Tykerb

Do not eat grapefruit or drink grapefruit juice while taking this medication.

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Dosage Forms And Strengths

250 mg tablets — oval, biconvex, orange, film-coated with GS XJG debossed on one side.

Storage And Handling

The 250 mg tablets of TYKERB are oval, biconvex, orange, and film-coated with GS XJG debossed on one side and are available in:

Bottles of 150 tablets: NDC 0078-0671-19

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. Revised: April 2017

Mechanism Of Action

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 greater than or equal to 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.

Pharmacokinetics

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 hours). 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.

At the dose of 1,250 mg daily, steady-state geometric mean [95% confidence interval (CI)] values of Cmax were 2.43 mcg/mL (1.57 to 3.77 mcg/mL) and AUC were 36.2 mcg.h/mL (23.4 to 56 mcg.h/mL).

Divided daily doses of TYKERB resulted in approximately 2-fold higher exposure at steady state (steady-state AUC) compared to the same total dose administered once daily.

Systemic exposure to lapatinib is increased when administered with food. Lapatinib AUC values were approximately 3- and 4-fold higher (Cmax approximately 2.5- and 3-fold higher) when administered with a low-fat (5% fat-500 calories) or with a high-fat (50% fat-1,000 calories) meal, respectively.

Lapatinib is highly bound (greater than 99%) to albumin and alpha-1 acid glycoprotein. In vitro studies indicate that lapatinib is a substrate for the transporters breast cancer-resistance protein (BCRP, ABCG2) and P-glycoprotein (P-gp, ABCB1). Lapatinib has also been shown to inhibit P-gp, BCRP, and the hepatic uptake transporter OATP 1B1, in vitro at clinically relevant concentrations.

Lapatinib undergoes extensive metabolism, primarily by CYP3A4 and CYP3A5, with minor contributions from CYP2C19 and CYP2C8 to a variety of oxidated metabolites, none of which accounts for more than 14% of the dose recovered in the feces or 10% of lapatinib concentration in plasma.

At clinical doses, the terminal phase half-life following a single dose was 14.2 hours; accumulation with repeated dosing indicates an effective half-life of 24 hours.

Elimination of lapatinib is predominantly through metabolism by CYP3A4/5 with negligible (less than 2%) renal excretion. Recovery of parent lapatinib in feces accounts for a median of 27% (range 3% to 67%) of an oral dose.

Studies of the effects of age, gender, or race on the pharmacokinetics of lapatinib have not been performed.

QT Prolongation

The QT prolongation potential of lapatinib was assessed as part of an uncontrolled, open-label, dose-escalation study in advanced cancer patients. Eighty-one patients received daily doses of lapatinib ranging from 175 mg/day to 1,800 mg/day. Serial ECGs were collected on Day 1 and Day 14 to evaluate the effect of lapatinib on QT intervals. Analysis of the data suggested a consistent concentration-dependent increase in QTc interval.

Pharmacogenomics

The HLA alleles DQA1*02:01 and DRB1*07:01 were associated with hepatotoxicity reactions in a genetic substudy of a monotherapy trial with TYKERB (n = 1,194). Severe liver injury (ALT greater than 5 times the upper limit of normal, NCI CTCAE Grade 3) occurred in 2% of patients overall; the incidence of severe liver injury among DQA1*02:01 or DRBI*07:01 allele carriers was 8% versus 0.5% in non-carriers. These HLA alleles are present in approximately 15% to 25% of Caucasian, Asian, African, and Hispanic populations and 1% in Japanese populations. Liver function should be monitored in all patients receiving therapy with TYKERB regardless of genotype.

Animal Toxicology And/Or Pharmacology

In 104-week repeat-dose studies in rodents, severe skin lesions that led to lethality were seen at the highest doses tested (300 mg/kg/day) in male mice and female rats. There was also an increase in renal infarcts and papillary necrosis in female rats at greater than or equal to 60 mg/kg/day and greater than or equal to 180 mg/kg/day, respectively (approximately 7 and 10 times the expected human clinical exposure based on AUC, respectively). The relevance of these findings for humans is uncertain.

