Zometa Special Precautions

General: All patients, including patients with mild to moderate renal impairment, must be assessed prior to administration of Zometa to assure that they are adequately hydrated.
Overhydration should be avoided in patients at risk of cardiac failure.
Standard hypercalcemia-related metabolic parameters eg, albumin-corrected serum levels of calcium, phosphate and magnesium as well as serum creatinine should be carefully monitored after initiating Zometa therapy. If hypocalcemia, hypophosphatemia or hypomagnesemia occur, short-term supplemental therapy may be necessary. Untreated hypercalcemia patients generally have some degree of renal function impairment, therefore careful renal function monitoring should be considered.
Zometa contains the same active ingredient as found in Aclasta (zoledronic acid). Patients being treated with Zometa should not be treated with Aclasta concomitantly. Zometa should also not be given together with other bisphosphonates since the combined effects of these agents are unknown.
While not observed in clinical trials with Zometa, there have been reports of bronchoconstriction in acetylsalicylic acid sensitive asthmatic patients receiving bisphosphonates.
Renal Impairment: Adult patients with HCM with evidence of impairment in renal function should be appropriately evaluated with consideration given as to whether the potential benefit of treatment with Zometa outweighs the possible risk.
The decision to treat patients with bone metastases for the prevention of skeletal-related events should consider that the onset of treatment effect is 2-3 months.
Bisphosphonates have been associated with reports of renal function deterioration. Factors that may increase the potential for deterioration in renal function include dehydration, preexisting renal impairment, multiple cycles of Zometa or other bisphosphonates as well as use of nephrotoxic drugs or using a shorter infusion time than currently recommended. While the risk is reduced with a dose of Zometa 4 mg administered over no less than 15 min, deterioration in renal function may still occur. Renal deterioration, progression to renal failure and dialysis have been reported in patients after the initial dose or a single dose of Zometa. Increases in serum creatinine also occur in some patients with chronic administration of Zometa at recommended doses for prevention of skeletal-related events, although less frequently.
Serum creatinine levels should be measured before each Zometa dose. In patients with mild to moderate renal impairment at the initiation of Zometa treatment, lower doses are recommended in all adult patients except patients with HCM. In patients who show evidence of renal deterioration during treatment, Zometa should only be resumed when creatinine level returns to within 10% of baseline value (see Dosage & Administration).
The use of Zometa is not recommended in patients with severe renal impairment because there are limited clinical safety and pharmacokinetic data in this population, and there is a risk of renal function deterioration in patients treated with bisphosphonates, including Zometa. In clinical trials, patients with severe renal impairment were defined as those with baseline serum creatinine ≥400 micromol/L or ≥4.5 mg/dL for patients with HCM and ≥265 micromol/L or ≥3 mg/dL for all other patients, respectively. In pharmacokinetic studies, patients with severe renal impairment were defined as those with baseline CrCl <30 mL/min (see Pharmacology: Pharmacokinetics under Actions).
Hepatic Impairment: As only limited clinical data are available in patients with severe hepatic impairment, no specific recommendations can be given for this patient population.
Osteonecrosis of the Jaw (ONJ): ONJ has been reported predominantly in adult cancer patients treated with bisphosphonates, including Zometa. Many of these patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures eg, tooth extraction. Many had signs of local infection, including osteomyelitis.
Post-marketing experience and the literature suggest a greater frequency of reports of ONJ based on tumor type (advanced breast cancer, multiple myeloma) and dental status (dental extraction, periodontal disease, local trauma including poorly fitting dentures).
Patients should maintain good oral hygiene and should have a dental examination with preventive dentistry prior to treatment with bisphosphonates.
While on treatment with bisphosphonates, patients should avoid invasive dental procedures if possible. For patients who develop ONJ while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.
Atypical Fractures of the Femur: Atypical subtrochanteric and diaphyseal femoral fractures have been reported in patients receiving bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore, the contralateral femur should be examined in Zometa-treated patients, who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of Zometa therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment. Reports of atypical femoral fracture have been received in patients treated with Zometa; however, causality with Zometa therapy has not been established.
During Zometa treatment, patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.
Musculoskeletal Pain: In post-marketing experience, severe and occasionally incapacitating bone, joint and/or muscle pain have been reported in patients taking bisphosphonates, including Zometa (see Adverse Reactions). The time to onset of symptoms varied from 1 day to several months after starting treatment. Most patients had relief of symptoms after stopping treatment. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.
Hypocalcemia: Hypocalcemia has been reported in patients treated with Zometa. Cardiac arrhythmias and neurologic adverse events (seizures, tetany and numbness) have been reported secondary to cases of severe hypocalcemia. In some instances, the hypocalcemia may be life-threatening.