IBANDRONATE SODIUM
Generic: IBANDRONATE SODIUM
Basic Information
Manufacturer
Sun Pharmaceutical Industries, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
be514be6-727a-4d6c-993b-52144f8e6de8
Indications & Usage
1 INDICATIONS AND USAGE Ibandronate sodium injection is a bisphosphonate indicated for the treatment of osteoporosis in postmenopausal women.
( 1.1 ) Limitations of Use 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 of Postmenopausal Osteoporosis Ibandronate sodium injection is indicated for the treatment of osteoporosis in postmenopausal women.
In postmenopausal women with osteoporosis, ibandronate sodium injection increases bone mineral density (BMD) and reduces the incidence of vertebral fractures [see Clinical Studies ( 14 )] .
1.2 Important Limitations of Use The safety and effectiveness of ibandronate sodium injection for the treatment of osteoporosis are based on clinical data of one year duration.
The optimal duration of use has not been determined.
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 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 of Postmenopausal Osteoporosis Ibandronate sodium injection is indicated for the treatment of osteoporosis in postmenopausal women.
In postmenopausal women with osteoporosis, ibandronate sodium injection increases bone mineral density (BMD) and reduces the incidence of vertebral fractures [see Clinical Studies ( 14 )] .
1.2 Important Limitations of Use The safety and effectiveness of ibandronate sodium injection for the treatment of osteoporosis are based on clinical data of one year duration.
The optimal duration of use has not been determined.
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: Hypocalcemia and Mineral Metabolism [see Warnings and Precautions ( 5.1 ) ] Anaphylactic Reaction [see Warnings and Precautions ( 5.2 )] Renal Impairment [see Warnings and Precautions ( 5.3 )] Tissue Damage Related to Inappropriate Drug Administration [see Warnings and Precautions ( 5.4 )] Osteonecrosis of the Jaw [see Warnings and Precautions ( 5.5 )] Musculoskeletal [see Warnings and Precautions ( 5.6 )] Atypical Fractures Including Femoral Fractures [see Warnings and Precautions ( 5.7 )] The most frequently reported adverse reactions (>5%) are arthralgia, back pain, and abdominal pain.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc.
at 1-800-818-4555 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.
Quarterly Intravenous Injection – In a 1-year, double-blind, multicenter study comparing ibandronate sodium injection administered intravenously as 3 mg every 3 months to ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet in women with postmenopausal osteoporosis, the overall safety and tolerability profiles of the two dosing regimens were similar.
The incidence of serious adverse reactions was 8% in the ibandronate sodium tablets 2.5 mg (ibandronate) daily group and 7.5% in the ibandronate sodium injection 3 mg once every 3 months group.
The percentage of patients who withdrew from treatment due to adverse reactions was approximately 6.7% in the ibandronate sodium tablets 2.5 mg (ibandronate) daily group and 8.5% in the ibandronate sodium injection 3 mg every 3 months group.
Table 1 lists the adverse reactions reported in greater than 2% of patients.
Table 1 Adverse Reactions With an Incidence of at Least 2% in Patients Treated with Ibandronate Sodium Injection (3 mg once every 3 months) or Ibandronate Sodium Tablets 2.5 mg (ibandronate) Daily Oral Tablet Body System/Adverse Reaction Ibandronate Sodium Tablets 2.5 mg (ibandronate) Daily (Oral) % (n=465) Ibandronate Sodium Injection 3 mg every 3 months (Intravenous) % (n=469) Infections and Infestations Influenza 8 5 Nasopharyngitis 6 3 Cystitis 3 2 Gastroenteritis 3 2 Urinary Tract Infection 3 3 Bronchitis 3 2 Upper Respiratory Tract Infection 3 1 Gastrointestinal Disorders Abdominal Pain Combination of abdominal pain and abdominal pain upper 6 5 Dyspepsia 4 4 Nausea 4 2 Constipation 4 3 Diarrhea 2 3 Gastritis 2 2 Musculoskeletal and Connective Tissue Disorders Arthralgia 9 10 Back Pain 8 7 Localized Osteoarthritis 2 2 Pain in Extremity 2 3 Myalgia 1 3 Nervous System Disorders Dizziness 3 2 Headache 3 4 Psychiatric Disorders Insomnia 3 1 Depression 2 1 General Disorders and Administration Site Conditions Influenza-like Illness Combination of influenza-like illness and acute phase reaction 1 5 Fatigue 1 3 Skin and Subcutaneous Tissue Disorders Rash Combination of rash, rash pruritic, rash macular, dermatitis, dermatitis allergic, exanthema, erythema, rash papular, rash generalized, dermatitis medicamentosa, rash erythematous 3 2 Acute Phase Reaction-like Events Symptoms consistent with acute phase reaction (APR) have been reported with intravenous bisphosphonate use.
