pharmacopeia
GET
/api/v1/drug/zoledronic-acid
2D structure
(1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid
SMILES C1=CN(C=N1)CC(O)(P(=O)(O)O)P(=O)(O)O
InChIKey XRASPMIURGNCCH-UHFFFAOYSA-N

Mechanism of action

Sourced from openFDA

The principal pharmacologic action of zoledronic acid is inhibition of bone resorption. Although the antiresorptive mechanism is not completely understood, several factors are thought to contribute to this action.

Indications

Sourced from openFDA
  • Zoledronic acid injection is a bisphosphonate indicated for the treatment of: Hypercalcemia of malignancy. (1.1) Patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy.ICD-10: C90.00, E83.52

Contraindications

Sourced from openFDA
  • Hypersensitivity to any component of zoledronic acid injection (4) Hypersensitivity to Zoledronic Acid or Any Components of Zoledronic Acid Injection Hypersensitivity reactions including rare cases of urticaria and angioedema, and very rare cases of anaphylactic reaction/shock have been reported [ see Adverse Reactions (6.2) ].contraindicated

Dosage & administration

Sourced from openFDA

Hypercalcemia of malignancy ( 2.1 ) 4 mg as a single-use intravenous infusion over no less than 15 minutes. 4 mg as retreatment after a minimum of 7 days. Multiple myeloma and bone metastasis from solid tumors. ( 2.2 ) 4 mg as a single-use intravenous infusion over no less than 15 minutes every 3 to 4 weeks for patients with creatinine clearance of greater than 60 mL/min. Reduce the dose for patients with renal impairment. Coadminister oral calcium supplements of 500 mg and a multiple vitamin containing 400 international units of vitamin D daily. Administer through a separate vented infusion line and do not allow to come in contact with any calcium or divalent cation-containing solutions. ( 2.3 ) Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 2.1 Hypercalcemia of Malignancy The maximum recommended dose of zoledronic acid injection in hypercalcemia of malignancy (albumin-corrected serum calcium greater than or equal to 12 mg/dL [3.0 mmol/L]) is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes . Patients who receive zoledronic acid injection should have serum creatinine assessed prior to each treatment. Dose adjustments of zoledronic acid injection are not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine less than 400 µmol/L or less than 4.5 mg/dL).

Warnings & precautions

Sourced from openFDA

Patients being treated with zoledronic acid injection should not be treated with Reclast ® . ( 5.1 ) Adequately rehydrate patients with hypercalcemia of malignancy prior to administration of zoledronic acid injection and monitor electrolytes during treatment. ( 5.2 ) Renal toxicity may be greater in patients with renal impairment. Do not use doses greater than 4 mg. Treatment in patients with severe renal impairment is not recommended. Monitor serum creatinine before each dose. ( 5.3 ) Osteonecrosis of the jaw (ONJ) has been reported. Preventive dental exams should be performed before starting zoledronic acid injection. Avoid invasive dental procedures. ( 5.4 ) Severe incapacitating bone, joint, and/or muscle pain may occur. Discontinue zoledronic acid injection if severe symptoms occur. ( 5.5 ) Atypical subtrochanteric and diaphyseal femoral fractures have been reported in patients receiving bisphosphonate therapy. These fractures may occur after minimal or no trauma. Evaluate patients with thigh or groin pain to rule out a femoral fracture. Consider drug discontinuation in patients suspected to have an atypical femur fracture. ( 5.6 ) Hypocalcemia: Correct before initiating zoledronic acid injection. Adequately supplement patients with calcium and vitamin D. Monitor serum calcium closely with concomitant administration of other drugs known to cause hypocalcemia to avoid severe or life-threatening hypocalcemia ( 5.9 ) Zoledronic acid injection can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.

Adverse reactions

Sourced from openFDA

The most common adverse events (greater than 25%) were nausea, fatigue, anemia, bone pain, constipation, fever, vomiting, and dyspnea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical 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. Hypercalcemia of Malignancy The safety of zoledronic acid injection was studied in 185 patients with hypercalcemia of malignancy (HCM) who received either zoledronic acid injection 4 mg given as a 5-minute intravenous infusion (n=86) or pamidronate 90 mg given as a 2-hour intravenous infusion (n=103). The population was aged 33 to 84 years, 60% male and 81% Caucasian, with breast, lung, head and neck, and renal cancer as the most common forms of malignancy. NOTE: pamidronate 90 mg was given as a 2-hour intravenous infusion. The relative safety of pamidronate 90 mg given as a 2-hour intravenous infusion compared to the same dose given as a 24-hour intravenous infusion has not been adequately studied in controlled clinical trials. Renal Toxicity Administration of zoledronic acid injection 4 mg given as a 5-minute intravenous infusion has been shown to result in an increased risk of renal toxicity, as measured by increases in serum creatinine, which can progress to renal failure.

