Zoledronic Acid Fresenius Kabi Adverse Reactions

Summary of the Safety Profile: Within three days after zoledronic acid administration, used as indicated in section Indications and Recommended dose and Mode of administration, an acute phase reaction has commonly been reported, with symptoms including bone pain, fever, fatigue, arthralgia, myalgia and rigors; these symptoms usually resolve within a few days (see Description of Selected Adverse Reactions).
The following are the important identified risks with Zoledronic acid in the approved indications: Renal function impairment, osteonecrosis of the jaw, acute phase reaction, hypocalcaemia, ocular adverse events, atrial fibrillation, anaphylaxis. The frequencies for each of these identified risks are shown in table as follows.
Tabulated List of Adverse Reactions: (See Table 2.)

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Description of Selected Adverse Reactions: Renal Function Impairment: Zoledronic acid, used as indicated in sections indications and Recommended dose and Mode of administration, has been associated with reports of renal dysfunction. (see Precautions).
Osteonecrosis of the jaw: Although causality has not been determined, it is recommended to avoid dental surgery as recovery may be prolonged (see Precautions).
Atrial Fibrillation: In one 3-year, randomized, double-blind controlled trial that evaluated the efficacy and safety of zoledronic acid 5 mg once yearly vs. placebo in the treatment of postmenopausal osteoporosis (PMO), the overall incidence of atrial fibrillation was 2.5% (96 out of 3,862) and 1.9% (75 out of 3,852) in patients receiving zoledronic acid 5 mg and placebo, respectively. The rate of atrial fibrillation serious adverse events was 1.3% (51 out of 3,862) and 0.6% (22 out of 3,852) in patients receiving zoledronic acid 5 mg and placebo, respectively. The imbalance observed in this trial has not been observed in other trails with zoledronic acid, including those with zoledronic acid 4 mg every 3-4 weeks in oncology patients. The mechanism behind the increased incidence of atrial fibrillation in this single clinical trial is unknown.
Acute phase reaction: This adverse drug reaction consists of a constellation of symptoms that includes fever, myalgia, headache, extremity pain, nausea, vomiting, diarrhoea and arthralgia. The onset time is ≤3 days post- zoledronic acid infusion, (used as indicated in section Recommended dose and Mode of administration), and the reaction is also referred to using the terms "flu-like" or "post-dose" symptoms.
Atypical Fractures of the Femur: During post-marketing experience the following reactions have been reported (frequency rare): Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).
Hypocalcaemia-related ADR's: There is evidence of an association between hypocalcaemia and secondary neurological events reported in these cases including; seizures, numbness and tetany (see Precautions).
Reporting of Suspected Adverse Reactions: Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.