Side effects can include
fatigue,
anemia,
muscle aches,
fever, and/or
swelling in the feet or legs.
Flu-like symptoms are common after the first infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human
gamma delta T cell (γδ T cells).
Kidneys There is a risk of severe renal impairment. Appropriate hydration is important before administration, as is adequate
calcium and
vitamin D intake before Aclasta therapy in patients with
hypocalcaemia, and for ten days following Aclasta in patients with Paget's disease of the bone. Monitoring for other mineral metabolism disorders and the avoidance of invasive dental procedures for those who develop
osteonecrosis of the jaw is recommended. Zoledronate is rapidly processed via the
kidneys; consequently its administration is not recommended for patients with reduced
renal function or kidney disease. Some cases of
acute kidney injury either requiring dialysis or having a fatal outcome following Reclast use have been reported to the U.S.
Food and Drug Administration (FDA). This assessment was confirmed by the
European Medicines Agency (EMA), whose Committee for Medicinal Products for Human Use (CHMP) specified new contraindications for the medication on 15 December 2011, which include hypocalcaemia and severe renal impairment with a
creatinine clearance of less than 35 ml/min.
Bone Osteonecrosis of the jaw A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is
osteonecrosis of the jaw. This has mainly been seen in patients with
multiple myeloma treated with zoledronic acid who have had
dental extractions.
Atypical fractures After approving the drug in July 2009, the
European Medicines Agency conducted a class review of all
bisphosphonates, including zoledronic acid, after several cases of atypical fractures were reported. In 2008, the EMA's Pharmacovigilance Working Party (PhVWP) noted that
alendronic acid was associated with an increased risk of atypical fracture of the
femur that developed with low or no trauma. In April 2010, the PhVWP noted that further data from both the published literature and post-marketing reports were now available which suggested that atypical stress fractures of the femur may be a class effect. The
European Medicines Agency then reviewed all case reports of stress fractures in patients treated with bisphosphonates, relevant data from the published literature, and data provided by the companies which market bisphosphonates. The Agency recommended that doctors who prescribe bisphosphonate-containing medicines should be aware that atypical fractures may occur rarely in the femur, especially after long-term use, and that doctors who are prescribing these medicines for the prevention or treatment of osteoporosis should regularly review the need for continued treatment, especially after five or more years of use. ==Pharmacology==