Bonsity
Generic: TERIPARATIDE
Basic Information
Manufacturer
Alvogen Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
2d0c89a2-3849-adf6-007d-aeca21cf417c
Indications & Usage
1 INDICATIONS AND USAGE BONSITY is indicated: For the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy.
In postmenopausal women with osteoporosis, BONSITY reduces the risk of vertebral and nonvertebral fractures.
To increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.
For the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.
BONSITY is a parathyroid hormone analog, (PTH 1-34), indicated for: Treatment of postmenopausal women with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy ( 1 ) Increase of bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy ( 1 ) Treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy ( 1 )
In postmenopausal women with osteoporosis, BONSITY reduces the risk of vertebral and nonvertebral fractures.
To increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.
For the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy.
BONSITY is a parathyroid hormone analog, (PTH 1-34), indicated for: Treatment of postmenopausal women with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy ( 1 ) Increase of bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy ( 1 ) Treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy ( 1 )
Adverse Reactions
6 ADVERSE REACTIONS Most common adverse reactions (>10%) include: arthralgia, pain, and nausea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alvogen, Inc.
at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Men with Primary or Hypogonadal Osteoporosis and Postmenopausal Women with Osteoporosis The safety of teriparatide in the treatment of osteoporosis in men and postmenopausal women was assessed in two randomized, double-blind, placebo-controlled trials of 1382 patients (21% men, 79% women) aged 28 to 86 years (mean 67 years) [see Clinical Studies ( 14.1 , 14.2 )] .
The median durations of the trials were 11 months for men and 19 months for women, with 691 patients exposed to teriparatide and 691 patients to placebo.
All patients received 1000 mg of calcium plus at least 400 IU of vitamin D supplementation per day.
The incidence of all-cause mortality was 1% in the teriparatide group and 1% in the placebo group.
The incidence of serious adverse events was 16% in the teriparatide group and 19% in the placebo group.
Early discontinuation due to adverse events occurred in 7% in the teriparatide group and 6% in the placebo group.
Table 1 lists adverse events from these two trials that occurred in ≥2% of teriparatide-treated and more frequently than placebo-treated patients.
Table 1.
Percentage of Patients with Adverse Events Reported by at Least 2% of Teriparatide-Treated Patients and in More Teriparatide-Treated Patients than Placebo-Treated Patients from the Two Principal Osteoporosis Trials in Women and Men (Adverse Events are Shown Without Attribution of Causality) Teriparatide N=691 Placebo N=691 Event Classification (%) (%) Body as a Whole Pain 21.3 20.5 Headache 7.5 7.4 Asthenia 8.7 6.8 Neck pain 3.0 2.7 Cardiovascular Hypertension 7.1 6.8 Angina pectoris 2.5 1.6 Syncope 2.6 1.4 Digestive System Nausea 8.5 6.7 Constipation 5.4 4.5 Diarrhea 5.1 4.6 Dyspepsia 5.2 4.1 Vomiting 3.0 2.3 Gastrointestinal disorder 2.3 2.0 Tooth disorder 2.0 1.3 Musculoskeletal Arthralgia 10.1 8.4 Leg cramps 2.6 1.3 Nervous System Dizziness 8.0 5.4 Depression 4.1 2.7 Insomnia 4.3 3.6 Vertigo 3.8 2.7 Respiratory System Rhinitis 9.6 8.8 Cough increased 6.4 5.5 Pharyngitis 5.5 4.8 Dyspnea 3.6 2.6 Pneumonia 3.9 3.3 Skin and Appendages Rash 4.9 4.5 Sweating 2.2 1.7 Laboratory Findings Serum Calcium - Teriparatide transiently increased serum calcium, with the maximal effect observed at approximately 4 to 6 hours post-dose.
Serum calcium measured at least 16 hours post-dose was not different from pretreatment levels.
In clinical trials, the frequency of at least 1 episode of transient hypercalcemia in the 4 to 6 hours after teriparatide administration was 11% of women and 6% of men treated with teriparatide compared to 2% of women and 0% of the men treated with placebo.
The percentage of patients treated with teriparatide whose transient hypercalcemia was verified on consecutive measurements was 3% of women and 1% of men.
Urinary Calcium - Teriparatide increased urinary calcium excretion, but the frequency of hypercalciuria in clinical trials was similar for patients treated with teriparatide and placebo [see Clinical Pharmacology ( 12.2 )] .
Serum Uric Acid - Teriparatide increased serum uric acid concentrations.
In clinical trials, 3% of teriparatide-treated patients had serum uric acid concentrations above the upper limit of normal compared with 1% of placebo-treated patients.
However, the hyperuricemia did not result in an increase in gout, arthralgia, or urolithiasis.
