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Zoledronic Acid 5 mg/100mL Injection, Solution — NDC 68083-0135-01 package photo
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Zoledronic Acid 5 mg/100mL Injection, Solution — NDC 68083-135-01 (Billing 68083-0135-01)

by Gland Pharma Limited · 1 VIAL, GLASS in 1 CARTON / 100 mL in 1 VIAL, GLASS

This is a package of Zoledronic Acid 5 mg/100mL Injection, Solution from Gland Pharma Limited, marketed since Sep 2016 and currently FDA-listed. It is this product's only package size.

NDC 68083-0135-01
🏷️ FDA NDC (as labeled) 68083-135-01 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

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68083-135-01
Product NDC 68083-135
11-digit billing NDC 68083013501
RxCUI 705824
UNII 6XC1PAD3KF
Application # ANDA204217
SPL Set ID 824eaeee-6b3d-4d62-b268-77f8bd8e7f10
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 2016-09-15
Route INTRAVENOUS
Dosage form INJECTION, SOLUTION
Substance ZOLEDRONIC ACID
TE code (Orange Book) AP · RLD · RS
Quick answers
  • RxCUI (RxNorm): 705824
Why two NDCs? The FDA registers this code as 68083-135-01 — 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 → 68083-0135-01. 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

📖 What it is MedlinePlus · NLM

Zoledronic acid is used to prevent or treat osteoporosis (condition in which the bones become thin and weak and break easily) and treat Paget's disease of bone (a condition in which the bones are soft and weak and may be deformed, painful, or easily broken). Zoledronic acid is also used to treat high levels of calcium in the blood that may be caused by certain types of cancer and to treat bone damage caused by multiple myeloma [cancer that begins in the plasma cells (white blood cells that produce substances needed to fight infection)] or by cancer that began in another part of the body but h...

Read the full MedlinePlus article ↗
📗 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
68083-0135-01 You're viewing this Main listing 1 VIAL, GLASS in 1 CARTON / 100 mL in 1 VIAL, GLASS 2016-09-15 — 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/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/100mLthis 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

🏛️
2016
On the market since
Sep 2016
📍
2026
Currently FDA-listed
10 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 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.
  • 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.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

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

LabelerGland Pharma Limited
Application holderGLAND PHARMA LTD
FDA applicationANDA204217 (ANDA)
Labeler code68083
First marketedSep 2016
Product typeHuman Prescription Drug
Portfolio263 products on file
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 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage ~2 min read ▾

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 reevaluated 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 reevaluated periodically.

⏱️ Dosage and Administration ~3 min read ▾

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 creatinine clearance 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… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 26 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 ( 3 )

⛔ Contraindications 119 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 Fractures Including Femoral Fractures have been reported. Patients with thigh or groin pain should be evaluated to rule out a femoral fracture.

Risk/benefit of continuing bisphosphonate therapy should be re-evaluated in these patients and interruption of bisphosphonate therapy should be considered ( 5.5 ) Severe Bone, Joint, and Muscle Pain may occur. Withhold future doses of zoledronic acid injection if severe symptoms occur ( 5.6 )

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 Preexisting 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) ]. 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) , 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 preexisting 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 cleara… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse drug reactions are described elsewhere in the labeling: • Drugs with Same Active Ingredient [see Warnings and Precautions ( 5.1 )] • Hypocalcemia and Mineral Metabolism [see Warnings and Precautions ( 5.2 )] • Renal Impairment [see Warnings and Precautions ( 5.3 )] • Osteonecrosis of the Jaw [see Warnings and Precautions ( 5.4 )] • Atypical Fractures Including Femoral Fractures [see Warnings and Precautions ( 5.5 )] • Musculoskeletal Pain [see Warnings and Precautions ( 5.6 )] • Patients with Asthma [see Warnings and Precautions ( 5.7 )] 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 Gland Pharma Limited at 866-770-7144 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. 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 BMD 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 osteoporosi… [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 (NSAIDs).

