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Zoledronic Acid 5 mg/100mL Injection, Solution, 100 mL — NDC 43598-331-11 (Billing 43598-0331-11)

by Dr.Reddy's Laboratories Inc · 100 mL in 1 BOTTLE, GLASS

This is a package of 100 mL of Zoledronic Acid 5 mg/100mL Injection, Solution from Dr.Reddy's Laboratories Inc, marketed since Aug 2013 and currently FDA-listed. It is this product's only package size.

NDC 43598-0331-11
🏷️ FDA NDC (as labeled) 43598-331-11 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

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Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 43598-331-11 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
43598 labeler · 331 product · 11 package
Package marketed since
Aug 19, 2013
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
100 mL per package
Barcode (UPC-A, from the NDC)
3 4359833111 9
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 43598-331-11
Product NDC 43598-331
11-digit billing NDC 43598033111
NCPDP billing unit ML — per mL (volume)
RxCUI 705824
UNII 6XC1PAD3KF
Application # ANDA091363
SPL Set ID c8e02635-4473-8ba2-248f-ced58dbeabce
Established class (EPC) Bisphosphonate
Chemical class Diphosphonates
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2013-08-19
Route INTRAVENOUS
Dosage form INJECTION, SOLUTION
Substance ZOLEDRONIC ACID
TE code (Orange Book) AP · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 30042090002020
GPI class Zoledronic Acid
GCN Seq No 059404
GCN 25026
HICL code 034717
Ingredient (HICL) Zoledronic Acid/Mannitol-Water
HIC1 code P
Therapeutic class — broad (HIC1) Endocrine System
HIC2 code P4
Therapeutic class — intermediate (HIC2) Parathyroid/Bone Resorption Drugs
HIC3 code P4L
Therapeutic class — specific (HIC3) Bone Resorption Inhibitors
AHFS code 92:24.00.00
AHFS class Bone Resorption Inhibitors
FDB label name ZOLEDRONIC ACID 5 MG/100 ML
FDB brand name Zoledronic Acid
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 059404
  • GCN: 25026
  • GPI-14 (Medi-Span): 30042090002020
  • HICL (First Databank): 034717
  • AHFS class code: 92:24.00.00
  • RxCUI (RxNorm): 705824
Why two NDCs? The FDA registers this code as 43598-331-11 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 43598-0331-11. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Bisphosphonate class.

Pharmacologic class Bisphosphonate
Drug family (ATC) Bisphosphonates
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name ZOLEDRONIC ACID 5 MG/100 ML Ingredient Zoledronic Acid/Mannitol-Water
📗 Our plain-language guide HelloPharmacist
  • It depends on the product. Reclast and similar zoledronic acid injections treat and prevent osteoporosis and treat Paget’s disease of bone. A different zoledronic acid injection tr...
  • It is an IV infusion given by a healthcare professional over at least 15 minutes. You should be well hydrated beforehand. Your team will tell you about calcium and vitamin D.
  • How is it given, and what should I do beforehand?
  • Fever, muscle or joint aches, headache and flu-like symptoms are common. They often come soon after an infusion. Acetaminophen afterward may ease them, if your prescriber agrees.
📖 Read our full Zoledronic Acid guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
43598-0331-11 You're viewing this Main listing 100 mL in 1 BOTTLE, GLASS 2013-08-19 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Zoledronic Acid 5 mg/100mL 55111-0688-52 Dr.Reddy's 100 ml $0.475 AP Availability likely —
Zoledronic Acid 5 mg/100mL 63323-0966-00 Fresenius 1 vial $0.475 AP Availability likely —
Zoledronic Acid 5 mg/100mL 67457-0619-10 Mylan 1 vial $0.475 AP Availability likely —
Zoledronic Acid 5 mg/100mL 71288-0806-51 Meitheal 1 bottle $0.475 AP Availability likely —
zoledronic acid .05 mg/mL 25021-0830-82 Sagent 100 ml — AP FDA listed —
Zoledronic Acid 5 mg/100mLthis 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 —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2013
On the market since
Aug 2013
📍
2026
Currently FDA-listed
13 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerDr.Reddy's Laboratories Inc
Application holderDR REDDYS LABORATORIES LTD
FDA applicationANDA091363 (ANDA)
Labeler code43598
First marketedAug 2013
Product typeHuman Prescription Drug
Portfolio30 products on file

More NDCs from Dr.Reddy's Laboratories Inc labeler code 43598

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🍼 Nursing Mothers 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 96 words ▾

1 INDICATIONS AND USAGE Zoledronic acid injection is a bisphosphonate indicated for: Treatment of Paget’s disease of bone in men and women ( 1.5 )

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) ].

