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Generic Name: Zoledronic Acid
Class: Bone Resorption Inhibitors
VA Class: HS900
Chemical Name: [1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene]bis-phosphonic acid monohydrate
Molecular Formula: C5H10N2O7P2•H2O
CAS Number: 165800-06-6

Introduction

Synthetic bisphosphonate; bone resorption inhibitor.1 4 5

Uses for Zometa

Hypercalcemia Associated with Malignancy

Used in conjunction with achievement and maintenance of adequate hydration for the treatment of moderate to severe hypercalcemia (albumin-corrected serum calcium concentration ≥12 mg/dL) associated with malignant neoplasms.1 2 3 5

Retreatment may be considered in patients with recurrent or refractory disease.1 2 3

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma

Used as an adjunct to antineoplastic therapy for the treatment of osteolytic bone metastases of solid tumors and osteolytic lesions of multiple myeloma.1 7

Second-line therapy of bone metastases associated with prostate cancer in patients with disease progression following one or more hormonal therapies.1 3

Prevention of Aromatase Inhibitor-associated Bone Loss in Postmenopausal Women

May be considered a reasonable choice (accepted, with possible conditions) in postmenopausal women with early-stage breast cancer receiving aromatase inhibitor therapy who have no additional risk factors and in whom BMD is at least 2.5 standard deviations below normal (T-scores at or below -2.5) either at baseline or during aromatase inhibitor therapy.27 10005

Slideshow: Flashback: FDA Drug Approvals 2013

May be considered a reasonable choice (accepted, with possible conditions) on an individualized basis in postmenopausal women with early-stage breast cancer receiving aromatase inhibitor therapy who have moderate osteopenia (T-scores at or below -2) and have a history of a prior fracture or another clinically important risk factor (e.g., age, maternal history of fracture, low weight or body mass index) or lifestyle-related factor as defined by WHO; such women are at moderate to high risk for fracture development.27

Osteoporosis

Treatment and prevention of osteoporosis in postmenopausal women.17 21 41

Used to increase bone mass in men with osteoporosis.17

Corticosteroid-induced Osteoporosis

Treatment and prevention of corticosteroid-induced osteoporosis in men and women receiving corticosteroids.17 39 40 Manufacturer recommends use of zoledronic acid in men and women who are either initiating or receiving long-term (≥12 months) systemic corticosteroid therapy in a daily dosage ≥7.5 mg of prednisone or equivalent.17 40

The American College of Rheumatology (ACR) currently recommends use of one of several bisphosphonates (i.e., alendronate, risedronate, zoledronic acid) in conjunction with lifestyle modification and calcium and vitamin D supplementation for the prevention and treatment of corticosteroid-induced osteoporosis in select postmenopausal women and men ≥50 years of age initiating or currently receiving corticosteroid therapy.39 ACR recommendations based on a risk-stratification approach in which an individual’s clinical risk level for developing a fracture is determined based on variables such as gender, age, race/ethnicity, and femoral neck density43 and the individual’s preexisting or anticipated corticosteroid dosage.39

ACR states that because of limited data, use of bisphosphonates for prevention or treatment of corticosteroid-induced osteoporosis in premenopausal women and men <50 years of age can be recommended only in those who have a history of fragility fracture.39

Paget’s Disease of Bone

Treatment of Paget’s disease of bone (osteitis deformans) in patients with serum alkaline phosphatase concentrations ≥ 2 times ULN or who are symptomatic or at risk for future complications.17

Prevention of Aromatase Inhibitor-associated Bone Loss in Premenopausal Women

Use not fully established because of unclear risk/benefit.27 Improvements in BMD observed in premenopausal women with early-stage breast cancer receiving zoledronic acid concurrently with an aromatase inhibitor-gonadotropin-releasing hormone agonist regimen.10004 However, long-term follow-up needed, especially as women enter menopause, to establish whether zoledronic acid is associated with clinically important fracture reduction.10004

Zometa Dosage and Administration

General

  • Evaluate renal function (Scr or Clcr) prior to administration of each dose.1 3 17 (See Renal Effects under Cautions.)