7.4Drugs Primarily Excreted by the Kidney Renal impairment has been observed following the administration of zoledronic acid in patients with preexisting 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 • Pregnancy: Discontinue when pregnancy is recognized ( 8.1 ) • Pediatric Use: Not indicated for use in pediatric patients ( 8.4 ) • Geriatric Use: Special care to monitor renal function ( 8.5 )

8.1Pregnancy Risk Summary Available data on the use of zoledronic acid injection in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue zoledronic acid injection when pregnancy is recognized. In animal reproduction studies, daily subcutaneous administration of zoledronic acid to pregnant rats during organogenesis resulted in increases in fetal skeletal, visceral, and external malformations, decreases in postimplantation survival, and decreases in viable fetuses and fetal weight starting at doses equivalent to 2 times the recommended human 5 mg intravenous dose (based on AUC).

Subcutaneous administration of zoledronic acid to rabbits during organogenesis did not cause adverse fetal effects at up to 0.4 times the human 5 mg intravenous dose (based on body surface area, mg/m 2 ), but resulted in maternal mortality and abortion associated with hypocalcemia starting at doses equivalent to 0.04 times the human 5 mg intravenous dose. Subcutaneous dosing of female rats from before mating through gestation and lactation and allowed to deliver caused maternal dystocia and periparturient mortality, increases in stillbirths and neonatal deaths, and reduced pup body weight starting at doses equivalent to 0.1 times the human 5 mg intravenous dose (based on AUC) ( see Data ).

Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. Consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, 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, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In pregnant rats given daily subcutaneous doses of zoledronic acid of 0.1, 0.2, or 0.4 mg/kg during organogenesis, fetal skeletal, visceral, and external malformations, increases in pre-and post-implantation loss, and decreases in viable fetuses and fetal weight were observed at 0.2 and 0.4 mg/kg/day (equivalent to 2 and 4 times the human 5 mg intravenous dose, based on AUC).

Adverse fetal skeletal effects at 0.4 mg/kg/day (4 times the human 5 mg dose) included unossified or incompletely ossified bones, thickened, curved or shortened bones, wavy ribs, and shortened jaw. Other adverse fetal effects at this dose included reduced lens, rudimentary cerebellum, reduction or absence of liver lobes, reduction of lung lobes, vessel dilation, cleft palate, and edema. Skeletal variations were observed in all groups starting at 0.1 mg/kg/day (1.2 times the human 5 mg dose).

Signs of maternal toxicity, including reduced body weight and food consumption were observed at 0.4 mg/kg/day (4 times the human 5 mg dose). In pregnant rabbits given daily subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg during gestation, no adverse fetal effects were observed up to 0.1 mg/kg/day (0.4 times the human 5 mg intravenous dose, based on body surface area, mg/m 2 ). Maternal mortali… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Available data on the use of zoledronic acid injection in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue zoledronic acid injection when pregnancy is recognized. In animal reproduction studies, daily subcutaneous administration of zoledronic acid to pregnant rats during organogenesis resulted in increases in fetal skeletal, visceral, and external malformations, decreases in postimplantation survival, and decreases in viable fetuses and fetal weight starting at doses equivalent to 2 times the recommended human 5 mg intravenous dose (based on AUC).

Subcutaneous administration of zoledronic acid to rabbits during organogenesis did not cause adverse fetal effects at up to 0.4 times the human 5 mg intravenous dose (based on body surface area, mg/m 2 ), but resulted in maternal mortality and abortion associated with hypocalcemia starting at doses equivalent to 0.04 times the human 5 mg intravenous dose. Subcutaneous dosing of female rats from before mating through gestation and lactation and allowed to deliver caused maternal dystocia and periparturient mortality, increases in stillbirths and neonatal deaths, and reduced pup body weight starting at doses equivalent to 0.1 times the human 5 mg intravenous dose (based on AUC) ( see Data ).

Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. Consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, 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, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In pregnant rats given daily subcutaneous doses of zoledronic acid of 0.1, 0.2, or 0.4 mg/kg during organogenesis, fetal skeletal, visceral, and external malformations, increases in pre-and post-implantation loss, and decreases in viable fetuses and fetal weight were observed at 0.2 and 0.4 mg/kg/day (equivalent to 2 and 4 times the human 5 mg intravenous dose, based on AUC).