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Infusion given intravenously over no less than 15 minutes: 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.

2.6Treatment 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 vitamin D daily, particularly in the 2 weeks following zoledronic acid injection administration [see Warnings and Precautions (5.2) ].

2.9Method of Administration The zoledronic acid injection infusion time must not be less than 15 minutes given over a constant infusion rate. The intravenous 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°C–8°C (36°F-46°F) [see How Supplied/Storage and Handling (16)] .

💊 Dosage Forms and Strengths 23 words ▾

3 DOSAGE FORMS AND STRENGTHS 5 mg in a 100 mL ready to infuse solution. 5 mg in a 100 mL ready-to-infuse solution

⛔ Contraindications 115 words ▾

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) ] .

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 ~3 min read ▾

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) Patient Counseling Information (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 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 described 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 at-risk… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

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 Dr. REDDY’S LABORATORIES Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical Trials 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. Paget's Disease of Bone In the Paget’s disease trials, two 6-month, double-blind, comparative, multinational studies of 349 men and women aged greater than 30 years with moderate to severe disease and with confirmed Paget’s disease of bone, 177 patients were exposed to zoledronic acid injection and 172 patients exposed to risedronate.

Zoledronic acid injection was administered once as a single 5 mg dose in 100 mL solution infused over at least 15 minutes. Risedronate was given as an oral daily dose of 30 mg for 2 months. The incidence of serious adverse events was 5.1% in the zoledronic acid injection group and 6.4% in the risedronate group.

The percentage of patients who withdrew from the study due to adverse events was 1.7% and 1.2% for the zoledronic acid injection and risedronate groups, respectively. Adverse reactions occurring in at least 2% of the Paget’s patients receiving zoledronic acid injection (single 5 mg intravenous infusion) or risedronate (30 mg oral daily dose for 2 months) over a 6-month study period are listed by system organ class in Table 1. Table 1.

Adverse Reactions Reported in at Least 2% of Paget’s Patients Receiving Zoledronic Acid Injection (Single 5 mg intravenous Infusion) or Risedronate (Oral 30 mg Daily for 2 Months) Over a 6-Month Follow-Up Period System Organ Class 5 mg IV Zoledronic Acid Injection % (N = 177) 30 mg/day x 2 Months risedronate % (N = 172) Infections and Infestations Influenza 7 5 Metabolism and Nutrition Disorders Hypocalcemia 3 1 Anorexia 2 2 Nervous System Disorders Headache 11 10 Dizziness 9 4 Lethargy 5 1 Paresthesia 2 0 Respiratory, Thoracic and Mediastinal Disorders Dyspnea 5 1 Gastrointestinal Disorders Nausea 9 6 Diarrhea 6 6 Constipation 6 5 Dyspepsia 5 4 Abdominal Distension 2 1 Abdominal Pain 2 2 Vomiting 2 2 Abdominal Pain Upper 1 2 Skin and Subcutaneous Tissue Disorders Rash 3 2 Musculoskeletal, Connective Tissue and Bone Disorders Arthralgia 9 11 Bone Pain 9 5 Myalgia 7 4 Back Pain 4 7 Musculoskeletal Stiffness 2 1 General Disorders and Administrative Site Conditions Influenza-like Illness 11 6 Pyrexia 9 2 Fatigue 8 4 Rigors 8 1 Pain 5 4 Peripheral Edema 3 1 Asthenia 2 1 Laboratory Findings In the Paget’s disease trials, early, transient decreases in serum calcium and phosphate levels were observed.

Approximately 21% of patients had serum calcium levels less than 8.4 mg/dL 9 to 11 days following zoledronic acid injection administration. Renal Impairment In clinical trials in Paget’s disease there were no cases of renal deterioration following a single 5 mg 15-minute infusion [see Warnings and Precautions (5.3) ]. Acute Phase Reaction The signs and symptoms of acute phase reaction (influenza-like illness, pyrexia, myalgia, arthralgia, and bone pain) were reported in 25% of patients in the zoledronic acid injection-treated group compared to 8% in the risedronate-treated group.

