Zoledronic Acid 5 mg/100mL Injection, Solution
Other active recalls for Zoledronic Acid (different manufacturers) — 1 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Bisphosphonate class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Great question — it surprised a lot of patients at first. Zoledronic acid binds extremely tightly to bone mineral, so after your infusion, it stays embedded in your bone tissue and...
- Why do I only need this infusion once a year? How can that be enough?
- The most common ones — especially after your first infusion — feel a lot like the flu: fever, muscle aches, joint pain, headache, and chills. These usually show up within the first...
- What side effects should I expect after my infusion?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Zoledronic Acid — tap one for details:
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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UNII 1Q73Q2JULR
Sodium citrate is a salt derived from citric acid. It works as a buffer to maintain the medicine's pH level and may also help improve taste or act as a preservative in the formulation.
2 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.477 | $47.74 / 100 ml |
| Medicaid paysCMS SDUD · 12 mo | $0.7805 | $78.05 / 100 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J3489 | $3.361 / J3489 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Zoledronic Acid 5 mg/100mL 55111-0688-52 | Dr.Reddy's | 100 ml | $0.477 | AP | Availability likely | — |
| Zoledronic Acid 5 mg/100mLthis 63323-0966-00 | Fresenius | 1 vial | $0.477 | AP | Availability likely | — |
| Zoledronic Acid 5 mg/100mL 67457-0619-10 | Mylan | 1 vial | $0.477 | AP | Availability likely | — |
| Zoledronic Acid 5 mg/100mL 71288-0806-51 | Meitheal | 1 bottle | $0.477 | AP | Availability likely | — |
| zoledronic acid .05 mg/mL 25021-0830-82 | Sagent | 100 ml | — | AP | FDA listed | — |
| Zoledronic Acid 5 mg/100mL 43598-0331-11 | Dr.Reddy's | 100 ml | — | AP | FDA listed | — |
| Zoledronic Acid 5 mg/100mL 55150-0283-99 | Eugia | 1 bottle | — | — | FDA listed | — |
| Reclast 5 mg/100mL 66758-0155-46 | Sandoz | 100 ml | — | AP | FDA listed | — |
| Zoledronic Acid 5 mg/100mL 67457-0794-10 | Mylan | 1 pouch | — | AP | FDA listed | — |
| Zoledronic acid 5 mg/100mL 68001-0611-33 | BluePoint | 100 ml | — | AP | FDA listed | — |
| Zoledronic Acid 5 mg/100mL 68083-0135-01 | Gland | 1 vial | — | AP | FDA listed | — |
| Zoledronic acid 5 mg/100mL 68083-0256-01 | Gland | 100 ml | — | AP | FDA listed | — |
| Zoledronic acid 5 mg/100mL 72266-0152-01 | FOSUN | 100 ml | — | AP | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 63323-0966-00 You're viewing this | 1 VIAL, GLASS in 1 CARTON (63323-966-00) / 100 mL in 1 VIAL, GLASS | 2017-02-17 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Zoledronic acid injection is a bisphosphonate indicated for: •Treatment and prevention of postmenopausal osteoporosis (1.1, 1.2) •Treatment to increase bone mass in men with osteoporosis (1.3) •Treatment and prevention of glucocorticoid-induced osteoporosis (1.4) •Treatment of Paget’s disease of bone in men and women (1.5) Limitations of Use Optimal duration of use has not been determined. For patients at low-risk for fracture, consider drug discontinuation after 3 to 5 years of use (1.6)
1.1Treatment of Osteoporosis in Postmenopausal Women Zoledronic acid injection is indicated for treatment of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, diagnosed by bone mineral density (BMD) or prevalent vertebral fracture, zoledronic acid injection reduces the incidence of fractures (hip, vertebral and non-vertebral osteoporosis-related fractures). In patients at high risk of fracture, defined as a recent low-trauma hip fracture, zoledronic acid injection reduces the incidence of new clinical fractures [ see Clinical Studies (14.1) ].
1.2Prevention of Osteoporosis in Postmenopausal Women Zoledronic acid injection is indicated for prevention of osteoporosis in postmenopausal women [ see Clinical Studies (14.2) ].
