Aclasta Special Precautions

General: The dose of 5 mg zoledronic acid must be administered over at least 15 minutes.
Aclasta contains the same active ingredient found in Zometa (zoledronic acid), used for oncology indications, and a patient being treated with Zometa should not be treated with Aclasta.
Patients must be appropriately hydrated prior to administration of Aclasta. This is especially important in the elderly and for patients receiving diuretic therapy. Pre-existing hypocalcaemia must be treated by adequate intake of calcium and vitamin D before initiating therapy with Aclasta (see CONTRAINDICATIONS). Other disturbances of mineral metabolism must also be effectively treated (e.g. diminished parathyroid reserve; thyroid surgery, parathyroid surgery, intestinal calcium malabsorption). Physicians should consider clinical monitoring for these patients.
Renal impairment: The use of Aclasta in patients with severe renal impairment (creatinine clearance <35 mL/min) is contraindicated due to an increased risk of renal failure in this population.
Renal impairment has been observed following the administration of Aclasta (see Adverse drug reactions from post-marketing spontaneous reports under ADVERSE REACTIONS), especially in patients with pre-existing renal impairment or other risk factors including advanced age, concomitant nephrotoxic medicinal products, concomitant diuretic therapy (see INTERACTIONS), or dehydration occurring after Aclasta administration. Renal impairment has been observed in patients after a single administration. Renal failure requiring dialysis or with a fatal outcome has rarely occurred in patients with underlying renal impairment or with any of the risk factors described previously.
The following precautions should be taken into account to minimize the risk of renal adverse reactions: Creatinine clearance should be calculated (e.g. Cockcroft-Gault formula) before each Aclasta dose. Transient increase in serum creatinine may be greater in patients with underlying impaired renal function; interim monitoring of serum creatinine should be considered in at-risk patients.
Aclasta should be used with caution when concomitantly used with other medicinal products that could impact renal function (see INTERACTIONS).
Patients, especially elderly patients and those receiving diuretic therapy, should be appropriately hydrated prior to administration of Aclasta.
A single dose of Aclasta should not exceed 5 mg and the duration of infusion should not be less than 15 minutes (see DOSAGE & ADMINISTRATION).
Calcium and Vitamin D Supplementation: Treatment and prevention of Osteoporosis: Adequate supplemental calcium and vitamin D intake is important in men and women with osteoporosis or treated to prevent postmenopausal osteoporosis if dietary intake is inadequate.
Prevention of Clinical Fractures after a Hip Fracture: Supplemental calcium and vitamin D intake is recommended for patients treated to prevent clinical fractures after a hip fracture.
Treatment of Paget's disease of bone: Elevated bone turnover is a characteristic of Paget's disease of bone. Due to the rapid onset of effect of zoledronic acid on bone turnover, transient hypocalcaemia, sometimes symptomatic, may develop and is usually maximal within the first 10 days after infusion of Aclasta (see ADVERSE REACTIONS). Adequate vitamin D intake is recommended in association with Aclasta administration. In addition, it is strongly advised that adequate supplemental calcium corresponding to at least 500 mg elemental calcium twice daily is ensured in patients with Paget's disease for at least 10 days following Aclasta administration. Patients should be informed about symptoms of hypocalcaemia. Physicians should consider clinical monitoring for patients at risk.
Musculoskeletal pain: Severe and occasionally incapacitating bone, joint, and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including Aclasta.
Osteonecrosis of the Jaw: Osteonecrosis of the jaw (ONJ): Osteonecrosis of the jaw has been reported predominantly in cancer patients treated with bisphosphonates, including zoledronic acid. 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, anti-angiogenic drugs, corticosteroids, poor oral hygiene). During the treatment with zoledronic acid, it is prudent to maintain good oral hygiene, undergo routine dental check-ups, and immediately report any oral symptoms. 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. The clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.
Osteonecrosis of other bones: Cases of osteonecrosis of other bones (including femur, hip, knee and humerus) have also been reported; however, causality has not been determined in the population treated with Aclasta.
Atypical fractures of the femur: Atypical subtrochanteric and diaphyseal femoral fractures have been reported in association with 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 weeks to months before a completed femoral fracture.
Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending an individual benefit risk assessment. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates.
During bisphosphonate treatment, including Aclasta, patients should be advised to report any thigh, hip or groin pain and any patient with such symptoms should be evaluated for possible femur fracture.