Clinical Studies

HER2-Positive Metastatic Breast Cancer

The efficacy and safety of TYKERB in combination with capecitabine in breast cancer were evaluated in a randomized, Phase 3 trial. Patients eligible for enrollment had HER2 (ErbB2) overexpressing (IHC 3+ or IHC 2+ confirmed by FISH), locally advanced or metastatic breast cancer, progressing after prior treatment that included anthracyclines, taxanes, and trastuzumab.

Patients were randomized to receive either TYKERB 1,250 mg once daily (continuously) plus capecitabine 2,000 mg/m2/day on Days 1-14 every 21 days, or to receive capecitabine alone at a dose of 2,500 mg/m2/day on Days 1-14 every 21 days. The endpoint was time to progression (TTP). TTP was defined as time from randomization to tumor progression or death related to breast cancer. Based on the results of a pre-specified interim analysis, further enrollment was discontinued. Three hundred and ninety-nine (399) patients were enrolled in this study. The median age was 53 years and 14% were older than 65 years. Ninety-one percent (91%) were Caucasian. Ninety-seven percent (97%) had stage IV breast cancer, 48% were estrogen receptor+ (ER+) or progesterone receptor+ (PR+), and 95% were ErbB2 IHC 3+ or IHC 2+ with FISH confirmation. Approximately 95% of patients had prior treatment with anthracyclines, taxanes, and trastuzumab.

Efficacy analyses 4 months after the interim analysis are presented in Table 5, Figure 1, and Figure 2.

Table 5. Efficacy Results

Figure 1. Kaplan-Meier Estimates for Independent Review Panel-evaluated Time to Progression

Figure 2. Kaplan-Meier Estimates for Investigator Assessment Time to Progression

At the time of above efficacy analysis, the overall survival data were not mature (32% events). However, based on the TTP results, the study was unblinded and patients receiving capecitabine alone were allowed to cross over to treatment with TYKERB plus capecitabine. The survival data were followed for an additional 2 years to be mature and the analysis is summarized in Table 6.

Table 6: Overall Survival Data

In two randomized trials, TYKERB-based chemotherapy regimens have been shown to be less effective than trastuzumab-based chemotherapy regimens. The first randomized, open-label study compared the safety and efficacy of TYKERB in combination with capecitabine relative to trastuzumab in combination with capecitabine in women with HER2-positive metastatic breast cancer (N = 540). The study was stopped early based on the findings of a pre-planned interim analysis showing a low incidence of CNS events (primary endpoint) and superior efficacy of the trastuzumab plus capecitabine. The median progression-free survival was 6.6 months in the group receiving TYKERB in combination with capecitabine compared with 8.0 months in the group receiving the trastuzumab combination [HR = 1.30 (95% CI: 1.04, 1.64)]. Overall survival was analyzed when 26% of deaths occurred in the group receiving TYKERB in combination with capecitabine and 22% in the group receiving the trastuzumab combination [HR = 1.34 (95% CI: 0.95, 1.92)].

The second randomized, open-label study compared the safety and efficacy of taxane-based chemotherapy plus TYKERB to taxane-based chemotherapy plus trastuzumab as first-line therapy in women with HER2-positive, metastatic breast cancer (N = 652). The study was stopped early based on findings from a pre-planned interim analysis. The median progression-free survival was 11.3 months in the trastuzumab combination treatment arm compared to 9.0 months in patients treated with TYKERB in the combination arm for the intent-to-treat population [HR = 1.37 (95% CI: 1.13, 1.65)].

Hormone Receptor-Positive, HER2-Positive Metastatic Breast Cancer

The efficacy and safety of TYKERB in combination with letrozole were evaluated in a double-blind, placebo-controlled, multi-center study. A total of 1,286 postmenopausal women with hormone receptor-positive (ER positive and/or PgR positive) metastatic breast cancer, who had not received prior therapy for metastatic disease, were randomly assigned to receive either TYKERB (1,500 mg once daily) plus letrozole (2.5 mg once daily) (n = 642) or letrozole (2.5 mg once daily) alone (n = 644). Of all patients randomized to treatment, 219 (17%) patients had tumors overexpressing the HER2 receptor, defined as fluorescence in situ hybridization (FISH) greater than or equal to 2 or 3+ immunohistochemistry (IHC). There were 952 (74%) patients who were HER2-negative and 115 (9%) patients did not have their HER2 receptor status confirmed. The primary objective was to evaluate and compare progression-free survival (PFS) in the HER2-positive population. Progression-free survival was defined as the interval of time between date of randomization and the earlier date of first documented sign of disease progression or death due to any cause.

