Ibandronic acid Accord · 4.1 Therapeutic indications · 2

HOS-216308 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the femur, osteonecrosis for the jaw, and ocular inflammation (see paragraph “description of selected adverse reactions” and section 4.4). 6 Treatment of tumour induced hypercalcaemia is most frequently associated with a rise in body temperature. Less frequently, a decrease in serum calcium below normal range (hypocalcaemia) is reported. In most cases no specific treatment is required and the symptoms subside after a couple of hours/days. In the prevention of skeletal events in patients with breast cancer and bone metastases, treatment is most frequently associated with asthenia followed by rise in body temperature and headache. Tabulated list of adverse reactions Table 1 lists adverse drug reactions from the pivotal phase III studies (Treatment of tumour induced hypercalcaemia: 311 patients treated with ibandronic acid 2 mg or 4 mg; Prevention of skeletal events in patients with breast cancer and bone metastases: 152 patients treated with ibandronic acid 6 mg), and from post-marketing experience. Adverse reactions 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. Table 1 Adverse Reactions Reported for Intravenous Administration of Ibandronic Acid System Organ Common Uncommon Rare Very rare Not known Class Infections and Infection Cystitis, vaginitis, infestations oral candidiasis Neoplasms Benign skin benign, neoplasm malignant, and unspecified Blood and Anaemia, blood lymphatic system dyscrasia disorders Immune system Hypersensitivity†, Asthma disorders bronchospasm†, exacerbation

Auszug; vollständigen Abschnitt im Original lesen.

HOS-216314 · has-adverse-reaction-information · PDF-Seite 19

Summary of the safety profile The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the femur, osteonecrosis for the jaw and ocular inflammation (see paragraph “Description of selected adverse reactions” and section 4.4). The most frequently reported adverse reactions are arthralgia and influenza-like symptoms. These symptoms are typically in association with the first dose, generally of short duration, mild or moderate 19 in intensity, and usually resolve during continuing treatment without requiring remedial measures (please see paragraph “Influenza like illness”). Tabulated list of adverse reactions In table 1 a complete list of known adverse reactions is presented. The safety of oral treatment with ibandronic acid 2.5 mg daily was evaluated in 1251 patients treated in 4 placebo-controlled clinical studies, with the large majority of patients coming from the pivotal three-year fracture study (MF 4411). In the pivotal two-year study in postmenopausal women with osteoporosis (BM16550), the overall safety of intravenous injection of ibandronic acid 3 mg every 3 months and oral ibandronic acid 2.5 mg daily were shown to be similar. The overall proportion of patients who experienced an adverse reaction was 26.0 % and 28.6 % for ibandronic acid 3 mg injection every 3 months after one year and two years, respectively. Most cases of adverse reactions did not lead to cessation of therapy. Adverse reactions 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. 20 Table 1: Adverse reactions occurring in postmenopausal women receiving ibandronic acid 3 mg injection every 3 months or ibandronic acid 2.5 mg daily in the phase III studies BM16550 and MF 4411, and in post-marketing experience. System Organ Common Uncommon Rare Very rare Not Class Known Immune system

Auszug; vollständigen Abschnitt im Original lesen.

HOS-216304 · has-contraindication-information · PDF-Seite 4

 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1  Hypocalcaemia

HOS-216310 · has-contraindication-information · PDF-Seite 17

 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  Hypocalcaemia

HOS-216303 · has-indication-information · PDF-Seite 2

Ibandronic acid is indicated in adults for  Prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy or surgery) in patients with breast cancer and bone metastases.  Treatment of tumour-induced hypercalcaemia with or without metastases.

HOS-216309 · has-indication-information · PDF-Seite 16

Treatment of osteoporosis in postmenopausal women at increased risk of fracture (see section 5.1). A reduction in the risk of vertebral fractures has been demonstrated, efficacy on femoral neck fractures has not been established.

HOS-216312 · has-interaction-information · PDF-Seite 19

Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats (see section 5.2). Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation.

HOS-216306 · has-interaction-information · PDF-Seite 6

Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats (see section 5.2). Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. Caution is advised when bisphosphonates are administered with aminoglycosides, since both substances can lower serum calcium levels for prolonged periods. Attention should also be paid to the possible existence of simultaneous hypomagnesaemia.

