RECLAST (zoledronic acid-mannitol-water)

RECLAST (zoledronic acid-mannitol-water)

OFFICE ADMINISTRATION

Indications for Prior Authorization:

• Treatment of Paget’s disease of the bone 
• Treatment and prevention of postmenopausal osteoporosis 
• Osteoporosis in men
• Glucocorticoid-induced Osteoporosis: concurrent therapy with systemic glucocorticoids with failure or clinically significant adverse effects to oral bisphosphonates

Criteria for Reclast® treatment:

All must have failed bisphosphonates prior to starting Reclast.  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 (2 cm or more), or occurrences of osteoporotic fractures despite therapy

Paget's disease

• Patient's ≥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)

Treatment and prevention of postmenopausal osteoporosis

• Patients with postmenopausal osteoporosis diagnosis
• Women with low-trauma fractures and low bone mineral density (BMD)
• Women with BMD T-scores of –2.5 and below
• Women with borderline-low BMD (e.g., T-scores of –1.5 and below) if risk factors are present
• Women in whom non-pharmacologic preventative measures are ineffective (bone loss continues or low-trauma fractures occur).⁵

Osteoporosis in men

• Male patients with osteoporosis diagnosis or high risk of osteoporosis

Glucocorticoid-induced Osteoporosis

• Concurrent therapy with systemic glucocorticoids with failure or clinically significant adverse effects to oral bisphosphonates

Reclast 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 8.4mg/dL or an ionized calcium level of less than 4.5mg/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 have 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) patients had relapsed after two years of follow-up. An addition dose of zoledronic acid may be indicated if alkaline phosphatase levels do not normalize

Dosing:

Paget’s Disease 

• Initial:  5 mg IV infusion over at least 15 minutes for one dose
• Retreatment:  Data is not available, retreatment may be considered for relapse (increase in alkaline phosphatase) if appropriate, for inadequate response, or in patients who are symptomatic - 5 mg one time every 6 months

Postmenopausal osteoporosis

• Prevention:  5mg IV every 2 years
• Treatment:  5mg IV infusion over at least 15 minutes once a year
• It is recommended that patients on bisphosphonate therapy for the treatment of postmenopausal osteoporosis should be on doses of 500mg to 1500 mg daily, in divided doses, of supplemental calcium and 400 to 800 international units daily of Vitamin D
• Retreatment: Specific re-treatment data are not available. Repeated administration of zoledronic acid may not be necessary for some years, since less than 1 percent of infusion of a single yearly 4 mg dose of zoledronic acid was shown to increase bone mineral density, in the lumbar spine and femoral neck.  The effects on bone mineral density and bone turnover at 12 months are equivalent to those seen with daily bisphosphonates

Osteoporosis in men

• Initial:  5 mg IV infusion over at least 15 minutes for one dose once a year
• Retreatment:  5 mg one time every year

Glucocorticoid-induced Osteoporosis

• Prevention or Treatment:  5mg IV infusion over at least 15 minutes once a year

References:

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)