1.3Osteoporosis in Men Zoledronic acid injection is indicated for treatment to increase bone mass in men with osteoporosis [ see Clinical Studies (14.3) ].
1.4Glucocorticoid-Induced Osteoporosis Zoledronic acid injection is indicated for the treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who are expected to remain on glucocorticoids for at least 12 months [ see Clinical Studies (14.4) ].
1.5Paget'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) ].
1.6Important Limitations of Use The safety and effectiveness of zoledronic acid injection for the treatment of osteoporosis is based on clinical data of three years duration. The optimal duration of use has not been determined. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis.
Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Infusion given intravenously over no less than 15 minutes: Treatment of postmenopausal osteoporosis (2.2); treatment to increase bone mass in men with osteoporosis (2.4): treatment and prevention of glucocorticoid-induced osteoporosis (2.5): 5 mg once a year Prevention of postmenopausal osteoporosis: 5 mg once every 2 years (2.3) Treatment of Paget’s disease of bone: a single 5 mg infusion. Patients should receive 1500 mg elemental calcium and 800 international units vitamin D daily (2.6)
2.1Important 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.
2.2Treatment of Osteoporosis in Postmenopausal Women The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes.
2.3Prevention of Osteoporosis in Postmenopausal Women The recommended regimen is a 5 mg infusion given once every 2 years intravenously over no less than 15 minutes.
2.4Osteoporosis in Men The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes.
2.5Treatment and Prevention of Glucocorticoid-Induced Osteoporosis The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes.
2.6Treatment 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.
2.7Laboratory 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) ].
2.8Calcium 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 1500 mg elemental calcium daily in divided doses (750 mg two times a day, or 500 mg three times a day) and 800 international units vit…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS & STRENGTHS 5 mg in a 100 mL ready to infuse solution. 5 mg in a 100 mL ready-to-infuse solution (3)
⛔ Contraindications ▾
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 Post- Marketing Experience (6.2) ].
Hypocalcemia (4) Patients with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment (4, 5.3) Hypersensitivity to any component of zoledronic acid injection (4, 6.2)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Products Containing Same Active Ingredient: Patients receiving Zometa should not receive zoledronic acid injection (5.1) Hypocalcemia may worsen during treatment . Patients must be adequately supplemented with calcium and vitamin D (5.2) Renal Impairment: A single dose should not exceed 5 mg and the duration of infusion should be no less than 15 minutes. Renal toxicity may be greater in patients with underlying renal impairment or with other risk factors, including advanced age or dehydration.
Monitor creatinine clearance before each dose (2.7, 5.3) Osteonecrosis of the Jaw (ONJ) has been reported. All patients should have a routine oral exam by the prescriber prior to treatment (5.4) Atypical Femur Fractures have been reported. Patients with thigh or groin pain should be evaluated to rule out a femoral fracture (5.5) Pregnancy: Zoledronic acid injection can cause fetal harm.
Women of childbearing potential should be advised (5.6, 8.1) Severe Bone, Joint, and Muscle Pain may occur. Withhold future doses of zoledronic acid injection if severe symptoms occur (5.7)
5.1Drug 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.
5.2Hypocalcemia 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), Information for Patients (17) ]. All osteoporosis patients should be instructed on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels [ see Dosage and Administration (2.8), Adverse Reactions (6.1), Information for Patients (17) ].
5.3Renal 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 Post-Marketing Experience (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 described in this section [ see Post-Marketing Experience (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 Coc…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most common adverse reactions (greater than 10%) were pyrexia, myalgia, headache, arthralgia, pain in extremity (6.1). Other important adverse reactions were flu-like illness, nausea, vomiting, diarrhea (6.2), and eye inflammation (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Treatment of Osteoporosis in Postmenopausal Women The safety of zoledronic acid injection in the treatment of postmenopausal osteoporosis was assessed in Study 1, a large, randomized, double-blind, placebo-controlled, multinational study of 7736 postmenopausal women aged 65 to 89 years with osteoporosis, diagnosed by bone mineral density or the presence of a prevalent vertebral fracture.
