Tykerb

Generic Name: Lapatinib Ditosylate
Product Name: Tykerb

Indication

Tykerb is the brand name for a new anti-cancer drug called lapatinib. Tykerb is given in combination with capecitabine (another anti-cancer medicine) for the treatment of advanced or metastatic (meaning the cancer has spread to other parts of the body) breast cancer. It is used in tumours that express a specific protein called HER2 and which have already been treated with certain other breast cancer treatments (in particular an anthracycline, a taxane, and Herceptin). Please refer to our chemotherapy treatment article for further information on how chemotherapeutic agents work. Studies have shown that combined therapy with Tykerb and capecitabine is better than capecitabine alone, and is effective at preventing tumour progression.

Action

When Tykerb is taken orally, it leads to the release of the active ingredient lapatinib, in the blood stream. Lapatinib then travels to the site of action and actually enters cancer cells to exert its effects. Within the cell, lapatinib acts by inhibiting specific proteins called kinases which are normally responsible for growth signaling within the cell. One of the main targets of action is HER2 receptors, thus lapatinib only works if the cancer expresses this particular protein. The alterations in growth signaling result in reduced tumour size and decreased tumour progression.

Dose advice

Precautions: There are currently no absolute contraindications to Tykerb therapy however, prior to commencing therapy you should tell your doctor:

• If you have any heart problems. Tykerb can cause a reduction in your left ventricular ejection fraction (LVEF) which is a measure of how well your heart can pump blood. It is important that you have this measured prior to and regularly during your treatment with Tykerb. If LVEF does fall you can sometimes stop treatment for a period and then recommence at a lower dose if symptoms do not persist.
• If you have any liver problems. If you have severe liver impairment, a lower dose may need to be prescribed.
• If you are pregnant or intend to become pregnant. There is limited experience with this medication during pregnancy so we are not sure of the possible adverse effects it could have on the fetus. Some studies in animals have shown adverse effects to the unborn fetus. You should discuss with your doctor the risks and benefits of treatment during pregnancy.
• If you are breastfeeding. It is not known whether Tykerb passes into your breast milk or if it can harm your baby. If you have or will have a baby, talk with your doctor about the safest way to feed your baby.
• All the medications you are taking. Tykerb has the potential for a variety of interactions including prescription and nonprescription medicines and herbal and dietary supplements. In particular let your doctor know if you take any antibiotics, anti-fungals, HIV (AIDS) treatments, anti-seizure medications, calcium channel blockers (for heart disorders or high blood pressure), antidepressants, anti-ulcer medications or St. John’s Wort or other herbal supplements. In addition you should not eat or drink any grapefruit products whilst taking Tykerb as they can alter the metabolism of the drug.

Product Description: Tykerb comes as oval, biconvex, orange film-coated tablets containing 250mg of the active agent lapatinib. Tablets should be swallowed whole. The recommended daily dose is 1,250 mg (5 tablets) taken all together at least one hour before or one hour after a meal. This is because administration with food can lead to increased systemic exposure. Dosage: Tykerb and capecitabine are taken in repeated 21 day cycles. On days 1-21 you should take 1,250 mg (5 tablets) of Tykerb once a day by mouth. Capecitabine is taken only on days 1-14 of the cycle. Your doctor will calculate the required dose of capecitabine based on your body surface area. This is taken in two divided doses approximately 12 hours apart. Capecitabine should be taken with food or within 30 minutes after food. Tykerb should always be taken as prescribed by your doctor. The above dosages are only a guide and your doctor may adjust your dose based on how well you tolerate the drug. You should keep taking Tykerb for as long as your doctor tells you. It should only be ceased if your disease continues to progress or if unacceptable toxicity occurs.

Schedule

S4 (prescription required).

Common side effects

Like all medications Tykerb has the potential to cause side effects. This is understandable as in order to treat cancer, Tykerb needs to alter some of the normal processes of the body. Most side effects of Tykerb are mild and reversible following discontinuation of treatment. Studies of Tykerb in up to 3,500 patients have confirmed it is a generally safe therapy. However it is important you are aware of some of the more serious side effects so you can seek medical treatment if needed. The most common side effects of Tykerb in combination with capecitabine include:

• Diarrhoea– This may occur in approximately 65% of patients (compared to 40% in patients treated with capecitabine alone) and is the most common reason for stopping treatment. If diarrhoea is severe it can lead to dehydration so aggressive treatment with anti-diarrhoea drugs and fluid and electrolyte replacement may be required.
• Nausea and vomiting– Affecting between 20-40% of patients receiving combination therapy.
• Rash- This occurs in approximately 28 percent of patients and approximately twice as common compared to capecitabine alone.
• Hand-foot syndrome- This is an unusual side effect causing numbness, tingling, redness, swelling and discomfort of hands and feet. It occurs in around 50% of patients.
• Fatigue and tiredness.
• Mouth sores.
• Loss of appetite.

Note that the above list of side effects is not exhaustive and it is impossible to predict entirely how this medication may affect you. If you experience any other symptoms that are troubling you do not hesitate to discuss them with your doctor. Furthermore, you may develop side effects from the capecitabine component of your treatment. You should talk to your doctor about possible side effects with capecitabine.

Uncommon side effects

Some more serious side effects of Tykerb include:

• Heart problems.
• Decreased pumping of blood from the heart- Tykerb like other HER2 inhibitors has the potential for toxicity to the heart. In particular, it reduces the left ventricular ejection fraction of the heart which is the proportion of blood within the left ventricle (largest chamber of the heart) expelled with each heart beat.
• Abnormal heart beat- A specific side effect called long QT syndrome can develop rarely in patients taking Tykerb. In general, the risk is higher for larger doses.

You should call your doctor immediately if you develop any symptoms that may suggest these side effects such as palpitations (increased awareness of the heart beating) or shortness of breath. Fortunately these serious side effects tend to be uncommon (less than approximately 2% of patients) and in most cases can be adequately treated if detected early.

References

1. Tykerb (lapatinib) – new anti-cancer treatment approved, Pharmaceutical News, 2007.
2. TYKERB (R) (lapatinib) tablets- Full Prescribing Information, GlaxoSmithKline, 2007. Available [online] at URL: http://us.gsk.com/products/assets/us_tykerb.pdf
3. TYKERB (R) (TIE-curb) (lapatinib) tablets- Patient Information, GlaxoSmithKline, 2007. Available [online] at URL: http://us.gsk.com/products/assets/us_tykerb.pdf

For further information talk to your doctor.