Tykerb tablets are categorized as anti-neoplastic agent, which is orally active drug used for treating breast cancer. Tykerb tablets are comes under biological category which is targeted chemotherapy. Tykerb tablets are classified as: Tyrosine kinase prohibitor, Stop the HER2/neu& epidermal growth factor receptor activity, Targeted therapy, Signal transduction prohibitor. Tykerb 250mg tablets containing 250mg of Lapatinib as an active substance. Tykerb is a synthetic oral tablet, chemically classified as quinazoline with strong anti-cancer effect.
PRESCRIBING INFORMATION OF TYKERB
Tykerb consist of Lapatinib is primarily indicated for advanced breast cancer.
Tykerb is used in combination with
Capecitabine with Tykerb tablets are usually indicated for the treatment of metastatic breast cancer patients in whose cancer cells expressed with EGFR 2 (HER2) and patients may already receive an anthracycline, taxane& Transtuzumab.
The major demerit of Tykerb
Patients should be produce advancement of disease during Transtuzumab therapy, prior initiation of Tykerb with Capecitabine. Tykerb tablet with letrozole is involved in the therapy of post menopausal women suffered with hormone receptor positive advanced breast cancer that contains HER 2 receptors. Tykerb concurrent with Aromatase inhibitors have not been correlates to Transtuzumab chemotherapy drug for breast cancer therapy.
LAPATINIB (TYKERB) MECHANISM OF ACTION
Chemically Lapatinib is categorized as 4-anilinoquinazoline derivative, which expels anti-cancer activity by prohibiting intracellular tyrosine kinase domains of EFGR & HER type 2.
The ErbB driven tumor cell production has been prohibited by Lapatinib. This growth factor receptor present on cell surface of tumors which may leads to cause cell death.
The absorption of Tykerb is incomplete and insufficient, the maximum plasma concentration time of Lapatinib occurs relatively 4 hours after drug intake. The steady state reaches within 6 to 7 days
Lapatinib is largely bounds to human plasma protein like albumin & alpha glycoprotein nearly 99%.
Lapatinib is a substrate of P-gp& BCRP and undergoes intensive metabolism by using CYPP3A4 & CYP3A5 with lesser contribution of CYP2C19 & CYP2C8.
Tykerb in single dose reaches half life time in 14.2 hours and repeated dosing reaches in 24 hours. Elimination occurs via feces & urine.
In HER2 positive advanced breast cancer
The recommended Tykerb dose is 1250mg should be administered orally as a single dose on day 1 to 21repeatedly combined with Capecitabine 2000mg/m2/day (should be taken orally in 2 doses relatively 12 hours apart) on day 1 to 14 in continuous 21 day cycle. Totally 5 tablets of Tykerb should be taken at a time as whole.
In hormone receptor positive HER 2 positive advance breast cancer
The prescribed dose is 1500mg should be administered orally as a single dose by combining with letrozole. The prescribed dose of letrozole is 2.5mg as a once a day. In these total 6 tablets of Tykerb should be administered as such.
In patients with reduction of left ventricular ejection fraction with grade 2, treatment with Tykerb should be discontinued. In this condition, the Tykerb dose should be initiated with 1000mg/day in combination with Capecitabine; whereas in combination with letrozole the dose of Tykerb restated with 1250mg/day after 2 weeks, if LVEF turns to normal.
For patient with severe hepatic impairment, the dose reduced from 1250mg/day to 750mg/day or from 1500mg/day to 1000mg/day.
Tykerb tablets should be restarted once the severity of diarrhea may reduced to grade I. permanently discontinued if diarrhea is persists.
Concurrent use of CYP3A4 inhibitors
Tykerb should not be combined with CYP3A4 inhibitors; because of elevation of plasma concentration of Lapatinib occurs. For eradicate this effect, the dose of Tykerb should be reduced to 500mg/day.
Concurrent use of CYP3A4 inducers
In this combinational study, the Tykerb dose should be elevate from 1250mg/day to 4500mg/day or from 1500mg/day to 5500mg/day.
In other toxicity
Postpone or stop the Tykerb therapy may happens, in case of developing higher grade of toxicities which is greater than or equal to grade II. Tykerb use in combination with Capecitabine should be resume at lower doses 1000mg/day and whereas in combination with letrozole should be resume at lower dose of 1250mg/day. Tykerb tablets should be taken without food; administer 1 hour earlier or 2 hours after the food uptake. Capecitabine should be administered with food or taken within 30 minutes after ingestion of food.
The Tykerb dosage ranges from 2500mg to 9000mg daily, the duration of therapy should be varied between 1 & 17 days. Symptoms occurred during over dose of Tykerb are; Sore scalp, sinus tachycardia & mucosal inflammation. Patients should be providing with supportive measures. Hemodialysis is not an effective method for overcoming the over dosage condition of Tykerb .
TYKERB SIDE EFFECTS
Diarrhea, Nausea, Vomiting, Stomatitis, Back pain, Dyspnea, Insomnia, Elevation of hemoglobulin, platelets, neutrophils, Increase in AST & ALT, bilirubin, Alopecia, Pruritus, Nail disorders, Asthenia, Headache, Epistaxis, Reduction of left ventricular ejection fraction, Liver toxicity, Interstitial lung disease, Anaphylactic reactions, Stevens Johnson syndrome, Ventricular arrhythmias, QT prolongation
Reduction in left ventricular ejection fraction:
Caution should be taken while using Tykerb in patient with LVEF The virulence of LVEF should be decreased within first 12 weeks of treatment Before starting the therapy with Tykerb , patient must be examining thoroughly if suspected with LVEF or not.
Increasing level of AST, ALT or bilirubin may leads to liver injury To prevent this condition, periodic LFT should be maintained
Severe diarrhea may lead to dehydration causes death also; if patient do not recover from this severity must discontinue with this therapy.
Interstitial lung disease:
Patient should be monitored with pulmonary symptoms and provide supportive measures. On severe condition, treatment should be interrupt or discontinue
Monitor ECG periodically Provide substituent for this adverse condition Hypokalemia and hypomagnesemia correction should be takes place
DRUG- DRUG INTERACTION
Tykerb tablets are inhibition of CYP3A4, CYP2C8 & P-gp drug transporters; weak inhibitor of CYP3A4.
The dose reduction of these concurrent uses of substrate drug should be advised, while allowing Tykerb combined with drugs metabolized by CYP3A4, CYP2C8 or P-gp.
use with Tykerb , increases the exposure of Midazolam
Increase in paclitaxel exposure occurs while concomitant with Tykerb
Serum digoxin concentration should be examined periodically before starting the concomitant use. If digoxin level in serum is greater than 1.2ng/ml, then the dose of digoxin reduced taken with half.
Ketoconazole with Tykerb , the dose reduced to 200mg as two times a day for 7 days. Carbamazepine with Tykerb, the dose of carbamazepine at 100mg as two times a day for 3 days & 200mg for two times a day for 17 days, the exposure of Tykerb reduced to 72%. While combining Tykerb with P-gp inhibitors causes increasing the concentration of Lapatinib Without regard to esomeprazole a proton pump inhibitor, taken as 40mg as a single dose for 7 days, did not result in significant reduction in Lapatinib steady state.