HOS-216313 · has-pregnancy-information · PDF-Seite 19

Pregnancy Ibandronic acid is only for use in postmenopausal women and must not be taken by women of child bearing potential. There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have shown some reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Ibandronic acid should not be used during pregnancy. Breast-feeding It is not known whether ibandronic acid is excreted in human milk. Studies in lactating rats have demonstrated the presence of low levels of ibandronic acid in the milk following intravenous administration. Ibandronic acid should not be used during breastfeeding. Fertility There are no data on the effects of ibandronic acid from humans. In reproductive studies in rats by the oral route, ibandronic acid decreased fertility. In studies in rats using the intravenous route, ibandronic acid decreased fertility at high daily doses (see section 5.3).

HOS-216307 · has-pregnancy-information · PDF-Seite 6

Pregnancy There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Therefore, ibandronic acid should not be used during pregnancy. Breast-feeding It is not known whether ibandronic acid is excreted in human milk. Studies in lactating rats have demonstrated the presence of low levels of ibandronic acid in the milk following intravenous administration. Ibandronic acid should not be used during breast-feeding. Fertility There are no data on the effects of ibandronic acid in humans. In reproductive studies in rats by the oral route, ibandronic acid decreased fertility. In studies in rats using the intravenous route, ibandronic acid decreased fertility at high daily doses (see section 5.3).

HOS-216311 · has-warning-information · PDF-Seite 17

Administration failures Care must be taken not to administer ibandronic acid injection via intra-arterial or paravenous administration as this could lead to tissue damage. Hypocalcaemia Ibandronic acid, like other bisphosphonates administered intravenously, may cause a transient decrease in serum calcium values. Existing hypocalcaemia must be corrected before starting ibandronic acid injection therapy. Other disturbances of bone and mineral metabolism should also be effectively treated before starting ibandronic acid injection therapy. All patients must receive adequate supplemental calcium and vitamin D. Anaphylactic reaction/shock Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with intravenous ibandronic acid. Appropriate medical support and monitoring measures should be readily available when ibandronic acid intravenous injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions occur, immediately discontinue the injection and initiate appropriate treatment. Renal impairment Patients with concomitant diseases, or who use medicinal products which have potential for undesirable effects on the kidney, should be reviewed regularly in line with good medical practice during treatment. Due to limited clinical experience, ibandronic acid injection is not recommended for patients with a serum creatinine above 200 μmol/l (2.3 mg/dl) or with a creatinine clearance below 30 ml/min (see section 4.2 and section 5.2). Patients with cardiac impairment 17 Overhydration should be avoided in patients at risk of cardiac failure. Osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) has been reported very rarely in the post marketing setting in patients receiving ibandronic acid for osteoporosis (see section 4.8). The start of treatment or of a new course of treatment should be delayed in patients with unhealed 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 ibandronic acid in patients with concomitant risk factors. The following risk factors should be considered when evaluating a patient’s risk of developing ONJ: - Potency of the medicinal product that inhibit bone resorption (higher risk for highly potent compounds), route of administration (higher risk for parenteral administration) and

Auszug; vollständigen Abschnitt im Original lesen.

HOS-216305 · has-warning-information · PDF-Seite 4

Patients with disturbances of bone and mineral metabolism Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated before starting ibandronic acid therapy for metastatic bone disease. Adequate intake of calcium and vitamin D is important in all patients. Patients should receive supplemental calcium and/or vitamin D if dietary intake is inadequate. Anaphylactic reaction/shock Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with intravenous ibandronic acid. Appropriate medical support and monitoring measures should be readily available when Ibandronic acid intravenous injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions occur, immediately discontinue the injection and initiate appropriate treatment. Osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) has been reported very rarely in the post marketing setting in patients receiving ibandronic acid for oncology indications (see section 4.8). The start of treatmentor of a new course of treatment should be delayed in patients with unhealed 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 ibandronic acid in patients with concomitant risk factors. The following risk factors should be considered when evaluating a patient’s risk of developing ONJ: - Potency of the medicinal product that inhibit bone resorption (higher risk for highly potent compounds), route of administration (higher risk for parenteral administration) and cumulative dose of bone resorption therapy - Cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking - Concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to head and neck - Poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease , invasive dental procedures e.g. tooth extractions 4 All patients should be encouraged to maintain good oral hygiene, undergo routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling, or non-healing of sores or discharge during treatment with ibandronic acid. While on treatment, invasive dental procedures should be performed only after careful consideration and be

Auszug; vollständigen Abschnitt im Original lesen.