similar in subjects with baseline mild hepatic impairment (Child-Pugh class A) and higher in subjects with baseline moderate hepatic impairment (Child-Pugh class B). No starting dose adjustment is required when administering INLYTA to patients with mild hepatic impairment (Child-Pugh class A). A starting dose decrease is recommended when administering INLYTA to patients with moderate hepatic impairment (Child-Pugh class B) [see Dosage and Administration (2.2), Warnings and Precautions (5.12), Clinical Pharmacology (12.3)] . INLYTA has not been studied in subjects with severe hepatic impairment (Child-Pugh class C). No dedicated renal impairment trial for axitinib has been conducted. Based on the population pharmacokinetic analyses, no significant difference in axitinib clearance was observed in patients with pre-existing mild to severe renal impairment (15 mL/min ≤creatinine clearance [CLcr] <89 mL/min) [see Clinical Pharmacology (12.3)] . No starting dose adjustment is needed for patients with pre-existing mild to severe renal impairment. Caution should be used in patients with end-stage renal disease (CLcr <15 mL/min).

Product summary:

INLYTA tablets are supplied as follows:

Authorization status:

New Drug Application

Summary of Product characteristics

INLYTA- AXITINIB TABLET, FILM COATED
PFIZER LABORATORIES DIV PFIZER INC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
INLYTA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR INLYTA.
INLYTA (AXITINIB) TABLETS, FOR ORAL ADMINISTRATION
INITIAL U.S. APPROVAL: 2012
RECENT MAJOR CHANGES
Dosage and Administration, Recommended Dosing (2.1)
9/2022
Dosage and Administration, Dose Modification Guidelines (2.2)
9/2022
Warnings and Precautions, Hypertension (5.1)
9/2022
Warnings and Precautions, Arterial Thromboembolic Events (5.2)
9/2022
Warnings and Precautions, Venous Thromboembolic Events (5.3)
9/2022
Warnings and Precautions, Hemorrhage (5.4)
9/2022
Warnings and Precautions, Cardiac Failure (5.5)
9/2022
Warnings and Precautions, Impaired Wound Healing (5.8)
9/2022
Warnings and Precautions, Reversible Posterior Leukoencephalopathy
Syndrome
(5.9)
9/2022
Warnings and Precautions, Proteinuria (5.10)
9/2022
Warnings and Precautions, Hepatotoxicity (5.11)
9/2022
Warnings and Precautions, Major Adverse Cardiovascular Events (5.13)
9/2022
INDICATIONS AND USAGE
INLYTA is a kinase inhibitor indicated:
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
1 mg and 5 mg tablets (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
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®
in combination with avelumab, for the first-line treatment of patients
with advanced renal cell
carcinoma (RCC). (1.1)
in combination with pembrolizumab, for the first-line treatment of
patients with advanced RCC. (1.1)
as a single agent, for the treatment of advanced renal cell carcinoma
(RCC) after failure of one prior
systemic therapy. (1.2)
INLYTA 5 mg orally twice daily with avelumab 800 mg every 2 weeks.
(2.1)
INLYTA 5 mg orally twice daily with pembrolizumab 200 mg every 3 weeks
or 400 mg every 6 weeks.
(2.1)
INLYTA as a single agent the starting dose is 5 mg orally twice daily.
(2.1)
Dose adjustments can be made based on individual safety and
tolerability. (2.2)