The duration of the trial was three years with 3862 patients exposed to zoledronic acid injection and 3852 patients exposed to placebo administered once annually as a single 5 mg dose in 100 mL solution infused over at least 15 minutes, for a total of three doses. All women received 1000 to 1500 mg of elemental calcium plus 400 to 1200 international units of vitamin D supplementation per day. The incidence of all-cause mortality was similar between groups: 3.4% in the zoledronic acid injection group and 2.9% in the placebo group.
The incidence of serious adverse events was 29.2% in the zoledronic acid injection group and 30.1% in the placebo group. The percentage of patients who withdrew from the study due to adverse events was 5.4% and 4.8% for the zoledronic acid injection and placebo groups, respectively. The safety of zoledronic acid injection in the treatment of osteoporosis patients with a recent (within 90 days) low-trauma hip fracture was assessed in Study 2, a randomized, double-blind, placebo-controlled, multinational endpoint-driven study of 2127 men and women aged 50 to 95 years; 1065 patients were randomized to zoledronic acid injection and 1062 patients were randomized to placebo.
Zoledronic acid injection was administered once annually as a single 5 mg dose in 100 mL solution infused over at least 15 minutes. The study continued until at least 211 patients had a confirmed clinical fracture in the study population who were followed for an average of approximately 2 years on study drug. Vitamin D levels were not routinely measured but a loading dose of vitamin D (50,000 to 125,000 international units orally or IM) was given to patients and they were started on 1000 to 1500 mg of elemental calcium plus 800 to 1200 international units of vitamin D supplementation per day for at least 14 days prior to the study drug infusions.
The incidence of all-cause mortality was 9.6% in the zoledronic acid injection group and 13.3% in the placebo group. The incidence of serious adverse events was 38.3% in the zoledronic acid injection group and 41.3% in the placebo group. The percentage of patients who withdrew from the study due to adverse events was 5.3% and 4.7% for the zoledronic acid injection and placebo groups, respectively.
Adverse reactions reported in at least 2% of patients with osteoporosis and more frequently in the zoledronic acid injection-treated patients than placebo-treated patients in either osteoporosis trial are shown below in Table 1. Table 1. Adverse Reactions Occurring in greater than or equal to 2.0% of Patients with Osteoporosis and More Frequently than in Placebo-Treated Patients System Organ Class Study 1 Study 2 5 mg IV zoledronic acid injection once per year % (N=3862) Placebo once per year % (N=3852) 5 mg IV zoledronic acid injection once per year % (N=1054) Placebo once per year % (N=1057) Blood and the Lymphatic System Disorders…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No in vivo drug interaction studies have been performed for zoledronic acid injection. In vitro and ex vivo studies showed low affinity of zoledronic acid for the cellular components of human blood. In vitro mean zoledronic acid protein binding in human plasma ranged from 28% at 200 ng/mL to 53% at 50 ng/mL.
In vivo studies showed that zoledronic acid is not metabolized, and is excreted into the urine as the intact drug. Aminoglycosides: May lower serum calcium for prolonged periods (7.1) Loop diuretics: May increase risk of hypocalcemia (7.2) Nephrotoxic drugs: Use with caution (7.3) Drugs primarily excreted by the kidney: Exposure may be increased with renal impairment. Monitor serum creatinine in patients at risk (7.4)
7.1Aminoglycosides Caution is advised when bisphosphonates, including zoledronic acid, are administered with aminoglycosides, since these agents may have an additive effect to lower serum calcium level for prolonged periods. This effect has not been reported in zoledronic acid clinical trials.
7.2Loop Diuretics Caution should also be exercised when zoledronic acid injection is used in combination with loop diuretics due to an increased risk of hypocalcemia.
7.3Nephrotoxic Drugs Caution is indicated when zoledronic acid injection is used with other potentially nephrotoxic drugs such as nonsteroidal anti-inflammatory drugs.
