Ibandronate Sodium
Generic: IBANDRONATE SODIUM
Basic Information
Manufacturer
Aurobindo Pharma Limited
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
86c0b4ae-5e38-4efe-88af-50ac560e294f
Indications & Usage
1 INDICATIONS AND USAGE Ibandronate sodium is a bisphosphonate indicated for the treatment and prevention of postmenopausal osteoporosis.
( 1.1 ) Limitations of Use The optimal duration of use has not been determined.
For patients at low -risk for fracture, consider drug discontinuation after 3 to 5 years of use.
( 1.2 ) 1.1 Treatment and Prevention of Postmenopausal Osteoporosis Ibandronate sodium tablets are indicated for the treatment and prevention of osteoporosis in postmenopausal women.
Ibandronate sodium tablets increase bone mineral density (BMD) and reduce the incidence of vertebral fractures.
1.2 Important Limitations of Use The optimal duration of use has not been determined.
The safety and effectiveness of ibandronate sodium tablets for the treatment of osteoporosis are based on clinical data of three years duration.
All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis.
Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use.
Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.
( 1.1 ) Limitations of Use The optimal duration of use has not been determined.
For patients at low -risk for fracture, consider drug discontinuation after 3 to 5 years of use.
( 1.2 ) 1.1 Treatment and Prevention of Postmenopausal Osteoporosis Ibandronate sodium tablets are indicated for the treatment and prevention of osteoporosis in postmenopausal women.
Ibandronate sodium tablets increase bone mineral density (BMD) and reduce the incidence of vertebral fractures.
1.2 Important Limitations of Use The optimal duration of use has not been determined.
The safety and effectiveness of ibandronate sodium tablets for the treatment of osteoporosis are based on clinical data of three years duration.
All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis.
Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use.
Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse drug reactions are described elsewhere in the labeling: Upper Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.1) ] Hypocalcemia and Mineral Metabolism [see Warnings and Precautions (5.2) ] Musculoskeletal [see Warnings and Precautions (5.3) ] Jaw Osteonecrosis [see Warnings and Precautions (5.4) ] Atypical Fractures Including Femoral Fractures [see Warnings and Precautions (5.5) ] Severe Renal Impairment [see Warnings and Precautions (5.6) ] The most common adverse reactions (greater than 5%) are back pain, dyspepsia, pain in extremity, diarrhea, headache, and myalgia.
(6) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc.
at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Treatment and Prevention of Postmenopausal Osteoporosis Daily Dosing The safety of ibandronate sodium 2.5 mg (ibandronate) once daily in the treatment and prevention of postmenopausal osteoporosis was assessed in 3577 patients aged 41 to 82 years.
The duration of the trials was 2 to 3 years, with 1134 patients exposed to placebo and 1140 exposed to ibandronate sodium 2.5 mg (ibandronate).
Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors and H 2 antagonists were included in these clinical trials.
All patients received 500 mg calcium plus 400 international units vitamin D supplementation daily.
The incidence of all-cause mortality was 1% in the placebo group and 1.2% in the ibandronate sodium 2.5 mg (ibandronate) daily group.
The incidence of serious adverse reactions was 20% in the placebo group and 23% in the ibandronate sodium 2.5 mg (ibandronate) daily group.
The percentage of patients who withdrew from treatment due to adverse reactions was approximately 17% in both the ibandronate sodium 2.5 mg (ibandronate) daily group and the placebo group.
Table 1 lists adverse reactions from the treatment and prevention studies reported in greater than or equal to 2% of patients and more frequently in patients treated daily with ibandronate sodium than patients treated with placebo.