  • Carefully monitor standard hypercalcemia-related metabolic parameters (e.g., serum concentrations of calcium, phosphate, magnesium, other electrolytes in patients with hypercalcemia of malignancy) following initiation of therapy.1 17

Osteoporosis

  • Supplemental calcium (average daily dose of 1.2 g) and vitamin D (average daily dose of 800–1000 international units [IU, units]) recommended if dietary intake insufficient.17

  • Appropriately hydrate patients prior to initiation of therapy.17 Withhold therapy if dehydration is evident; may resume once normovolemic status achieved.17

Paget’s Disease of Bone

  • To reduce risk of hypocalcemia, administer supplemental calcium and vitamin D, especially during first 2 weeks of therapy; recommended daily intake is 1.5 g of elemental calcium in divided doses (750 mg twice daily or 500 mg 3 times daily) and 800 units of vitamin D.17

  • Appropriately hydrate patients prior to initiation of therapy.17 Withhold therapy if dehydration is evident; may resume once normovolemic status achieved.17

Hypercalcemia Associated with Malignancy

  • Adequately hydrate patients prior to treatment initiation and throughout treatment.1 3 Avoid overhydration, especially in patients at risk for the development of heart failure.1 3 Attempt to restore urine output to 2 L/day throughout treatment.1

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma

  • Supplemental calcium (500 mg of elemental calcium daily) and a multivitamin containing vitamin D (400 units daily) is recommended in patients with multiple myeloma or bone metastases associated with solid tumors.1 7 (See Metabolic Effects under Cautions.)

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1 3 7

Available as Zometa as a 4 mg/5 mL solution concentrate and a 4 mg/100 mL ready-to-use infusion for patients with cancer-related indications.1 Also available as Reclast as a ready-to-use 5 mg/100 mL infusion for use in the prevention or treatment of patients with osteoporosis or treatment of Paget’s disease of bone.17

Must dilute concentrated solution of Zometa prior to administration.1 To avoid inadvertent injection of the concentrated solution, do not store the undiluted concentrate in a syringe.1

The ready-to-use solution of Zometa must be administered directly without further dilution to provide a dose of 4 mg.1 To prepare reduced doses, withdraw appropriate volume of solution from the 100-mL ready-to-use bottle and replace with an equal volume of an appropriate diluent (0.9% sodium chloride or 5% dextrose injection).1 For dose of 3.5 mg, withdraw 12 mL of drug solution and replace with 12 mL of diluent.1 For dose of 3.3 mg, withdraw 18 mL of drug solution and replace with 18 mL of diluent.1 For dose of 3 mg, withdraw 25 mL of drug solution and replace with 25 mL of diluent.1

May store diluted solutions of Zometa at 2–8°C; allow solution to reach room temperature prior to administration.1 Must be administered within 24 hours of preparation.1

Administer Zometa or Reclast through separate vented IV lines apart from other drugs.1 17 Do not allow contact with any calcium or other divalent cation-containing solutions.1 17

Follow each dose of Reclast with 10 mL of a 0.9% sodium chloride flush.17

Dilution

For dilution of the zoledronic acid concentrate (Zometa), withdraw the appropriate volume of solution needed to provide the prescribed dose (see Table 1) from the 5-mL vial and dilute in 100 mL of 0.9% sodium chloride or 5% dextrose injection.1 Increased risk of renal impairment or failure associated with smaller infusion volumes (e.g., 50 mL).3 4 7

Table 1. Zoledronic Acid Dose and Corresponding Volume of Concentrate for Dilution

Zoledronic Acid Dose

Volume of Concentrate to be Diluted

4 mg

5 mL

3.5 mg

4.4 mL

3.3 mg

4.1 mL

3 mg

3.8 mL

Rate of Administration

Administer by IV infusion over ≥15 minutes.1 3 7 17 Rapid IV infusion rates (5 minutes) are associated with an increased risk of renal impairment and renal failure.1 3 4 7

Dosage

Available as zoledronic acid (as the monohydrate); dosage expressed in terms of the anhydrous drug.1

Adults

Hypercalcemia Associated with Malignancy
IV

4 mg as a single dose in patients with an albumin-corrected serum calcium concentration of ≥12 mg/dL.1 3

Consider retreatment if serum calcium concentrations do not return to normal or do not remain normal.1 May repeat initial dose ≥7 days after treatment initiation to allow full response to initial dose.1