7.4Drugs Primarily Excreted by the Kidney Renal impairment has been observed following the administration of zoledronic acid in patients with pre-existing renal compromise or other risk factors [ see Warnings and Precautions (5.3) ]. In patients with renal impairment, the exposure to concomitant medications that are primarily renally excreted (e.g., digoxin) may increase. Consider monitoring serum creatinine in patients at risk for renal impairment who are taking concomitant medications that are primarily excreted by the kidney.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Nursing Mothers: Zoledronic acid injection should not be given to nursing women (8.3) Pediatric Use: Not indicated for use in pediatric patients (8.4) Geriatric Use: Special care to monitor renal function (8.5)
8.1Pregnancy Pregnancy Category D [ see Warnings and Precautions (5.6) ]. ZOLEDRONIC ACID INJECTION SHOULD NOT BE USED DURING PREGNANCY . If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving zoledronic acid injection. Bisphosphonates are incorporated into the bone matrix, from where they are gradually released over periods of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the total dose and duration of bisphosphonate use.
Although there are no data on fetal risk in humans, bisphosphonates do cause fetal harm in animals, and animal data suggest that uptake of bisphosphonates into fetal bone is greater than into maternal bone. Therefore, there is a theoretical risk of fetal harm (e.g., skeletal and other abnormalities) if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception space, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on this risk has not been established.
In female rats given daily subcutaneous doses of zoledronic acid beginning 15 days before mating and continuing through gestation, the number of stillbirths was increased and survival of neonates was decreased at approximately greater than or equal to 0.3 times the anticipated human systemic exposure following a 5 mg intravenous dose (based on an AUC comparison). Adverse maternal effects were observed in all dose groups at greater than or equal to 0.1 times the human systemic exposure following a 5 mg intravenous dose (based on an AUC comparison) and included dystocia and periparturient mortality in pregnant rats allowed to deliver.
Maternal mortality was considered related to drug-induced inhibition of skeletal calcium mobilization, resulting in periparturient hypocalcemia. This appears to be a bisphosphonate class effect. In pregnant rats given daily subcutaneous dose of zoledronic acid during gestation, adverse fetal effects were observed at about 2 and 4 times human systemic exposure following a 5 mg intravenous dose (based on an AUC comparison).
These adverse effects included increases in pre- and post-implantation losses, decreases in viable fetuses, and fetal skeletal, visceral, and external malformations. In pregnant rabbits given daily subcutaneous doses of zoledronic acid during gestation at doses less than or equal to 0.4 times the anticipated human systemic exposure following a 5 mg intravenous dose (based on a mg/m 2 comparison) no adverse fetal effects were observed. Maternal mortality and abortion occurred in all treatment groups (at doses greater than or equal to 0.04 times the human 5 mg intravenous dose, based on a mg/m 2 comparison).
Adverse maternal effects were associated with, and may have been caused by, drug-induced hypocalcemia [ see Nonclinical Toxicology (13.3) ].
8.3Nursing Mothers It is not known whether zoledronic acid injection is excreted in human milk. Because many drugs are excreted in human milk, and because zoledronic acid injection binds to bone long-term, zoledronic acid injection should not be administered to a nursing woman.
8.4Pediatric Use Zoledronic acid injection is not indicated for use in children. The safety and effectiveness of zoledronic acid was studied in a one-year active controlled trial of 152 pediatric subjects (74 receiving zoledronic acid). The enrolled population was subjects with severe osteogenesis imperfecta, aged 1…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category D [ see Warnings and Precautions (5.6) ]. ZOLEDRONIC ACID INJECTION SHOULD NOT BE USED DURING PREGNANCY . If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving zoledronic acid injection. Bisphosphonates are incorporated into the bone matrix, from where they are gradually released over periods of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the total dose and duration of bisphosphonate use.
Although there are no data on fetal risk in humans, bisphosphonates do cause fetal harm in animals, and animal data suggest that uptake of bisphosphonates into fetal bone is greater than into maternal bone. Therefore, there is a theoretical risk of fetal harm (e.g., skeletal and other abnormalities) if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception space, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on this risk has not been established.
In female rats given daily subcutaneous doses of zoledronic acid beginning 15 days before mating and continuing through gestation, the number of stillbirths was increased and survival of neonates was decreased at approximately greater than or equal to 0.3 times the anticipated human systemic exposure following a 5 mg intravenous dose (based on an AUC comparison). Adverse maternal effects were observed in all dose groups at greater than or equal to 0.1 times the human systemic exposure following a 5 mg intravenous dose (based on an AUC comparison) and included dystocia and periparturient mortality in pregnant rats allowed to deliver.
