নির্দেশনা
Alpelisib is indicated in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CAmutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.
Composition
ফার্মাকোলজি
Alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models. In breast cancer cell lines, Alpelisib inhibited the phosphorylation of PI3K downstream targets, including Akt and showed activity in cell lines harboring a PIK3CA mutation. In vivo, Alpelisib inhibited the PI3K/Akt signaling pathway and reduced tumor growth in xenograft models, including models of breast cancer. PI3K inhibition by Alpelisib treatment has been shown to induce an increase in estrogen receptor (ER) transcription in breast cancer cells. The combination of Alpelisib and fulvestrant demonstrated increased antitumor activity compared to either treatment alone in xenograft models derived from ER-positive, PIK3CA mutated breast cancer cell lines.
মাত্রা ও সেবনবিধি
The recommended dose of Alpelisib is 300 mg (two 150 mg film coated tablets) taken orally, once daily, with food. Continue treatment until disease progression or unacceptable toxicity occurs. Patients should take their dose of Alpelisib at approximately the same time each day. Swallow Alpelisib tablets whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact. If a dose of Alpelisib is missed, it can be taken with food within 9 hours after the time it is usually taken. After more than 9 hours, skip the dose for that day. The next day, take Alpelisib at the usual time. If the patient vomits after taking the dose, advise the patient not to take an additional dose on that day, and to resume the dosing schedule the next day at the usual time. When given with Alpelisib, the recommended dose of fulvestrant is 500 mg administered on Days 1, 15, and 29, and once monthly thereafter.
প্রতিনির্দেশনা
Alpelisib is contraindicated in patients with severe hypersensitivity to it or any of its components.
পার্শ্ব প্রতিক্রিয়া
Severe allergic reactions Diarrhea Severe skin reactions Lung problems (pneumonitis) High blood sugar levels (hyperglycemia)
গর্ভাবস্থায় ও স্তন্যদানকালে
Pregnancy : Based on animal data and mechanism of action, Alpelisib can cause fetal harm when administered to a pregnant woman. Lactation : There is no data on the presence of Alpelisib in human milk, its effects on milk production, or the breastfed child. Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeed during treatment with Alpelisib and for 1 week after the last dose. Infertility : Based on findings from animal studies, Alpelisib may impair fertility in males and females of reproductive potential.
সতর্কতা
Severe Hypersensitivity : Advise patients of the signs and symptoms of severe hypersensitivity reactions. Permanently discontinue Alpelisib in the event of severe hypersensitivity. Severe Cutaneous Reactions : Severe cutaneous reactions, including Stevens-Johnson Syndrome (SJS) and Erythema Multiforme (EM) were reported in patients treated with Alpelisib. Advise patients of the signs and symptoms of severe cutaneous reactions (e.g., a prodrome of fever, flu-like symptoms, mucosal lesions or progressive skin rash). Hyperglycemia : Before initiating treatment with Alpelisib, test FPG, HbA1c, and optimize blood glucose. After initiating treatment with Alpelisib, monitor blood glucose and/or FPG at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated. Monitor HbA1c every 3 months and as clinically indicated. Based on the severity of the hyperglycemia, Alpelisib may require dose interruption, reduction, or discontinuation. Pneumonitis : Permanently discontinue Alpelisib in all patients with confirmed pneumonitis. Advise patients to immediately report new or worsening respiratory symptoms. Diarrhea : Advise patients to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs while taking Alpelisib. Embryo-Fetal Toxicity : Based on findings in animals and its mechanism of action, Alpelisib can cause fetal harm when administered to a pregnant woman.
থেরাপিউটিক ক্লাস
Cytotoxic Chemotherapy