Hernix40 mg

Extended Adjuvant Treatment of Early-Stage Breast Cancer: Hernix 40 mg as a single agent is indicated for the extended adjuvant treatment of adult patients with early-stage human epidermal growth factor receptor 2 (HER 2 )- positive breast cancer, to follow adjuvant Trastuzumab-based therapy ... Read moreExtended Adjuvant Treatment of Early-Stage Breast Cancer: Hernix 40 mg as a single agent is indicated for the extended adjuvant treatment of adult patients with early-stage human epidermal growth factor receptor 2 (HER 2 )- positive breast cancer, to follow adjuvant Trastuzumab-based therapy.Advanced or Metastatic Breast Cancer: Hernix 40 mg in combination with Capecitabine is indicated for the treatment of adult patients with advanced or metastatic HER 2 -positive breast cancer who have received two or more prior anti-HER 2 based regimens in the metastatic setting.

Tyrosine Kinase Inhibitor

Hernix 40 mg is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. In vitro, Hernix 40 mg reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Hernix 40 mg human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2 and HER4 in vitro. In vivo, oral administration of Hernix 40 mg inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR.

Antidiarrheal prophylaxis: Initiate loperamide with the first dose of Hernix 40 mg and continue during first 2 cycles (56 days) of treatment. Instruct patients to maintain 1-2 bowel movements per day and on how to use antidiarrheal treatment regimensRecommended dose: 240 mg (6 tablets) given orally once daily with food, continuously for one year. Dose interruptions and/or dose reductions are recommended based on individual safety and tolerabilityHepatic Impairment: Reduce starting dose to 80 mg in patients with severe hepatic impairment.

Antidiarrheal Prophylaxis: Antidiarrheal prophylaxis is recommended during the first 2 cycles (56 days) of treatment and should be initiated with the first dose of Hernix 40 mg. Additional antidiarrheal agents may be required to manage diarrhea in patients with loperamide-refractory diarrhea. Hernix 40 mg dose interruptions and dose reductions may also be required to manage diarrhea. The recommended dose of Hernix 40 mg is 240 mg (six tablets) given orally once daily with food, continuously for one year. Patients should be instructed to take Hernix 40 mg at approximately the same time every day. Hernix 40 mg tablets should be swallowed whole (tablets should not be chewed, crushed, or split prior to swallowing). If a patient misses a dose, missed dose should not be replaced, and patients should be instructed to resume Hernix 40 mg with the next scheduled daily dose. Or, as directed by the registered physicians. Dose Modifications: For Adverse Reactions: Hernix 40 mg dose modification is recommended based on individual safety and tolerability. Hernix 40 mg should be discontinued for patients who fail to recover to Grade 0-1 from treatment-related toxicity, for toxicities that result in a treatment delay >3 weeks, or for patients that are unable to tolerate 120 mg daily. Additional clinical situations may result in dose adjustments as clinically indicated (e.g. intolerable toxicities, persistent Grade 2 adverse reactions, etc.).Recommended starting dose: 240 mg dailyFirst dose reduction: 200 mg dailySecond dose reduction: 160 mg dailyThird dose reduction: 120 mg daily

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists. Separate Hernix 40 mg by 3 hours after antacid dosing.Strong or moderate CYP3A4 inhibitors: Avoid concomitant use. Strong or moderate CYP3A4 inducers: Avoid concomitant use. P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with Hernix 40 mg.

It is contraindicated in patients with known hypersensitivity to Hernix 40 mg or any other components of this product.

Diarrhea, Hepatotoxicity.

There are no available data in pregnant women to inform the drug-associated risk. No data are available regarding the presence of Hernix 40 mg or its metabolites in human milk or itseffects on the breastfed infant or on milk production.

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold Meratinib in patients experiencing severe and/or persistent diarrhea. Permanently discontinue Meratinib in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold Meratinib in patients experiencing Grade 3 liver abnormalities and permanently discontinue Meratinib in patients experiencing Grade 4 liver abnormalities.Embryo-Fetal Toxicity: Meratinib can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.

