Zometa

Hypercalcemia Of Malignancy

Zometa is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected calcium (cCa) of greater than or equal to 12 mg/dL [3.0 mmol/L] using the formula: cCa in mg/dL=Ca in mg/dL + 0.8 (4.0 g/dL -patient albumin [g/dL]).

Multiple Myeloma And Bone Metastases Of Solid Tumors

Zometa is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Prostate cancer should have progressed after treatment with at least one hormonal therapy.

Important Limitation Of Use

The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other nontumor-related conditions have not been established.

Keep all medical and laboratory appointments. If you miss an appointment to receive a Zometa infusion, call your healthcare provider right away.

Synthetic bisphosphonate; bone resorption inhibitor.1 4 5

Storage

Parenteral

25°C (may be exposed to 15–30°C).1 Following dilution, 2–8°C; use within 24 hours.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Do not admix with other agents.1

Solution Compatibility1

Zoledronic acid injection is used to treat hypercalcemia (high levels of calcium in the blood) that may occur in patients with some types of cancer. It is also used to treat a cancer called multiple myeloma (tumors formed by the cells of the bone marrow) or certain types of bone metastases (the spread of cancer to the bone).

Zoledronic acid injection is also used to treat Paget's disease of the bone in men and women. It is also used in men with osteoporosis and in women with osteoporosis who have gone through menopause. This medicine is used to reduce the risk of having more fractures in patients who have had a recent hip fracture.

This medicine is to be given only by or under the direct supervision of your doctor.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Zoledronic acid injection is not indicated for use in children.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of zoledronic acid injection in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution in patients receiving zoledronic acid injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Bleeding problems or
• Cancer, history of or
• Dental or tooth problems or
• Dental procedures or
• Poor oral hygiene, or
• Surgery (eg, dental surgery)—May increase risk for severe jaw problems.

• Asthma, aspirin-sensitive or
• Heart disease or
• Kidney disease or
• Mineral imbalance (eg, high or low calcium, magnesium, phosphorus, or potassium in the blood)—Use with caution. May make these conditions worse.

• Bowel resection or
• Parathyroid disease (eg, hypoparathyroidism) or
• Parathyroid surgery or
• Stomach absorption problems or
• Thyroid surgery—These conditions may increase your risk of having hypocalcemia (low levels of calcium in the blood).

• Dehydration (not enough water or fluid in your body)—May increase risk of severe kidney problems.

• Hypocalcemia (low calcium in the blood) or
• Kidney disease, severe (eg, kidney failure)—Should not be used in patients with these conditions.

• If you have an allergy to zoledronic acid or any other part of Zometa (zoledronic acid (zometa)).
• 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 low calcium levels.
• If you have kidney disease.
• If you are taking or will be taking another drug like this one.
• If you are taking another drug that has the same drug in it.
• If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.
• If you are breast-feeding or plan to breast-feed.

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

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.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low calcium levels like muscle cramps or spasms, numbness and tingling, or seizures.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Very bad bone, joint, or muscle pain.
• Any new or strange groin, hip, or thigh pain.
• Chest pain.
• A heartbeat that does not feel normal.
• Fast or slow heartbeat.
• Change in eyesight, eye pain, or very bad eye irritation.
• Mouth sores.
• Trouble swallowing.
• Very bad pain when swallowing.
• Fever or chills.
• Sore throat.
• Any unexplained bruising or bleeding.
• Feeling very tired or weak.
• Mood changes.
• Pain where the shot was given.
• Redness or swelling where the shot is given.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• This medicine may cause jawbone problems. The chance may be higher the longer you take Zometa. The chance may be higher if you have cancer, dental problems, dentures that do not fit well, anemia, blood clotting problems, or an infection. The chance may also be higher if you are having dental work, getting chemo or radiation, or taking other drugs that may cause jawbone problems like some steroid drugs. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure. Call your doctor right away if you have jaw swelling or pain.

Zometa contains zoledronic acid, a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. Zoledronic acid is designated chemically as (1-Hydroxy-2-imidazol-1-yl-phosphonoethyl) phosphonic acid monohydrate and its structural formula is:

Zoledronic acid is a white crystalline powder. Its molecular formula is C5H10N2O7P2•H2O and its molar mass is 290.1g/mol. Zoledronic acid is highly soluble in 0.1N sodium hydroxide solution, sparingly soluble in water and 0.1N hydrochloric acid, and practically insoluble in organic solvents. The pH of a 0.7% solution of zoledronic acid in water is approximately 2.0.

Zometa is available in 100 mL bottles as a sterile liquid ready-to-use solution for intravenous infusion and in 5 mL vials as a sterile liquid concentrate solution for intravenous infusion.

• Each 100 mL ready-to-use bottle contains 4.264 mg zoledronic acid monohydrate, corresponding to 4 mg zoledronic acid on an anhydrous basis, 5100 mg of mannitol, USP, water for injection, and 24 mg of sodium citrate, USP.
  
• Each 5 mL concentrate vial contains 4.264 mg zoledronic acid monohydrate, corresponding to 4 mg zoledronic acid on an anhydrous basis, 220 mg of mannitol, USP, water for injection, and 24 mg of sodium citrate, USP.

Inactive Ingredients: mannitol, USP, as bulking agent, water for injection, and sodium citrate, USP, as buffering agent.

Do not use Zometa if you are pregnant. It could harm the unborn baby.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Your doctor may recommend you have a dental exam for preventive tooth and gum care before you start your treatment with Zometa. This is especially important if you have cancer, if you are undergoing chemotherapy or using steroids, or if you have poor dental health.

Some people using medicines similar to Zometa have developed bone loss in the jaw, also called osteonecrosis of the jaw. Symptoms of this condition may include jaw pain, swelling, numbness, loose teeth, gum infection, or slow healing after injury or surgery involving the gums. You may be more likely to develop osteonecrosis of the jaw if you have cancer or have been treated with chemotherapy, radiation, or steroids. Other conditions associated with osteonecrosis of the jaw include blood clotting disorders, anemia (low red blood cells), and pre-existing dental problems.

Avoid having any type of dental surgery while you are being treated with Zometa. It may take longer than normal for you to recover.

Zometa can harm your kidneys. This effect is increased when you also use other medicines harmful to the kidneys, such as: chemotherapy, antiviral medication, pain or arthritis medicine, injected antibiotics, or medicines to treat a bowel disorder or prevent organ transplant rejection.

Get emergency medical help if you have any signs of an allergic reaction to Zometa: hives; wheezing, chest tightness, trouble breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• fever, chills, flu symptoms, flushing (warmth, redness, or tingly feeling);

• severe joint, bone, or muscle pain;

• new or unusual pain in your hip, thigh or groin;

• a loose tooth, mouth pain, mouth sores;

• pale skin, feeling light-headed or short of breath;

• hypocalcemia - numbness or tingly feeling in your fingers or toes or around your mouth, twitching, muscle spasms or cramps;

• signs of a kidney problem - little or no urinating; painful or difficult urination; swelling, rapid weight gain; feeling tired or short of breath; or

• severe skin reaction - fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Serious side effects on the kidneys may be more likely in older adults.

Common Zometa side effects may include:

• nausea, vomiting, diarrhea, constipation;

• bone pain, muscle or joint pain;

• fever or other flu symptoms;

• pain in your arms or legs;

• headache, tiredness; or

• trouble breathing.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.