Table 1 Adverse Reactions Occurring at an Incidence Greater Than or Equal to 2% and in More Patients Treated with Ibandronate Sodiu m Than in Patients Treated with Placebo Daily in the Osteoporosis Treatment and Prevention Studies Body System Placebo % (n=1134) Ibandronate Sodium 2.5 mg (ibandronate) % (n=1140) Body as a Whole Back Pain 12 14 Pain in Extremity 6 8 Asthenia 2 4 Allergic Reaction 2 3 Digestive System Dyspepsia 10 12 Diarrhea 5 7 Tooth Disorder 2 4 Vomiting 2 3 Gastritis 2 2 Musculoskeletal System Myalgia 5 6 Joint Disorder 3 4 Arthritis 3 3 Nervous System Headache 6 7 Dizziness 3 4 Vertigo 3 3 Respiratory System Upper Respiratory Infection 33 34 Bronchitis 7 10 Pneumonia 4 6 Pharyngitis 2 3 Urogenital System Urinary Tract Infection 4 6 Gastrointestinal Adverse Reactions The incidence of selected gastrointestinal adverse reactions in the placebo and ibandronate sodium 2.5 mg (ibandronate) daily groups were: dyspepsia (10% vs.
12%), diarrhea (5% vs.
7%), and abdominal pain (5% vs.
6%).
Musculoskeletal Adverse Reactions The incidence of selected musculoskeletal adverse reactions in the placebo and ibandronate sodium 2.5 mg (ibandronate) daily groups were: back pain (12% vs.
14%), arthralgia (14% vs.
14%) and myalgia (5% vs.
6%).
Ocular Adverse Events Reports in the medical literature indicate that bisphosphonates may be associated with ocular inflammation such as iritis and scleritis.
In some cases, these events did not resolve until the bisphosphonate was discontinued.
There were no reports of ocular inflammation in studies with ibandronate sodium 2.5 mg (ibandronate) daily.
Monthly Dosing The safety of ibandronate sodium 150 mg (ibandronate) once monthly in the treatment of postmenopausal osteoporosis was assessed in a two year trial which enrolled 1583 patients aged 54 to 81 years, with 395 patients exposed to ibandronate sodium 2.5 mg (ibandronate) daily and 396 exposed to ibandronate sodium 150 mg (ibandronate) monthly.
Patients with active or significant pre-existing gastrointestinal disease were excluded from this trial.
Patients with dyspepsia or concomitant use of nonsteroidal anti-inflammatory drugs, proton pump inhibitors and H 2 antagonists were included in this study.
All patients received 500 mg calcium plus 400 international units vitamin D supplementation daily.
After one year, the incidence of all-cause mortality was 0.3% in both the ibandronate sodium 2.5 mg (ibandronate) daily group and the ibandronate sodium 150 mg (ibandronate) monthly group.
The incidence of serious adverse events was 5% in the ibandronate sodium 2.5 mg (ibandronate) daily group and 7% in the ibandronate sodium 150 mg (ibandronate) monthly group.
The percentage of patients who withdrew from treatment due to adverse events was 9% in the ibandronate sodium 2.5 mg (ibandronate) daily group and 8% in the ibandronate sodium 150 mg (ibandronate) monthly group.
Table 2 lists the adverse events reported in greater than or equal to 2% of patients.
Table 2 Adverse Events with an Incidence of at Least 2% in Patients Treated with Ibandronate Sodium 2.5 mg (ibandronate) Daily or Ibandronate Sodium 150 mg (ibandronate) Once-Monthly for Treatment of Postmenopausal Osteoporosis Body System/Adverse Event Ibandronate Sodium 2.5 mg (ibandronate) Daily % (n=395) Ibandronate Sodium 150 mg (ibandronate) Monthly % (n=396) a Combination of abdominal pain and abdominal pain upper b Combination of influenza-like illness and acute phase reaction c Combination of rash pruritic, rash macular, rash papular, rash generalized, rash erythematous, dermatitis, dermatitis allergic, dermatitis medicamentosa, erythema and exanthema Vascular Disorders Hypertension 7.3 6.3 Gastrointestinal Disorders Dyspepsia 7.1 5.6 Nausea 4.8 5.1 Diarrhea 4.1 5.1 Constipation 2.5 4 Abdominal Pain a 5.3 7.8 Musculoskeletal and Connective Tissue Disorders Arthralgia 3.5 5.6 Back Pain 4.3 4.5 Pain in Extremity 1.3 4 Localized Osteoarthritis 1.3 3 Myalgia 0.8 2 Muscle Cramp 2 1.8 Infections and Infestations Influenza 3.8 4 Nasopharyngitis 4.3 3.5 Bronchitis 3.5 2.5 Urinary Tract Infection 1.8 2.3 Upper Respiratory Tract Infection 2 2 Nervous System Disorders Headache 4.1 3.3 Dizziness 1 2.3 General Disorders and Administration Site Conditions Influenza-like Illness b 0.8 3.3 Skin and Subcutaneous Tissue Disorders Rash c 1.3 2.3 Psychiatric Disorders Insomnia 0.8 2 Gastrointestinal Adverse Events The incidence of adverse events in the ibandronate sodium 2.5 mg (ibandronate) daily and ibandronate sodium 150 mg (ibandronate) monthly groups were: dyspepsia (7% vs.