Maternal mortality was considered related to drug-induced inhibition of skeletal calcium mobilization, resulting in periparturient hypocalcemia. This appears to be a bisphosphonate class effect. In pregnant rats given daily subcutaneous dose of zoledronic acid during gestation, adverse fetal effects were observed at about 2 and 4 times human systemic exposure following a 5 mg intravenous dose (based on an AUC comparison).
These adverse effects included increases in pre- and post-implantation losses, decreases in viable fetuses, and fetal skeletal, visceral, and external malformations. In pregnant rabbits given daily subcutaneous doses of zoledronic acid during gestation at doses less than or equal to 0.4 times the anticipated human systemic exposure following a 5 mg intravenous dose (based on a mg/m 2 comparison) no adverse fetal effects were observed. Maternal mortality and abortion occurred in all treatment groups (at doses greater than or equal to 0.04 times the human 5 mg intravenous dose, based on a mg/m 2 comparison).
Adverse maternal effects were associated with, and may have been caused by, drug-induced hypocalcemia [ see Nonclinical Toxicology (13.3) ].
🧒 Pediatric Use ▾
8.4Pediatric Use Zoledronic acid injection is not indicated for use in children. The safety and effectiveness of zoledronic acid was studied in a one-year active controlled trial of 152 pediatric subjects (74 receiving zoledronic acid). The enrolled population was subjects with severe osteogenesis imperfecta, aged 1 to 17 years, 55% male, 84% Caucasian, with a mean lumbar spine BMD of 0.431 gm/cm 2 , which is 2.7 standard deviations below the mean for age-matched controls (BMD Z-score of -2.7).
At one year, increases in BMD were observed in the zoledronic acid treatment group. However, changes in BMD in individual patients with severe osteogenesis imperfecta did not necessarily correlate with the risk for fracture or the incidence or severity of chronic bone pain. The adverse events observed with zoledronic acid use in children did not raise any new safety findings beyond those previously seen in adults treated for Paget’s disease of bone and treatment of osteoporosis including osteonecrosis of the jaw (ONJ) and renal impairment.
However, adverse reactions seen more commonly in pediatric patients included pyrexia (61%), arthralgia (26%), hypocalcemia (22%) and headache (22%). These reactions, excluding arthralgia, occurred most frequently within three days after the first infusion and became less common with repeat dosing. No cases of ONJ or renal impairment were observed in this study.
Because of long-term retention in bone, zoledronic acid injection should only be used in children if the potential benefit outweighs the potential risk. Plasma zoledronic acid concentration data was obtained from 10 patients with severe osteogenesis imperfecta (4 in the age group of 3 to 8 years and 6 in the age group of 9 to 17 years) infused with 0.05 mg/kg dose over 30 minutes. Mean C max and AUC (0-last) was 167 ng/mL and 220 ng.h/mL respectively.
The plasma concentration time profile of zoledronic acid in pediatric patients represent a multi-exponential decline, as observed in adult cancer patients at an approximately equivalent mg/kg dose.
🧓 Geriatric Use ▾
8.5Geriatric Use The combined osteoporosis trials included 4863 zoledronic acid injection-treated patients who were at least 65 years of age, while 2101 patients were at least 75 years old. No overall differences in efficacy or safety were observed between patients under 75 years of age with those at least 75 years of age, except that the acute phase reactions occurred less frequently in the older patients. Of the patients receiving zoledronic acid injection in the osteoporosis study in men, glucocorticoid-induced osteoporosis, and Paget’s disease studies, 83, 116, and 132 patients, respectively were 65 years of age or over, while 24, 29, and 68 patients, respectively were at least 75 years of age.
However, because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function.
🆘 Overdosage ▾
10 OVERDOSAGE Clinical experience with acute overdosage of zoledronic acid injection solution for intravenous infusion is limited. Patients who have received doses higher than those recommended should be carefully monitored. Overdosage may cause clinically significant renal impairment, hypocalcemia, hypophosphatemia, and hypomagnesemia.
