Zoledronic Acid
Generic: ZOLEDRONIC ACID
Basic Information
Manufacturer
Dr.Reddy's Laboratories Inc
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
c8e02635-4473-8ba2-248f-ced58dbeabce
Indications & Usage
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 ) 1.5 Paget's Disease of Bone Zoledronic acid injection is indicated for treatment of Paget's disease of bone in men and women.
Treatment is indicated in patients with Paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see Clinical Studies (14.5) ].
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) ].
Adverse Reactions
6 ADVERSE REACTIONS The most common adverse reactions (greater than 10%) were pyrexia, myalgia, headache, arthralgia, pain in extremity ( 6.1 ) Other important adverse reactions were flu-like illness, nausea, vomiting, diarrhea ( 6.2 ), and eye inflammation ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact Dr. REDDY’S LABORATORIES Inc., at 1-888-375-3784 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.
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) ].
6.2 Post-Marketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been identified during post approval use of zoledronic acid injection: Acute Phase Reactions Fever, headache, flu-like symptoms, nausea, vomiting, diarrhea, arthralgia, and myalgia.
Symptoms may be significant and lead to dehydration.
Acute Renal Failure Acute renal failure requiring hospitalization and/or dialysis or with a fatal outcome have been rarely reported.Increased serum creatinine was reported in patients with 1) underlying renal disease, 2) dehydration secondary to fever, sepsis, gastrointestinal losses, or diuretic therapy, or 3) other risk factors such as advanced age, or concomitant nephrotoxic drugs in the post-infusion period.
Transient rise in serum creatinine can be correctable with intravenous fluids.
Allergic Reactions Allergic reactions with intravenous zoledronic acid including anaphylactic reaction/shock, urticaria, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, and bronchoconstriction have been reported.
Asthma Exacerbations Asthma exacerbations have been reported.
Hypocalcemia Hypocalcemia has been reported.
Hypophosphatemia Hypophosphatemia has been reported.
Osteonecrosis of the Jaw Osteonecrosis of the jaw has been reported.
Osteonecrosis of other bones Cases of osteonecrosis of other bones (including femur, hip, knee, ankle, wrist and humerus) have been reported; causality has not been determined in the population treated with zoledronic acid injection.
Ocular Adverse Events Cases of the following events have been reported: conjunctivitis, iritis, iridocyclitis, uveitis, episcleritis, scleritis, and orbital inflammation/edema.
Other Hypotension in patients with underlying risk factors have been reported.
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 6.1 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.
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) ].
6.2 Post-Marketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been identified during post approval use of zoledronic acid injection: Acute Phase Reactions Fever, headache, flu-like symptoms, nausea, vomiting, diarrhea, arthralgia, and myalgia.
Symptoms may be significant and lead to dehydration.
Acute Renal Failure Acute renal failure requiring hospitalization and/or dialysis or with a fatal outcome have been rarely reported.Increased serum creatinine was reported in patients with 1) underlying renal disease, 2) dehydration secondary to fever, sepsis, gastrointestinal losses, or diuretic therapy, or 3) other risk factors such as advanced age, or concomitant nephrotoxic drugs in the post-infusion period.
Transient rise in serum creatinine can be correctable with intravenous fluids.
Allergic Reactions Allergic reactions with intravenous zoledronic acid including anaphylactic reaction/shock, urticaria, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, and bronchoconstriction have been reported.
Asthma Exacerbations Asthma exacerbations have been reported.
Hypocalcemia Hypocalcemia has been reported.
Hypophosphatemia Hypophosphatemia has been reported.
Osteonecrosis of the Jaw Osteonecrosis of the jaw has been reported.
Osteonecrosis of other bones Cases of osteonecrosis of other bones (including femur, hip, knee, ankle, wrist and humerus) have been reported; causality has not been determined in the population treated with zoledronic acid injection.
Ocular Adverse Events Cases of the following events have been reported: conjunctivitis, iritis, iridocyclitis, uveitis, episcleritis, scleritis, and orbital inflammation/edema.
Other Hypotension in patients with underlying risk factors have been reported.