6%), diarrhea (4% vs.
5%), and abdominal pain (5% vs.
8%).
Musculoskeletal Adverse Events The incidence of adverse events in the ibandronate sodium 2.5 mg (ibandronate) daily and ibandronate sodium 150 mg (ibandronate) monthly groups were: back pain (4% vs.
5%), arthralgia (4% vs.
6%) and myalgia (1% vs.
2%).
Acute Phase Reactions Symptoms consistent with acute phase reactions have been reported with bisphosphonate use.
Over the two years of the study, the overall incidence of acute phase reaction symptoms was 3% in the ibandronate sodium 2.5 mg (ibandronate) daily group and 9% in the ibandronate sodium 150 mg (ibandronate) monthly group.
These incidence rates are based on the reporting of any of 33 acute-phase reaction like symptoms within 3 days of the monthly dosing and lasting 7 days or less.
Influenza like illness was reported in no patients in the ibandronate sodium 2.5 mg (ibandronate) daily group and 2% in the ibandronate sodium 150 mg (ibandronate) monthly group.
Ocular Adverse Events Two patients who received ibandronate sodium 150 mg (ibandronate) once-monthly experienced ocular inflammation, one was a case of uveitis and the other scleritis.
One hundred sixty (160) postmenopausal women without osteoporosis participated in a 1-year, double-blind, placebo-controlled study of ibandronate sodium 150 mg (ibandronate) once-monthly for prevention of bone loss.
Seventy-seven subjects received ibandronate sodium and 83 subjects received placebo.
The overall pattern of adverse events was similar to that previously observed.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ibandronate sodium or bisphosphonate products.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity Allergic reactions including anaphylactic reaction/shock with fatalities, angioedema, bronchospasm, asthma exacerbations, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous have been reported (see CONTRAINDICATIONS [4] ) .
Hypocalcemia Hypocalcemia has been reported in patients treated with ibandronate sodium (see WARNINGS AND PRECAUTIONS [5.2] ) .
Musculoskeletal Bone, joint, or muscle pain, described as severe or incapacitating, have been reported rarely [see Warnings and Precautions (5.3) ]; low-energy femoral shaft and subtrochanteric fractures, and atypical fractures of other bones [see WARNINGS AND PRECAUTIONS (5.5) ].
Jaw Osteonecrosis Osteonecrosis of the jaw and other oro-facial sites, including the external auditory canal, have been reported in patients treated with ibandronate sodium (see WARNINGS AND PRECAUTIONS [5.4] ) .
(6) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc.
at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Treatment and Prevention of Postmenopausal Osteoporosis Daily Dosing The safety of ibandronate sodium 2.5 mg (ibandronate) once daily in the treatment and prevention of postmenopausal osteoporosis was assessed in 3577 patients aged 41 to 82 years.
The duration of the trials was 2 to 3 years, with 1134 patients exposed to placebo and 1140 exposed to ibandronate sodium 2.5 mg (ibandronate).
Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors and H 2 antagonists were included in these clinical trials.
All patients received 500 mg calcium plus 400 international units vitamin D supplementation daily.
The incidence of all-cause mortality was 1% in the placebo group and 1.2% in the ibandronate sodium 2.5 mg (ibandronate) daily group.
The incidence of serious adverse reactions was 20% in the placebo group and 23% in the ibandronate sodium 2.5 mg (ibandronate) daily group.
