Aclasta

Posology Patients must be appropriately hydrated prior to administration of Aclasta. This is especially important for the elderly (≥65 years)and for patients receiving diuretic therapy. Adequate calcium and vitamin D intake are recommended in association with Aclasta administration.

Osteoporosis For the treatment of post-menopausal osteoporosis, osteoporosis in men and the treatment of osteoporosis associated with long-term systemic glucocorticoid therapy, the recommended dose is a single intravenous infusion of 5 mg Aclasta administered once a year.

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of Aclasta on an individual patient basis, particularly after 5 or more years of use.

1). In patients with a recent low-trauma hip 3 fracture, a loading dose of 50 000 to 125 000 IU of vitamin D given orally or via the intramuscular route is recommended prior to the first Aclasta infusion. Paget’s disease For the treatment of Paget’s disease, Aclasta should be prescribed only by physicians with experience in the treatment of Paget’s disease of the bone.

The recommended dose is a single intravenous infusion of 5 mg Aclasta. 4).

Re-treatment of Paget’s disease:

After initial treatment with Aclasta in Paget’s disease, an extended remission period is observed in responding patients. Re-treatment consists of an additional intravenous infusion of 5 mg Aclasta after an interval of one year or longer from initial treatment in patients who have relapsed.

1). 4). No dose adjustment is necessary in patients with creatinine clearance ≥ 35 ml/min. 2). Elderly (≥ 65 years) No dose adjustment is necessary since bioavailability, distribution and elimination were similar in elderly patients and younger subjects.

Paediatric population Aclasta should not be used in children and adolescents below 18 years of age. There are no data available for children under 5 years of age. 1. Method of administration Intravenous use. Aclasta is administered via a vented infusion line and given slowly at a constant infusion rate.

The infusion time must not be less than 15 minutes. 6. Patients treated with Aclasta should be given the package leaflet and the patient reminder card.

2% after the first, second and third infusion, respectively. 1%), see “acute phase reactions” below. Tabulated list of adverse reactions Adverse reactions in Table 1 are listed according to MedDRA system organ class and frequency category.

Frequency categories are defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 8 Class effects) Renal and urinary disorders Uncommon Blood creatinine increased, pollakiuria, proteinuria Not known** Renal impairment.

8 Class effects) General disorders and administration site conditions Very common Pyrexia Common Influenza-like illness, chills, fatigue, asthenia, pain, malaise, infusion site reaction Uncommon Peripheral oedema, thirst, acute phase reaction, non-cardiac chest pain Not known** Dehydration secondary to acute phase reactions (post-dose symptoms such as pyrexia, vomiting and diarrhoea) Investigations Common C-reactive protein increased Uncommon Blood calcium decreased # Observed in patients taking concomitant glucocorticosteroids.

* Common in Paget’s disease only. ** Based on post-marketing reports. Frequency cannot be estimated from available data. † Identified in post-marketing experience. 9% (75 out of 3,852) in patients receiving Aclasta and placebo, respectively.

6%) (22 out of 3,852). The mechanism behind the increased incidence of atrial fibrillation is unknown. 1%). 8% for placebo. e. increased serum creatinine) and in rare cases acute renal failure. g advanced age, oncology patients with chemotherapy, concomitant nephrotoxic medicinal products, concomitant diuretic therapy, severe dehydration), with the majority of them receiving a 4 mg dose every 3–4 weeks, but it has been observed in patients after a single administration.

Renal function 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. 5), 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 above.

The following precautions should be taken into account to minimise the risk of renal adverse reactions: • Creatinine clearance should be calculated based on actual body weight using the Cockcroft-Gault formula before each Aclasta dose.

• Transient increase in serum creatinine may be greater in patients with underlying impaired renal function. • Monitoring of serum creatinine should be considered in at-risk patients. 5). • Patients, especially elderly patients and those receiving diuretic therapy, should be appropriately hydrated prior to administration of Aclasta.

2). 3). g. diminished parathyroid reserve, intestinal calcium malabsorption). Physicians should consider clinical monitoring for these patients. Elevated bone turnover is a characteristic of Paget’s disease of the bone. 8). Adequate calcium and vitamin D intake are recommended in association with Aclasta administration.

2). Patients should be informed about symptoms of hypocalcaemia and receive adequate clinical monitoring during the period of risk. Measurement of serum calcium before infusion of Aclasta is recommended for patients with Paget´s disease.

8). 8). The start of treatment or of a new course of treatment should be delayed in patients with unhealed 5 open soft tissue lesions in the mouth. A dental examination with preventive dentistry and an individual benefit-risk assessment is recommended prior to treatment with Aclasta in patients with concomitant risk factors.

1. 4). 4). 6). 4