Vandetanib is available in film-coated tablets (100 mg and 300 mg). It is used to treat medullary thyroid cancer that is called Rearranged during Transfection (RET) mutant and which cannot be removed by surgery or has spread to other parts of the body.

Vandetanib works by slowing down the growth of new blood vessels in tumours (cancers). This cuts off the supply of food and oxygen to the tumour. Vandetanib may also act directly on cancer cells to kill them or slow down their growth.

The calculation of the dose of vandetanib is made by the treating physician, based on the body surface area (BSA), depending on the height and weight of the patient.

The treatment schedule will correspond to one of the 3 following schemes:

 . “daily” schedule (same dose every day)

 . “every other day” schedule (same dose every other day)

 . “7-day” schedule (treatment every day but two different doses alternately)

Please note that the dosing scheme can change during treatment.

For example, you can follow a “daily” schedule for the starting dose period and switch to a “7-day” schedule after a dose adjustment.

Medullary Thyroid Cancer

Indicated for treatment of symptomatic or progressive medullary thyroid cancer in patients with unrespectable locally advanced or metastatic disease.

It works by slowing or stopping the growth of cancer cells. Vandetanib belongs to a class of drugs known as tyrosine kinase inhibitors.

Continued until disease progression or unacceptable toxicity occurs.

Tyrosine kinase inhibitor (TKI) with selective activity against RET, VEGFR-2, and EGFR; TKI inhibition blocks angiogenesis and cellular proliferation.

There is no evidence of a relationship between RET mutations and the efficacy of vandetanib.

20% of medullary thyroid carcinomas are associated with 1 of 3 inherited endocrine syndromes caused by germline mutations of the RET gene. RET encodes a receptor tyrosine kinase for the glial cell line-derived neurotropic factor family of extracellular signalling molecules.

Gain-of-function mutations are associated with cancer (e.g., medullary thyroid carcinoma, multiple endocrine neoplasias).

Vandetanib has activity against RET as well as vascular endothelial growth factor (VEGF).

Oral Administration

Take with or without food.

Swallow tablets whole with water; do not crush.

The prescribed calculated dose should be taken:

• at about the same time every day.

• with or without food.

The total daily dose in children must not exceed 300 mg.

If you/your child have trouble swallowing the tablet, you can mix it with water as follows:

• Take half a glass of still (non-carbonated) water. Only use water; do not use any other liquids.

• Put the tablet into the water.

• Stir the tablet until it has dispersed into the water. This may take about 10 minutes.

• Then ensure you/your child drinks the solution straight away.

• To make sure there is no medicine left, half-fill the glass with water again and ensure that you/your child drink all of the water.

Nausea, decreased appetite, changes in taste, dry mouth, stomach pain, vomiting, diarrhea, headache, or blurred vision may occur.

Nail problems (such as nail bed swelling/tenderness/infection) may also occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

If you have diarrhoea or vomiting that is severe or doesn't stop, your doctor may need to check your blood mineral levels and adjust your vandetanib treatment. Temporary hair loss may occur. Normal hair growth should return after treatment has ended.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Vandetanib can commonly cause a rash that is usually not serious. Mild to moderate skin reactions include acne, dry skin, or a mildly irritated/red/itchy rash. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe reaction. Get medical help right away if you develop any rash.

Tell your doctor right away if you have any serious side effects, including redness/pain/swelling of the palms of the hands or soles of the feet, depression, slow wound healing, signs of heart failure (such as shortness of breath, swelling ankles/feet, unusual tiredness, or unusual/sudden weight gain), signs of an underactive thyroid (such as weight gain, cold intolerance, slow heartbeat, constipation, or unusual tiredness), or signs of kidney problems (such as a change in the amount of urine).

This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high. Vandetanib may cause a rare (possibly fatal) type of breathing problem (interstitial lung disease).

Get medical help right away if you have sudden/worsening shortness of breath, cough, or fever. Vandetanib may also rarely cause a serious brain condition.

Get medical help right away if you develop headaches, seizures, vision changes, confusion, or problems thinking.

Get medical help right away if you have any serious side effects, including signs of bleeding (such as bloody vomit, vomit that looks like coffee grounds, or black/bloody stools), signs of a stroke (such as weakness on one side of the body, trouble speaking, sudden vision changes, or confusion), or sudden/severe pain in the stomach/chest/back.

A very serious allergic reaction to this drug is rare.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/non-prescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval. Many drugs besides vandetanib may affect the heart rhythm (QT prolongation), including amiodarone, chloroquine, disopyramide, dofetilide, granisetron, haloperidol, methadone, moxifloxacin, pimozide, procainamide, sotalol, macrolide antibiotics (such as clarithromycin), and others. Other medications can affect the removal of vandetanib from your body, which may affect how vandetanib works. Examples include dexamethasone, St. John's wort, rifamycins (such as rifabutin and rifampin), and drugs used to treat seizures (such as carbamazepine, phenytoin, phenobarbital, and primidone), among others.

Store at room temperature (20-25ºC [68-77ºF]); excursions permitted to 15-30ºC (59-86ºF).

Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so.

Properly discard this product when it is expired or no longer needed.

Consult your pharmacist or local waste disposal company.

Before taking vandetanib, tell your doctor or pharmacist if you are allergic to it or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details. Before using this medication, tell your doctor or pharmacist your medical history, especially of kidney disease, high blood pressure, recent bleeding (including recently coughing up blood), blood vessel problems (such as an aneurysm or a tear/break in the aorta or other blood vessels), and recent surgery/injury. This drug may cause blurred vision.

This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Get medical help right away if you get sunburned or have skin blisters/redness. Follow these instructions while taking vandetanib and for 4 months after stopping treatment. Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, non-prescription drugs, and herbal products). This medication may cause wounds to heal slowly or poorly. Before having surgery, talk with your doctor about the risks and benefits of this medication. Your doctor may tell you to temporarily stop treatment with this medication at least 1 month before surgery. Ask your doctor for specific instructions about when to stop and when to restart treatment with vandetanib. Tell your doctor right away if you have wounds that are not healing well.