Tykerb (Lapatinib Ditosylate)

Serious Warnings and Precautions

TYKERB should be prescribed and managed by a doctor experienced in anticancer drugs. Serious side effects of TYKERB include:

• Liver toxicity can be severe and deaths have happened (harmful effect on the liver)
• Decreased left ventricular ejection fraction (decreased pumping of blood from the left ventricle of the heart)
• Abnormal heartbeat (QT prolongation)
• Severe diarrhea, which can be life-threatening

BEFORE you use TYKERB, talk to your doctor or pharmacist if:

• You have or have had heart problems, such as abnormal heartbeat (arrhythmias or dysrhythmias) or fainting spells
• You have electrolyte disturbances, such as low blood potassium, low blood magnesium, low blood calcium, or conditions that could lead to electrolyte disturbances such as eating disorder, vomiting, diarrhea, dehydration, diabetes (with nerve disorders)
• You have a family history of sudden cardiac death at younger than 50 years of age
• You have lung problems
• You have liver problems
• You have diarrhea or any changes in bowel patterns
• You are pregnant, or are planning to become pregnant
• You are breastfeeding or are planning to do so.

TYKERB may cause harm to your unborn baby. Therefore, you should use effective methods of contraception while taking TYKERB. If you become pregnant during treatment with TYKERB, tell your doctor immediately. It is not known whether TYKERB passes into breast milk, therefore breastfeeding is not recommended while you are taking TYKERB.

TYKERB has an effect on the electrical activity of the heart known as QT/QTc prolongation. This may lead to disturbances in the heartbeat (heart rhythm) that could result in dizziness, palpitations (sensation of rapid, pounding, or irregular heart beat), fainting (syncope) or death. These heart rhythm disturbances are more likely in patients with risk factors, such as heart problems, taking medicines that affect the heart, being female or being over 65 years of age. It is important to follow the instructions of your doctor with regard to dosing or any special tests. If you experience any symptoms of a possible heart rhythm disturbance, such as dizziness, palpitations (sensation of rapid, pounding, or irregular heart beat), fainting, or seizures, you should seek immediate medical attention. Safety and efficacy of TYKERB have not been established in children.

TYKERB can make you feel drowsy or sleepy.

• Don’t drive or use machines unless you are sure you are not affected.

Severe Skin Reactions:

Severe skin reactions have been seen with TYKERB. Symptoms may include skin rash, blisters and skin peeling. Tell your doctor as soon as possible if you get any of these symptoms. As severe skin reactions can be life threatening, your doctor may tell you to stop TYKERB.

Like all medicines, TYKERB can cause side effects. Most of the side effects are mild to moderate. Tell your doctor or pharmacist if any of the side effects listed becomes severe or bothers you, or if you notice any side effects not listed in this leaflet.

Side effects of TYKERB in combination with capecitabine (XELODA) or letrozole (FEMARA) include:

Very common side effects:

These side effects may affect more than 10 in every 100 patients:

• Diarrhea (which if severe can be life-threatening), contact your doctor immediately at the first sign of diarrhea (loose stool), to treat it right away. Also tell your doctor immediately if your diarrhea worsens.
• Loss of appetite
• Indigestion or stomach/abdominal pain
• Feeling or being sick (nausea or vomiting)
• Constipation
• Tiredness
• Unusual hair loss or thinning
• Nose bleed
• Difficulty breathing
• Sore mouth or mouth ulcers
• Trouble sleeping (insomnia)
• Back pain or pain in extremities
• Rash or dry skin
• A skin reaction or pain on the palms of the hands or soles of the feet (including tingling, numbness, pain, swelling or reddening)

Supportive skin care regimens are available. Please talk to your healthcare provider for guidance. Before you go out in the sun, use a sun protection product with a high protection factor (SPF 30 or higher).

Common side effects:

These side effects may affect between 1 to 10 in every 100 people:

• An effect on how your heart works—this may cause an irregular heartbeat and shortness of breath
• Headache
• Fever
• Swelling in extremities
• Pain in joints or bones
• Nosebleed
• Nail disorders—such as tender infection and swelling of the cuticles

If you experience any symptoms of a possible heart rhythm disturbance, such as dizziness, palpitations, fainting, or seizures, you should seek immediate medical attention.

Uncommon side effects:

These side effects may affect up to 1 in every 100 people:

• Liver problems—this may cause itching, yellow eyes or skin (jaundice), dark urine or pain or discomfort in the right upper area of the stomach.
• Swelling or inflammation of the lungs—this may cause coughing or shortness of breath.

Tell your doctor immediately if you get any of these symptoms. These symptoms may persist after you stop taking TYKERB.

Rare side effects:

These side effects may affect up to 1 in every 1000 people:

• Severe allergic reactions—symptoms may include: skin rash (including itchy, bumpy rash); unusual wheezing or difficulty in breathing; swollen eyelids, lips or tongue; pains in muscles or joints; collapse or blackout.

There are certain groups of medicines that interact with TYKERB. The following list includes some, but not all, medicines that interact with TYKERB. Tell your doctor or pharmacist if you're taking any other medicines, if you’ve taken any recently, or if you start taking new ones. This includes non-prescription medicines, vitamins, and natural health products.

• drugs used to treat infections (antibiotics and antifungals)
• drugs used to treat HIV (AIDS)
• drugs used to treat chronic inflammation or asthma (steroids)
• drugs used to treat seizures (anticonvulsant drugs)
• drugs used to treat certain heart disorders and high blood pressure (calcium channel blockers)
• water pills (diuretics)
• opioids (e.g. methadone)
• antidepressants
• antipsychotics
• drugs that decrease stomach acidity (used to treat stomach ulcers or indigestion)
• herbal products (St. John's Wort)

You should also avoid grapefruit juice or products containing grapefruit juice.

Because TYKERB is given with another drug, either capecitabine or letrozole, you should also discuss with your doctor any medicines that should be avoided when taking capecitabine (Xeloda) or letrozole.

Ask your health professional for advice before taking any medicine if you are unsure.

How to take:

Swallow the tablets whole with water.

TYKERB should be taken at least one hour before or at least one hour after a low fat meal.

TYKERB tablets should be taken at about the same time each day.

Do not drink grapefruit juice while you are taking TYKERB.

If you have any problems/questions regarding the use of TYKERB, please consult with your health professional.

Overdose:

Dosage directions should be followed carefully. Never exceed the prescribed dose.

If you have accidentally taken more TYKERB tablets than you should, contact your doctor, or poison control centre, or go to the emergency room of the nearest hospital.

Missed dose:

Do not take a double dose to make up for a forgotten dose on a given day, simply resume your dosing with the next scheduled dose the following day. If you have further questions on the use of TYKERB, ask your health professional.