|Information here is extracted from prescription information on September 4, 2011. For details, please, consult with your doctor,
pharmacist or review the product insert.
TYKERB® is indicated in combination with:
capecitabine (Tradename - Xeloda) for the treatment of patients with advanced or metastatic breast cancer whose
tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and
letrozole (Tradename- Femara) for the treatment of postmenopausal women with hormone receptor positive
metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated.
Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. Lapatinib is a
yellow solid, and its solubility in water is 0.007 mg/mL and in 0.1N HCl is 0.001 mg/mL at 25°C. Each 250 mg tablet
of TYKERB contains 405 mg of lapatinib ditosylate monohydrate, equivalent to 398 mg of lapatinib ditosylate or
250 mg lapatinib free base. The inactive ingredients of TYKERB are: Tablet Core: Magnesium stearate,
microcrystalline cellulose, povidone, sodium starch glycolate. Coating: Orange film-coat: FD&C yellow No.
6/sunset yellow FCF aluminum lake, hypromellose, macrogol/PEG 400, polysorbate 80, titanium dioxide.
Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both Epidermal
Growth Factor Receptor (EGFR [ErbB1]) and of Human Epidermal Receptor Type 2 (HER2 [ErbB2]) receptors
(estimated Kiapp values of 3nM and 13nM, respectively) with a dissociation half-life of ≥300 minutes. Lapatinib
inhibits ErbB-driven tumor cell growth in vitro and in various animal models.
An additive effect was demonstrated in an in vitro study when lapatinib and 5-FU (the active metabolite of
capecitabine) were used in combination in the 4 tumor cell lines tested. The growth inhibitory effects of lapatinib
were evaluated in trastuzumab-conditioned cell lines. Lapatinib retained significant activity against breast cancer
cell lines selected for long-term growth in trastuzumab-containing medium in vitro. These in vitro findings suggest
non-cross-resistance between these two agents.
Hormone receptor positive breast cancer cells (with ER [Estrogen Receptor] and/or PgR [Progesterone
Receptor]) that coexpress the HER2 tend to be resistant to established endocrine therapies. Similarly, hormone
receptor positive breast cancer cells that initially lack EGFR or HER2 upregulate these receptor proteins as the
tumor becomes resistant to endocrine therapy.
Absorption following oral administration of TYKERB is incomplete and variable. Serum concentrations appear
after a median lag time of 0.25 hours (range 0 to 1.5 hour). Peak plasma concentrations (Cmax) of lapatinib are
achieved approximately 4 hours after administration. Daily dosing of TYKERB results in achievement of steady
state within 6 to 7 days, indicating an effective half-life of 24 hours. For details, please, review the product insert.
Tykerb Herceptin Comparison and Contrast
Tykerb Herceptin - Mechanism
Herceptin blocks the HER2 activities by binding to it on the outside of the cell. While, tykerb blocks the HER2
breast cancer factor and EGFR (the same molecular target of cancer medications such as Iressa).
Tykerb Herceptin - Usage
Tykerb is a once-a-day pill, while Herceptin is a monthly infusion.
Tykerb Herceptin - Complication
Herceptin may cause heart failure
Tykerb Herceptin - Structure and Effects
Tykerb is a small molecule that can be administered orally. It inhibits the tyrosine kinase components of ErbB1
and ErbB2 receptors. Stimulation of ErbB1 and ErbB2 is associated with cell proliferation and with multiple
processes involved in tumor progression, invasion, and metastasis. Overexpression of these receptors has
been reported in a variety of human tumors. Glaxo is using pharmacogenetics and other advanced
technologies to better define patient populations that may respond to Tykerb.
Herceptin (Trastuzumab) is actually a monoclonal antibody bioengineered from a mouse antibody. Herceptin
(Trastuzumab) binds to HER2 on the surface of some normal cells and plays a role in regulating cell growth. In
the experimental studies, Herceptin (Trastuzumab) demonstrated its ability to inhibit tumor cell growth by this
binding action. In metastatic breast cancer cells, about 30% of tumors produce excess amounts of HER2.
Studies show that cancer may be more aggressive when breast cancer tumors produce excess amounts of the
HER2 protein. In studies, patients suffered from breast cancers showed better responses when they had
higher levels of HER2 protein. Herceptin (Trastuzumab) was approved for use alone for certain patients who
have tried chemotherapy with little success or as a first-line treatment for metastatic disease when used in
combination with paclitaxel (trade-name Taxol) on September 25, 1998. It was described as a new biologic
approach for the treatment of metastatic breast cancer, or cancer that has spread beyond the breast and
lymph nodes under the arm.
Tykerb and Xeloda
Tykerb® (lapatinib) plus Xeloda® (capecitabine) was superior to capecitabine alone, study shows.
