What is the Difference Between Zometa® and Reclast®?

Joanna M. Pangilinan, PharmD, BCOP

Disclosures

January 28, 2010

Question

What is the difference between Zometa® and Reclast®?

Response from Joanna M. Pangilinan, PharmD, BCOP
Pharmacist, Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan

Bisphosphonates promote apoptosis of osteoclasts actively involved in the degradation of bone surface mineral. As a result they are useful for managing skeletal conditions, such as hypercalcemia of malignancy, metastatic bone disease, osteoporosis, and Paget's disease.[1] Many bisphosphonates are available, each with different indications, dosing, and dosage forms. The intravenous (IV) bisphosphonate zoledronic acid is the same active ingredient in both Zometa® and Reclast®, yet these products have several important differences:

Dose

Zometa® was approved by the Food and Drug Administration (FDA) for hypercalcemia of malignancy in 2001. Noting that zoledronic acid had substantial effects on bone, researchers evaluated the agent for other indications, such as osteoporosis. Zoledronic acid, 4 mg, was studied for up to 5 years in postmenopausal women with low bone mineral density. Although the drug was well-tolerated and effective in decreasing biomarkers, further analysis of bone marker changes suggested that 4 mg was a suboptimal dose for a significant number of patients.[2] A further study established the utility of zoledronic acid, 5 mg, administered annually for postmenopausal osteoporosis.[3] In 2007, the FDA approved a second zoledronic acid product, Reclast®.

How Supplied

Zometa® is available as a 4 mg/5 mL concentrate for IV infusion. Further dilution is required. Reclast® is available as a 5 mg/100 mL solution for IV infusion (ie, ready-to-infuse).

Indications

Zometa® is indicated for (1) hypercalcemia of malignancy and (2) multiple myeloma and bone metastases of solid tumors.[4] Reclast® is indicated for (1) treatment of osteoporosis in postmenopausal women, (2) prevention of osteoporosis in postmenopausal women, (3) treatment of osteoporosis in men, (4) treatment and prevention of glucocorticoid-induced osteoporosis, and (5) treatment of Paget's disease of bone.[5]

Dosing Interval

The dosing interval is quite different between agents. Common dosing intervals for Zometa® include every 3-4 weeks or as a single treatment, depending on indication.[4] Reclast® may be administered as a single treatment, annually, or biennially depending on indication.[5]

Adverse Effects

Adverse effects of zoledronic acid include renal toxicity, an acute phase response (characterized by fever, rigors, fatigue, malaise, arthralgia, and bone pain), musculoskeletal pain, and osteonecrosis of the jaw.[1]

Patients receiving monthly bisphosphonates (ie, Zometa®) have a 1%-10% incidence of osteonecrosis of the jaw. The incidence may be much lower in patients receiving zoledronic acid for osteoporosis or Paget's disease (ie, Reclast®). Studies demonstrate that the incidence of osteonecrosis of the jaw is proportional to the cumulative bisphosphonate dose.[6]

A possible association between zoledronic acid and risk for atrial fibrillation was noted after patients receiving 5 mg had a higher frequency of atrial fibrillation than patients receiving placebo.[3] The FDA has since analyzed clinical trial data and found no clear association between atrial fibrillation and bisphosphonate treatment across all studies. The FDA continues to do postmarketing surveillance on this issue.[7]

Renal Adjustment

As noted above, renal toxicity may occur with zoledronic acid use. Dose reductions are recommended for Zometa® in patients with calculated creatinine clearance ≥ 30 mL/min and ≤ 60 mL/min.[4] Limited data are available for dosing with creatinine clearance < 30 mL/min. Reclast® should not be given to patients with creatinine clearance < 35 mL/min. No dosage adjustment is required for patients with creatinine clearance ≥ 35 mL/min.[5]

Although the "same" drug, Zometa® and Reclast® are actually very different. Clinicians should refer to product information and clinical research on dosing, adverse effects, and treatment guidelines for each product.

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