Alecensa150 mg

Alecensa 150 mg indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

Anti neoplastic preparations, Protein kinase inhibitor

Alecensa 150 mg is a highly selective and potent ALK and RET tyrosine kinase inhibitor.In nonclinicalstudies, inhibition of ALK tyrosine kinase activity led to blockage of downstream signaling pathways including STAT 3 and PI3K/AKT and inducedtumor cell death (apoptosis). Alecensa 150 mg demonstratedin vitroand in vivoactivity against mutant forms of the ALK enzyme, including mutations responsible forresistance to crizotinib.The major metabolite of Alecensa 150 mg (M4) has shown similar in vitropotency and activity. Based on nonclinicaldata, Alecensa 150 mg is not a substrate of p-glycoprotein (P-gp) or breast cancer resistance protein (BCRP), which are both efflux transporters in the blood brain barrier, and is therefore able to distribute into and be retained within the central nervous system. Alecensa 150 mginducedtumor regressionin nonclinicalmousexenograft models, including antitumor activity in the brain, and prolonged survival inintracranial tumor animal models.

The recommended dose of Alecensa 150 mg is 600 mg (four 150 mg capsules) given orally, twice daily (total daily dose of 1200 mg). Patients with underlying severe hepatic impairment should receive a dose of 450 mg given orally twice daily (total daily dose of 900 mg). Alecensa 150 mg hard capsules should be taken with food, swallowed whole and must not be opened or dissolved.

Duration of Treatment: It is recommended that patients are treated with Alecensa 150 mg until disease progression or unmanageable toxicity.Dose Modifications: Management of adverse events may require temporary interruption, dosereduction, or discontinuation of treatment with Alecensa 150 mg. The dose of Alecensa 150 mg should be reduced in steps of 150 mg twice daily based on tolerability. Alecensa 150 mg treatment should be permanently discontinued if patients are unable to tolerate the 300 mg twice-daily dose.

In vitro studies indicate that neither Alecensa 150 mg nor its major active metabolite (M4) inhibits CYP1A2, CYP2B6, CYP2C9, CYP2C19, or CYP2D6 at clinically relevant concentrations. Alecensa 150 mg and M4 show weak time-dependent inhibition of CYP3A4. In vitro, Alecensa 150 mg exhibits a weak induction potential of CYP3A4 and CYP2B6 at clinical concentrations. Results from a clinical drug-drug interaction study in ALK-positive NSCLC patients demonstrated that multiple doses of Alecensa 150 mg had no influence on the exposure of midazolam, a sensitive CYP3A substrate. Therefore, no dose adjustment is required for co-administered CYP3A substrates. Although in vitro studies indicate that Alecensa 150 mg is an inhibitor of CYP2C8, physiologically based pharmacokinetic (PBPK) modeling supports that at clinically relevant concentrations Alecensa 150 mg does not have the potential to increase plasma concentrations of co-administered substrates of CYP2C8.

Alecensa 150 mg is contraindicated in patients with a known hypersensitivity to Alecensa 150 mg or any of the excipients.

The most common adverse drug reactions were constipation, edema including peripheral, generalized, eyelid, periorbital; myalgia (31% including myalgia and musculoskeletal pain), nausea, increased bilirubin (21% including increased blood bilirubin, hyperbilirubinemia and increased bilirubin conjugated), anemia (20%, including anemia and hemoglobin decreased), and rash (20%, including rash, rash maculopapular, dermatitis acneiform, erythema, rash generalized, rash papular, rash pruritic and rash macular).

Pregnancy: Women of childbearing potential must be advised to avoid pregnancy while on Alecensa 150 mg. No clinical studies of Alecensa 150 mg in pregnant women have been performed. Based on its mechanism of action, Alecensa 150 mg may cause fetal harm when administered to a pregnant woman. Female patients or women who are partners of male patients receiving Alecensa 150 mg, who become pregnant while taking Alecensa 150 mg or during the 3 months following the last dose of Alecensa 150 mg must contact their doctor and should be advised of the potential harm to the fetus.Lactation: It is not known whether Alecensa 150 mg is excreted in human breast milk. No studies have been conducted to assess the impact of Alecensa 150 mg on milk production or its presence in breast milk. As many drugs are excreted in human milk and because of the potential harm to the infant, mothers should be advised against breastfeeding while receiving Alecensa 150 mg.Contraception: Female patients of child-bearing potential, or women of child-bearing potential who are partners of male patients receiving Alecensa 150 mg, must use highly effective contraceptive methods during treatment and for at least 3 months following the last dose of Alecensa 150 mg