Symptoms usually occur within the first 3 days following zoledronic acid injection administration. The majority of these symptoms resolved within 4 days of onset. Osteonecrosis of the Jaw Osteonecrosis of the jaw has been reported with zoledronic acid [see Warnings and Precautions (5.4) ].

6.2Post-Marketing Experience Because these reactions are reported voluntarily from a population of uncertain si… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

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 ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

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 ~1 min read ▾

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 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 53 words ▾

8.5Geriatric Use Of the patients receiving zoledronic acid injection in the Paget’s disease studies, 132 patients, were 65 years of age or over, while 68 patients, were at least 75 years of age. Because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function.

🆘 Overdosage 100 words ▾

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 ~3 min read ▾

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.

12.3Pharmacokinetics Pharmacokinetic data in patients with Paget's disease of bone are not available. Distribution: Single or multiple (every 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 0-24h ) 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 0-24h 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 L/h. Zoledronic acid clearance was independent of dose but dependent upon the patient’s creatinine clearance. In a study in patients with cancer and bone metastases, increasing the infusion time of a 4 mg dose of zoledronic acid from 5 minutes (n=5) to 15 minutes (n=7) resulted in a 34% decrease in the zoledronic acid concentration at the end of the infusion ([mean ± SD] 403 ± 118 ng/mL vs.

264 ± 86 ng/mL) and a 10% increase in the total AUC (378 ± 116 ng x h/mL vs. 420 ± 218 ng x h/mL). The difference between the AUC means was not statistically significant.

Specific Populations Pediatrics: Zoledronic acid injection is not indicated for use in children [see Pediatric Use (8.4) ]. Geriatrics: The pharmacokinetics of zoledronic acid was not… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 91 words ▾

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 56 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Each bottle contains 5 mg per 100 mL: NDC 43598- 331 -11 Handling After opening the solution, it is stable for 24 hours at 2°C–8°C (36°F-46°F). If refrigerated, allow the refrigerated solution to reach room temperature before administration. Storage Store at 20°-25°C (68°-77°F); [see USP Controlled Room Temperature]. Single use vial.

📋 Description 144 words ▾

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 monohydrate is sparingly soluble in 0.1N sodium hydroxide solution. The pH of the zoledronic acid injection solution for infusion is approximately 6 to 7.

Zoledronic acid injection is available as a sterile solution in bottles for intravenous infusion. One bottle 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.

💬 Information for Patients 8 words ▾

17 PATIENT COUNSELING INFORMATION See FDA-Approved Medication Guide

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE Zoledronic acid Injection (ZOE-le-DRON-ik AS-id) 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 z oledronic 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 certain men and women who have Paget’s disease of the bone.

Zoledronic acid injection is not for use in children. Who should not take Zoledronic acid injection? Do not take zoledronic acid injection if you: Have low levels of calcium in your blood Have kidney problems Are allergic to zoledronic acid or any of its ingredients.

A list of ingredients is at the end of this leaflet. What should I tell my doctor before taking z oledronic acid injection? Before you start z oledronic acid injection, be sure to talk to your… [Excerpted — this section continues on DailyMed.]

🍼 Nursing Mothers 44 words ▾

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.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Pharmacokinetic data in patients with Paget's disease of bone are not available. Distribution: Single or multiple (every 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 0-24h ) 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 0-24h 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 L/h. Zoledronic acid clearance was independent of dose but dependent upon the patient’s creatinine clearance. In a study in patients with cancer and bone metastases, increasing the infusion time of a 4 mg dose of zoledronic acid from 5 minutes (n=5) to 15 minutes (n=7) resulted in a 34% decrease in the zoledronic acid concentration at the end of the infusion ([mean ± SD] 403 ± 118 ng/mL vs.

264 ± 86 ng/mL) and a 10% increase in the total AUC (378 ± 116 ng x h/mL vs. 420 ± 218 ng x h/mL). The difference between the AUC means was not statistically significant.

