Axinix Tablet

Axinix Tablet is used for: Advanced renal cell carcinoma

Oral Advanced renal cell carcinoma Adult: Initially, 5 mg bid (given approx 12 hrly), may be increased further to 7 mg bid, then 10 mg bid, if the initial dose is tolerated (patients w/ no AR above grade 2, w/ normal BP, and are not receiving antihypertensive therapy) for at least 2 consecutive wk. Combination therapy with avelumab Indicated in combination with avelumab for first-line treatment of advanced RCC Axitinib 5 mg PO BID, plus Avelumab 800 mg IV q2Weeks Combination therapy with pembrolizumab Indicated in combination with pembrolizumab for first-line treatment of advanced RCC Axitinib 5 mg PO BID, plus Pembrolizumab 200 mg IV q3Weeks or 400 mg IV q6Weeks

<18 years: Safety and efficacy not established

Renal impairment No dedicated renal impairment trial has been conducted Based on population pharmacokinetic analyses, no significant difference in clearance observed in patients with pre-existing mild-to-severe renal impairment

May be taken with or without food

Recent active GI bleeding, untreated brain metastases. Severe hepatic impairment (Child-Pugh Class C). Lactation.

Hypertension: Hypertension including hypertensive crisis has been observed. Blood pressure should be well-controlled prior to initiating Axitinib. Monitor for hypertension and treat as needed. Withhold and then dose reduces Axitinib or permanently discontinue based on the severity of hypertension. Arterial and Venous Thromboembolic Events: Arterial and venous thrombotic events have been observed and can be fatal. Use with caution in patients who are at increased risk for these events. Permanently discontinue Axitinib if an arterial thromboembolic event occurs during treatment. Withhold Axitinib and then resume at the same dose or permanently discontinue based on the severity of VTE. Hemorrhage: Hemorrhagic events, including fatal events, have been reported. Axitinib has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. Withhold and then dose reduces Axitinib or discontinue based on severity and persistence of hemorrhage. Cardiac Failure: Cardiac failure has been observed and can be fatal. Monitor for signs or symptoms of cardiac failure throughout treatment with Axitinib. Management of cardiac failure may require dose reduction, dose interruption or permanent discontinuation of Axitinib. Gastrointestinal Perforation and Fistula Formation: Gastrointestinal perforation and fistula, including death, have occurred. Use with caution in patients at risk for gastrointestinal perforation or fistula. Hypothyroidism: Hypothyroidism requiring thyroid hormone replacement has been reported. Monitor thyroid function before initiation of, and periodically throughout, treatment with Axitinib. Impaired Wound Healing: Withhold Axitinib for at least 2 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. Resume Axitinib at a reduced dose or discontinue based on the severity and persistence of the impaired wound healing. The safety of resumption of Axitinib after the resolution of wound healing complications has not been established. Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS has been observed. Permanently discontinue Axitinib if signs or symptoms of RPLS occur. Proteinuria: Monitor for proteinuria before initiation of, and periodically throughout, treatment with INLYTA. For moderate to severe proteinuria, withhold and then dose reduce Axitinib. Hepatotoxicity: Liver enzyme elevation has occurred during treatment with Axitinib as a single agent. Monitor ALT, AST and bilirubin before initiation of, and periodically throughout, treatment with Axitinib. When used in combination with avelumab or pembrolizumab, higher frequencies of Grade 3 and 4 ALT and AST elevation may occur. Consider more frequent monitoring of liver enzymes. Withhold Axitinib and avelumab or pembrolizumab, initiate corticosteroid therapy as needed, and/or permanently discontinue the combination for severe or life-threatening hepatotoxicity. Use in Patients with Hepatic Impairment: Decrease the starting dose of Axitinib if used in patients with moderate hepatic impairment. Axitinib has not been studied in patients with severe hepatic impairment. Major adverse cardiovascular events (Axitinib in combination with avelumab): Optimize management of cardiovascular risk factors. Permanently discontinue Axitinib in combination with avelumab for Grade 3-4 events. Embryo-Fetal Toxicity: Axitinib can cause fetal harm. Advise patients of the potential risk to the fetus and to use effective contraception. Monitoring Parameters Monitor for thyroid dysfunction. Monitor hemoglobin or hematocrit before and during treatment. Monitor for symptoms of gastro-intestinal perforation. Monitor for symptoms of fistula. Monitor for proteinuria before and during treatment. Monitor liver function before and during treatment. Monitor liver enzymes before initiation of and periodically throughout treatment; consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents; for elevated liver enzymes, interrupt or permanently discontinue therapy and avelumab or pembrolizumab, and administer corticosteroids as needed.

