Zoledronic Acid

ZOLEDRONIC ACID- zoledronic acid solution
Akorn

1 INDICATIONS AND USAGE

1.5 Paget’s Disease of Bone

Zoledronic acid injection is indicated for treatment of Paget’s disease of bone in men and women. Treatment is indicated in patients with Paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see Clinical Studies (14.5) ].

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

Zoledronic acid injection must be administered as an intravenous infusion over no less than 15 minutes.

  • Patients must be appropriately hydrated prior to administration of zoledronic acid injection [see Warnings and Precautions (5.3)].
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
  • Intravenous infusion should be followed by a 10 mL normal saline flush of the intravenous line.
  • Administration of acetaminophen following zoledronic acid injection administration may reduce the incidence of acute-phase reaction symptoms.

Caution: After removing the overwrap check for minute leaks by squeezing the inner bag firmly. If leaks are found, discard container as sterility may be compromised. Use only if solution is clear and the container is undamaged.

2.6 Treatment of Paget’s Disease of Bone

The recommended dose is a 5 mg infusion. The infusion time must not be less than 15 minutes given over a constant infusion rate.

Re-treatment of Paget’s Disease

After a single treatment with zoledronic acid injection in Paget’s disease an extended remission period is observed. Specific re-treatment data are not available. However, re-treatment with zoledronic acid injection may be considered in patients who have relapsed, based on increases in serum alkaline phosphatase, or in those patients who failed to achieve normalization of their serum alkaline phosphatase, or in those patients with symptoms, as dictated by medical practice.

2.7 Laboratory Testing and Oral Examination Prior to Administration

  • Prior to administration of each dose of zoledronic acid injection, obtain a serum creatinine and creatinine clearance should be calculated based on actual body weight using Cockcroft-Gault formula before each zoledronic acid injection dose. Zoledronic acid injection is contraindicated in patients with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment. A 5 mg dose of zoledronic acid injection administered intravenously is recommended for patients with creatinine clearance greater than or equal to 35 mL/min. There are no safety or efficacy data to support the adjustment of the zoledronic acid injection dose based on baseline renal function. Therefore, no dose adjustment is required in patients with CrCl greater than or equal to 35 mL/min [see Contraindications (4), Warnings and Precautions (5.3)].
  • A routine oral examination should be performed by the prescriber prior to initiation of zoledronic acid injection treatment [see Warnings and Precautions (5.4) ].

2.8 Calcium and Vitamin D Supplementation

  • Instruct patients being treated for Paget’s disease of bone on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels, and on the symptoms of hypocalcemia. All patients should take 1,500 mg elemental calcium daily in divided doses (750 mg two times a day, or 500 mg three times a day) and 800 international units vitamin D daily, particularly in the 2 weeks following zoledronic acid injection administration [see Warnings and Precautions (5.2) ].

2.9 Method of Administration

The zoledronic acid injection infusion time must not be less than 15 minutes given over a constant infusion rate.

The i.v. infusion should be followed by a 10 mL normal saline flush of the intravenous line.

Zoledronic acid injection solution for infusion must not be allowed to come in contact with any calcium or other divalent cation-containing solutions, and should be administered as a single intravenous solution through a separate vented infusion line.

If refrigerated, allow the refrigerated solution to reach room temperature before administration. After opening, the solution is stable for 24 hours at 2° to 8°C (36° to 46°F) [see How Supplied/Storage and Handling (16) ].

3 DOSAGE FORMS AND STRENGTHS

5 mg in a 100 mL ready to infuse solution.

4 CONTRAINDICATIONS

Zoledronic acid injection is contraindicated in patients with the following conditions:

  • Hypocalcemia [see Warnings and Precautions (5.2) ]
  • Creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment due to an increased risk of renal failure [see Warnings and Precautions (5.3) ]
  • Known hypersensitivity to zoledronic acid or any components of zoledronic acid injection. Hypersensitivity reactions including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see Adverse Reactions (6.2) ].

5 WARNINGS AND PRECAUTIONS

5.1 Drug Products with Same Active Ingredient

Zoledronic acid injection contains the same active ingredient found in Zometa, used for oncology indications, and a patient being treated with Zometa should not be treated with zoledronic acid injection.

5.2 Hypocalcemia and Mineral Metabolism

Pre-existing hypocalcemia and disturbances of mineral metabolism (e.g., hypoparathyroidism, thyroid surgery, parathyroid surgery; malabsorption syndromes, excision of small intestine) must be effectively treated before initiating therapy with zoledronic acid injection. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) is highly recommended for these patients [see Contraindications (4) ].

Hypocalcemia following zoledronic acid injection administration is a significant risk in Paget’s disease. All patients should be instructed about the symptoms of hypocalcemia and the importance of calcium and vitamin D supplementation in maintaining serum calcium levels [see Dosage and Administration (2.8), Adverse Reactions (6.1), Patient Counseling Information (17)].

5.3 Renal Impairment

A single dose of zoledronic acid injection should not exceed 5 mg and the duration of infusion should be no less than 15 minutes [see Dosage and Administration (2) ].

Zoledronic acid injection is contraindicated in patients with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment [see Contraindications (4) ]. If history or physical signs suggest dehydration, zoledronic acid injection therapy should be withheld until normovolemic status has been achieved [see Adverse Reactions (6.2) ].

Zoledronic acid injection should be used with caution in patients with chronic renal impairment. Acute renal impairment, including renal failure has been observed following the administration of zoledronic acid, especially in patients with pre-existing renal compromise, advanced age, concomitant nephrotoxic medications, concomitant diuretic therapy, or severe dehydration occurring before or after zoledronic acid injection administration. Acute renal failure (ARF) has been observed in patients after a single administration. Rare reports of hospitalization and/or dialysis or fatal outcome occurred in patients with underlying moderate to severe renal impairment or with any of the risk factors decribed in this section [see Adverse Reactions (6.2) ]. Renal impairment may lead to increased exposure of concomitant medications and/or their metabolites that are primarily renally excreted [see Drug Interactions (7.4) ].

Creatinine clearance should be calculated based on actual body weight using Cockcroft-Gault formula before each zoledronic acid injection dose. Transient increase in serum creatinine may be greater in patients with impaired renal function; interim monitoring of creatinine clearance should be performed in atrisk patients. Elderly patients and those receiving diuretic therapy are at increased risk of acute renal failure. These patients should have their fluid status assessed and be appropriately hydrated prior to administration of zoledronic acid injection. Zoledronic acid injection should be used with caution with other nephrotoxic drugs [see Drug Interactions (7.3) ]. Consider monitoring creatinine clearance in patients at-risk for ARF who are taking concomitant medications that are primarily excreted by the kidney [see Drug Interactions (7.4) ].

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.