There is no specific antidote, and the benefit of hemodialysis in the treatment of Hernix 40 mg overdose is unknown. In the event of an overdose, administration should be withheld and general supportive measures undertaken. In the clinical trial setting, a limited number of patients reported overdose. The adverse reactions experienced by these patients were diarrhea, nausea, vomiting, and dehydration. The frequency and severity of gastrointestinal disorders (diarrhea, abdominal pain, nausea and vomiting) appear to be dose related.

Store below 30°C in a cool and dry place, away from sunlight. Keep out of reach of children.

Pediatric Use: The safety and efficacy of Hernix 40 mg in pediatric patients has not been established.

Tyrosine Kinase Inhibitor

Hernix 40 mg is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. In vitro, Hernix 40 mg reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Hernix 40 mg human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2 and HER4 in vitro. In vivo, oral administration of Hernix 40 mg inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR.Absorption: The Hernix 40 mg and major active metabolites M3, M6 and M7 peak concentrations are reached in the range of 2 to 8 hours after oral administration.Distribution: In patients, following multiple doses of Hernix 40 mg, the mean (%CV) apparent volume of distribution at steady-state (Vss/F) was 6433 (19%) L. In vitro protein binding of Hernix 40 mg in human plasma was greater than 99% and independent of concentration. Hernix 40 mg bound predominantly to human serum albumin and human alpha-1 acid glycoprotein.Elimination: Following 7 days of daily 240 mg oral doses of Hernix 40 mg in healthy subjects, the mean (%CV) plasma half-life of Hernix 40 mg, M3, M6, and M7 was 14.6 (38%), 21.6 (77%), 13.8 (50%) and 10.4 (33%) hours, respectively. The mean elimination half-life of Hernix 40 mg ranged from 7 to 17 hours following a single oral dose in patients. Following multiple doses of Hernix 40 mg at once daily 240 mg in cancer patients, the mean (%CV) CL/F after first dose and at steady state (day 21) were 216 (34%) and 281 (40%) L/hour, respectively.Metabolism: Hernix 40 mg is metabolized primarily in the liver by CYP3A4 and to a lesser extent by flavin-containing monooxygenase (FMO).Excretion: After oral administration of 200 mg (0.83 times of approved recommended dosage) radiolabeled Hernix 40 mg oral formulation, fecal excretion accounted for approximately 97.1% and urinary excretion accounted for 1.13% of the total dose. Sixty one percent of the excreted radioactivity was recovered within 96 hours and 98% was recovered after 10 days.

Hernix 40 mg can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Pregnant women should be advised of the potential risk to a fetus. No data are available regarding the presence of Hernix 40 mg or its metabolites in human milk or its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants from Hernix 40 mg, lactating women should be advised not to breastfeed while taking Hernix 40 mg and for at least 1 month after the last dose.Hernix 40 mg can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should have a pregnancy test prior to starting treatment with Hernix 40 mg. Females: Females of reproductive potential should be advised to use effective contraception during treatment with Hernix 40 mg and for at least 1 month after the last dose. Males: Male patients with female partners of reproductive potential should be advised to use effective contraception during treatment and for 3 months after the last dose of Hernix 40 mg.

Pediatric Use: The safety and efficacy of Hernix 40 mg in pediatric patients has not been established.Geriatric Use: The incidence of serious adverse reactions in the Hernix 40 mg arm vs. placebo arm was 7.0% vs. 5.7% (<65 years-old) and 9.9% vs. 8.1% (≥65 years-old). The serious adverse reactions most frequently reported in the ≥ 65 years-old group were vomiting (2.3%), diarrhea (1.7%), renal failure (1.7%), and dehydration (1.2%).Hepatic Impairment: No dose modifications are recommended for patients with mild to moderate hepatic impairment (Child Pugh A or B). Patients with severe, pre-existing hepatic impairment (Child Pugh Class C) experienced a reduction in Hernix 40 mg clearance and an increase in Cmax and AUC. Hernix 40 mg dosage should be reduced for patients with severe hepatic impairment.