নির্দেশনা
Alectinib as monotherapy is indicated for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). Alectinib as monotherapy is indicated for the treatment of adult patients with ALK-positive advanced NSCLC previously treated with crizotinib.
Composition
ফার্মাকোলজি
Alectinib 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). Alectinib demonstratedin vitroand in vivoactivity against mutant forms of the ALK enzyme, including mutations responsible forresistance to crizotinib.The major metabolite of alectinib (M4) has shown similar in vitropotency and activity. Based on nonclinicaldata, alectinib 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. Alectinibinducedtumor regressionin nonclinicalmousexenograft models, including antitumor activity in the brain, and prolonged survival inintracranial tumor animal models.
মাত্রা ও সেবনবিধি
Recommended dose : Alectinib is 600 mg (four 150 mg capsules) taken twice daily with food (total daily dose of 1200 mg). Patients with underlying severe hepatic impairment (Child-Pugh C) should receive a starting dose of 450 mg taken twice daily with food (total daily dose of 900 mg). Duration of treatment : Treatment with Alectinib should be continued until disease progression or unacceptable toxicity. Delayed or missed doses : If a planned dose of Alectinib is missed, patients can make up that dose unless the next dose is due within 6 hours. Patients should not take two doses at the same time to make up for a missed dose. If vomiting occurs after taking a dose of Alectinib , patients should take the next dose at the scheduled time. Dose adjustments : Management of adverse events may require dose reduction, temporary interruption, or discontinuation of treatment with Alectinib. The dose of Alectinib should be reduced in steps of 150 mg twice daily based on tolerability. Alectinib treatment should be permanently discontinued if patients are unable to tolerate the 300 mg twice daily dose. Method of administration : Alectinib is for oral use. The hard capsules should be swallowed whole, and must not be opened or dissolved. They must be taken with food.
প্রতিনির্দেশনা
Alectinib is contraindicated in patients with a known hypersensitivity to alectinib or any of the excipients.
পার্শ্ব প্রতিক্রিয়া
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).
গর্ভাবস্থায় ও স্তন্যদানকালে
Pregnancy : There are no or limited amount of data from the use of Alectinib in pregnant women. Based on its mechanism of action, Alectinib may cause foetal harm when administered to a pregnant woman. Studies in animals have shown reproductive toxicity. Female patients, who become pregnant while taking Alectinib or during the 3 months following the last dose of Alectinib must contact their doctor and should be advised of the potential harm to the foetus. Breast-feeding : It is unknown whether Alectinib and its metabolites are excreted in human milk. A risk to the newborn/infant cannot be excluded. Mothers should be advised against breast-feeding while receiving Alectinib. Fertility : No fertility studies in animals have been performed to evaluate the effect of Alectinib. No adverse effects on male and female reproductive organs were observed in general toxicology studies.
সতর্কতা
Interstitial lung disease (ILD)/pneumonitis : Cases of ILD/pneumonitishave been reported in clinical trials with Alectinib. Patients should be monitored for pulmonary symptoms indicative of pneumonitis. Alectinib 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 identified Hepatotoxicity : 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 Alectinib. The majority of these events occurred during the first 3months of treatment. In the pivotal Alectinib 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 Alectinib clinical trials. Bradycardia : Symptomatic bradycardia can occur with Alectinib. Heart rate and blood pressure should be monitored as clinically indicated. Dose modification is not required in case of asymptomatic bradycardia. If patients experience symptomatic bradycardia or life-threatening events, concomitant medicinal products known to cause bradycardia, as well as anti-hypertensive medicinal products should be evaluated and Alectinib treatment should be adjusted. Photosensitivity : Photosensitivity to sunlight has been reported with Alectinib administration. Patients should be advised to avoid prolonged sun exposure while taking Alectinib, and for at least 7 days after discontinuation of treatment. Patients should also be advised to use a broad-spectrum Ultraviolet A (UVA)/ Ultraviolet B (UVB) sun screen and lip balm (SPF >50) to help protect against potential sunburn. Women of child-bearing potential : Alectinib may cause foetal harm when administered to a pregnant woman. Female patients of child-bearing potential receiving Alectinib, must use highly effective contraceptive methods during treatment and for at least 3 months following the last dose of Alectinib. Lactose intolerance : This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, a congenital lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Sodium content : This medicinal product contains 48 mg sodium per daily dose (1200 mg), equivalent to 2.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
থেরাপিউটিক ক্লাস
Anti neoplastic preparations, Protein kinase inhibitor