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Zoledronic Acid


Pronunciation: ZOE-le-DRON-ik AS-id
Class: Bisphosphonate

Trade Names

- Injection, solution 5 mg per 100 mL

- Injection, solution, concentrate 4 mg per 5 mL

Aclasta (Canada)


Inhibition of osteoclastic bone resorption.

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In vitro protein binding ranges from 28% to 53%.


Does not undergo biotransformation.


Excreted unchanged by the kidney (less than 3% in feces). The 0- to 24-h renal Cl is approximately 3.7 L/h. The half-life is 146 h.

Special Populations

Renal Function Impairment

Mild renal impairment (CrCl 50 to 80 mL/min) increased AUC by an average of 15%. Moderate renal impairment (CrCl 30 to 50 mL/min) increased AUC by an average of 43%. The risk of renal deterioration appears to increase with AUC, which doubled at a CrCl of 10 mL/min.

Hepatic Function Impairment

No pharmacokinetic studies have been conducted.


Pharmacokinetics not affected by age in patients with cancer and bone metastases.


Pharmacokinetics not affected by race in patients with cancer and bone metastases.

Indications and Usage


Treatment and prevention of osteoporosis in postmenopausal women; treatment to increase bone mass in men with osteoporosis; treatment and prevention of glucocorticoid-induced osteoporosis in men and women; treatment of Paget disease of bone in men and women.


Treatment of hypercalcemia of malignancy; treatment of patients with multiple myeloma and bone metastases from solid tumors in conjunction with standard antineoplastic therapy.


Hypersensitivity to zoledronic acid or any component of the product; hypocalcemia ( Reclast ).

Dosage and Administration

Hypercalcemia of Malignancy ( Zometa )

IV 4 mg max dose given as a single infusion over no less than 15 min. Retreatment with 4 mg may be considered if serum calcium does not return to normal or does not remain normal after initial treatment. To allow a full response, it is recommended that a minimum of 7 days elapse before retreatment.

Multiple Myeloma and Metastatic Bone Lesions From Solid Tumors ( Zometa )

IV 4 mg infused over no less than 15 min every 3 to 4 wk in patients with CrCl more than 60 mL/min. Reduce dose in patients with renal function impairment as follows: CrCl 50 to 60 mL/min: 3.5 mg/dose; CrCl 40 to 49 mL/min: 3.3 mg/dose; CrCl 30 to 39 mL/min: 3 mg/dose.

Paget Disease ( Reclast )

IV 5 mg at a constant infusion rate over no less than 15 min. Retreatment may be considered in patients who have relapsed, based on increases in serum alkaline phosphatase, in patients who failed to achieve normalization of their serum alkaline phosphatase, or in those with symptoms, as indicated by medical practice. All patients with Paget disease should receive elemental calcium 750 mg twice daily or 500 mg 3 times daily and vitamin D 800 units daily, particularly in the 2 wk following Reclast administration.

Postmenopausal Osteoporosis Treatment, Osteoporosis in Men, Glucocorticoid-Induced Osteoporosis ( Reclast )

IV 5 mg infusion once yearly given over no less than 15 min. If dietary intake is insufficient, supplement with calcium 1,200 mg daily and vitamin D 800 to 1,000 units daily.

Prevention of Osteoporosis in Postmenopausal Women ( Reclast )

IV 5 mg infusion once every 2 yr given over no less than 15 min. If dietary intake is insufficient, supplement with calcium 1,200 mg daily and vitamin D 800 to 1,000 units daily.