Specific Populations Pediatrics: Zoledronic acid injection is not indicated for use in children [see Pediatric Use (8.4) ]. Geriatrics: The pharmacokinetics of zoledronic acid was not affected by age in patients with cancer and bone metastases whose age ranged from 38 years to 84 years. Race: The pharmacokinetics of zoledronic acid was not affected by race in patients with cancer and bone metastases.

Hepatic Impairment: No clinical studies were conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of zoledronic acid. Renal Impairment: The pharmacokinetic studies conducted in 64 cancer patients represented typical clinical populations with normal to moderately-impaired renal function. Compared to patients with creatinine clearance greater than 80 mL/min (N=37), patients with creatinine clearanc… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES

14.5Treatment of Paget’s Disease of Bone Zoledronic acid injection was studied in male and female patients with moderate to severe Paget’s disease of bone, defined as serum alkaline phosphatase level at least twice the upper limit of the age-specific normal reference range at the time of study entry. Diagnosis was confirmed by radiographic evidence. The efficacy of one infusion of 5 mg zoledronic acid injection vs. oral daily doses of 30 mg risedronate for 2 months was demonstrated in two identically designed 6-month randomized, double blind trials.

The mean age of patients in the two trials was 70. Ninety-three percent (93%) of patients were Caucasian. Therapeutic response was defined as either normalization of serum alkaline phosphatase (SAP) or a reduction of at least 75% from baseline in total SAP excess at the end of 6 months.

SAP excess was defined as the difference between the measured level and midpoint of normal range. In both trials zoledronic acid injection demonstrated a superior and more rapid therapeutic response compared with risedronate and returned more patients to normal levels of bone turnover, as evidenced by biochemical markers of formation (SAP, serum N-terminal propeptide of type I collagen [P1NP]) and resorption (serum CTx 1 [cross-linked C-telopeptides of type I collagen] and urine α-CTx). The 6-month combined data from both trials showed that 96% (169/176) of zoledronic acid injection-treated patients achieved a therapeutic response as compared with 74% (127/171) of patients treated with risedronate.

Most zoledronic acid injection patients achieved a therapeutic response by the Day 63 visit. In addition, at 6 months, 89% (156/176) of zoledronic acid injection-treated patients achieved normalization of SAP levels, compared to 58% (99/171) of patients treated with risedronate (p<0.0001) (see Figure 1). Figure 1.

Therapeutic Response/Serum Alkaline Phosphatase (SAP) Normalization Over Time The therapeutic response to zoledronic acid injection was similar across demographic and disease-severity groups defined by gender, age, previous bisphosphonate use, and disease severity. At 6 months, the percentage of zoledronic acid injection-treated patients who achieved therapeutic response was 97% and 95%, respectively, in each of the baseline disease severity subgroups (baseline SAP less than 3xULN, greater than or equal to 3xULN) compared to 75% and 74%, respectively, for the same disease severity subgroups of risedronate-treated patients.

In patients who had previously received treatment with oral bisphosphonates, therapeutic response rates were 96% and 55% for zoledronic acid injection and risedronate, respectively. The comparatively low risedronate response was due to the low response rate (7/23, 30%) in patients previously treated with risedronate. In patients naïve to previous treatment, a greater therapeutic response was also observed with zoledronic acid injection (98%) relative to risedronate (86%).

In patients with symptomatic pain at screening, therapeutic response rates were 94% and 70% for zoledronic acid injection and risedronate respectively. For patients without pain at screening, therapeutic response rates were 100% and 82% for zoledronic acid injection and risedronate respectively. Bone histology was evaluated in 7 patients with Paget’s disease 6 months after being treated with zoledronic acid injection 5 mg.

Bone biopsy results showed bone of normal quality with no evidence of impaired bone remodeling and no evidence of mineralization defect.

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis: Standard lifetime carcinogenicity bioassays were conducted in mice and rats. Mice were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2 mg/kg/day. There was an increased incidence of Harderian gland adenomas in males and females in all treatment groups (at doses greater than or equal to 0.002 times the human intravenous dose of 5 mg, based on a mg/m 2 comparison).

Rats were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2 mg/kg/day. No increased incidence of tumors was observed (at doses less than or equal to 0.1 times the human intravenous dose of 5 mg, based on a mg/m 2 comparison). Mutagenesis: Zoledronic acid was not genotoxic in the Ames bacterial mutagenicity assay, in the Chinese hamster ovary cell assay, or in the Chinese hamster gene mutation assay, with or without metabolic activation.