Clinically relevant reductions in serum levels of calcium, phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate, and magnesium sulfate, respectively. Single doses of zoledronic acid injection should not exceed 5 mg and the duration of the intravenous infusion should be no less than 15 minutes [ see Dosage and Administration (2) ].
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Zoledronic acid injection is a bisphosphonate and acts primarily on bone. It is an inhibitor of osteoclast-mediated bone resorption. The selective action of bisphosphonates on bone is based on their high affinity for mineralized bone.
Intravenously administered zoledronic acid rapidly partitions to bone and localizes preferentially at sites of high bone turnover. The main molecular target of zoledronic acid in the osteoclast is the enzyme farnesyl pyrophosphate synthase. The relatively long duration of action of zoledronic acid is attributable to its high binding affinity to bone mineral.
12.2Pharmacodynamics In the osteoporosis treatment trial, the effect of zoledronic acid injection treatment on markers of bone resorption (serum beta-C-telopeptides [b-CTx]) and bone formation (bone specific alkaline phosphatase [BSAP], serum N-terminal propeptide of type I collagen [P1NP]) was evaluated in patients (subsets ranging from 517 to 1246 patients) at periodic intervals. Treatment with a 5 mg annual dose of zoledronic acid injection reduces bone turnover markers to the pre-menopausal range with an approximate 55% reduction in b-CTx, a 29% reduction in BSAP and a 52% reduction in P1NP over 36 months.
There was no progressive reduction of bone turnover markers with repeated annual dosing.
12.3Pharmacokinetics Pharmacokinetic data in patients with osteoporosis and Paget's disease of bone are not available. D istribution: Single or multiple (q 28 days) 5-minute or 15-minute infusions of 2, 4, 8 or 16 mg zoledronic acid were given to 64 patients with cancer and bone metastases. The post-infusion decline of zoledronic acid concentrations in plasma was consistent with a triphasic process showing a rapid decrease from peak concentrations at end-of-infusion to less than 1% of C max 24 hours post infusion with population half-lives of t 1/2α 0.24 hour and t 1/2β 1.87 hours for the early disposition phases of the drug.
The terminal elimination phase of zoledronic acid was prolonged, with very low concentrations in plasma between Days 2 and 28 post infusion, and a terminal elimination half-life t 1/2γ of 146 hours. The area under the plasma concentration versus time curve (AUC 0 to 24h ) of zoledronic acid was dose proportional from 2 to 16 mg. The accumulation of zoledronic acid measured over three cycles was low, with mean AUC 0 to 24h ratios for cycles 2 and 3 versus 1 of 1.13 ± 0.30 and 1.16 ± 0.36, respectively.
In vitro and ex vivo studies showed low affinity of zoledronic acid for the cellular components of human blood. In vitro mean zoledronic acid protein binding in human plasma ranged from 28% at 200 ng/mL to 53% at 50 ng/mL. Metabolism: Zoledronic acid does not inhibit human P450 enzymes in vitro .
Zoledronic acid does not undergo biotransformation in vivo . In animal studies, less than 3% of the administered intravenous dose was found in the feces, with the balance either recovered in the urine or taken up by bone, indicating that the drug is eliminated intact via the kidney. Following an intravenous dose of 20 nCi 14 C-zoledronic acid in a patient with cancer and bone metastases, only a single radioactive species with chromatographic properties identical to those of parent drug was recovered in urine, which suggests that zoledronic acid is not metabolized.
Excretion: In 64 patients with cancer and bone metastases on average (± SD) 39 ± 16% of the administered zoledronic acid dose was recovered in the urine within 24 hours, with only trace amounts of drug found in urine post Day 2. The cumulative percent of drug excreted in the urine over 0 to 24 hours was independent of dose. The balance of drug not recovered in urine over 0 to 24 hours, representing drug presumably bound to bone, is slowly released back into the systemic circulation, giving rise to the observed prolonged low plasma concentrations.
The 0 to 24 hour renal clearance of zoledronic acid was 3.7 ±
2.0L/h. Zoledronic…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Zoledronic acid injection is a bisphosphonate and acts primarily on bone. It is an inhibitor of osteoclast-mediated bone resorption. The selective action of bisphosphonates on bone is based on their high affinity for mineralized bone.