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma
IV

4 mg once every 3–4 weeks in patients with baseline Clcr >60 mL/minute.1 3 Optimum duration of such therapy is not known.1 3 7

If renal function deteriorates (defined as an increase in Scr of ≥0.5 mg/dL) in patients with a baseline Scr of <1.4 mg/dL, withhold therapy until Scr returns to within 10% of baseline levels.1 3 7 Reinitiate therapy at the same dosage used prior to treatment interruption.1 3 7

Osteoporosis
Prevention in Postmenopausal Women
IV

5 mg once every 2 years.17

Treatment in Postmenopausal Women
IV

5 mg once yearly.17

Reevaluate need for continued therapy periodically in all patients receiving bisphosphonates.17

Treatment in Men
IV

5 mg once yearly.17

Reevaluate need for continued therapy periodically in all patients receiving bisphosphonates.17

Corticosteroid-induced Osteoporosis
IV

5 mg once yearly.17

ACR recommends that bisphosphonate therapy be administered as long as corticosteroid therapy continues.39

Paget’s Disease of Bone
IV

Single dose of 5 mg.17

May consider retreatment if relapse occurs based on increases in serum alkaline phosphatase, if initial dose fails to normalize serum alkaline phosphatase concentrations, or if patient is symptomatic; however, no specific data available on effects of retreatment.17

Prevention of Aromatase Inhibitor-associated Bone Loss in Postmenopausal Women
IV

Dosage of 4 mg once every 6 months has been used in clinical trials in women with early-stage breast cancer.10001

Prescribing Limits

Adults

Hypercalcemia Associated with Malignancy
IV

Maximum 4 mg as a single dose.1 3 5 7 Safety and efficacy of >1 course of retreatment not established.2 3

Special Populations

Hepatic Impairment

No dosage recommendations at this time.1

Renal Impairment

Hypercalcemia Associated with Malignancy
IV

Dosage adjustments are not necessary in patients with mild to moderate renal impairment (Scr <4.5 mg/dL).1

Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma
IV

In patients with mild to moderate renal impairment (baseline Clcr of 30–60 mL/minute), lower initial dosages of zoledronic acid are recommended.1 (See Table 2.)

Table 2. Initial Dosage in Adults with Bone Metastases of Solid Tumors and Osteolytic Lesions of Multiple Myeloma Based on Renal Function

Calculated Clcr (mL/minute)

IV Dosage

>60

4 mg every 3–4 weeks

50–60

3.5 mg every 3–4 weeks

40–49

3.3 mg every 3–4 weeks

30–39

3 mg every 3–4 weeks

If renal function deteriorates (defined as an increase in Scr of ≥1 mg/dL) in patients with a baseline Scr of ≥1.4 mg/dL, withhold therapy until Scr returns to within 10% of baseline levels.1 3 7 Reinitiate therapy at the same dosage that was used prior to the treatment interruption.1 Studies in this patient population included individuals with Scr <3 mg/dL.1 3 7

Osteoporosis
IV

Dosage adjustments not necessary in patients with Clcr ≥35 mL/minute.17 Do not use in patients with Clcr<35 mL/minute.17

Paget’s Disease of Bone
IV

Dosage adjustments not necessary in patients with Clcr ≥35 mL/minute.17 Do not use in patients with Clcr<35 mL/minute.17

Geriatric Patients

No dosage recommendations at this time.1

Cautions for Zometa

Contraindications

  • Known hypersensitivity to zoledronic acid, other bisphosphonates, or any ingredient in the formulation.1 2 17

  • Hypocalcemia (in patients with osteoporosis or Paget’s disease of bone).17

  • Reclast also contraindicated in patients with Clcr <35 mL/minute or evidence of acute renal impairment.17

Warnings/Precautions

Fetal/Neonatal Morbidity

May cause fetal harm; use not recommended in pregnant women, and women of childbearing potential should avoid conception during therapy.1 17 (See Advice to Patients.)

