Lapatinib

Before taking lapatinib,

• tell your doctor and pharmacist if you are allergic to lapatinib, any other medications, or any of the ingredients in lapatinib tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: certain antibiotics such as clarithromycin (Biaxin, in Prevpac), erythromycin (E.E.S., E-Mycin, Erythrocin), moxifloxacin (Avelox), rifabutin (Mycobutin), rifampin (Rifadin, in Rifamate, in Rifater, Rimactane), rifapentine (Priftin), sparfloxacin (Zagam) (not available in the U.S.), and telithromycin (Ketek); antifungals such as itraconazole (Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend); calcium channel blockers such as amlodipine (Norvasc, in Caduet and Lotrel), diltiazem (Cardizem, Dilacor, Tiazac, others), felodipine (Plendil, in Lexxel), nifedipine (Adalat, Nifedical XL, Procardia, others), nisoldipine (Sular), and verapamil (Calan, Isoptin, Verelan, others); cisapride (Propulsid) (not available in the U.S.); dexamethasone (Decadron, Dexpak); certain medications for depression such as nefazodone; certain chemotherapy medications including daunorubicin (Cerubidine, DaunoXome), doxorubicin (Adriamycin, Doxil, Rubex), epirubicin (Ellence), idarubicin (Idamycin), tamoxifen (Nolvadex), valrubicin (Valstar), vinblastine, and vincristine; certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) including atazanavir (Reyataz), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase); medications for irregular heartbeat including amiodarone (Cordarone), disopyramide (Norpace), dofetilide (Tikosyn), procainamide (Procanbid), quinidine, and sotalol (Betapace, Betapace AF, Sorine); certain medications for seizures such as carbamazepine (Carbatrol, Epitol, Tegretol), phenobarbital (Luminal), and phenytoin (Dilantin, Phenytek); pimozide (Orap); and thioridazine. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with lapatinib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor and pharmacist what herbal products you are taking, especially St. John's wort.
• tell your doctor if you have or have ever had a slow, fast, or irregular heartbeat; a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death); a low level of magnesium or potassium in your blood;or heart or lung disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. You should not become pregnant while you are taking lapatinib. Talk to your doctor about birth control methods that you can use during your treatment. If you become pregnant while taking lapatinib, call your doctor immediately. Lapatinib may harm the fetus.
• you should know that lapatinib often causes diarrhea, which can be severe. Call your doctor if you have diarrhea while taking lapatinib. Your doctor may tell you to drink plenty of liquids, make changes in your diet, and take medication to control the diarrhea and prevent dehydration (loss of too much water from your body). Call your doctor immediately if you experience any of the following symptoms of dehydration: extreme thirst, dry mouth and/or skin, decreased urination, sunken eyes, or fast heartbeat.

Lapatinib is harmful to the fetus and should not be used during pregnancy.

It is not known whether lapatinib is excreted in human milk. Some related drugs are excreted in breast milk. To avoid any risk to the infant, nursing mothers should consider discontinuing nursing or lapatinib.

Lapatinib is a cancer medication.

Lapatinib is used together with another medicine called capecitabine (Xeloda) or letrozole (Femara) to treat a certain type of advanced breast cancer that has spread to other parts of the body.

Lapatinib is often given after other cancer medications have been tried without successful treatment of symptoms.

Lapatinib may also be used for purposes not listed in this medication guide.

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.

There is no known antidote for overdoses of TYKERB. The maximum oral doses of lapatinib that have been administered in clinical trials are 1,800 mg once daily. More frequent ingestion of TYKERB could result in serum concentrations exceeding those observed in clinical trials and could result in increased toxicity. Therefore, missed doses should not be replaced and dosing should resume with the next scheduled daily dose.

Asymptomatic and symptomatic cases of overdose have been reported. The doses ranged from 2,500 to 9,000 mg daily and where reported, the duration varied between 1 and 17 days. Symptoms observed include lapatinib-associated events [see ADVERSE REACTIONS] and in some cases sore scalp, sinus tachycardia (with otherwise normal ECG), and/or mucosal inflammation.

Because lapatinib is not significantly renally excreted and is highly bound to plasma proteins, hemodialysis would not be expected to be an effective method to enhance the elimination of lapatinib.

Treatment of overdose with TYKERB should consist of general supportive measures.

Breast cancer is a cancer that forms in the cells of the breasts. Some women have (HER2+) breast cancer. (HER2+) stands for Human Epidermal growth factor receptor 2 positive. (HER2) is a special protein found on breast cancer cells that controls cancer growth and spread.

