Zoledronic Acid

Trade Names:
Reclast
- Injection, solution 5 mg per 100 mL

Trade Names:
Zometa
- Injection, solution, concentrate 4 mg per 5 mL

Pharmacology

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Inhibition of osteoclastic bone resorption.

Pharmacokinetics

Distribution

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

Metabolism

Does not undergo biotransformation.

Elimination

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

Special Populations

Mild renal function impairment increased AUC by an average of 15%. Moderate renal function impairment 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.

No pharmacokinetic studies have been conducted.

Indications and Usage

Treatment of osteoporosis in postmenopausal women; treatment to increase bone mass in men with osteoporosis; 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.

Contraindications

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

Dosage and Administration

IV 4 mg max dose given as 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.

IV 4 mg max dose 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.

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 dictated 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.

IV 5 mg infusion once a year given over no less than 15 minutes. 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 not be infused in 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.
• Patients must be appropriately hydrated prior to treatment, especially patients receiving diuretic therapy.

• Is a ready-to-infuse solution administered IV via a vented infusion line.

• 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, and add concentrate to 100 mL of infusion solution.

Storage/Stability

Store unopened vials at room temperature (59° to 86°F). 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. After opening, Reclast is stable for 24 h at 36° to 46°F. If refrigerated, allow solution to reach room temperature before administration.

Drug Interactions

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

Increased risk of nephrotoxicity; use with caution.

Increased risk of renal function impairment.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

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

CNS

Fatigue (39%); pyrexia (32%); weakness (24%); headache (19%); dizziness (18%); insomnia (16%); paresthesia (15%); anxiety, depression (14%); agitation, confusion (13%); hypoesthesia (12%); somnolence (less than 10%); malaise (7%); lethargy (5%); hyperesthesia, taste disturbance, tremor (postmarketing).

Dermatologic

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

EENT

Sore throat (8%); vertigo (4%); eye pain (2%); blurred vision, episclerosis, scleritis, uveitis (postmarketing).

GI

Nausea (46%); vomiting (32%); constipation (31%); diarrhea (24%); abdominal pain (16%); dyspepsia (10%); dysphagia (less than 10%); stomatitis (8%); upper abdominal pain (5%); abdominal distension (2%); dry mouth (postmarketing).

Genitourinary

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

Hematologic-Lymphatic

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

Hypersensitivity

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

Lab Tests

Hypophosphatemia (13%); hypokalemia (12%); hypomagnesemia (11%); hypocalcemia (less than 10%); increased blood creatinine (2%); hyperkalemia, hypernatremia (postmarketing).

Local

Local-site reactions (3%).

Metabolic-Nutritional

Anorexia (22%); decreased weight (16%); dehydration (14%); decreased appetite (13%); musculoskeletal stiffness (5%); weight increase (postmarketing).

Musculoskeletal

Bone pain (55%); arthralgia (24%); myalgia (23%); back pain (15%); limb pain (14%); musculoskeletal pain, skeletal pain (12%); pain in extremity, rigors (11%); shoulder pain (7%); musculoskeletal stiffness (5%); muscle spasm, neck pain (4%); incapacitating bone, joint, and/or muscle pain, muscle cramps, osteonecrosis primarily of the jaw (postmarketing).

Respiratory

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

Miscellaneous

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

Precautions

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

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.

Asthma

Use with caution in patients with aspirin-sensitive asthma.

Hypocalcemia

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 in patients receiving treatment regimens that include 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.

Overdosage

Symptoms

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, 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.

• Reclast
• Instruct patients to inform health care provider if they have kidney problems, have had surgery to remove some or all of the parathyroid glands or had sections of intestine removed, or are unable to take calcium supplements.

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