Renal Effects

Risk of renal toxicity.1 2 3 4 7 17 38 Acute renal failure requiring dialysis and sometimes resulting in hospitalization and/or death reported during postmarketing experience with Reclast.17 38 42 Transient increases in Scr also observed.42 Renal function deterioration progressing to renal failure and dialysis also observed in clinical trials and during postmarketing experience with Zometa; occurred following administration of higher than recommended doses and with usual dosages.1

Evaluate renal function (Scr or Clcr) prior to administering each dose and more frequently in patients at high risk of acute renal failure (e.g., geriatric patients, those receiving diuretic therapy).1 17

Do not use Reclast in patients with Clcr <35 mL/minute or in those with evidence of acute renal impairment; use with caution in those with chronic renal impairment.17

Risk of renal toxicity appears to be increased in patients with underlying renal disease or other risk factors (e.g., dehydration, advanced age, concomitant use of nephrotoxic agents).1 17 38 42 Such risk factors should be identified and managed.1 17 To prevent renal impairment, appropriately hydrate patients prior to initiation of therapy.17 May correct transient increases in Scr with administration of IV fluids.17

Weigh the risks versus the potential benefits of subsequent treatment in patients with hypercalcemia of malignancy and severe renal impairment if renal function deteriorates during therapy.1

Metabolic Effects

Possible hypocalcemia, hypophosphatemia, or hypomagnesemia.1 17

Correct hypocalcemia and manage other factors affecting bone and mineral metabolism (e.g., hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine) before initiating therapy in patients with Paget’s disease of bone or osteoporosis.17

Carefully monitor standard hypercalcemia-related metabolic parameters (e.g., serum concentrations of calcium, phosphate, magnesium, and potassium in patients with hypercalcemia of malignancy) following initiation of therapy.1 3 17 Short-term supplemental therapy may be necessary if hypocalcemia, hypophosphatemia, or hypomagnesemia occurs.1 3

Musculoskeletal Effects

Osteonecrosis and osteomyelitis of the jaw have been reported in cancer patients receiving bisphosphonates.1 12 13 14 Most patients were receiving concurrent chemotherapy and corticosteroids1 13 14 and the majority of cases were associated with dental procedures (e.g., tooth extraction).1 12 13 14

A dental examination with appropriate preventive dentistry recommended prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids, poor oral hygiene).1 12 13 Avoid invasive dental procedures if possible during therapy in such patients.1 13

Severe and occasionally incapacitating bone, joint, and/or muscle pain reported infrequently with bisphosphonate therapy.1 Time to onset of symptoms varied from 1 day to years (mean onset about 3 months) after treatment initiation.1 Such pain generally improves following discontinuance of the drug, but may recur upon subsequent rechallenge.1

Atypical (subtrochanteric or diaphyseal) femur fractures reported rarely with long-term use (>3 years) of bisphosphonates, mostly in patients receiving these drugs for osteoporosis.17 30 32 33 Often occurs with minimal or no trauma, and may be bilateral.17 29 30 32 36 Causality not established; atypical fractures also occur in osteoporotic patients not receiving bisphosphonates.17 30 31 32 33 Risk may be increased with concomitant use of glucocorticoid, estrogen, and proton-pump inhibitor therapy.17 32 34 35 37

Evaluate patients who present with new thigh or groin pain for possibility of an atypical femoral fracture; include assessment of the contralateral limb.17 29 30 32 Consider interruption of bisphosphonate therapy in patients with manifestations of possible femoral fracture; weigh risks versus benefits of continued treatment.17 29 Discontinue if a femoral shaft fracture is confirmed.30 31 32

Atrial Fibrillation

Although data are conflicting, possible increased risk of atrial fibrillation with use of bisphosphonates.21 22 23 FDA analysis of data from long-term (6 months to 3 years) controlled trials identified a higher rate of atrial fibrillation in patients receiving bisphosphonates (alendronate, ibandronate, risedronate, or zoledronic acid) versus placebo; however, only a few events reported in each study.23 FDA is continuing to monitor this safety concern.23

Hematologic Effects

Possible anemia; monitor hematocrit and hemoglobin regularly throughout treatment.1

Respiratory Effects

Possible bronchoconstriction in aspirin-sensitive asthmatic patients.1 Use with caution in such patients.1

Formulation Considerations

Patients receiving Zometa should not receive Reclast or vice versa since both preparations contain the same active ingredient.1 17

Specific Populations

Pregnancy

Category D.1 17 (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Not known if zoledronic acid is distributed into milk; discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1 Because of long-term retention in bone, use recommended only if the potential benefit from the drug outweighs the possible risk.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1

Possible age-related impaired renal function.1 Careful renal function monitoring recommended.1

Renal Impairment

Possible renal toxicity.1 17 (See Renal Effects under Cautions.)