Dr. Charles E. Geyer at Allegheny General Hospital, Pittsburg, concluded that Tykerb® (lapatinib) plus
Xeloda® (capecitabine) was superior to capecitabine alone in women with HER2 (ErbB2) positive advanced
breast cancer who had progressed following prior therapy, including Herceptin® (trastuzumab) in a Phase III
study of women with HER2-positive, locally advanced or metastatic breast cancer.
The study also showed that the combination-therapy was not associated with higher incidence in either serious
toxicity or rates of discontinuation related to adverse side effects, compared to capecitabine treatment alone.
The most common side effects were diarrhea, hand-foot syndrome and rash distinct from hand-foot syndrome.
Tykerb Side Effects
The most commonly reported Tykerb-related side effects included diarrhea, nausea, vomiting, rash and
hand-foot syndrome which may include numbness, tingling, redness, swelling and discomfort of hands and
feet. Generally reversible decreases in heart function (that can lead to shortness of breath) have also been
reported in a small percentage of patients. Patients should talk to their doctor about potential side effects,
potential drug interactions, and other medical conditions including heart and liver problems. 
Tykerb will be distributed by GlaxoSmithKline, of Research Triangle Park, North Carolina.
SOURCES Glaxo's Tykerb Pill Shows the Advance of Breast Cancer in Study Bloomberg June 3 2006.
GlaxoSmithKline Initiates Trial of Tykerb (Lapatinib) in Patients With ErbB2-Overexpressing Breast Cancer
Brain Metastasis Following Herceptin and Cranial Radiotherapy. PRNewswire Dec 9 2005  GlaxoSmithKline
Reports Positive New Data on Tykerb (R) (Lapatinib Ditosylate) PR Newswire June 3 2006  Lapatinib plus
Capecitabine for HER2-Positive Advanced Breast Cancer New England Journal of Medicine (NEJM) Volume
355:2733-2743 December 28, 2006 Number 26.  FDA Approves Tykerb for Advanced Breast Cancer
Patients, FDA News, March 13, 2007.
Tykerb side effects
tykerb and xeloda, tykerb dosing, tykerb herceptin September 4, 2011
THIS WEBSITE TALKS ABOUT THE SIDE EFFECTS AND THE POTENTIAL HEALTH BENEFITS OF HERBS, SUPPLEMENTS. However, the information in this
website is for reference only. Please, discuss with your doctor before taking any medicine or supplement. All rights reserved 2011.
DOSAGE AND ADMINISTRATION
HER2 Positive Metastatic Breast Cancer: The recommended dose of TYKERB is 1,250 mg given orally once
daily on Days 1-21 continuously in combination with capecitabine 2,000 mg/m2/day (administered orally in 2
doses approximately 12 hours apart) on Days 1-14 in a repeating 21 day cycle. TYKERB should be taken at
least one hour before or one hour after a meal. The dose of TYKERB should be once daily (5 tablets
administered all at once); dividing the daily dose is not recommended [see Clinical Pharmacology (12.3)].
Capecitabine should be taken with food or within 30 minutes after food. If a day’s dose is missed, the patient
should not double the dose the next day. Treatment should be continued until disease progression or
unacceptable toxicity occurs.
Hormone Receptor Positive, HER2 Positive Metastatic Breast Cancer: The recommended dose of TYKERB is
1,500 mg given orally once daily continuously in combination with letrozole. When coadministered with TYKERB,
the recommended dose of letrozole is 2.5 mg once daily. TYKERB should be taken at least one hour before or
one hour after a meal. The dose of TYKERB should be once daily (6 tablets administered all at once); dividing
the daily dose is not recommended [see Clinical Pharmacology (12.3)].
Dose Modification Guidelines
Cardiac Events: TYKERB should be discontinued in patients with a decreased left ventricular ejection fraction
(LVEF) that is Grade 2 or greater by National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI CTCAE) and in patients with an LVEF that drops below the institution’s lower limit of normal [see Warnings
and Precautions (5.1) and Adverse Reactions (6.1)]. TYKERB in combination with capecitabine may be
restarted at a reduced dose (1,000 mg/day) and in combination with letrozole may be restarted at a reduced
dose of 1,250 mg/day after a minimum of 2 weeks if the LVEF recovers to normal and the patient is
Hepatic Impairment: Patients with severe hepatic impairment (Child-Pugh Class C) should have their dose of
TYKERB reduced. A dose reduction from 1,250 mg/day to 750 mg/day (HER2 positive metastatic breast cancer
indication) or from 1,500 mg/day to 1,000 mg/day (hormone receptor positive, HER2 positive breast cancer
indication) in patients with severe hepatic impairment is predicted to adjust the area under the curve (AUC) to
the normal range and should be considered. However, there are no clinical data with this dose adjustment in
patients with severe hepatic impairment.
