ZOLEDRONIC ACID

Zoledronic acid belongs to the family of medications known as bisphosphonates. It is used to treat hypercalcemia (high blood calcium) for people who have cancer. Zoledronic acid is also used to prevent or delay complications (e.g., bone fractures or bone pain requiring surgery or radiotherapy) due to cancer that has spread to bones (bone metastases) from different types of tumours and multiple myeloma (cancer of the bone marrow).

This medication works by slowing the rate of bone change and may prevent bone breakdown and uncontrolled bone growth caused by cancer that has spread to the bone.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are being given this medication, speak to your doctor. Do not stop receiving this medication without consulting your doctor.

What form(s) does this medication come in?

Each 5 mL vial of concentrated sterile liquid for intravenous (IV) injection contains 4 mg of zoledronic acid, corresponding to 4.264 mg of zoledronic acid monohydrate. Nonmedicinal ingredients: mannitol, sodium citrate, and water for injection.

How should I use this medication?

The dosage of this medication depends on the condition that is being treated.

For tumour-induced hypercalcemia (high calcium levels in the blood), the recommended starting dose of zoledronic acid for hypercalcemia is 4 mg given as a single intravenous injection (into the vein) over no less than 15 minutes. This dose may be repeated after at least 1 week for people who do not respond completely to this dose or whose calcium level does not remain normal.

For bone metastases and multiple myeloma, the recommended dose of zoledronic acid is 4 mg given as a single intravenous injection (into the vein) over no less than 15 minutes every 3 to 4 weeks. For people receiving chemotherapy, zoledronic acid may be given either before or after treatment. It is important to take a calcium supplement of 500 mg by mouth and a multivitamin containing at least 400 IU of vitamin D daily, unless high blood calcium levels develop. If this occurs, calcium and vitamin D supplements should be discontinued as advised by your doctor. Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here,do not change the way that you are receiving the medication without consulting your doctor.

It is important this medication be given exactly as recommended by your doctor. If you miss an appointment to receive zoledronic acid, contact your doctor as soon as possible to reschedule your appointment.

This medication is stored at room temperature. After mixing, it is stored in the refrigerator. Keep this medication out of the sight and reach of children and pets.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take zoledronic acid if you:

• are allergic to zoledronic acid, or any ingredients of this medication
• are allergic to other bisphosphonates (e.g., alendronate, etidronate, risedronate)
• have low levels of calcium in the blood at the time this medication is given
• are breast-feeding
• are pregnant

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• bone or joint pain
• drowsiness
• eye redness or excessive tearing
• fever
• fatigue
• loss of appetite
• nausea
• redness or swelling at the site of the infusion
• sleepiness
• thirst
• vomiting

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not check with your doctor or seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• chest pain
• dizziness
• eye pain, redness or swelling, vision changes, or sensitivity to light
• flu-like symptoms (fever, chills, bone pain, or muscle and joint pain)
• itchy rash
• signs of high blood calcium levels (e.g., loss of appetite, nausea, vomiting, constipation, or stomach pain)
• signs of low blood calcium levels (e.g., muscle spasms, tingling or numbness of the fingers and mouth, twitching, or memory loss)
• symptoms of jaw problems (numbness or feeling of heaviness in the jaw; poor healing of the gums; loose teeth; exposed bone in the mouth; swelling or gum infections; bad breath; or pain in the mouth, teeth, or jaw)
• symptoms of a change in kidney function (change in urine colour, little or no urine, lower back pain, fatigue, nausea, loss of appetite)
• thigh pain or weakness

Stop taking the medication and seek immediate medical attention if any of the following occur:

• breathing difficulty
• irregular heartbeat
• symptoms of a severe allergic reaction (hives; rash; difficulty breathing; swelling of the face, eyes, or tongue)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Asthma and acetylsalicylic acid (ASA) allergy: Other medications similar to zoledronic acid have caused difficulty breathing for people with asthma who are allergic to ASA. If you have asthma and are allergic to ASA, discuss with your doctor how this medication may affect your medical condition and whether any special monitoring is needed.

Atypical femur fracture: There is evidence that long term use of this class of medication may contribute to a type of rare fracture of the long bone in the thigh (femur).

If you experience new or unusual pain in the groin, hip, or thigh area, contact your doctor as soon as possible.

Low blood calcium levels: Before starting zoledronic acid, people who have low blood calcium levels must adjust their levels with calcium and vitamin D supplements as recommended by their doctors. Your doctor may recommend that you continue to take calcium and vitamin D while you are receiving zoledronic.

This medication may cause decreases in blood calcium levels, which can be life-threatening when severely low. If you experience muscle spasms or muscle pain, irregular heart beat or seizures, contact your doctor immediately.

Deterioration of the jaw bone: People with cancer treated with zoledronic acid (or other bisphosphonates) have a higher risk of developing osteonecrosis of the jaw (deterioration of the jaw bone). If you experience numbness or feeling of heaviness in the jaw; poor healing of the gums; loose teeth; exposed bone in the mouth; swelling or gum infections; bad breath; or mouth, teeth, or jaw pain, contact your doctor. Before starting treatment with zoledronic acid, your doctor may recommend that you see a dentist for an examination. While receiving zoledronic acid, try to postpone invasive dental procedures such as tooth extractions until your treatment with zoledronic acid is finished.

Drowsiness/reduced alertness: Zoledronic acid may cause sleepiness and dizziness. If these symptoms occur, avoid driving, operating machinery, or participating in other possibly hazardous activities requiring alertness.

Kidney function: Kidney disease or reduced kidney function may cause this medication to build up in the body, causing side effects. If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. The use of zoledronic acid is not recommended for people with severe kidney disease.

This medication can cause reduced kidney function. Your doctor should closely monitor your condition while you are taking zoledronic acid.

You will probably need to have regular tests to check kidney function before and after receiving this medication.

Liver function: If you have reduced liver function or liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Pregnancy: This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: It is not known if zoledronic acid passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children.

What other drugs could interact with this medication?

There may be an interaction between zoledronic acid and any of the following:

• acetylsalicylic acid (ASA)
• aminoglycosides (e.g., tobramycin, gentamicin)
• angiogenesis inhibitors (e.g., axitinib, bevacizumab, lenalidomide, pazopanib, sorafenib, sunitinib, vandetanib)
• calcitonin
• nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., naproxen, ibuprofen, diclofenac)
• other bisphosphonates (e.g., clodronate, alendronate, risedronate, etidronate, or another form of zoledronic acid)
• potassium phosphate
• proton pump inhibitors (e.g., lansoprazole, omeprazole)
• thalidomide

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.