Zoledronic Acid for injection- ZOMETA®
- Treatment of hypercalcemia of malignancy
- Treatment of patients with multiple myeloma
- Treatment of patients with documented bone metastases from solid tumors, which include prostate cancer, lung cancer, breast cancer and other solid tumor types 1
- Treatment of Paget’s disease
Criteria for Zometa® treatment:
All must have failed bisphosphonates prior to starting Zometa. Failing bisphosphonates is defined as:
- Patients with a contraindication to oral bisphosphonates. Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia, inability to stand or sit upright for at least 30 minutes, increased risk of aspiration, hypersensitivity to any component of an orally administered bisphosphonate.2
- Patients who have failed treatment with an oral bisphosphonate due to esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, and gastric or duodenal ulcers. 3
- Patients who have failed treatment with an oral bisphosphonate, defined as significant loss of height (2cm or more), or occurrences of osteoporotic fractures despite therapy
Hypercalcemia of malignancy
- Patients ≥18 years of age with histologic or cytologic confirmation of cancer and severe hypercalcemia of malignancy (corrected serum calcium* ≥12.0 mg/dL).
- Patient without renal insufficiency (studies in hypercalcemia of malignancy excluded patients with SCr>4.5 mg/dL)
- Patients with multiple myeloma and is treated with standard antineoplastic therapy.
Documented bone metastases from solid tumors, which include prostate cancer, lung cancer, breast cancer and other solid tumor types. 1
- Diagnosis of bone metastases from solid tumors, AND
- Documentation of metastatic bone disease by scan or x-ray
- The treatment of prostate cancer should be done after the cancer has progressed after treatment with at least one hormonal therapy.
- Patient without renal insufficiency (studies in bone metastasis SCr>3.0 mg/dL)
- Patients ≥18 years of age with radiologically confirmed Paget’s disease of the bone.
- Does not have renal insufficiency (studies in Paget's disease Clcr < 30 ml per minute)
Zometa NOT approved for the following:
- Patients with a history of allergic reaction or sensitivity to bisphosphonates
- Patients who are severely dehydrated or could not tolerate IV hydration
- Pregnancy Category D
- Patients with preexisting hypocalcemia (defined as a serum calcium level less than 8.4 mg/dL or an ionized calcium level of less than 4.5 mg/dL) or documented vitamin D deficiency. Deficiency must be treated before receiving any bisphosphonate. 8
- Nursing mothers - unknown whether excreted in human milk
- Pediatric use-safety and effectiveness has not been established
- Patients with aspirin-sensitive asthma (bronchoconstriction with other bisphosphonates have occurred in patients with aspirin-sensitive asthma)
* Albumin-corrected serum calcium (CCa, mg/dL)=serum calcium(mg/dL) + 0.8 (4.0-serum albumin(g/dL)) † Off-label use (not FDA approved for this indication)Western Health Advantage Pharmacy and Therapeutics Committee Approved: August 2009 | Revised: July 2015 | Reviewed: July 2016
Hypercalcemia of Malignancy
- Initial: Recommended dose of 4 mg IV dose of Zometa®. The 4mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes.
- Retreatment: May be considered if serum calcium does not return to normal or remain normal after initial treatment.
- It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose.
- Zometa® should be used in conjunction with vigorous saline hydration, and an attempt should be made to restore urine output to about 2 L/day throughout treatment. Overhydration should be avoided, especially in patients who have potential of cardiac failure.
Multiple Myeloma and patients with documented bone metastases from solid tumors
- 4 mg IV once every 3 weeks
- Duration of treatment in clinical studies was 15 months for prostate cancer, 12 months for breast cancer and multiple myeloma, and 9 months for other solid tumors. In addition to antineoplastic therapy and Zometa®, patients should be administered 500mg of oral calcium supplement and 400 IU of Vitamin D daily
- It is expected that doses of 4 mg zoledronic acid will have similar results in Paget's Disease as they have been effective in patients with osteoporosis. Doses less than 5 mg may be used as long as remission is present.
1. Zometa® prescribing information. December 2005. Novartis.
2. Fosamax® prescribing information. February 2006. Merck.
3. Carey JJ. What is a 'failure' of bisphosphonate therapy for osteoporosis? Cleve Clin J Med. 2005 Nov;72(11):1033-9
4. Aclasta® prescribing information . April 2006. Novartis Canada
5. American Association of Clinical Endrocrinologists Medical Guidelines for Clinical Practice for the Prevention and Treatment of Postmenopausal Osteoporosis: 2001 Edition, with Selected Updates for 2003
6. Major P, Lortholary A, Hon J, Abdi E, Mills G, Menssen HD, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001;19(2):558-67.
7. Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001;7:377-87.
8. Rosen CJ, Brown S. Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med 2003;348:1503-4
9. Reid I, Miller P, Lyles K, et al. Comparison of a Single Infusion of Zoledronic Acid with Risedronate for Paget’s Disease. N Engl J Med 353;9:898-908
10. Rendina D, DeFilippo G, Mossetti G. Paget’s disease and bisphosphonates. N Engl J Med. 2005 Dec 15;353(24):2616-8; author reply 2616-8
11. Reid IR, Brown JP, Burckhardt P, et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002 Feb 28;346(9):653-61.
12. Schnitzer, T., et al. Therapeutic Equivalence of Alendronate 70 mg Once-weekly and Alendronate 10 mg Daily in the Treatment of Osteoporosis. Aging Clinical Exp Res. 2000 Feb; 12(1):1-12
13. Durie BG, Katz M, Crowley J. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005 Jul 7;353(1):99-102; discussion 99-102
Written by: Katie Bredeman, PharmD. candidate (2/02); Melissa Abueg, PharmD., pharmacy practice resident (10/02); Forrest Shirkey, PharmD (11/06)
Reviewed by: Timothy Cutler, PharmD. Robert Mowers, PharmD.
Approved by: Mercy Medical Group
* Albumin-corrected serum calcium (CCa, mg/dL)=serum calcium(mg/dL) + 0.8 (4.0-serum albumin(g/dL)) † Off-label use (not FDA approved for this indication)
Western Health Advantage Pharmacy and Therapeutics Committee
Approved: August 2009
Last review date: July 21, 2016