The baseline demographic and disease characteristics were balanced between the two treatment arms. The median age was 63 years and 45% were 65 years of age or older. Eighty-four percent (84%) of the patients were white. Approximately 50% of the HER2-positive population had prior adjuvant/neo-adjuvant chemotherapy and 56% had prior hormonal therapy. Only 2 patients had prior trastuzumab.

In the HER2-positive subgroup (n = 219), the addition of TYKERB to letrozole resulted in an improvement in PFS. In the HER2-negative subgroup, there was no improvement in PFS of the combination of TYKERB plus letrozole compared to the letrozole plus placebo. Overall response rate (ORR) was also improved with the combination of TYKERB plus letrozole. The overall survival (OS) data were not mature. Efficacy analyses for the hormone receptor-positive, HER2-positive and HER2-negative subgroups are presented in Table 7 and Figure 3.

Table 7. Efficacy Results

Figure 3. Kaplan-Meier Estimates for Progression-Free Survival for the HER2-Positive Population

Do not use lapatinib if you are pregnant. It could harm the unborn baby.

Before you take lapatinib, tell your doctor if you have heart disease, liver disease, an electrolyte imbalance (low potassium or magnesium), or a personal or family history of Long QT syndrome.

To make sure you can safely take lapatinib, your heart function will need to be checked before you start treatment. Your liver function will need to be checked every 4 to 6 weeks during treatment.

Take lapatinib on an empty stomach.

Take this medication for the entire length of time prescribed by your doctor.

You should not use lapatinib if you are allergic to it.

To make sure you can safely take lapatinib, tell your doctor if you have any of these other conditions:

• heart disease;
• liver disease;
• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood); or
• a personal or family history of Long QT syndrome.

FDA pregnancy category D. Do not use lapatinib if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether lapatinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking this medication.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction 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.

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 [see Clinical Studies]. Adverse reactions which occurred in at least 10% of patients in either treatment arm and were higher in the combination arm are shown in Table 1.

The most common adverse reactions (greater than 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 reaction resulting in discontinuation of study medication.

The most common Grade 3 and 4 adverse reactions (NCI CTCAE v3) were diarrhea and palmar-plantar erythrodysesthesia. Selected laboratory abnormalities are shown in Table 2.

Table 1. Adverse Reactions Occurring in Greater Than or Equal to 10% of Patients

Table 2. Selected Laboratory Abnormalities

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 shown in Table 3. Selected laboratory abnormalities are shown in Table 4.

Table 3. Adverse Reactions Occurring in Greater Than or Equal to 10% of Patients

Table 4. Selected Laboratory Abnormalities

Due to potential cardiac toxicity with HER2 (ErbB2) inhibitors, LVEF was monitored in clinical trials at approximately 8-week intervals. LVEF decreases were defined as signs or symptoms of deterioration in left ventricular cardiac function that are greater than or equal to Grade 3 (NCI CTCAE), or a greater than or equal to 20% decrease in left ventricular cardiac ejection fraction relative to baseline which is below the institution's lower limit of normal. Among 198 patients who received combination treatment with TYKERB/capecitabine, 3 experienced Grade 2 and one had Grade 3 LVEF adverse reactions (NCI CTCAE v3) [see WARNINGS AND PRECAUTIONS]. Among 654 patients who received combination treatment with TYKERB/letrozole, 26 patients experienced Grade 1 or 2 and 6 patients had Grade 3 or 4 LVEF adverse reactions.

TYKERB has been associated with hepatotoxicity [see BOX WARNING and WARNINGS AND PRECAUTIONS].

TYKERB has been associated with interstitial lung disease and pneumonitis in monotherapy or in combination with other chemotherapies [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of TYKERB. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Hypersensitivity reactions including anaphylaxis [see CONTRAINDICATIONS].

Skin and Subcutaneous Tissue Disorders: Nail disorders including paronychia. Severe cutaneous adverse reactions including Stevens Johnson Syndrome (SJS) and toxic epidural necrolysis (TEN).