Lapatinib is approved for treatment of HER2 positive breast cancer, because it is specifically designed to target the HER2 protein. By binding to the HER2 protein, lapatinib prevents the growth of cancer cells.

HER2 testing is done to see whether treatment with lapatinib will likely be effective in treating breast cancer. If testing is not done, treatment with this medication may not be an effective treatment.

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

• ever had a severe allergic (hypersensitivity) reaction to lapatinib. Check with your doctor if you think this applies to you. Don’t take lapatinib.
• have heart problems.
• have liver problems. You may need a lower dose of lapatinib.
• are pregnant or may become pregnant. Lapatinib may harm an unborn baby. If you become pregnant during treatment with lapatinib, tell your doctor as soon as possible.
• are breastfeeding. It is not known if lapatinib 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.

Lapatinib is a cancer medication.

Lapatinib is used together with another medicine called capecitabine (Xeloda) or letrozole (Femara) to treat a certain type of advanced breast cancer that has spread to other parts of the body.

Lapatinib is often given after other cancer medications have been tried without successful treatment of symptoms.

Lapatinib may also be used for purposes not listed in this medication guide.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Lapatinib is used in combination with capecitabine to treat advanced or metastatic HER2-receptor positive breast cancer (breast cancer that has already spread) after other treatments have failed. It belongs to the group of medicines called antineoplastics (cancer medicines).

Lapatinib is also used together with letrozole to treat postmenopausal women with hormone-receptor positive and HER2-receptor positive metastatic breast cancer.

Lapatinib interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells may also be affected by the medicine, other unwanted effects will also occur. Some of these may be serious and must be reported to your doctor.

lapatinib is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits to make sure lapatinib is working properly. Blood tests may be needed to check for unwanted effects.

Using lapatinib while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Serious heart problems can occur with lapatinib. Check with your doctor right away if you are having fast, pounding, or irregular heartbeats, shortness of breath, or unusual tiredness or weakness.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, a loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Check with your doctor right away if diarrhea occurs while taking lapatinib. You may need medicines to help manage or prevent the diarrhea.

Check with your doctor right away if you start having breathing problems, shortness of breath, a cough, chest pain, fever, or chills. These could be symptoms of a serious lung problem.

Contact your doctor right away if you have any changes to your heart rhythm. You might feel dizzy or faint, or you might have a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you or anyone in your family has ever had a heart rhythm problem such as QT prolongation.

Serious skin reactions can occur with lapatinib. Check with your doctor right away if you have blistering, peeling, or loose skin, red skin lesions, severe acne or skin rash, sores or ulcers on the skin, or fever or chills while you are using lapatinib.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

• It is used to treat breast cancer.

• If you have an allergy to lapatinib or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Low potassium or magnesium levels.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with lapatinib.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

(la PA ti nib)

Tyrosine kinase (dual kinase) inhibitor; inhibits EGFR (ErbB1) and HER2 (ErbB2) by reversibly binding to tyrosine kinase, blocking phosphorylation and activation of downstream second messengers (Erk1/2 and Akt), regulating cellular proliferation and survival in ErbB- and ErbB2-expressing tumors. Combination therapy with lapatinib and endocrine therapy may overcome endocrine resistance occurring in HER2+ and hormone receptor positive disease.

Absorption

Incomplete and variable

Metabolism

Hepatic; extensive via CYP3A4 and 3A5, and to a lesser extent via CYP2C19 and 2C8 to oxidized metabolites

Excretion

Feces (27% as unchanged drug; range 3% to 67%); urine (<2%)

Time to Peak

~4 hours (Burris 2009)

Half-Life Elimination

~24 hours

Protein Binding

>99% to albumin and alpha1-acid glycoprotein

Store at room temperature of 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

An oral suspension (50 mg/mL) prepared using lapatinib 250 mg tablets and Ora-Plus:Ora-Sweet (1:1 vehicle) is stable for at least 28 days at room temperature; do not refrigerate due to potential increased viscosity (Li 2016).

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dry skin, itching, headache, hair loss, back pain, nosebleed, nail changes, mouth sores, mouth irritation, loss of strength and energy, lack of appetite, or insomnia. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), shortness of breath, excessive weight gain, swelling of arms or legs, abnormal heartbeat, angina, tachycardia, dizziness, passing out, severe abdominal pain, severe nausea, vomiting, diarrhea, abdominal cramps, dehydration, redness of irritation on palms or soles of feet, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.