The percentage of patients who withdrew from treatment due to adverse reactions was approximately 17% in both the ibandronate sodium 2.5 mg (ibandronate) daily group and the placebo group.
Table 1 lists adverse reactions from the treatment and prevention studies reported in greater than or equal to 2% of patients and more frequently in patients treated daily with ibandronate sodium than patients treated with placebo.
Table 1 Adverse Reactions Occurring at an Incidence Greater Than or Equal to 2% and in More Patients Treated with Ibandronate Sodiu m Than in Patients Treated with Placebo Daily in the Osteoporosis Treatment and Prevention Studies Body System Placebo % (n=1134) Ibandronate Sodium 2.5 mg (ibandronate) % (n=1140) Body as a Whole Back Pain 12 14 Pain in Extremity 6 8 Asthenia 2 4 Allergic Reaction 2 3 Digestive System Dyspepsia 10 12 Diarrhea 5 7 Tooth Disorder 2 4 Vomiting 2 3 Gastritis 2 2 Musculoskeletal System Myalgia 5 6 Joint Disorder 3 4 Arthritis 3 3 Nervous System Headache 6 7 Dizziness 3 4 Vertigo 3 3 Respiratory System Upper Respiratory Infection 33 34 Bronchitis 7 10 Pneumonia 4 6 Pharyngitis 2 3 Urogenital System Urinary Tract Infection 4 6 Gastrointestinal Adverse Reactions The incidence of selected gastrointestinal adverse reactions in the placebo and ibandronate sodium 2.5 mg (ibandronate) daily groups were: dyspepsia (10% vs.
12%), diarrhea (5% vs.
7%), and abdominal pain (5% vs.
6%).
Musculoskeletal Adverse Reactions The incidence of selected musculoskeletal adverse reactions in the placebo and ibandronate sodium 2.5 mg (ibandronate) daily groups were: back pain (12% vs.
14%), arthralgia (14% vs.
14%) and myalgia (5% vs.
6%).
Ocular Adverse Events Reports in the medical literature indicate that bisphosphonates may be associated with ocular inflammation such as iritis and scleritis.
In some cases, these events did not resolve until the bisphosphonate was discontinued.
There were no reports of ocular inflammation in studies with ibandronate sodium 2.5 mg (ibandronate) daily.
Monthly Dosing The safety of ibandronate sodium 150 mg (ibandronate) once monthly in the treatment of postmenopausal osteoporosis was assessed in a two year trial which enrolled 1583 patients aged 54 to 81 years, with 395 patients exposed to ibandronate sodium 2.5 mg (ibandronate) daily and 396 exposed to ibandronate sodium 150 mg (ibandronate) monthly.
Patients with active or significant pre-existing gastrointestinal disease were excluded from this trial.
Patients with dyspepsia or concomitant use of nonsteroidal anti-inflammatory drugs, proton pump inhibitors and H 2 antagonists were included in this study.
All patients received 500 mg calcium plus 400 international units vitamin D supplementation daily.
After one year, the incidence of all-cause mortality was 0.3% in both the ibandronate sodium 2.5 mg (ibandronate) daily group and the ibandronate sodium 150 mg (ibandronate) monthly group.
The incidence of serious adverse events was 5% in the ibandronate sodium 2.5 mg (ibandronate) daily group and 7% in the ibandronate sodium 150 mg (ibandronate) monthly group.
The percentage of patients who withdrew from treatment due to adverse events was 9% in the ibandronate sodium 2.5 mg (ibandronate) daily group and 8% in the ibandronate sodium 150 mg (ibandronate) monthly group.
Table 2 lists the adverse events reported in greater than or equal to 2% of patients.