General Advice

  • For IV administration only. Not for intradermal, subcutaneous, IM, intra-arterial, or oral administration.
  • Must be infused over no less than 15 min.
  • Do not administer if particulate matter or discoloration is noted.
  • Do not mix zoledronic acid with calcium-containing or other divalent cation–containing IV solutions (eg, Ringer's lactate solution) or other IV medications.
  • Administer as a single IV solution in a line separate from all other drugs.
  • Patients must be appropriately hydrated prior to treatment, especially patients receiving diuretic therapy.
  • A 5 mg dose IV is recommended for patients with CrCl 35 mL/min or more.
  • Administer ready-to-infuse solution IV via a separate vented infusion line.
  • Administration of acetaminophen following Reclast administration may reduce the incidence of actue-phase reaction symptoms.
  • Administer diluted solution via separate IV line.
  • Ensure patients being treated for multiple myeloma or metastatic bone lesions from solid tumors also receive an oral calcium supplement of 500 mg and a multivitamin containing 400 units of vitamin D daily.
  • Concentrated injection solution must be further diluted before administration.
  • To prepare 4 mg dose, withdraw 5 mL of concentrated injection solution and immediately dilute in 100 mL of sterile sodium chloride 0.9% injection or dextrose 5% injection. To avoid inadvertent injection of concentrate, do not store undiluted concentrate in syringe.
  • To prepare 3.5 mg dose, withdraw 4.4 mL of injection concentrate; to prepare 3.3 mg dose, withdraw 4.1 mL of injection concentrate; to prepare 3 mg dose, withdraw 3.8 mL of injection concentrate. Add concentrate to 100 mL of infusion solution.


Store unopened vials at room temperature (59° to 86°F). After opening, Reclast is stable for 24 h at 36° to 46°F. If refrigerated, allow solution to reach room temperature before administration. If not used immediately, Zometa diluted solution for infusion may be stored in refrigerator (36° to 46°F) and then equilibrated to room temperature before administration. Total time between dilution, storage in refrigerator, and end of administration must not exceed 24 h.

Drug Interactions

Aminoglycosides, loop diuretics (eg, furosemide)

Increased risk of hypocalcemia. Avoid loop diuretics until patient is rehydrated.

Nephrotoxic drugs (eg, NSAIDs)

Increased risk of nephrotoxicity; use with caution.

Renally excreted drugs (eg, digoxin)

Exposure to concomitant medications that are primarily renally excreted may increase. Consider monitoring serum creatinine in patients at risk for renal impairment taking concomitant medications primarily excreted by the kidney.


Increased risk of renal function impairment.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Hypertension (13%); hypotension (11%); atrial fibrillation, palpitations (3%); bradycardia (postmarketing).


Fatigue (39%); pyrexia (32%); weakness (24%); headache (20%); dizziness (18%); insomnia (16%); paresthesia (15%); anxiety, depression (14%); agitation, confusion (13%); hypoesthesia (12%); asthenia, somnolence (less than 10%); malaise (7%); lethargy (5%); hyperesthesia, taste disturbance, tremor (postmarketing).


Alopecia (12%); dermatitis (11%); hyperhidrosis, rash (3%); increased sweating, urticaria (postmarketing).


Sore throat (8%); vertigo (4%); eye pain (2%); iritis/uveitis (1%); blurred vision, episcleritis, scleritis (postmarketing).


Nausea (46%); vomiting (32%); constipation (31%); diarrhea (24%); abdominal pain (14%); dyspepsia (10%); dysphagia (less than 10%); stomatitis (8%); upper abdominal pain (5%); abdominal discomfort, abdominal distension (2%); dry mouth (postmarketing).


UTI (14%); CrCl decreased (2%); hematuria, proteinuria, renal deterioration progressing to renal failure and dialysis (postmarketing).


Anemia (33%); neutropenia (12%); thrombocytopenia (10%); granulocytopenia, pancytopenia (less than 10%).


Anaphylactic reaction/shock, angioedema, hypersensitivity reaction (postmarketing).

Lab Tests

Hypophosphatemia (51%); hypokalemia (12%); hypomagnesemia (11%); hypocalcemia (less than 10%); increased blood creatinine (2%); hyperkalemia, hypernatremia (postmarketing).


Local-site reactions (3%).


Anorexia (22%); decreased weight (16%); dehydration (14%); decreased appetite (13%); weight increase (postmarketing).