Pregnancy Based on mechanism of action and findings from animal studies, drug can cause fetal harm when administered to a pregnant woman; there are no available human data to inform drug-associated risk; in developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at recommended clinical dose When used in combination with avelumab or pembrolizumab, refer to full prescribing information of avelumab or pembrolizumab for pregnancy information Animal data Therapy administered twice daily to female mice prior to mating and through first week of pregnancy caused increase in post-implantation loss at all doses tested (greater than or equal 15 mg/kg/dose, approximately 10 times the systemic exposure (AUC) in patients at recommended starting dose) Based on findings in animal studies, drug can cause fetal harm when administered to a pregnant woman; females of reproductive potential should have a pregnancy test prior to starting treatment Contraception Females: Therapy can cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment and for 1 week after 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 last dose When is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for contraception information Infertility Based on findings in animals, therapy may impair fertility in females and males of reproductive potential Lactation There are no data on presence of drug in human milk, or effects on breastfed child or on milk production; because of potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment and for 2 weeks after final dose When used in combination with avelumab or pembrolizumab, refer to full prescribing information of avelumab or pembrolizumab for lactation information

Plasma concentration is increased by strong CYP3A4/5 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin) and decreased by strong CYP3A4/5 inducers (e.g. rifampicin, phenytoin, carbamazepine). May enhance adverse effects (e.g. osteonecrosis of the jaw) of bisphosphonate derivatives. Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the INLYTA dose. Avoid strong CYP3A4/5 inducers.

Side effects of Axitinib : >10% Diarrhea (55%) Hypertension (40%) Fatigue (39%) Decreased appetite (34%) Nausea (32%) Dysphonia (31%) Palmar-plantar erythrodysesthesia syndrome (27%) Weight decreased (25%) Vomiting (24%) Asthenia (21%) Constipation (20%) Hypothyroidism (19%) Cough (15%) Mucosal inflammation (15%) Arthralgia (15%) Stomatitis (15%) Dyspnea (15%) Abdominal pain (14%) Headache (14%) Extremity pain (13%) Rash (13%) Proteinuria (11%) Dysgeusia (11%) 1-10% Dry skin (10%) Dyspepsia (10%) Dizziness (9%) Upper abdominal pain (8%) Myalgia (7%) Pruritus (7%) Dehydration (6%) Epistaxis (6%) Hypercalcemia (6%) Anemia (4%) Alopecia (4%) Hemorrhoids (4%) Hematuria (3%) Tinnitus (3%) Increased lipase (3%) Glossodynia (3%) Pulmonary embolism (2%) Rectal hemorrhage (2%) Hemoptysis (2%) Erythema (2%) DVT (1%) Retinal vein occlusion/thrombosis (1%) Polycythemia (1%) TIA (1%) <1% Reversible posterior leukoencephalopathy syndrome Potentially Fatal: Cardiac failure, arterial thrombotic events (e.g. MI, TIA, CVA, retinal artery exclusion), venous thrombotic events (e.g. DVT, pulmonary embolism, retinal vein occlusion or thrombosis), hypertensive crisis, haemorrhagic events (e.g. GI or cerebral haemorrhage, haemoptysis, haematuria, melaena), GI perforation and fistula formation.

Axitinib, a selective 2nd generation tyrosine kinase inhibitor, blocks angiogenesis, tumour growth, and cancer progression by inhibiting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3).

Axinix 5mg Tablet manufactured by Beacon Pharmaceuticals Ltd.. Its generic name is Axitinib. Axinix is availble in Bangladesh. Farmaco BD drug index information on Axinix Tablet is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.