Interstitial lung disease (ILD)/pneumonitis: Cases of ILD/pneumonitishave been reported in clinical trials with Alecensa 150 mg. Patients should be monitored for pulmonary symptoms indicative of pneumonitis. Alecensa 150 mg should be immediately interrupted in patients diagnosed with ILD/pneumonitis and should be permanently discontinued if no other potential causes of ILD/pneumonitis have been identifiedHepatotoxicity: Elevations in alanine amino transferase (ALT) and aspartate amino transferase (AST) greater than 5 times the upper limit of normal (ULN) as well as bilirubin elevations of more than 3 times the ULN occurred in patients in pivotal clinical trials with Alecensa 150 mg. The majority of these events occurred during the first 3months of treatment. In the pivotal Alecensa 150 mg clinical trials it was reported that three patients with Grade 3‒4 AST/ALT elevations had drug-induced liver injury. Concurrent elevations in ALT or AST greater than or equal to three times the ULN and total bilirubin greater than or equal to two times the ULN, with normal alkaline phosphatase, occurred in 1 patient treated in Alecensa 150 mg clinical trials.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Pediatric use: The safety and efficacy of Alecensa 150 mg in children and adolescents (<18 years) have not been studied.Geriatric use: No dose adjustment of Alecensa 150 mg is required in patients≥65 years of age.Renal impairment: No dose adjustment is required in patients with mild or moderate renal impairment. Alecensa 150 mg has not been studied in patients with severe renal impairment, however,since Alecensa 150 mg elimination via the kidney is negligible, no dose adjustment is required inpatients with severe renal impairment Hepatic impairment: No dose adjustment is required in patients with underlying mild or moderate hepatic impairment. Patients with underlying severe hepatic impairment should receive a dose of 450 mg given orally twice daily (total daily dose of 900 mg)

Anti neoplastic preparations, Protein kinase inhibitor

Alecensa 150 mg is a highly selective and potent ALK and RET tyrosine kinase inhibitor.In nonclinicalstudies, inhibition of ALK tyrosine kinase activity led to blockage of downstream signaling pathways including STAT 3 and PI3K/AKT and inducedtumor cell death (apoptosis). Alecensa 150 mg demonstratedin vitroand in vivoactivity against mutant forms of the ALK enzyme, including mutations responsible forresistance to crizotinib.The major metabolite of Alecensa 150 mg (M4) has shown similar in vitropotency and activity. Based on nonclinicaldata, Alecensa 150 mg is not a substrate of p-glycoprotein (P-gp) or breast cancer resistance protein (BCRP), which are both efflux transporters in the blood brain barrier, and is therefore able to distribute into and be retained within the central nervous system. Alecensa 150 mginducedtumor regressionin nonclinicalmousexenograft models, including antitumor activity in the brain, and prolonged survival inintracranial tumor animal models.

Pregnancy: Women of childbearing potential must be advised to avoid pregnancy while on Alecensa 150 mg. No clinical studies of Alecensa 150 mg in pregnant women have been performed. Based on its mechanism of action, Alecensa 150 mg may cause fetal harm when administered to a pregnant woman. Female patients or women who are partners of male patients receiving Alecensa 150 mg, who become pregnant while taking Alecensa 150 mg or during the 3 months following the last dose of Alecensa 150 mg must contact their doctor and should be advised of the potential harm to the fetus.Lactation: It is not known whether Alecensa 150 mg is excreted in human breast milk. No studies have been conducted to assess the impact of Alecensa 150 mg on milk production or its presence in breast milk. As many drugs are excreted in human milk and because of the potential harm to the infant, mothers should be advised against breastfeeding while receiving Alecensa 150 mg.Contraception: Female patients of child-bearing potential, or women of child-bearing potential who are partners of male patients receiving Alecensa 150 mg, must use highly effective contraceptive methods during treatment and for at least 3 months following the last dose of Alecensa 150 mg

Pediatric use: The safety and efficacy of Alecensa 150 mg in children and adolescents (<18 years) have not been studied.Geriatric use: No dose adjustment of Alecensa 150 mg is required in patients≥65 years of age.Renal impairment: No dose adjustment is required in patients with mild or moderate renal impairment. Alecensa 150 mg has not been studied in patients with severe renal impairment, however,since Alecensa 150 mg elimination via the kidney is negligible, no dose adjustment is required inpatients with severe renal impairment Hepatic impairment: No dose adjustment is required in patients with underlying mild or moderate hepatic impairment. Patients with underlying severe hepatic impairment should receive a dose of 450 mg given orally twice daily (total daily dose of 900 mg)