Adverse fetal skeletal effects at 0.4 mg/kg/day (4 times the human 5 mg dose) included unossified or incompletely ossified bones, thickened, curved or shortened bones, wavy ribs, and shortened jaw. Other adverse fetal effects at this dose included reduced lens, rudimentary cerebellum, reduction or absence of liver lobes, reduction of lung lobes, vessel dilation, cleft palate, and edema. Skeletal variations were observed in all groups starting at 0.1 mg/kg/day (1.2 times the human 5 mg dose).

Signs of maternal toxicity, including reduced body weight and food consumption were observed at 0.4 mg/kg/day (4 times the human 5 mg dose). In pregnant rabbits given daily subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg during gestation, no adverse fetal effects were observed up to 0.1 mg/kg/day (0.4 times the human 5 mg intravenous dose, based on body surface area, mg/m 2 ). Maternal mortality and abortion were observed in all dose groups (starting at 0.04 times the human 5 mg dose).

Adverse maternal effects were associated with drug-induced hypocalcemia. In female rats given daily subcutaneous doses of 0.01, 0.… [Excerpted — this section continues on DailyMed.]

🧒 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 and treatment of osteoporosis, including 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 133 words ▾

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 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.

12.2Pharmacodynamics 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. 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 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. Zoledro… [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 78 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Zoledronic acid injection, 5 mg/100 mL is supplied as follows: NDC Container Package Factor 68083-135-01 100 mL clear glass vial 1 vial per carton 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 150 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 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. structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (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 [see Warnings and Precautions ( 5.3 )]. Zoledronic acid injection should not be given if the patient is pregnant or plans to become pregnant, or if she is breastfeeding [see Use in Specific Populations ( 8.1 , 8.2 , 8.3 )]. 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 to 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 any oral symptoms, they should immediately report them to 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… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

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. Unusual breaks in thigh and other bones 5.

Bone, joint or muscle pain 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 breaks in thigh and other bones.

Some people have had unusual bone breaks, including thigh bone, when taking zoledronic acid injection. A break in the thigh bone can feel like a new pain in your hip, groin, or thigh. People taking zoledronic acid injection can also have breaks in other bones.

5. 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 determine if zoledronic acid injection is still right for you.

Zoledronic acid injection is not for us… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Pharmacokinetic data in patients with osteoporosis and 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 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 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),… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 105 words ▾

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.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Treatment of Postmenopausal Osteoporosis Study 1 : The efficacy and safety of zoledronic acid injection in the treatment of postmenopausal osteoporosis was demonstrated in Study 1, a randomized, double-blind, placebo-controlled, multinational study of 7736 women aged 65 to 89 years (mean age of 73) with either: a femoral neck BMD T-score less than or equal to -1.5 and at least two mild or one moderate existing vertebral fracture(s); or a femoral neck BMD T-score less than or equal to -2.5 with or without evidence of an existing vertebral fracture(s).

Women were stratified into two groups: Stratum I: no concomitant use of osteoporosis therapy or Stratum II: baseline concomitant use of osteoporosis therapies, which included calcitonin, raloxifene, tamoxifen, and hormone replacement therapy, but excluded other bisphosphonates. Women enrolled in Stratum I (n = 5661) were evaluated annually for incidence of vertebral fractures. All women (Strata I and II) were evaluated for the incidence of hip and other clinical fractures.

Zoledronic acid injection was administered once a year for three consecutive years, 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 two primary efficacy variables were the incidence of morphometric vertebral fractures at 3 years and the incidence of hip fractures over a median duration of 3 years.

The diagnosis of an incident vertebral fracture was based on both qualitative diagnosis by the radiologist and quantitative morphometric criterion. The morphometric criterion required the dual occurrence of 2 events: a relative height ratio or relative height reduction in a vertebral body of at least 20%, together with at least a 4 mm absolute decrease in height. Effect on Vertebral Fractures Zoledronic acid injection significantly decreased the incidence of new vertebral fractures at one, two, and three years as shown in Table 5.

