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mmended doses for prevention of skeletal related events, although less frequently.Patients should have their serum creatinine levels assessed prior to each dose of Zometa. Upon initiation of treatment in patients with bone metastases with mild to moderate renal impairment, lower doses of Zometa are recommended. In patients who show evidence of renal deterioration during treatment, Zometa should be withheld. Zometa should only be resumed when serum creatinine returns to within 10% of baseline.In view of the potential impact of bisphosphonates, including Zometa, on renal function, the lack of clinical safety data in patients with severe renal impairment (in clinical trials defined as serum creatinine 400 µmol/l or 4.5 mg/dl for patients with TIH and 265 µmol/l or 3.0 mg/dl for patients with cancer and bone metastases, respectively) at baseline and only limited pharmacokinetic data in patients with severe renal impairment at baseline (creatinine clearance < 30 ml/min), the use of Zometa is not recommended in patients with severe renal impairment.Hepatic insufficiencyAs only limited clinical data are available in patients with severe hepatic insufficiency, no specific recommendations can be given for this patient population.Osteonecrosis of the jawOsteonecrosis of the jaw has been reported in patients, predominantly those with cancer, receiving treatment 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 such as tooth extraction. Many had signs of local infection including osteomyelitis.A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, corticosteroids, poor oral hygiene).While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw 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 judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.Musculoskeletal painIn post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain have been reported in patients taking bisphosphonates. However, such reports have been infrequent. This category of drugs includes Zometa (zoledronic acid). The time to onset of symptoms varied from one 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.
Interactions
In clinical studies, Zometa has been administered concomitantly with commonly used anticancer agents, diuretics, antibiotics and analgesics without clinically apparent interactions occurring. Zoledronic acid shows no appreciable binding to plasma proteins and does not inhibit human P450 enzymes in vitro, but no formal clinical interaction studies have been performed. Caution is advised when bisphosphonates are administered with aminoglycosides, since both agents may have an additive effect, re |
