Summary of the safety profile
The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the femur, osteonecrosis of the jaw, gastrointestinal irritation, 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 in intensity, and usually resolve during continuing treatment without requiring remedial measures (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 2.5mg 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 (MF4411).
In a two-year study in postmenopausal women with osteoporosis (BM 16549) the overall safety of ibandronic acid 150mg once monthly and ibandronic acid 2.5mg daily was similar. The overall proportion of patients, who experienced an adverse reaction, was 22.7% and 25.0% for ibandronic acid 150mg once monthly after one and two years, respectively. Most cases 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.
Table 1: Adverse reactions occurring in postmenopausal women receiving ibandronic acid 150mg once monthly or ibandronic acid 2.5mg daily in the phase III studies BM16549 and MF4411 and in post-marketing experience.
|
System Organ Class |
Common |
Uncommon |
Rare |
Very rare |
|
Immune system disorders |
|
Asthma exacerbation |
Hypersensitivity reaction |
Anaphylactic reaction/shock*† |
|
Nervous system disorders |
Headache |
Dizziness |
|
|
|
Eye disorders |
|
|
Ocular inflammation*† |
|
|
Gastrointestinal disorders* |
Oesophagitis,
Gastritis,
Gastro
oesophageal
reflux disease,
Dyspepsia,
Diarrhoea,
Abdominal
pain, Nausea |
Oesophagitis including oesophageal ulcerations or strictures and dysphagia, Vomiting, Flatulence |
Duodenitis |
|
|
Skin and subcutaneous tissues disorders |
Rash |
|
Angio-oedema, Face oedema, Urticaria |
|
|
Musculoskeletal and connective tissue disorders |
Arthralgia, Myalgia, Musculoskeletal pain, Muscle cramp,
Musculoskeletal stiffness |
Back pain |
Atypical subtrochanteric and diaphyseal femoral fractures† |
Osteonecrosis of jaw*†
Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction) |
|
General disorders and administration site conditions |
Influenza like illness* |
Fatigue |
|
|
** See further information below
† Identified in post-marketing experience.
Description of selected adverse reactions
Gastrointestinal adverse reactions
Patients with a previous history of gastrointestinal disease including patients with peptic ulcer without recent bleeding or hospitalisation, and patients with dyspepsia or reflux controlled by medication were included in the once monthly treatment study. For these patients, there was no difference in the incidence of upper gastrointestinal adverse events with the 150mg once monthly regimen compared to the 2.5mg daily regimen.
Influenza-like illness
Influenza-like illness includes events reported as acute phase reaction or symptoms including myalgia, arthralgia, fever, chills, fatigue, nausea, loss of appetite, or bone pain.
Osteonecrosis of the jaw
Cases of osteonecrosis of the jaw have been reported, predominantly in cancer patients treated with medicinal products that inhibit bone resorption, such as ibandronic acid (see section 4.4.) Cases of ONJ have been reported in the post marketing setting for ibandronic acid.
Ocular inflammation
Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with ibandronic acid. In some cases, these events did not resolve until the ibandronic acid was discontinued.
Anaphylactic reaction/shock
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with intravenous ibandronic acid.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Summary of the safety profile
The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the femur, osteonecrosis of the jaw, gastrointestinal irritation, 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 in intensity, and usually resolve during continuing treatment without requiring remedial measures (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 2.5mg 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 (MF4411).
In a two-year study in postmenopausal women with osteoporosis (BM 16549) the overall safety of ibandronic acid 150mg once monthly and ibandronic acid 2.5mg daily was similar. The overall proportion of patients, who experienced an adverse reaction, was 22.7% and 25.0% for ibandronic acid 150mg once monthly after one and two years, respectively. Most cases 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.
Table 1: Adverse reactions occurring in postmenopausal women receiving ibandronic acid 150mg once monthly or ibandronic acid 2.5mg daily in the phase III studies BM16549 and MF4411 and in post-marketing experience.
|
System Organ Class |
Common |
Uncommon |
Rare |
Very rare |
|
Immune system disorders |
|
Asthma exacerbation |
Hypersensitivity reaction |
Anaphylactic reaction/shock*† |
|
Nervous system disorders |
Headache |
Dizziness |
|
|
|
Eye disorders |
|
|
Ocular inflammation*† |
|
|
Gastrointestinal disorders* |
Oesophagitis,
Gastritis,
Gastro
oesophageal
reflux disease,
Dyspepsia,
Diarrhoea,
Abdominal
pain, Nausea |
Oesophagitis including oesophageal ulcerations or strictures and dysphagia, Vomiting, Flatulence |
Duodenitis |
|
|
Skin and subcutaneous tissues disorders |
Rash |
|
Angio-oedema, Face oedema, Urticaria |
Stevens-Johnson Syndrome†,
Erythema Multiforme†,
Dermatitis Bullous† |
|
Musculoskeletal and connective tissue disorders |
Arthralgia, Myalgia, Musculoskeletal pain, Muscle cramp,
Musculoskeletal stiffness |
Back pain |
Atypical subtrochanteric and diaphyseal femoral fractures† |
Osteonecrosis of jaw*†
Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction) |
|
General disorders and administration site conditions |
Influenza like illness* |
Fatigue |
|
|
** See further information below
† Identified in post-marketing experience.
Description of selected adverse reactions
Gastrointestinal adverse reactions
Patients with a previous history of gastrointestinal disease including patients with peptic ulcer without recent bleeding or hospitalisation, and patients with dyspepsia or reflux controlled by medication were included in the once monthly treatment study. For these patients, there was no difference in the incidence of upper gastrointestinal adverse events with the 150mg once monthly regimen compared to the 2.5mg daily regimen.
Influenza-like illness
Influenza-like illness includes events reported as acute phase reaction or symptoms including myalgia, arthralgia, fever, chills, fatigue, nausea, loss of appetite, or bone pain.
Osteonecrosis of the jaw
Cases of osteonecrosis of the jaw have been reported, predominantly in cancer patients treated with medicinal products that inhibit bone resorption, such as ibandronic acid (see section 4.4.) Cases of ONJ have been reported in the post marketing setting for ibandronic acid.
Ocular inflammation
Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with ibandronic acid. In some cases, these events did not resolve until the ibandronic acid was discontinued.
Anaphylactic reaction/shock
Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with intravenous ibandronic acid.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.