Table 5. Proportion of Patients with New Morphometric Vertebral Fractures Outcome Zoledronic acid injection (%) Placebo (%) Absolute Reduction in Fracture Incidence % (95% CI) Relative Reduction in Fracture Incidence % (95% CI) At least one new vertebral fracture (0 to 1 year) 1.5 3.7 2.2 (1.4, 3.1) 60 (43, 72) 1 At least one new vertebral fracture (0 to 2 years) 2.2 7.7 5.5 (4.4, 6.6) 71 (62, 78) 1 At least one new vertebral fracture (0 to 3 years) 3.3 10.9 7.6 (6.3, 9.0) 70 (62, 76) 1 1. p <0.0001 The reductions in vertebral fractures over three years were consistent (including new/worsening and multiple vertebral fractures) and significantly greater than placebo regardless of age, geographical region, baseline body mass index, number of baseline vertebral fractures, femoral neck BMD T-score, or prior bisphosphonate usage.

Effect on Hip Fracture Over 3 years Zoledronic acid injection demonstrated a 1.1% absolute reduction and 41% relative reduction in the risk of hip fractures over a median duration of follow-up of 3 years. The hip fracture event rate was 1.4% for zoledronic acid injection-treated patients compared to 2.5% for placebo-treated patients. Figure 1.

Cumulative Incidence of Hip Fracture Over 3 Years The reductions in hip fractures over three years were greater for zoledronic acid injection than placebo regardless of femoral neck BMD T-score. Effect on All Clinical Fractures Zoledronic acid injection demonstrated superiority to placebo in reducing the incidence of all clinical fractures, clinical (symptomatic) vertebral and non-vertebral fractures (excluding finger, toe, facial, and clinical thoracic and lumbar vertebral fractures). All clinical fractures were verified based on the radiographic and/or clinical evidence.

A summary of results is presented in Table 6. Table 6. Between-Treatment Comparisons of the Incidence of Clinical Fracture Variables Over 3 Years Outco… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Lifetime carcinogenicity bioassays were conducted in mice and rats. Mice were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2.0 mg/kg/day for 2 years. There was an increased incidence of Harderian gland adenomas in males and females in all treatment groups (starting at doses equivalent to 0.002 times the human 5 mg intravenous dose, based on body surface area, mg/m 2 ).

Rats were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2.0 mg/kg/day for 2 years. No increased incidence of tumors was observed at any dose (up to 0.1 times the human intravenous dose of 5 mg, based on body surface area, mg/m 2 ). 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. Inhibition of ovulation and a decrease in the number of pregnant rats were observed at 0.1 mg/kg/day (equivalent to the human 5 mg intravenous dose, based on AUC).

An increase in preimplantation loss and a decrease in the number of implantations and live fetuses were observed at 0.03 and 1 mg/kg/day (0.3 to 1 times the human 5 mg human intravenous dose).

13.2Animal Pharmacology 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 (0.1 to 3.5 times the human 5 mg intravenous dose, based on body surface area, mg/m 2 ) 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 human 5 mg intravenous dose, based on body surface area, mg/m 2 . Bone tissue was normal and there was no evidence of a mineralization defect, no accumulation of osteoid, and no woven bone.

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

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Lifetime carcinogenicity bioassays were conducted in mice and rats. Mice were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2.0 mg/kg/day for 2 years. There was an increased incidence of Harderian gland adenomas in males and females in all treatment groups (starting at doses equivalent to 0.002 times the human 5 mg intravenous dose, based on body surface area, mg/m 2 ).

Rats were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2.0 mg/kg/day for 2 years. No increased incidence of tumors was observed at any dose (up to 0.1 times the human intravenous dose of 5 mg, based on body surface area, mg/m 2 ). 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. Inhibition of ovulation and a decrease in the number of pregnant rats were observed at 0.1 mg/kg/day (equivalent to the human 5 mg intravenous dose, based on AUC).

An increase in preimplantation loss and a decrease in the number of implantations and live fetuses were observed at 0.03 and 1 mg/kg/day (0.3 to 1 times the human 5 mg human intravenous dose).

📄 Recent Major Changes 12 words ▾

Warnings and Precautions, Atypical Fractures Including Femoral Fractures ( 5.5 )...................... 02/2026

📄 Package Label / Principal Display Panel 28 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 68083-135-01 Rx only Zoledronic Acid Injection 5 mg/100 mL (0.05 mg/mL) Zoledronic Acid Injection Vial Label Zoledronic Acid Injection Carton Label zoledronic-container zoledronic-carton

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

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

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.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Gland Pharma Limited. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Gland Pharma Limited is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
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.
← 68083-0134-10 · Gland 68083-0136-25 · Gland →
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.