Use in specific populations

Sourced from openFDA

Lactation: Advise not to breastfeed ( 8.2 ) Females and Males of Reproductive Potential: Verify pregnancy status prior to initiation of zoledronic acid injection. May impair fertility. Counsel patients on pregnancy planning and prevention. ( 8.3 ) Pediatric Use: Not indicated for use in pediatric patients. ( 8.4 ) Geriatric Use: Special care to monitor renal function. ( 8.5 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, zoledronic acid injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )]. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of zoledronic acid to pregnant rats during organogenesis resulted in fetal malformations and embryo-fetal lethality at maternal exposures that were ≥2.4 times the human clinical exposure based on AUC (see Data). Bisphosphonates, such as zoledronic acid injection, are incorporated into the bone matrix, from where they are gradually released over periods of weeks to years. There may be a risk of fetal harm (e.g., skeletal and other abnormalities) if a woman becomes pregnant after completing a course of bisphosphonate therapy. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

Pharmacokinetics

Sourced from openFDA
Metabolism
Pharmacokinetic data in patients with hypercalcemia 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 injection were given to 64 patients with cancer and bone metastases.

Overdosage

Sourced from openFDA

Clinical experience with acute overdosage of zoledronic acid injection is limited. Two patients received zoledronic acid injection 32 mg over 5 minutes in clinical trials. Neither patient experienced any clinical or laboratory toxicity. Overdosage may cause clinically significant 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. In an open-label study of zoledronic acid 4 mg in breast cancer patients, a female patient received a single 48-mg dose of zoledronic acid in error. Two days after the overdose, the patient experienced a single episode of hyperthermia (38°C), which resolved after treatment. All other evaluations were normal, and the patient was discharged seven days after the overdose. A patient with non-Hodgkin's lymphoma received zoledronic acid 4 mg daily on four successive days for a total dose of 16 mg. The patient developed paresthesia and abnormal liver function tests with increased GGT (nearly 100 unit/L, each value unknown).

Approval history

Sourced from openFDA
  • Apr 16, 2007NDANDA021817Sandoz
  • Mar 4, 2013ANDAANDA091186Dr Reddys Labs Ltd
  • Mar 4, 2013ANDAANDA202650Mylan Labs Ltd
  • Mar 12, 2013ANDAANDA201783Avet Lifesciences
  • Mar 29, 2013ANDAANDA091363Dr Reddys Labs Ltd
  • Jun 3, 2013ANDAANDA202182Hikma Farmaceutica
  • Aug 2, 2013NDANDA203231Inforlife
  • Aug 5, 2013ANDAANDA202930Gland

FAERS reports

View JSON
Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
39,014 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Arthralgia3,1438.1%
  2. 2Pain3,0897.9%
  3. 3Pyrexia2,7547.1%
  4. 4Nausea2,7367.0%
  5. 5Fatigue2,7066.9%
  6. 6Osteonecrosis Of Jaw2,6546.8%
  7. 7Death2,4686.3%
  8. 8Headache2,3236.0%
  9. 9Diarrhoea2,2235.7%
  10. 10Vomiting2,0185.2%
  11. 11Asthenia1,9304.9%
  12. 12Myalgia1,8314.7%
  13. 13Off Label Use1,7074.4%
  14. 14Pain In Extremity1,6474.2%
  15. 15Dyspnoea1,6144.1%

Literature

View JSON

Recent PubMed references pinned to Zoledronic Acid as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 401 ClinicalTrials.gov registrations naming Zoledronic Acid as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Zoledronic Acid work?
The principal pharmacologic action of zoledronic acid is inhibition of bone resorption. Although the antiresorptive mechanism is not completely understood, several factors are thought to contribute to this action.
What is Zoledronic Acid used for?
According to FDA labeling, Zoledronic Acid carries indications including: Zoledronic acid injection is a bisphosphonate indicated for the treatment of: Hypercalcemia of malignancy. (1.1) Patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Zoledronic Acid?
Zoledronic Acid is classified as Bisphosphonates, Bone Surface Interactions, Bone Resorption Inhibition.
What are the brand names for Zoledronic Acid?
Zoledronic Acid is marketed under brand names including Reclast.
What are the contraindications for Zoledronic Acid?
Zoledronic Acid labeling lists contraindications including: Hypersensitivity to any component of zoledronic acid injection (4) Hypersensitivity to Zoledronic Acid or Any Components of Zoledronic Acid Injection Hypersensitivity reactions including rare cases of urticaria and angioedema, and very rare cases of anaphylactic reaction/shock have been reported [ see Adverse Reactions (6.2) ].. Always consult the full prescribing information and a clinician.
Note. Data for zoledronic-acid is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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