Use in patients with hypercalcemia of malignancy and severe renal impairment only after consideration of other treatment options.1 3 Carefully weigh the possible benefits and risks of therapy.1 3 Use not recommended in patients with bone metastases and severe renal impairment.1 3

Reclast contraindicated in patients with osteoporosis or Paget’s disease of bone who have a Clcr <35 mL/minute or in those with evidence of acute renal impairment; use with caution in those with chronic renal impairment.17

Common Adverse Effects

Patients with hypercalcemia of malignancy: Fever,1 2 3 5 nausea,1 2 3 5 constipation,1 2 3 5 anemia,1 2 3 5 dyspnea,1 2 3 5 diarrhea,1 2 3 progression of cancer,1 3 abdominal pain,1 2 3 insomnia,1 2 3 vomiting,1 2 3 urinary tract infection,1 3 anxiety,1 hypophosphatemia,1 confusion,1 2 3 5 agitation,1 moniliasis,1 hypokalemia,1 2 3 5 skeletal pain,1 3 cough,1 hypotension,1 hypomagnesemia.1

Patients with bone metastases of solid tumors and osteolytic lesions of multiple myeloma: Nausea,1 3 5 7 fatigue,1 3 7 anemia,1 3 5 7 vomiting,1 3 7 fever,1 3 5 7 constipation,1 3 5 7 dyspnea,1 3 5 7 diarrhea,1 3 7 myalgia,1 cough,1 7 edema of the lower extremities,1 7 arthralgia,1 3 7 headache,1 3 7 dizziness,1 3 weight loss,1 3 7 paresthesia,1 3 depression,1 3 abdominal pain,1 3 dehydration,1 3 limb pain,1 decreased appetite,1 neutropenia,1 3 urinary tract infection,1 3 hypoesthesia,1 3 anxiety,1 alopecia,1 7 dermatitis,1 3 rigors,1 3 thrombocytopenia,3 dyspepsia,1 upper respiratory tract infection.1

Postmenopausal women with osteoporosis: Arthralgia,17 21 fever,17 21 headache,17 21 hypertension,17 myalgia,17 21 extremity pain,17 flu-like illness,17 21 dizziness,17 shoulder pain,17 diarrhea,17 bone pain,17 fatigue,17 chills,17 asthenia.17

Postmenopausal women with osteopenia: Headache, dizziness, hypoesthesia, hypertension, nausea, diarrhea, vomiting, dyspepsia, abdominal pain, constipation, arthralgia, myalgia, back pain, extremity pain, muscle spasms, musculoskeletal pain, bone pain, neck pain, generalized pain, pyrexia, chills, fatigue, asthenia, peripheral edema, noncardiac chest pain.17

Patients with corticosteroid-induced osteoporosis: Adverse effects generally similar to those reported in women with postmenopausal osteoporosis.17 Common adverse effects not reported or reported more frequently than in postmenopausal osteoporosis patients include abdominal pain, musculoskeletal pain, back pain, bone pain, extremity pain, nausea, and dyspepsia.17

Men with osteoporosis: Myalgia,17 fatigue,17 headache,17 musculoskeletal pain,17 pain (unspecified),17 chills,17 flu-like illness,17 abdominal pain,17 malaise,17 dyspnea.17

Patients with Paget’s disease of bone: Headache,17 nausea,17 dizziness,17 arthralgia,17 bone pain,17 influenza/flu-like illness,17 fever,17 fatigue,17 rigors,17 myalgia,17 diarrhea,17 constipation, lethargy,17 dypsnea,17 dyspepsia,17 pain.17

Interactions for Zometa

Does not inhibit CYP isoenzymes.1

Drugs Eliminated by Renal Excretion

Potential pharmacokinetic interaction (increased exposure of concomitant drugs eliminated renally).17 Consider more frequent renal function monitoring in patients at high risk of renal impairment.17

Nephrotoxic Agents

Potential pharmacologic interaction (increased risk of renal toxicity).1 Use concomitantly with caution.1 (See Renal Effects under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

Potential for additive effect in lowering serum calcium concentrations1

Use caution1 17

Digoxin

Potential increased exposure of digoxin17

Consider more frequent renal function monitoring in patients at high risk of renal impairment17