Table 2 Adverse Events with an Incidence of at Least 2% in Patients Treated with Ibandronate Sodium 2.5 mg (ibandronate) Daily or Ibandronate Sodium 150 mg (ibandronate) Once-Monthly for Treatment of Postmenopausal Osteoporosis Body System/Adverse Event Ibandronate Sodium 2.5 mg (ibandronate) Daily % (n=395) Ibandronate Sodium 150 mg (ibandronate) Monthly % (n=396) a Combination of abdominal pain and abdominal pain upper b Combination of influenza-like illness and acute phase reaction c Combination of rash pruritic, rash macular, rash papular, rash generalized, rash erythematous, dermatitis, dermatitis allergic, dermatitis medicamentosa, erythema and exanthema Vascular Disorders Hypertension 7.3 6.3 Gastrointestinal Disorders Dyspepsia 7.1 5.6 Nausea 4.8 5.1 Diarrhea 4.1 5.1 Constipation 2.5 4 Abdominal Pain a 5.3 7.8 Musculoskeletal and Connective Tissue Disorders Arthralgia 3.5 5.6 Back Pain 4.3 4.5 Pain in Extremity 1.3 4 Localized Osteoarthritis 1.3 3 Myalgia 0.8 2 Muscle Cramp 2 1.8 Infections and Infestations Influenza 3.8 4 Nasopharyngitis 4.3 3.5 Bronchitis 3.5 2.5 Urinary Tract Infection 1.8 2.3 Upper Respiratory Tract Infection 2 2 Nervous System Disorders Headache 4.1 3.3 Dizziness 1 2.3 General Disorders and Administration Site Conditions Influenza-like Illness b 0.8 3.3 Skin and Subcutaneous Tissue Disorders Rash c 1.3 2.3 Psychiatric Disorders Insomnia 0.8 2 Gastrointestinal Adverse Events The incidence of adverse events in the ibandronate sodium 2.5 mg (ibandronate) daily and ibandronate sodium 150 mg (ibandronate) monthly groups were: dyspepsia (7% vs.
6%), diarrhea (4% vs.
5%), and abdominal pain (5% vs.
8%).
Musculoskeletal Adverse Events The incidence of adverse events in the ibandronate sodium 2.5 mg (ibandronate) daily and ibandronate sodium 150 mg (ibandronate) monthly groups were: back pain (4% vs.
5%), arthralgia (4% vs.
6%) and myalgia (1% vs.
2%).
Acute Phase Reactions Symptoms consistent with acute phase reactions have been reported with bisphosphonate use.
Over the two years of the study, the overall incidence of acute phase reaction symptoms was 3% in the ibandronate sodium 2.5 mg (ibandronate) daily group and 9% in the ibandronate sodium 150 mg (ibandronate) monthly group.
These incidence rates are based on the reporting of any of 33 acute-phase reaction like symptoms within 3 days of the monthly dosing and lasting 7 days or less.
Influenza like illness was reported in no patients in the ibandronate sodium 2.5 mg (ibandronate) daily group and 2% in the ibandronate sodium 150 mg (ibandronate) monthly group.
Ocular Adverse Events Two patients who received ibandronate sodium 150 mg (ibandronate) once-monthly experienced ocular inflammation, one was a case of uveitis and the other scleritis.
One hundred sixty (160) postmenopausal women without osteoporosis participated in a 1-year, double-blind, placebo-controlled study of ibandronate sodium 150 mg (ibandronate) once-monthly for prevention of bone loss.
Seventy-seven subjects received ibandronate sodium and 83 subjects received placebo.
The overall pattern of adverse events was similar to that previously observed.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ibandronate sodium or bisphosphonate products.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity Allergic reactions including anaphylactic reaction/shock with fatalities, angioedema, bronchospasm, asthma exacerbations, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous have been reported (see CONTRAINDICATIONS [4] ) .
Hypocalcemia Hypocalcemia has been reported in patients treated with ibandronate sodium (see WARNINGS AND PRECAUTIONS [5.2] ) .
Musculoskeletal Bone, joint, or muscle pain, described as severe or incapacitating, have been reported rarely [see Warnings and Precautions (5.3) ]; low-energy femoral shaft and subtrochanteric fractures, and atypical fractures of other bones [see WARNINGS AND PRECAUTIONS (5.5) ].
Jaw Osteonecrosis Osteonecrosis of the jaw and other oro-facial sites, including the external auditory canal, have been reported in patients treated with ibandronate sodium (see WARNINGS AND PRECAUTIONS [5.4] ) .