Cardiac Disorders: Ventricular arrhythmias/Torsades de Points (TdP). Electrocardiogram QT prolongation.

Read the entire FDA prescribing information for Tykerb (Lapatinib)

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Diarrhea or
• Liver disease, or history of or
• Lung disease (eg, interstitial lung disease, pneumonitis), history of—Use with caution. May make these conditions worse.

• Heart disease, history of or
• Heart rhythm problems (eg, congenital long QT syndrome) or
• Hypokalemia (low potassium in the blood), uncorrected or
• Hypomagnesemia (low magnesium in the blood), uncorrected—Use with caution. May cause side effects to become worse.

Before you start taking Tykerb, tell your doctor about all of your medical conditions, including if you:

• ever had a severe allergic (hypersensitivity) reaction to Tykerb. Check with your doctor if you think this applies to you. Don’t take Tykerb.
• have heart problems.
• have liver problems. You may need a lower dose of Tykerb.
• are pregnant or may become pregnant. Tykerb may harm an unborn baby. If you become pregnant during treatment with Tykerb, tell your doctor as soon as possible.
• are breastfeeding. It is not known if Tykerb passes into your breast milk or if it can harm your baby. If you are a woman who has or will have a baby, talk with your doctor about the best way to feed your baby.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal and dietary supplements.

• Store Tykerb tablets at room temperature at 59° to 86°F (15° to 30°C). Keep the container closed tightly.
• Do not keep medicine that is out of date or that you no longer need. Be sure that if you throw any medicine away, it is out of the reach of children.
• Keep Tykerb and all medicines out of the reach of children.

• Tell all of your health care providers that you take Tykerb. This includes your doctors, nurses, pharmacists, and dentists.
• If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
• Loose stools (diarrhea) have happened with this medicine. Sometimes, diarrhea has been very bad and deaths have happened. Talk with your doctor.
• If you have loose stools (diarrhea), talk with your doctor. Do not try to treat diarrhea without first checking with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• You will need to have heart function tests while taking Tykerb. Talk with the doctor.
• Avoid grapefruit and grapefruit juice.
• If you are taking digoxin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this medicine.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• Use birth control that you can trust to prevent pregnancy while taking Tykerb.
• If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

Use Tykerb as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take on an empty stomach.
• Take 1 hour before or 1 hour after a meal.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of lung or breathing problems like shortness of breath or other trouble breathing, cough, or fever.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• A heartbeat that does not feel normal.
• Chest pain or pressure or a fast heartbeat.
• Dizziness or passing out.
• Very bad belly pain.
• Very upset stomach or throwing up.
• Loose stools (diarrhea) or loose stools with stomach cramps, upset stomach, throwing up, fever, or fluid loss.
• Redness or irritation of the palms of hands or soles of feet.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Tykerb, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Tykerb (lapatinib). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Tykerb.

Review Date: October 4, 2017

Take Tykerb exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions. Be sure to also read the medication guides for Xeloda or Femara.

When used with Femara, the usual dose of Tykerb is 6 tablets taken once daily every day. Femara is also taken every day.

When used with Xeloda, Tykerb is usually taken in a 21-day cycle. You will take Tykerb in a dose of 5 tablets once daily for all 21 days in a row. You will take Xeloda twice daily for only the first 14 days of the cycle. This 21-day cycle is then repeated.

Your doctor will tell you how much Xeloda or Femara to take. Follow your doctor's dosing instructions very carefully.

Take Tykerb on an empty stomach, at least 1 hour before or 1 hour after a meal.

You may swallow each tablet one at a time, but take the entire dose (all 5 or 6 tablets) at the same time each day.

Xeloda must be taken with food or within 30 minutes of eating.

You will need blood tests every 4 to 6 weeks to check your liver function. Your heart function may also need to be checked using an electrocardiograph or ECG (sometimes called an EKG).

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

Your doctor will determine how long to treat you with Tykerb and Xeloda or Femara. Take your medications for the full prescribed length of time. Combination chemotherapy is usually continued unless your condition gets worse or you have serious side effects.

Usual Adult Dose for Breast Cancer:

-HER2-POSITIVE METASTATIC BREAST CANCER (in combination with Xeloda): 1250 mg orally once a day on Days 1 to 21 continuously in repeating 21-day cycles until disease progression or unacceptable toxicity.