Intravenously administered zoledronic acid rapidly partitions to bone and localizes preferentially at sites of high bone turnover. The main molecular target of zoledronic acid in the osteoclast is the enzyme farnesyl pyrophosphate synthase. The relatively long duration of action of zoledronic acid is attributable to its high binding affinity to bone mineral.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Zoledronic acid injection, 5 mg/100 mL is supplied as follows: Product Code Unit of Sale Strength 966100 NDC 63323-966-00 Individually packaged 5 mg/100 mL in a clear glass Single Dose Vial Handling After opening the solution, it is stable for 24 hours at 2 to 8°C (36 to 46°F). If refrigerated, allow the refrigerated solution to reach room temperature before administration. Storage Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Zoledronic acid injection contains zoledronic acid, a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. Zoledronic acid is designated chemically as (1-Hydroxy-2-imidazol-1-yl-phosphonoethyl) phosphonic acid monohydrate and its structural formula is: Zoledronic acid monohydrate is a white crystalline powder. Its molecular formula is C 5 H 10 N 2 O 7 P 2 • H 2 O and a molar mass of 290.1 g/Mol.
Zoledronic acid is sparingly soluble in 0.1N sodium hydroxide solution and slightly soluble in water. The pH of the zoledronic acid injection solution for infusion is approximately 6.0 to 7.0. Zoledronic acid injection is available as a sterile solution in vials for intravenous infusion.
One vial with 100 mL solution contains 5.330 mg of zoledronic acid monohydrate, equivalent to 5 mg zoledronic acid on an anhydrous basis. Inactive Ingredients : 4950 mg of mannitol, USP; and 30 mg of sodium citrate, USP. zoledronic01
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-Approved Medication Guide Information for Patients Patients should be made aware that zoledronic acid injection contains the same active ingredient (zoledronic acid) found in Zometa ® , and that patients being treated with Zometa should not be treated with zoledronic acid injection. Zoledronic acid injection is contraindicated in patients with creatinine clearance less than 35 mL/min [ see Contraindications (4) ]. Before being given zoledronic acid injection, patients should tell their doctor if they have kidney problems and what medications they are taking.
Zoledronic acid injection should not be given if the patient is pregnant or plans to become pregnant, or if she is breast-feeding [ see Warnings and Precautions (5.6) ]. There have been reports of bronchoconstriction in aspirin-sensitive patients receiving bisphosphonates, including zoledronic acid injection. Before being given zoledronic acid injection, patients should tell their doctor if they are aspirin-sensitive.
If the patient had surgery to remove some or all of the parathyroid glands in their neck, or had sections of their intestine removed, or are unable to take calcium supplements they should tell their doctor. Zoledronic acid injection is given as an infusion into a vein by a nurse or a doctor, and the infusion time must not be less than 15 minutes. On the day of treatment the patient should eat and drink normally, which includes drinking at least 2 glasses of fluid such as water within a few hours prior to the infusion, as directed by their doctor, before receiving zoledronic acid injection.
After getting zoledronic acid injection it is strongly recommended patients with Paget’s disease take calcium in divided doses (for example, 2 to 4 times a day) for a total of 1500 mg calcium a day to prevent low blood calcium levels. This is especially important for the two weeks after getting zoledronic acid injection [ see Warnings and Precautions (5.2) ]. Adequate calcium and vitamin D intake is important in patients with osteoporosis and the current recommended daily intake of calcium is 1200 mg and vitamin D is 800 international units – 1000 international units daily.
All patients should be instructed on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels. Patients should be aware of the most commonly associated side effects of therapy. Patients may experience one or more side effects that could include: fever, flu-like symptoms, myalgia, arthralgia, and headache.
Most of these side effects occur within the first 3 days following the dose of zoledronic acid injection. They usually resolve within 3 days of onset but may last for up to 7 to 14 days. Patients should consult their physician if they have questions or if these symptoms persist.