Loop diuretics

Increased risk of hypocalcemia1

Use caution1

Thalidomide

No substantial change in pharmacokinetics of zoledronic acid 1

Dosage adjustments not necessary1

Zometa Pharmacokinetics

Absorption

Onset

Hypercalcemia of malignancy: Normocalcemia usually is apparent within 7–10 days.1 2 3

Duration

Hypercalcemia of malignancy: Median time to recurrence (time to last corrected serum calcium concentration of <11.6 mg/dL) was 30 days.1

Prostate cancer: Bone-related complications not observed within 10.5 months of therapy.1

Bone metastases of breast cancer and osteolytic lesions of multiple myeloma: Median time to first bone-related complication was 373 days.1

Bone metastases of solid tumors other than breast or prostate cancer: Median time to the first bone-related complication was 230 days.1

Special Populations

In adults with mild or moderate renal impairment, the AUC is increased 15 or 43%, respectively, compared with patients with normal renal function.1

Distribution

Extent

Distributes rapidly to skeletal tissues.1 Subsequently, the drug is released systemically via bone turnover.1 Not known whether distributed into breast milk.1

Plasma Protein Binding

Approximately 22%.1

Elimination

Metabolism

No evidence of metabolism.1

Elimination Route

In patients with cancer and bone metastases, excreted in urine (39% within 24 hours) as unchanged drug.1

Half-life

Terminal half-life is 146 hours.1

Special Populations

Pharmacokinetics not evaluated in patients with hepatic impairment and in pediatric patients.1

Pharmacokinetics not affected by age or race in patients with cancer and bone metastases.1

Stability

Storage

Parenteral

Solution for Injection

25°C (may be exposed to 15–30°C).1 Following dilution, 2–8°C; use within 24 hours.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Do not admix with other agents.1

Solution Compatibility1

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Incompatible

Ringer’s injection, lactated

Actions

  • Incorporates into bone and selectively inhibits osteoclast-mediated bone resorption.1 4 5

  • Inhibits increased osteoclastic activity and skeletal calcium release induced by tumors.1

  • Decreases serum calcium and phosphorus and increases urinary calcium and phosphorus excretion in patients with hypercalcemia of malignancy.1

Advice to Patients

  • Importance of calcium and vitamin D supplementation for maintenance of serum calcium concentrations in patients with Paget’s disease of bone, multiple myeloma and bone metastasis of solid tumors, or osteoporosis.1 17 Importance of contacting a clinician promptly if symptoms of hypocalcemia (e.g., numbness or tingling feeling [especially in or around the mouth], muscle spasms) occur.17

  • Importance of informing a clinician if severe bone pain, joint pain, muscular pain, or jaw disease develops.20 25

  • Importance of informing a clinician if new thigh or groin pain develops.30

  • Importance of informing patients that Reclast should not be used in patients with severe renal impairment.17

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 3 Advise women of childbearing potential to avoid pregnancy.1 If pregnant, apprise of potential fetal hazard.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant conditions (e.g., kidney disease, aspirin sensitivity).1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Zoledronic Acid

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, concentrate, for IV infusion

4 mg (of anhydrous zoledronic acid) per 5 mL

Zometa

Novartis

For injection, for IV infusion

0.04 mg (of anhydrous zoledronic acid) per mL

Zometa

Novartis

0.05 mg (of anhydrous zoledronic acid) per mL

Reclast

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Reclast 5MG/100ML Solution (NOVARTIS): 100/$1,140.02 or 300/$3,289.87

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 14, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Novartis. Zometa (zoledronic acid) injection prescribing information. East Hanover, NJ; 2011 Jun.