Concomitant Strong CYP3A4 Inhibitors: The concomitant use of strong CYP3A4 inhibitors should be avoided (e.
g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
telithromycin, voriconazole). Grapefruit may also increase plasma concentrations of lapatinib and should be
avoided. If patients must be coadministered a strong CYP3A4 inhibitor, based on pharmacokinetic studies, a
dose reduction to 500 mg/day of lapatinib is predicted to adjust the lapatinib AUC to the range observed without
inhibitors and should be considered.
Concomitant Strong CYP3A4 Inducers: The concomitant use of strong CYP3A4 inducers should be avoided (e.
g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John’s Wort). If
patients must be coadministered a strong CYP3A4 inducer, based on pharmacokinetic studies, the dose of
lapatinib should be titrated gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast
cancer indication) or from 1,500 mg/day up to 5,500 mg/day (hormone receptor positive, HER2 positive breast
cancer indication) based on tolerability. This dose of lapatinib is predicted to adjust the lapatinib AUC to the
range observed without inducers and should be considered. However, there are no clinical data with this dose
adjustment in patients receiving strong CYP3A4 inducers. If the strong inducer is discontinued the lapatinib dose
should be reduced to the indicated dose. [See Drug Interactions (7.2).]
Other Toxicities: Discontinuation or interruption of dosing with TYKERB may be considered when patients
develop ≥Grade 2 NCI CTCAE toxicity and can be restarted at 1,250 mg/day when the toxicity improves to
Grade 1 or less. If the toxicity recurs, then TYKERB in combination with capecitabine should be restarted at a
lower dose (1,000 mg/day) and in combination with letrozole should be restarted at a lower dose of 1,250
See manufacturer’s prescribing information for the coadministered product dosage adjustment guidelines in the
event of toxicity and other relevant safety information or contraindications.
Tykerb Side Effects
Because clinical trials are conducted under widely varying conditions, adverse side effect rates observed in the
clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not
reflect the rates observed in practice.
HER2 Positive Metastatic Breast Cancer: The safety of TYKERB has been evaluated in more than 12,000
patients in clinical trials. The efficacy and safety of TYKERB in combination with capecitabine in breast cancer
was evaluated in 198 patients in a randomized, Phase 3 trial. Adverse side effects which occurred in at least
10% of patients in either treatment arm and were higher in the combination arm are  GI side effects -
diarrhea, nausea, stomatitis, and dyspepsia,  skin side effects - palmar-plantar erthrodysesthesia, rash and
dry skin,  general side effects - mucosal inflammation,  musculoskeletal and conective tissue side effects -
pain in extremity and back issues,  respiratory, thoracic side effects - dyspnea and  psychiatric disorders -
The most common adverse side effects (>20%) during therapy with TYKERB plus capecitabine were
gastrointestinal (diarrhea, nausea, and vomiting), dermatologic (palmar-plantar erythrodysesthesia and rash),
and fatigue. Diarrhea was the most common adverse side effects resulting in discontinuation of study medication.
The most common Grade 3 and 4 adverse side effects were diarrhea and palmar-plantar erythrodysesthesia.
Hormone Receptor Positive, Metastatic Breast Cancer: In a randomized clinical trial of patients (N = 1,286) with
hormone receptor positive, metastatic breast cancer, who had not received chemotherapy for their metastatic
disease, patients received letrozole with or without TYKERB. In this trial, the safety profile of TYKERB was
consistent with previously reported results from trials of TYKERB in the advanced or metastatic breast cancer
population. Adverse reactions which occurred in at least 10% of patients in either treatment arm and were
higher in the combination arm are:  GI side effects - diarrhea, nausea, vomiting and anorexia,  skin side
effects - rash, dry skin, alopecia, pruritus, and nail issues,  general side effects - fatigue and asthenia, 
nervous system side effects - headache, and  respiratory side effects - epistaxis.
Herbal / Dietary Supplements / Foods that may lower the risk of certain types of cancer: Avocados
Banana, Bitter Melon, Brown Seaweed, Capsicum, Cauliflower, Celery, Chlorophyll, Cordyceps, Curcumin,
Dandelion, Ellagic acid, Oldenlandia, Falcarinol, Fenugreek, Feverfew, Fish Oil, Forskolin, Galangal, Garlic,
Gotu Kola, Green Tea, Grape Seed Extract, Honokiol, Orange, Isothiocyanates, Linseed Oil, Limes, Lycopene,
Maitake, Milk Thistle, Onion, Peony, Phellinus, Quercetin, Pterostibene, Pycnogenol, Reishi, Rhubarb, Saffron,
Stinging Nettle, Sweet Potatoes, and more.
Drugs listed in this website for chemotherapy:
Xeloda, Avastin, Herceptin, Tykerb,