Zoledronic acid was not genotoxic in the in vivo rat micronucleus assay. Impairment of Fertility: Female rats were given daily subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg beginning 15 days before mating and continuing through gestation. Effects observed in the high-dose group (equivalent to human systemic exposure following a 5 mg intravenous dose, based on an AUC comparison) included inhibition of ovulation and a decrease in the number of pregnant rats.

Effects observed in both the mid-dose group and high-dose group (0.3 to 1 times human systemic exposure following a 5 mg intravenous dose, based on an AUC comparison) included an increase in pre-implantation losses and a decrease in the number of implantations and live fetuses.

13.2Animal Pharmacology and/or Toxicology Bone Safety Studies: Zoledronic acid is a potent inhibitor of osteoclastic bone resorption. In the ovariectomized rat, single IV doses of zoledronic acid of 4 to 500 mcg/kg (less than 0.1 to 3.5 times human exposure at the 5 mg intravenous dose, based on a mg/m 2 comparison) suppressed bone turnover and protected against trabecular bone loss, cortical thinning and the reduction in vertebral and femoral bone strength in a dose-dependent manner. At a dose equivalent to human exposure at the 5 mg intravenous dose, the effect persisted for 8 months, which corresponds to approximately 8 remodeling cycles or 3 years in humans.

In ovariectomized rats and monkeys, weekly treatment with zoledronic acid dose-dependently suppressed bone turnover and prevented the decrease in cancellous and cortical BMD and bone strength, at yearly cumulative doses up to 3.5 times the intravenous human dose of 5 mg, based on a mg/m 2 comparison. Bone tissue was normal and there was no evidence of a mineralization defect, no accumulation of osteoid, and no woven bone.

13.3Reproductive and Developmental Toxicology In female rats given subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg/day beginning 15 days before mating and continuing through gestation, the number of stillbirths was increased and survival of neonates was decreased in the mid- and high-dose groups (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 (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 of 0.1, 0.2, or 0.4 mg/kg during gestation, adverse fetal effects were observed in the mid-and high-dose groups (about 2 and 4 times human systemic exposure following a 5 mg intravenous dose, based on an AUC comparison).

Th… [Excerpted — this section continues on DailyMed.]

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis: Standard lifetime carcinogenicity bioassays were conducted in mice and rats. Mice were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2 mg/kg/day. There was an increased incidence of Harderian gland adenomas in males and females in all treatment groups (at doses greater than or equal to 0.002 times the human intravenous dose of 5 mg, based on a mg/m 2 comparison).

Rats were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2 mg/kg/day. No increased incidence of tumors was observed (at doses less than or equal to 0.1 times the human intravenous dose of 5 mg, based on a mg/m 2 comparison). Mutagenesis: Zoledronic acid was not genotoxic in the Ames bacterial mutagenicity assay, in the Chinese hamster ovary cell assay, or in the Chinese hamster gene mutation assay, with or without metabolic activation.

Zoledronic acid was not genotoxic in the in vivo rat micronucleus assay. Impairment of Fertility: Female rats were given daily subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg beginning 15 days before mating and continuing through gestation. Effects observed in the high-dose group (equivalent to human systemic exposure following a 5 mg intravenous dose, based on an AUC comparison) included inhibition of ovulation and a decrease in the number of pregnant rats.

Effects observed in both the mid-dose group and high-dose group (0.3 to 1 times human systemic exposure following a 5 mg intravenous dose, based on an AUC comparison) included an increase in pre-implantation losses and a decrease in the number of implantations and live fetuses.

📄 Package Label / Principal Display Panel 19 words ▾

Unvarnished Area Consists of: 2D Barcode, Lot Number, Expiry Date and Serial Number 5 mg/100 mL Vial Carton Label

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Zoledronic Acid — the program that covers self-administered drugs. 7 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Zoledronic Acid. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$499K
Claims incl. refills
3.6K
Beneficiaries
3.5K
Spend / beneficiary
$141.19
Spend / claim
$140.32
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

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Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
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Orange Book / therapeutic-equivalence data ✓ Available
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Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
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Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 43598-0330-11 · Dr. 43598-0339-60 · Dr. →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.