2. Major P, Lortholary A, Han J 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; 19:558-67. [IDIS 460631] [PubMed 11208851]

3. Novartis Pharmaceuticals, East Hanover, NJ; Personal communication.

4. Brown DL, Robbins R. Developments in the therapeutic applications of bisphosphonates. J Clin Pharmacol. 1999; 39:651-60. [IDIS 430233] [PubMed 10392318]

5. Cheer SM, Noble S. Zoledronic acid. Drugs. 2001; 61:799-805. [PubMed 11398911]

6. Anon. Zoledronate (Zometa). Med Lett Drugs Ther. 2001; 43:110-11. [PubMed 11740412]

7. Rosen LS, Gordon D, Kaminski M 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. [PubMed 11693896]

8. Green JR. Chemical and biological prerequisites for novel bisphosphonate molecules: Results of comparative preclinical studies. Semin Oncol. 2001; 28(Suppl. 6):4-10 [PubMed 11346859]

9. Plosker GL, Goa KL. Clodronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs. 1994; 47:945-82. [PubMed 7521833]

10. Coukell AJ, Markham A. Pamidronate. A review of its use in the management of osteolytic bone metastases, tumor-induced hypercalcaemia and Paget’s disease of bone. Drugs Aging. 1998; 12:149-68. [PubMed 9509293]

11. Bone HG, Santora AC. Ten years of alendronate treatment for osteoporosis in postmenopausal women. N Engl J Med. 2004; 351:191-2.

12. Ruggiero SL, Mehrotra B, Rosenberg TJ et al. Osteonecrosis of the jaw associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004; 62:527-34. [IDIS 518769] [PubMed 15122554]

13. Hohneker JA. Dear doctor letter regarding osteonecrosis of the jaw in patients with cancer receiving bisphophonates. East Hanover, NJ: Novartis; 2004 September 24.

14. Ruggiero SL, Mehrotra B. Ten years of alendronate treatment for osteoporosis in postmenopausal women. N Engl J Med. 2004; 351:191.

15. Hohneker JA. Dear dental professional letter: important drug precautions for dental health professional with patients being treated for cancer. East Hanover, NJ: Novartis; 2005 May 5. From FDA website.

16. Food and Drug Administration. Oncologic Drugs Advisory Committee meeting. Expert panel recommendation for the prevention, diagnosis, and treatment of osteonecrosis of the jaw. Bethesda, MD; Mar. 4, 2005. From FDA website.

17. Novartis. Zoledronic acid (Reclast) injection solution for IV infusion prescribing information. East Hanover, NJ. 2011 Aug.

18. Procter & Gamble Pharmaceuticals. Actonel (risedronate sodium) tablets prescribing information. Cincinnati, OH; 2008 Apr.

19. Center for Drug Evaluation and Research, Food and Drug Administration. FDA Alert: Information on bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa). 2008 Jan 7. Available from FDA website. Accessed 2008 Oct 28.

20. Wysowski DK, Chang JT. Alendronate and risedronate: reports of severe bone, joint, and muscle pain. Arch Intern Med. 2005; 165:346-7. [PubMed 15710802]

21. Black DM, Delmas PD, Eastell R et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007; 356:1809-22. [PubMed 17476007]

22. Cummings SR, Schwartz AV, Black DM. Alendronate and atrial fibrillation. N Engl J Med. 2007; 356:1895-6. [PubMed 17476024]

23. Center for Drug Evaluation and Research, Food and Drug Administration. Update of safety review follow-up to the October 1, 2007 early communication about the ongoing safety review of bisphosphonates. Bisphosphonates: alendronate (Fosamax, Fosamax plus D) etidronate (Didronel), ibandronate (Boniva), pamidronate (Aredia), risedronate (Actonel, Actonel w/calcium), tiludronate (Skelid), and zoledronic acid (Reclast, Zometa). 2008 Nov 12. Available at FDA website. Accessed 2008 Nov 21.

24. Dawson-Hughes B and National Osteoporosis Foundation Guide Committee. Clinician’s guide to prevention and treatment of osteoporosis. 2008. Available from website. Accessed 2008 Dec 2.

25. Procter & Gamble Pharmaceuticals. Actonel (risedronate sodium) tablets patient information. Cincinnati, OH; 2008 Apr.

26. Eidtmann H, Bundred NJ, DeBoer R et al. The effect of zoledronic acid on aromatase inhibitor associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36 months follow up of ZO-FAST. Oral presentation at Annual San Antonio Breast Cancer Symposium. San Antonio, TX: 2008 Dec 12. Accessed from website on 12/15/2008.

27. Zoledronic Acid Final Determination. Published May 2008. From AHFS website.

28. Gnant M, Mlineritsch B, Luschin-Ebengreuth G et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density study. Lancet Oncol. 2008; 9:840-49. [PubMed 18718815]

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