Bondronat is indicated in adults for

- Prevention of bone complications (pathological fractures, complications, bone requiring radiotherapy or surgery) in patients with breast cancer and bone metastases

- Treatment of tumor-induced hypercalcemia with or without metastasis

Treatment with Bondronat should be initiated only by doctors with experience in the management of cancers

Dosage

Prevention of bone complications in patients with breast cancer and bone metastases

The recommended dose for the prevention of bone complications in patients with breast cancer and bone metastases is 6 mg intravenously administered every 3-4 weeks. The dose should be perfused for at least 15 minutes. For infusion, the contents of the vial (s) should be added to 100 ml of isotonic sodium chloride solution or 100 ml of 5% glucose solution.

A shorter duration of infusion (ie 15 minutes) should be used only in patients with normal renal function or renal impairment. There is no data available describing the use of a shorter duration of infusion in patients with creatinine clearance less than 50 ml / min. Prescribers should refer to the section on Insufficient Renal (see section 4.2) and the method of administration for dosage and administration recommendations for Bondronat. >

Treatment of hypercalcemia induced by tumors

Before Bondronat treatment, the patient should be properly hydrated, if necessary with sodium chloride 9 mg / ml (0.9%). The severity of hypercalcemia and tumor type must be taken into account. In general, patients with osteolytic bone metastases require doses lower than those in patients with hypercalcemia of humoral origin. In most patients with severe hypercalcaemia (serum corrected calcium, albumin * ≥ 3 mmol / l or ≥ 12 mg / dl), the dosage is 4 mg as a single dose. In patients with moderate hypercalcemia (serum calcium, albumin corrected

Osteonecrosis of the jaw (ONM)

Osteonecrosis of the jaw, usually associated with dental extraction and / or local infection (including osteomyelitis) has been reported, in patients with cancer receiving medication, including bisphosphonates, administered primarily Intravenously. Most of these patients also received chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis treated with bisphosphonates per os.

Dental examination as well as appropriate preventive dental care should be considered prior to initiation of treatment with bisphosphonates in patients with associated risk factors (eg cancer, chemotherapy, radiotherapy, corticosteroids, poor hygiene ; Buccale).

During treatment, these patients should avoid invasive dental procedures if possible. In patients who develop osteonecrosis of the jaw during a bisphosphonate treatment, dental surgery may aggravate this involvement. In patients requiring dental procedures, there is no evidence to suggest that discontinuation of bisphosphonate therapy reduces the risk of osteonecrosis of the jaw. The assessment of the clinical condition by the attending physician should guide the management of each patient based on the individual assessment of the benefit / risk ratio. >

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported as bisphosphonates, mainly in patients treated for osteoporosis. These short transverse or oblique fractures can occur on any part of the femur from below the small trochanter to the top of the supracondylar zone. These fractures occur after minimal trauma or trauma, and some patients have pain in the thigh or groin, often associated with radiological signs of stress fractures weeks or months before the femoral fracture. Fractures are often bilateral, so the contralateral femur should be examined in patients treated with bisphosphonates with a diaphyseal femoral fracture, and poor consolidation of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients in whom an atypical femoral fracture is suspected should be considered based on the patient's benefit / risk assessment. During treatment with bisphosphonates, patients should be informed that any pain in the thigh, hip or groin should be reported and all patients with such symptoms should be examined for Fracture, femoral atypical.

Renal insufficiency

Clinical studies did not demonstrate deterioration of renal function during long-term treatment with Bondronat. However, depending on the clinical condition of the patient, renal function, serum calcium, phosphate and magnesemia should be monitored in patients treated with Bondronat.

Insufficient liver disease

In the absence of clinical data, dosage recommendations may not be given in patients with severe hepatic impairment
Insufficient heart disease

Hyperhydration should be avoided in patients with a risk of heart failure.

Interaction studies have only been performed in adults

No interaction was observed when ibandronic acid was administered concomitantly with melphalan / prednisolone in patients with multiple myeloma.

Other interacting studies in postmenopausal women have demonstrated the absence of interaction with tamoxifen or hormone replacement therapy (estrogen). >
Because of its pharmacokinetics, clinically significant drug interactions are unlikely. The ibandronic acid is eliminated only by renal excretion and it undergoes no biotransformation. The pathway of secretion does not appear to include known acidic or basic transport systems involved in the excretion of other active substances. In addition, ibandronic acid does not inhibit the main human hepatic isoenzymes of cytochrome P450 nor does it induce the hepatic cytochrome P450 system in rats. Plasma protein binding is low at therapeutic doses, therefore it is unlikely that ibandronic acid will be able to displace other active substances.

Caution is advised when bisphosphonates are administered together with aminoglycosides, both of which are likely to lower serum calcium levels for prolonged periods. On the other hand, care should be taken to ensure the possible existence of hypomagnesemia, simultaneously.
In clinical studies, Bondronat was administered concomitantly with commonly used antineoplastic agents, diuretics, antibiotics and analgesics and no clinical interaction was observed.

In order to avoid potential incompatibilities, Bondronat diluent for infusion will only be diluted in an isotonic solution of sodium chloride or 5% glucose solution.

Bondronat should not be mixed with solutions containing calcium

To date no cases of acute poisoning by Bondronat solution to be diluted for infusion have been reported. Since preclinical studies using high doses have revealed the kidneys and liver as the target organs of toxicity, monitoring of renal and hepatic function is necessary. Any hypocalcemia with clinical symptoms should be corrected by intravenous administration of calcium gluconate.
Pregnancy

There is insufficient data on the use of ibandronic acid in pregnant women. Studies in rats have shown reproductive toxicity (see section Preclinical safety data). The potential in man is unknown. Therefore, Bondronat should not be used during pregnancy.


It is not known whether ibandronic acid is excreted in human milk. Studies in lactating rats have demonstrated the presence of low amounts of ibandronic acid in milk after intravenous administration. Bondronat should not be used during breastfeeding

Fertility

There are no data on the effects of ibandronic acid in humans.) In rat oral studies, ibandronic acid decreased fertility. In studies in the intravenous rat, ibandronic acid decreased fertility at high daily doses (see section Data, safety, preclinical).

The undesirable effects are classified in descending order of frequency according to the following convention, very common (≥ 1/10), frequent (≥ 1/100 and