The overall incidence of patients with APR-like events was higher in the intravenous treatment group (4% in the ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet group vs.
10% in the ibandronate sodium injection 3 mg once every 3 months group).
These incidence rates are based upon reporting of any of 33 potential APR-like symptoms within 3 days of an intravenous dose and lasting 7 days or less.
In most cases, no specific treatment was required and the symptoms subsided within 24 to 48 hours.
Injection Site Reactions Local reactions at the injection site, such as redness or swelling, were observed at a higher incidence in patients treated with ibandronate sodium injection 3 mg every 3 months (1.7%; 8/469) than in patients treated with placebo injections (0.2%; 1/465).
In most cases, the reaction was of mild to moderate severity.
Daily Oral Tablet - The safety of ibandronate sodium tablets 2.5 mg (ibandronate) once daily in the treatment and prevention of postmenopausal osteoporosis was assessed in 3,577 patients aged 41 to 82 years.
The duration of the trials was 2 to 3 years, with 1,134 patients exposed to placebo and 1,140 exposed to ibandronate sodium tablets 2.5 mg (ibandronate).
Patients with preexisting gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors and H2 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 tablets 2.5 mg (ibandronate) daily group.
The incidence of serious adverse reactions was 20% in the placebo group and 23% in the ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet group.
The percentage of patients who withdrew from treatment due to adverse reactions was approximately 17% in both the placebo group and the ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet group.
Table 2 lists adverse reactions from the Treatment and Prevention Studies reported in greater than or equal to 2% of patients and in more patients treated with ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet than patients treated with placebo.
Table 2 Adverse Reactions Occurring at an Incidence greater than or equal to 2% and in More Patients Treated with Ibandronate Sodium Tablets 2.5 mg (ibandronate) Daily Oral Tablet than in Patients Treated with Placebo in the Osteoporosis Treatment and Prevention Studies Body System Placebo % (n=1,134) Ibandronate Sodium Tablets 2.5 mg (ibandronate) daily % (n=1,140) 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 tablets 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 tablets 2.5 mg (ibandronate) daily groups were: back pain (12% vs.
14%), arthralgia (14% vs.
14%) and myalgia (5% vs.
6%).
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ibandronate sodium injection 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 anaphylaxis with fatalities, angioedema, asthma exacerbation, bronchospasm, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] .
Hypocalcemia : Hypocalcemia [see Warnings and Precautions ( 5.1 )].
Renal Toxicity : Acute renal failure [see Warnings and Precautions ( 5.3 )].
Osteonecrosis of the Jaw : Osteonecrosis of the jaw and other oro-facial sites, including the external auditory canal [see Warnings and Precautions ( 5.5 )] .
Musculoskeletal : Bone, joint, or muscle pain, described as severe or incapacitating, have been reported rarely [see Warnings and Precautions (5.6)]; low-energy femoral shaft and subtrochanteric fractures, and atypical fractures of other bones [see Warnings and Precautions (5.7)].
Eye Inflammation : Iritis and uveitis.
In some cases with other bisphosphonates, these events did not resolve until the bisphosphonate was discontinued.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc.
at 1-800-818-4555 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.
Quarterly Intravenous Injection – In a 1-year, double-blind, multicenter study comparing ibandronate sodium injection administered intravenously as 3 mg every 3 months to ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet in women with postmenopausal osteoporosis, the overall safety and tolerability profiles of the two dosing regimens were similar.
The incidence of serious adverse reactions was 8% in the ibandronate sodium tablets 2.5 mg (ibandronate) daily group and 7.5% in the ibandronate sodium injection 3 mg once every 3 months group.
The percentage of patients who withdrew from treatment due to adverse reactions was approximately 6.7% in the ibandronate sodium tablets 2.5 mg (ibandronate) daily group and 8.5% in the ibandronate sodium injection 3 mg every 3 months group.
Table 1 lists the adverse reactions reported in greater than 2% of patients.