Renal Function - No clinically important adverse renal effects were observed in clinical studies.
Assessments included creatinine clearance; measurements of blood urea nitrogen (BUN), creatinine, and electrolytes in serum; urine specific gravity and pH; and examination of urine sediment.
Men and Women with Glucocorticoid-Induced Osteoporosis The safety of teriparatide in the treatment of men and women with glucocorticoid-induced osteoporosis was assessed in a randomized, double-blind, active-controlled trial of 428 patients (19% men, 81% women) aged 22 to 89 years (mean 57 years) treated with ≥5 mg per day prednisone or equivalent for a minimum of 3 months [see Clinical Studies (14.3)].
The duration of the trial was 18 months with 214 patients exposed to teriparatide and 214 patients exposed to an oral daily bisphosphonate (active control).
All patients received 1000 mg of calcium plus 800 IU of vitamin D supplementation per day.
There was no increase in mortality in the teriparatide group compared to the active control group.
The incidence of serious adverse events was 21% in teriparatide patients and 18% in active control patients, and included pneumonia (3% teriparatide, 1% active control).
Early discontinuation because of adverse events occurred in 15% of teriparatide patients and 12% of active control patients, and included dizziness (2% teriparatide, 0% active control).
Adverse events reported at a higher incidence in the teriparatide group and with at least a 2% difference in teriparatide-treated patients compared with active control-treated patients were: nausea (14%, 7%), gastritis (7%, 3%), pneumonia (6%, 3%), dyspnea (6%, 3%), insomnia (5%, 1%), anxiety (4%, 1%), and herpes zoster (3%, 1%), respectively.
6.2 Postmarketing Experience Adverse Reactions from Postmarketing Spontaneous Reports The following adverse reactions have been identified during post-approval use of teriparatide.
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.
Cases of bone tumor and osteosarcoma have been reported rarely in the postmarketing period [see Warnings and Precautions ( 5.1 )] .
Hypercalcemia greater than 13 mg/dL has been reported with teriparatide use.
Adverse events reported since market introduction that were temporally related to teriparatide therapy include the following: Allergic Reactions: Anaphylactic reactions, drug hypersensitivity, angioedema, urticaria Investigations: Hyperuricemia Respiratory System: Acute dyspnea, chest pain Musculoskeletal: Muscle spasms of the leg or back Other: Injection site reactions including injection site pain, swelling and bruising; oro-facial edema Adverse Reactions from Observational Studies to Assess Incidence of Osteosarcoma Two osteosarcoma surveillance safety studies (U.S.
claims-based database studies) were designed to obtain data on the incidence rate of osteosarcoma among teriparatide-treated patients.
In these two studies, three and zero osteosarcoma cases were identified among 379,283 and 153,316 teriparatide users, respectively.
The study results suggest a similar risk for osteosarcoma between teriparatide users and their comparators.
However, the interpretation of the study results calls for caution owing to the limitations of the data sources which do not allow for complete measurement and control for confounders.
at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Men with Primary or Hypogonadal Osteoporosis and Postmenopausal Women with Osteoporosis The safety of teriparatide in the treatment of osteoporosis in men and postmenopausal women was assessed in two randomized, double-blind, placebo-controlled trials of 1382 patients (21% men, 79% women) aged 28 to 86 years (mean 67 years) [see Clinical Studies ( 14.1 , 14.2 )] .
The median durations of the trials were 11 months for men and 19 months for women, with 691 patients exposed to teriparatide and 691 patients to placebo.
All patients received 1000 mg of calcium plus at least 400 IU of vitamin D supplementation per day.
The incidence of all-cause mortality was 1% in the teriparatide group and 1% in the placebo group.
The incidence of serious adverse events was 16% in the teriparatide group and 19% in the placebo group.
Early discontinuation due to adverse events occurred in 7% in the teriparatide group and 6% in the placebo group.
Table 1 lists adverse events from these two trials that occurred in ≥2% of teriparatide-treated and more frequently than placebo-treated patients.
Table 1.
