Zoledronic Acid (zoledronic acid in mannitol and water for injection)

Dosage of zoledronic acid, which is commercially available for parenteral use as the monohydrate, is calculated on the anhydrous basis.

Zoledronic acid is administered by IV infusion over no less than 15 minutes. (See Renal Effects under Cautions: Warnings/Precautions.)

Zoledronic acid is commercially available as a solution concentrate containing 4 mg of the drug per 5 mL (Zometa(R) concentrate or generic equivalents) and as a ready-to-use injection containing 4 mg of the drug per 100 mL (Zometa(R) ready-to-use or generic equivalents) for use in patients with cancer-related indications. Zoledronic acid also is available as a ready-to-use injection containing 5 mg of the drug per 100 mL (Reclast(R) or generic equivalents) for use in the prevention or treatment of osteoporosis or for treatment of Paget disease of bone.

Zoledronic acid should be administered through separate vented infusion lines apart from other drugs and should not be allowed to come in contact with any solutions containing calcium or other divalent cations.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Zoledronic Acid/Diuretics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Concurrent use of zoledronic acid and a diuretic may have adverse effects on the renal system.(1,2)

CLINICAL EFFECTS: Concurrent use of zoledronic acid and a diuretic may result in renal dysfunction. Deterioration in renal function, acute renal failure requiring dialysis, and death have been reported.(1)

PREDISPOSING FACTORS: The interaction may be more likely in elderly patients, patients who are taking other drugs that impact renal function, patients with pre-existing renal compromise, and patients who are dehydrated.(1)

PATIENT MANAGEMENT: Patients should be adequately hydrated with 500 ml (2 glasses of water) before and after zoledronic acid administration.(1) Creatinine clearance should be monitored before and after therapy and zoledronic acid should not be administered in patients with a creatinine clearance less than 35 ml/min.(1,3)

DISCUSSION: Zoledronic acid has been associated with renal dysfunction, including deterioration in renal function, acute renal failure requiring dialysis, and death. Risk factors include advanced age, concomitant nephrotoxic agents, and dehydration.(1) The FDA has received 16 reports of fatal acute renal failure and 9 reports of renal injury requiring dialysis following the administration of Reclast (zoledronic acid).(3)

Known hypersensitivity to zoledronic acid, other bisphosphonates, or any ingredient in the formulations.

Hypocalcemia.

Use of zoledronic acid for prevention or treatment of osteoporosis or for treatment of Paget disease of bone is contraindicated in patients with creatinine clearance of less than 35 mL/minute or those with evidence of acute renal impairment.

• Acute renal failure
• Anuria
• Capillary fragility
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Lactation
• Pulmonary congestion
• Severe chronic heart failure
• Severe dehydration

• Aseptic necrosis of jaw bone
• Atypical femoral fracture
• Dehydration
• Hypernatremia
• Hypocalcemia
• Hypomagnesemia
• Hypophosphatemia
• Intracranial bleeding
• Invasive dental procedure
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Periodontitis
• Pregnancy

• Arthralgia
• Aspirin exacerbated respiratory disease
• Hyperkalemia
• Hyponatremia
• Hypovolemia
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Myalgia

There is no enhanced messaging for this drug.

More Frequent

• Bone pain
• Dyspnea
• Hypertension
• Hypokalemia
• Hypomagnesemia
• Hypophosphatemia

Less Frequent

• Anemia
• Atrial fibrillation
• Granulocytopenic disorder
• Hypotension
• Infection
• Thrombocytopenic disorder

Rare or Very Rare

• Acute renal failure
• Anaphylaxis
• Angioedema
• Aseptic necrosis of bone in orofacial region
• Aseptic necrosis of jaw bone
• Asthma exacerbation
• Atypical femoral fracture
• Atypical stress fracture
• Avascular necrosis of bone
• Bradycardia
• Bronchospastic pulmonary disease
• Fanconi syndrome
• Hypersensitivity drug reaction
• Hyperthermia
• Hypocalcemia
• Injection site sequelae
• Interstitial lung disease
• Iritis
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Scleritis
• Seizure disorder
• Stevens-johnson syndrome
• Toxic epidermal necrolysis
• Uveitis

More Frequent

• Acute abdominal pain
• Allergic dermatitis
• Arthralgia
• Back pain
• Chills
• Constipation
• Cough
• Diarrhea
• Dizziness
• Fatigue
• Fever
• Flu-like symptoms
• Headache disorder
• Insomnia
• Myalgia
• Nausea
• Ocular inflammation
• Peripheral edema
• Urinary tract infection
• Vomiting

Less Frequent

• Acute cognitive impairment
• Agitation
• Anorexia
• Cramps
• Dysgeusia
• Dyspepsia
• Dysphagia
• General weakness
• Hyperhidrosis
• Paresthesia
• Stomatitis
• Upper abdominal pain

Rare or Very Rare

• Arthritis
• Chest pain
• Cramps in legs
• Dehydration
• Hypoesthesia
• Malaise
• Pruritus of skin
• Skin rash
• Tremor
• Urticaria

No enhanced messaging available.

Zoledronic acid is not indicated for use in children.

Category D. (See Users Guide and see Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)

It is not known whether zoledronic acid is distributed into milk; because of the potential for serious adverse effects in nursing infants from zoledronic acid, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. It is also important to consider that zoledronic acid is retained by bone for prolonged periods and may be released over weeks to years, possibly affecting nursing infants.

No overall differences in safety and efficacy of zoledronic acid relative to younger adults; however, the incidence of acute-phase inflammatory reactions was less in geriatric patients with osteoporosis or Paget disease of bone than in younger adults. Because of the greater frequency of impaired renal function in geriatric patients, the manufacturer states that renal function should be monitored with particular care in this age group.