Drug type

Third-generation bisphosphonate

• A synthetic imidazole bisphosphonate analog of pyrophosphate with anti-bone resorption activit


• Oncology (Zometa)

—Pain reduction associated with bone metastases

—Hypercalcemia caused by neoplasm

—Osteolytic lesions of multiple myeloma

• Other

—Osteoporosis (Reclast)

—Paget disease of bone

—Both treatment and prevention of postmenopausal osteoporosis

—Glucocorticoid-induced osteoporosis treatment and prevention

Unlabeled use

• Prevention of osteoporosis resulting from androgen ablation or aromatase inhibitor therapy

Mechanism of action

• Works via various mechanisms that focus on inhibition of bone resorption and osteoclastic activity

• Decreased bone turnover and stabilization of the bone matrix contribute to analgesic effect on painful osteoblastic lesions

• Also reduces serum calcium concentrations associated with hypercalcemia

Dosage and administration

• Dosage may vary based on indication and patient’s renal function

• Hypercalcemia of malignancy: 4 mg IV (wait at least 7 days prior to retreatment)

• Multiple myeloma or metastatic bone disease: 4 mg IV every 3 to 4 weeks

• Administration of acetaminophen following zoledronic acid infusion may reduce the incidence of acute-phase inflammatory reactions such as fever, myalgia, flulike symptoms, headache, and arthralgia

Common IV compatabilities

• Not compatible with calcium-containing solutions (eg, lactated Ringer’s)

Pregnancy and lactation

• Pregnancy category D

—May cause fetal harm when administered to a pregnant woman

• Absolute lactation contraindication

—Should not be administered during lactation because it binds to bone long-term

Cautions and adverse effects

• Cautions

—General: Osteonecrosis, primarily of the jaw, can occur in any patient population

—Pediatric: Not FDA-approved for children; increased risk of fever, arthralgia, hypocalcemia

—Geriatric: Risk of renal toxicity; monitor renal function and avoid in patients with severe impairment

• Adverse effects

Most frequent: Allergic dermatitis, arthralgia, back pain, bone pain, chills, constipation, diarrhea, dizziness, dyspnea, fatigue, fever, general weakness, headache, myalgia, nausea, paresthesia, peripheral edema, vomiting

Less frequent: Anemia, anorexia, hypomagnesemia, pain, upper abdominal pain

Rare: Acute renal disease, alopecia, angioedema, anxiety, aseptic necrosis of jaw bone, blurred vision, cough, dehydration, depression, dyspepsia, agitation, flulike symptoms, hypertension, hypesthesia, hypocalcemia, hypokalemia, hypophosphatemia, hypotension, impaired cognition, injection site sequelae, insomnia, muscle spasm, neutropenic disorder, ocular inflammation, renal disease, scleritis, thrombocytopenic disorder, upper respiratory infection, urinary tract infection, urticaria, uveitis

Drug interactions

• Mineral supplements (especially those containing calcium, magnesium, or phosphorus)

• Aminoglycoside antibiotics

• Amphotericin B (Abelcet, Ambisome, Amphocin, Amphotec, Fungizone, generics)

• Cyclosporine (Gengraf, Neoral, Sandimmune, generics)


• Tacrolimus (Prograf, generics)

• Vancomycin (Vancocin Hydrochloride, generics)

• Loop diuretics


• Dental examination and preventative dentistry for patients at risk of osteonecrosis

• Screen for electrolytes, phosphate, magnesium, hemoglobin, hematocrit

What to tell your patient

• You have been prescribed zoledronic acid, which belongs to a class of drugs known as bisphosphonates.

• Administered intravenously, it works by reducing the amount of calcium released from your bones into your blood.

• It may take up to 7 days before the full benefit of this drug takes effect.

• Remember that your doctor has prescribed this medication only after judging that the benefit is greater than the risk of side effects. Many patients on zoledronic acid do not have serious side effects.

• You may experience


Stomach pain




Flulike symptoms (fever, chills, muscle/joint aches)

Pain/redness/swelling at the injection site

• Contact your nurse or doctor immediately, day or night, if you should experience any of the following symptoms:

Increased or severe bone/joint/muscle pain

Jaw pain

Unusual weakness or tiredness

Trouble sleeping

Trouble swallowing

Eye problems (“pink-eye”/conjunctivitis)

Vision problems (trouble seeing)

Swelling legs

Numb/tingling skin

Fast/pounding/irregular heartbeat

Persistent sore throat with fever

Unusual bruising/bleeding

Change in the amount of urine

Burning/painful urination

Mental/mood changes (such as agitation, anxiety, and confusion) ONA

Prepared by Bette Weinstein Kaplan. Reviewed by Maribel Pereiras, Pharm D, BCPS, BCOP.