-HORMONE RECEPTOR-POSITIVE, HER2-POSITIVE METASTATIC BREAST CANCER (in combination with Femara): 1500 mg orally once a day continuously.

Comments:
-Consult the manufacturer product information for Xeloda and Femara dosing recommendations.
-HER2-positive metastatic breast cancer patients should have disease progression on trastuzumab prior to initiation of treatment with this drug in combination with Xeloda.

Uses:
-In combination with Xeloda for 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 trastuzumab.
-In combination with Femara for treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated.

Tykerb is a prescription drug that’s used to treat breast cancer. It’s used in combination with capecitabine or letrozole.

Tykerb comes as a tablet that you take by mouth.

Tykerb is a brand name for the drug lapatinib. It’s not available as a generic drug.

• Food and Drink Administration warning See Details

• Heart problems See Details

• Severe diarrhea See Details

What is Tykerb?

This drug is a prescription drug. It comes as a tablet you take by mouth.

This drug is available as the brand-name drug Tykerb. It is not available as a generic drug.

This drug may be used as part of a combination therapy. That means you may need to take it with other drugs to treat your condition. This drug may be prescribed with capecitabine or letrozole.

Why it's used

This drug is used to treat breast cancer. It’s used with a drug called capecitabine to treat advanced or metastatic breast cancer that is HER2-positive (has a protein in your body). It’s used when certain other breast cancer treatments have not worked. It’s also used with a drug called letrozole to treat hormone receptor-positive, HER2-positive metastatic breast cancer in postmenopausal women who need hormonal therapy.

How it works

This drug belongs to a drug class called kinase inhibitors. A class of drugs refers to medications that work in a similar way. These drugs are often used to treat similar conditions.

This drug works by blocking the action of certain proteins called kinases that tell cancer cells in your body to multiply. This action helps slow or stop the spread of cancer cells in your body.

Tykerb can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Medications that might interact with this drug

• midazolam

Using these drugs together increases your risk of side effects. Your doctor may lower your dosage of midazolam if you’re using it with Tykerb.

• paclitaxel

Using these drugs together increases your risk of side effects. Your doctor may lower your dosage of the medication if you’re using it with Tykerb.

• digoxin

Using these drugs together increases your risk of side effects. Your doctor may lower your dosage of the medication if you’re using it with Tykerb.

• ketoconazole

Using these drugs together increases your risk of side effects. Your doctor may lower your dosage of the medication if you’re using it with Tykerb.

• carbamazepine

Using these drugs together will decrease the effect of Tykerb. Your doctor may increase your dosage of Tykerb.

Examples of these drugs include:

• propranolol
• pravastatin
• quinidine
• ranitidine
• risperidone

Using any of these drugs with Tykerb increases your risk of side effects. Your doctor may lower your dosage of these medications if you’re using any of them with Tykerb.

People with liver problems

This drug may cause severe liver damage that may be fatal (cause death). If you already have decreased liver function, your doctor may start you on a reduced dosage.

People with heart problems

This drug can cause heart problems and worsen existing heart conditions such as heart failure or congenital long QT syndrome.

Pregnant women

This drug is a category D pregnancy drug. That means two things:

1. Research in humans has shown adverse effects to the fetus when the mother takes the drug.
2. This drug should only be used during pregnancy in serious cases where it's needed to treat a dangerous condition in the mother.

Talk to your doctor if you’re pregnant or planning to become pregnant. Ask your doctor to tell you about the specific harm that may be done to the fetus. This drug should only be used if the potential risk to the fetus is acceptable given the drug’s potential benefit.

Women who are breast-feeding

It isn’t known if this drug passes into breast milk. If it does, it may cause serious effects in a child who is breastfed.

Talk to your doctor about breastfeeding your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may monitor you more closely while taking this drug.

For children

This drug hasn’t been established as safe and effective for use in people younger than 18 years.

When to call the doctor

Call your doctor if you become pregnant while taking this drug.

Allergies

This drug can cause a severe allergic reaction. Symptoms can include:

• trouble breathing
• swelling of your throat or tongue
• hives

If you have an allergic reaction, call your doctor or local poison control center right away. If your symptoms are severe, call 9-1-1 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).