Bone pain (55%); arthralgia (27%); myalgia (23%); back pain (18%); pain in extremity (16%); limb pain (14%); musculoskeletal pain, skeletal pain (12%); rigors (11%); osteoarthritis (9%); neck pain, shoulder pain (7%); muscle spasms (6%); musculoskeletal stiffness (5%); arthritis, joint stiffness, pain in jaw (4%); joint swelling (3%); flank pain (2%); incapacitating bone, joint, and/or muscle pain, muscle cramps, osteonecrosis primarily of the jaw (postmarketing).


Dyspnea (27%); cough (22%); upper respiratory tract infection (10%); bronchoconstriction (postmarketing).


Fever (44%); acute phase reaction (25%); pain (24%); lower limb edema (21%); malignant neoplasm aggravated (20%); chills (18%); progression of cancer (16%); moniliasis (12%); influenza-like illness (11%); chest pain, leg edema, mucositis, nonspecific infection (less than 10%); noncardiac chest pain (8%); influenza (7%); peripheral edema (6%); increased C-reactive protein (5%); hyperthermia (2%).



Assess serum creatinine before each treatment with zoledronic acid. Monitor serum calcium, phosphorous, magnesium, electrolytes, and renal function. Perform a routine oral examination prior to bisphosphonate treatment.


Category D .




Safety and efficacy not established.


Because decreased renal function occurs more commonly in elderly patients, take special care to monitor renal function.

Renal Function

Has been reported following administration of zoledronic acid, especially in patients with preexisting renal compromise or additional risk factors. Reclast is not recommended in patients with severe renal function impairment (CrCl less than 35 mL/min). Zometa treatment is not recommended in patients with bone metastases with severe renal function impairment.

Hepatic Function

No clinical data available.


Use with caution in patients with aspirin-sensitive asthma.


Because hypocalcemia may occur, preexisting hypocalcemia must be treated by adequate calcium and vitamin D before initiating therapy.

Musculoskeletal pain

Severe and occasionally incapacitating bone, joint, and/or muscle pain, starting 1 day to several months after starting therapy, has been reported in patients taking bisphosphonates. Symptoms usually resolve following discontinuation of therapy and may recur with rechallenge with the same or different bisphosphonate.

Osteonecrosis of the jaw

Has been reported predominantly in cancer patients treated with IV bisphosphonates. Risk factors include cancer chemotherapy, corticosteroid administration, and dental procedures. Consider a dental examination with appropriate preventive dentistry prior to treatment with zoledronic acid in patients with concomitant risk factors.



Hypocalcemia, hypomagnesemia, hypophosphatemia, renal function impairment.

Patient Information

  • Advise patient that medication will be prepared and administered by health care provider in a health care setting.
  • Advise patient that infusion-site reactions (eg, hardness, pain, redness, swelling) can be treated with local measures (eg, warm or cold packs) and oral OTC analgesics (eg, acetaminophen, ibuprofen). Advise patient to report infusion-site reactions that do not respond to symptomatic treatment to health care provider.
  • Instruct patient to report the following symptoms to health care provider: appetite loss, constipation, diarrhea, difficulty breathing, fatigue or unexplained tiredness, fever, inflammation of the mouth, muscle or bone pain, muscle spasms, nausea, numbness, stomach pain, swelling, tingling, weakness, weight loss, vomiting.
  • Instruct patient to maintain good oral hygiene and to avoid, if possible, invasive dental procedures (eg, tooth extractions) during treatment with zoledronic acid.
  • Advise women of childbearing potential to use effective contraception during treatment with zoledronic acid.
  • Instruct patients that they may have to take calcium and vitamin D supplements and to take them as directed by health care provider.
  • Instruct patients to inform health care provider if they have kidney problems and inform them of the importance of getting their blood creatinine tested during therapy.
  • Reclast
  • Instruct patients to inform health care provider if they have had surgery to remove some or all of the parathyroid glands, have had sections of intestine removed, or are unable to take calcium supplements.

Copyright © 2009 Wolters Kluwer Health.