The incidence of these symptoms decreased markedly with subsequent doses of zoledronic acid injection. Administration of acetaminophen following zoledronic acid injection administration may reduce the incidence of these symptoms. Physicians should inform their patients that there have been reports of persistent pain and/or a non-healing sore of the mouth or jaw, primarily in patients treated with bisphosphonates for other illnesses.
During treatment with zoledronic acid, patients should be instructed to maintain good oral hygiene and undergo routine dental check-ups. If they experience these symptoms, they should inform their physician or dentist. Severe and occasionally incapacitating bone, joint, and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including zoledronic acid injection.
Consider withholding future zoledronic acid injection treatment if severe symptoms develop. Atypical femur fractures in patients on bisphosphonate therapy have been reported; patients with thigh or groin pain should be evaluated to rule out a femoral fracture. Zometa is a registered trademark of Novartis Pharmaceuticals Corporation.
Manu…
💬 Medication Guide ▾
MEDICATION GUIDE Zoledronic Acid (ZOE-le-DRON-ik AS-id) Injection Read the Medication Guide that comes with zoledronic acid injection before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or treatment.
Talk to your doctor if you have any questions about zoledronic acid injection. What is the most important information I should know about zoledronic acid injection? You should not receive zoledronic acid injection if you are already receiving Zometa.
Both zoledronic acid injection and Zometa contain zoledronic acid. Zoledronic acid injection can cause serious side effects including: 1. Low calcium levels in your blood (hypocalcemia) 2.
Severe kidney problems 3. Severe jaw bone problems (osteonecrosis) 4. Bone, joint or muscle pain 5.
Unusual thigh bone fractures 1. Low calcium levels in your blood (hypocalcemia) . Zoledronic acid injection may lower the calcium levels in your blood.
If you have low blood calcium before you start taking zoledronic acid injection, it may get worse during treatment. Your low blood calcium must be treated before you take zoledronic acid injection. Most people with low blood calcium levels do not have symptoms, but some people may have symptoms.
Call your doctor right away if you have symptoms of low blood calcium such as: Spasms, twitches, or cramps in your muscles Numbness or tingling in your fingers, toes, or around your mouth Your doctor may prescribe calcium and vitamin D to help prevent low calcium levels in your blood, while you take zoledronic acid injection. Take calcium and vitamin D as your doctor tells you to. 2.
Severe kidney problems. Severe kidney problems may happen when you take zoledronic acid injection. Severe kidney problems may lead to hospitalization or kidney dialysis and can be life-threatening.
Your risk of kidney problems is higher if you: already have kidney problems take a diuretic or “water pill” do not have enough water in your body (dehydrated) before or after you receive zoledronic acid injection are of advanced age since the risk increases as you get older take any medicines known to harm your kidneys You should drink at least 2 glasses of fluid within a few hours before receiving zoledronic acid injection to reduce the risk of kidney problems 3. Severe jaw bone problems (osteonecrosis). Severe jaw bone problems may happen when you take zoledronic acid injection.
Your doctor should examine your mouth before you start zoledronic acid injection. Your doctor may tell you to see your dentist before you start zoledronic acid injection. It is important for you to practice good mouth care during treatment with zoledronic acid injection.
4. Unusual thigh bone fractures. Some people have developed unusual fractures in their thigh bone.
Symptoms of a fracture may include new or unusual pain in your hip, groin, or thigh. 5. Possible harm to your unborn baby.
Zoledronic acid injection should not be used if you are pregnant. Tell your doctor right away if you are pregnant or plan to become pregnant. Zoledronic acid injection may harm your unborn baby.
6. Bone, joint, or muscle pain. Some people who take bisphosphonates develop severe bone, joint, or muscle pain.
Call your doctor right away if you have any of these side effects. What is zoledronic acid injection ? Zoledronic acid injection is a prescription medicine used to: Treat or prevent osteoporosis in women after menopause.
Zoledronic acid injection helps reduce the chance of having a hip or spinal fracture (break). Increase bone mass in men with osteoporosis. Treat or prevent osteoporosis in either men or women who will be taking corticosteroid medicines for at least one year.
Treat certain men and women who have Paget’s disease of the bone. It is not known how long zoledronic acid injection works for the treatment and prevention of osteoporosis. You should see your doctor regularly to det…