Zoledronic Acid

1
Zoledronic Acid
Brands

DEA Class; Rx

Common Brand Names; Reclast, Zometa

  • Calcium Metabolism Modifiers; 
  • Bisphosphonate Derivatives

Potent third-generation intravenous bisphosphonate; carefully select product based on indication for use
Used for hypercalcemia of malignancy and bone metastases (e.g., Zometa); given as a single dose for Paget’s disease (e.g., Reclast)
Given once-yearly for osteoporosis and corticosteroid-induced osteoporosis and prevention in both men and women, and every 2 years for osteoporosis prophylaxis in postmenopausal women (e.g., Reclast)

Indicated for the treatment of hypercalcemia of malignancy (i.e., albumin-corrected serum calcium 12 mg/dL or higher).
Reduction in incidence of fractures (hip, vertebral, and nonvertebral osteoporosis-related fractures)
For the treatment of patients with multiple myeloma or with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy.
For the treatment of Paget’s disease.

Pregnancy

All indications: Hypersensitivity, including rare cases of urticaria, angioedema, and anaphylactic reaction or shock

Nononcologic uses: Hypocalcemia, severe renal impairment (CrCl <35 mL/min or evidence of acute renal impairment)

  • Bone pain (55%)
  • Nausea (29-46%)
  • Fever (32-44%)
  • Fatigue (39%)
  • Anemia (22-33%)
  • Vomiting (14-32%)
  • Constipation (27-31%)
  • Dyspnea (22-27%)
  • Diarrhea (17-24%)
  • Anorexia (9-22%)
  • Arthralgia (5-21%)
  • Headache (5-19%)
  • Dizziness (18%)
  • Insomnia (15-16%)
  • Urinary tract infection (UTI; 12-14%)
  • Anxiety (11-14%)
  • Hypophosphatemia (5-14%)
  • Hypokalemia (12%)
  • Hypotension (11%)
  • Hypomagnesemia (11%)
  • Rash (11%)

Assess renal function before and after treatment; if renal function is decreased after treatment, withhold additional treatment until it returns to within 10% of baseline

Before each Reclast dose, calculate CrCl on basis of actual body weight, using Cockcroft-Gault formula

Other risks for renal impairment include coadministration of zoledronic acid with nephrotoxic or diuretic medications, severe dehydration before or after zoledronic acid administration, and advanced age

Previous renal insufficiency (serum creatinine >3 mg/dL [265 mmol/L]), hepatic insufficiency, musculoskeletal pain

Infuse over ≥15 minutes; faster infusion increases renal toxicity

May cause significant risk of hypocalcemia (seizures, tetany, and numbness); hypocalcemia must be corrected before initiation of therapy; adequately supplement patients with calcium and vitamin D; monitor serum calcium closely with concomitant administration of other drugs known to cause hypocalcemia to avoid severe or life-threatening hypocalcemia

Use with caution in aspirin-sensitive asthma; may cause bronchoconstriction

Increased risk of osteonecrosis of jaw (advise patients against dental work); reported predominantly in cancer patients treated with IV bisphosphonates, including zoledronic acid; many patients were also receiving chemotherapy and corticosteroids which may be risk factors; risk may increase with duration of exposure to bisphosphonates; perform preventive dental exams before initiating therapy; avoid invasive dental procedures; monitor diabetic patients carefully

Cases of osteonecrosis (primarily involving the jaw but also of other anatomical sites including hip, femur and external auditory canal) reported predominantly in cancer patients

Risk of osteonecrosis of the jaw may increase with duration of exposure to bisphosphonates

Possible increased risk for atypical subtrochanteric and diaphyseal femur fractures; consider periodic reevaluation of need for continued bisphosphonate therapy, particularly if treatment lasts >5 years

If patients are receiving Zometa, they should not receive Reclast

Severe bone, joint, and muscle pain may occur; withhold future doses of zoledronic acid if severe symptoms occur

There are no available data in pregnant women to inform the drug-associated risk

Not known whether drug is present in human milk, or whether it affects milk production, or breastfed child; drug binds to bone long term and may be released over weeks to years

Adults

4 mg/dose IV for hypercalcemia/oncology indications; 5 mg/dose IV for Paget’s disease/osteoporosis.

Geriatric

4 mg/dose IV for hypercalcemia/oncology indications; 5 mg/dose IV for Paget’s disease/osteoporosis.

Adolescents

Safety and efficacy have not been established; however, 5 mg IV once yearly or doses up to 0.1 mg/kg/cycle IV every 4 to 6 months have been used off-label for osteogenesis imperfecta.

Children

3 to 12 years: Safety and efficacy have not been established; however, 5 mg IV once yearly or doses up to 0.1 mg/kg/cycle IV every 4 to 6 months have been used off-label for osteogenesis imperfecta.
2 years: Safety and efficacy have not been established; however, 5 mg IV once yearly or doses up to 0.05 mg/kg/cycle IV every 3 months or 0.1 mg/kg/cycle IV every 6 months have been used off-label for osteogenesis imperfecta.
1 year: Safety and efficacy have not been established; however, doses up to 0.05 mg/kg/cycle IV every 3 months or 0.1 mg/kg/cycle IV every 6 months have been used off-label for osteogenesis imperfecta.

Infants

Safety and efficacy have not been established; however, doses up to 0.05 mg/kg/cycle IV every 3 months or 0.1 mg/kg/cycle IV every 6 months have been used off-label for osteogenesis imperfecta.

Neonates

Safety and efficacy have not been established.

Zoledronic acid

IV injectable solution

  • 4mg/5mL (5mL)
  • 5mg/100mL
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