Table 1 Adverse Reactions With an Incidence of at Least 2% in Patients Treated with Ibandronate Sodium Injection (3 mg once every 3 months) or Ibandronate Sodium Tablets 2.5 mg (ibandronate) Daily Oral Tablet Body System/Adverse Reaction Ibandronate Sodium Tablets 2.5 mg (ibandronate) Daily (Oral) % (n=465) Ibandronate Sodium Injection 3 mg every 3 months (Intravenous) % (n=469) Infections and Infestations Influenza 8 5 Nasopharyngitis 6 3 Cystitis 3 2 Gastroenteritis 3 2 Urinary Tract Infection 3 3 Bronchitis 3 2 Upper Respiratory Tract Infection 3 1 Gastrointestinal Disorders Abdominal Pain Combination of abdominal pain and abdominal pain upper 6 5 Dyspepsia 4 4 Nausea 4 2 Constipation 4 3 Diarrhea 2 3 Gastritis 2 2 Musculoskeletal and Connective Tissue Disorders Arthralgia 9 10 Back Pain 8 7 Localized Osteoarthritis 2 2 Pain in Extremity 2 3 Myalgia 1 3 Nervous System Disorders Dizziness 3 2 Headache 3 4 Psychiatric Disorders Insomnia 3 1 Depression 2 1 General Disorders and Administration Site Conditions Influenza-like Illness Combination of influenza-like illness and acute phase reaction 1 5 Fatigue 1 3 Skin and Subcutaneous Tissue Disorders Rash Combination of rash, rash pruritic, rash macular, dermatitis, dermatitis allergic, exanthema, erythema, rash papular, rash generalized, dermatitis medicamentosa, rash erythematous 3 2 Acute Phase Reaction-like Events Symptoms consistent with acute phase reaction (APR) have been reported with intravenous bisphosphonate use.
The overall incidence of patients with APR-like events was higher in the intravenous treatment group (4% in the ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet group vs.
10% in the ibandronate sodium injection 3 mg once every 3 months group).
These incidence rates are based upon reporting of any of 33 potential APR-like symptoms within 3 days of an intravenous dose and lasting 7 days or less.
In most cases, no specific treatment was required and the symptoms subsided within 24 to 48 hours.
Injection Site Reactions Local reactions at the injection site, such as redness or swelling, were observed at a higher incidence in patients treated with ibandronate sodium injection 3 mg every 3 months (1.7%; 8/469) than in patients treated with placebo injections (0.2%; 1/465).
In most cases, the reaction was of mild to moderate severity.
Daily Oral Tablet - The safety of ibandronate sodium tablets 2.5 mg (ibandronate) once daily in the treatment and prevention of postmenopausal osteoporosis was assessed in 3,577 patients aged 41 to 82 years.
The duration of the trials was 2 to 3 years, with 1,134 patients exposed to placebo and 1,140 exposed to ibandronate sodium tablets 2.5 mg (ibandronate).
Patients with preexisting gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors and H2 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 tablets 2.5 mg (ibandronate) daily group.
The incidence of serious adverse reactions was 20% in the placebo group and 23% in the ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet group.
The percentage of patients who withdrew from treatment due to adverse reactions was approximately 17% in both the placebo group and the ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet group.
Table 2 lists adverse reactions from the Treatment and Prevention Studies reported in greater than or equal to 2% of patients and in more patients treated with ibandronate sodium tablets 2.5 mg (ibandronate) daily oral tablet than patients treated with placebo.
Table 2 Adverse Reactions Occurring at an Incidence greater than or equal to 2% and in More Patients Treated with Ibandronate Sodium Tablets 2.5 mg (ibandronate) Daily Oral Tablet than in Patients Treated with Placebo in the Osteoporosis Treatment and Prevention Studies Body System Placebo % (n=1,134) Ibandronate Sodium Tablets 2.5 mg (ibandronate) daily % (n=1,140) 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 tablets 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 tablets 2.5 mg (ibandronate) daily groups were: back pain (12% vs.
14%), arthralgia (14% vs.
14%) and myalgia (5% vs.
6%).
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ibandronate sodium injection 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 anaphylaxis with fatalities, angioedema, asthma exacerbation, bronchospasm, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] .
Hypocalcemia : Hypocalcemia [see Warnings and Precautions ( 5.1 )].
Renal Toxicity : Acute renal failure [see Warnings and Precautions ( 5.3 )].
Osteonecrosis of the Jaw : Osteonecrosis of the jaw and other oro-facial sites, including the external auditory canal [see Warnings and Precautions ( 5.5 )] .
Musculoskeletal : Bone, joint, or muscle pain, described as severe or incapacitating, have been reported rarely [see Warnings and Precautions (5.6)]; low-energy femoral shaft and subtrochanteric fractures, and atypical fractures of other bones [see Warnings and Precautions (5.7)].
Eye Inflammation : Iritis and uveitis.
In some cases with other bisphosphonates, these events did not resolve until the bisphosphonate was discontinued.