Percentage of Patients with Adverse Events Reported by at Least 2% of Teriparatide-Treated Patients and in More Teriparatide-Treated Patients than Placebo-Treated Patients from the Two Principal Osteoporosis Trials in Women and Men (Adverse Events are Shown Without Attribution of Causality) Teriparatide N=691 Placebo N=691 Event Classification (%) (%) Body as a Whole Pain 21.3 20.5 Headache 7.5 7.4 Asthenia 8.7 6.8 Neck pain 3.0 2.7 Cardiovascular Hypertension 7.1 6.8 Angina pectoris 2.5 1.6 Syncope 2.6 1.4 Digestive System Nausea 8.5 6.7 Constipation 5.4 4.5 Diarrhea 5.1 4.6 Dyspepsia 5.2 4.1 Vomiting 3.0 2.3 Gastrointestinal disorder 2.3 2.0 Tooth disorder 2.0 1.3 Musculoskeletal Arthralgia 10.1 8.4 Leg cramps 2.6 1.3 Nervous System Dizziness 8.0 5.4 Depression 4.1 2.7 Insomnia 4.3 3.6 Vertigo 3.8 2.7 Respiratory System Rhinitis 9.6 8.8 Cough increased 6.4 5.5 Pharyngitis 5.5 4.8 Dyspnea 3.6 2.6 Pneumonia 3.9 3.3 Skin and Appendages Rash 4.9 4.5 Sweating 2.2 1.7 Laboratory Findings Serum Calcium - Teriparatide transiently increased serum calcium, with the maximal effect observed at approximately 4 to 6 hours post-dose.
Serum calcium measured at least 16 hours post-dose was not different from pretreatment levels.
In clinical trials, the frequency of at least 1 episode of transient hypercalcemia in the 4 to 6 hours after teriparatide administration was 11% of women and 6% of men treated with teriparatide compared to 2% of women and 0% of the men treated with placebo.
The percentage of patients treated with teriparatide whose transient hypercalcemia was verified on consecutive measurements was 3% of women and 1% of men.
Urinary Calcium - Teriparatide increased urinary calcium excretion, but the frequency of hypercalciuria in clinical trials was similar for patients treated with teriparatide and placebo [see Clinical Pharmacology ( 12.2 )] .
Serum Uric Acid - Teriparatide increased serum uric acid concentrations.
In clinical trials, 3% of teriparatide-treated patients had serum uric acid concentrations above the upper limit of normal compared with 1% of placebo-treated patients.
However, the hyperuricemia did not result in an increase in gout, arthralgia, or urolithiasis.
Renal Function - No clinically important adverse renal effects were observed in clinical studies.
Assessments included creatinine clearance; measurements of blood urea nitrogen (BUN), creatinine, and electrolytes in serum; urine specific gravity and pH; and examination of urine sediment.
Men and Women with Glucocorticoid-Induced Osteoporosis The safety of teriparatide in the treatment of men and women with glucocorticoid-induced osteoporosis was assessed in a randomized, double-blind, active-controlled trial of 428 patients (19% men, 81% women) aged 22 to 89 years (mean 57 years) treated with ≥5 mg per day prednisone or equivalent for a minimum of 3 months [see Clinical Studies (14.3)].
The duration of the trial was 18 months with 214 patients exposed to teriparatide and 214 patients exposed to an oral daily bisphosphonate (active control).
All patients received 1000 mg of calcium plus 800 IU of vitamin D supplementation per day.
There was no increase in mortality in the teriparatide group compared to the active control group.
The incidence of serious adverse events was 21% in teriparatide patients and 18% in active control patients, and included pneumonia (3% teriparatide, 1% active control).
Early discontinuation because of adverse events occurred in 15% of teriparatide patients and 12% of active control patients, and included dizziness (2% teriparatide, 0% active control).
Adverse events reported at a higher incidence in the teriparatide group and with at least a 2% difference in teriparatide-treated patients compared with active control-treated patients were: nausea (14%, 7%), gastritis (7%, 3%), pneumonia (6%, 3%), dyspnea (6%, 3%), insomnia (5%, 1%), anxiety (4%, 1%), and herpes zoster (3%, 1%), respectively.
6.2 Postmarketing Experience Adverse Reactions from Postmarketing Spontaneous Reports The following adverse reactions have been identified during post-approval use of teriparatide.
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.
Cases of bone tumor and osteosarcoma have been reported rarely in the postmarketing period [see Warnings and Precautions ( 5.1 )] .
Hypercalcemia greater than 13 mg/dL has been reported with teriparatide use.
Adverse events reported since market introduction that were temporally related to teriparatide therapy include the following: Allergic Reactions: Anaphylactic reactions, drug hypersensitivity, angioedema, urticaria Investigations: Hyperuricemia Respiratory System: Acute dyspnea, chest pain Musculoskeletal: Muscle spasms of the leg or back Other: Injection site reactions including injection site pain, swelling and bruising; oro-facial edema Adverse Reactions from Observational Studies to Assess Incidence of Osteosarcoma Two osteosarcoma surveillance safety studies (U.S.
claims-based database studies) were designed to obtain data on the incidence rate of osteosarcoma among teriparatide-treated patients.
In these two studies, three and zero osteosarcoma cases were identified among 379,283 and 153,316 teriparatide users, respectively.
The study results suggest a similar risk for osteosarcoma between teriparatide users and their comparators.
However, the interpretation of the study results calls for caution owing to the limitations of the data sources which do not allow for complete measurement and control for confounders.