Teriparatide
Generic: TERIPARATIDE
Basic Information
Manufacturer
Prasco Laboratories
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
ab322675-4769-45b0-b146-14fbaa3135d0
Indications & Usage
1 INDICATIONS AND USAGE Teriparatide Injection 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, Teriparatide Injection 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.
Teriparatide Injection 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, Teriparatide Injection 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.
Teriparatide Injection 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 Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) 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 Injection 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 Injection 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 Injection group and 1% in the placebo group.
The incidence of serious adverse events was 16% in the Teriparatide Injection group and 19% in the placebo group.
Early discontinuation due to adverse events occurred in 7% in the Teriparatide Injection group and 6% in the placebo group.
Table 1 lists adverse events from these two trials that occurred in ≥2% of Teriparatide Injection-treated and more frequently than placebo-treated patients.
Table 1: Percentage of Patients with Adverse Events Reported by at Least 2% of Teriparatide Injection-Treated Patients and in More Teriparatide Injection-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 Injection 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 Injection 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 Injection administration was 11% of women and 6% of men treated with Teriparatide Injection compared to 2% of women and 0% of the men treated with placebo.
The percentage of patients treated with Teriparatide Injection whose transient hypercalcemia was verified on consecutive measurements was 3% of women and 1% of men.
Urinary Calcium — Teriparatide Injection increased urinary calcium excretion, but the frequency of hypercalciuria in clinical trials was similar for patients treated with Teriparatide Injection and placebo [see Clinical Pharmacology ( 12.2 )] .
Serum Uric Acid — Teriparatide Injection increased serum uric acid concentrations.
In clinical trials, 3% of Teriparatide Injection-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 Injection 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 ≥5mg 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 Injection 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 Injection group compared to the active control group.
The incidence of serious adverse events was 21% in Teriparatide Injection patients and 18% in active control patients, and included pneumonia (3% Teriparatide Injection, 1% active control).
Early discontinuation because of adverse events occurred in 15% of Teriparatide Injection patients and 12% of active control patients, and included dizziness (2% Teriparatide Injection, 0% active control).
Adverse events reported at a higher incidence in the Teriparatide Injection group and with at least a 2% difference in Teriparatide Injection-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 Immunogenicity As with all peptides, there is potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other Teriparatide products may be misleading.
In the clinical trial of postmenopausal women with osteoporosis [see Clinical Studies ( 14.1 )] , antibodies that cross reacted with Teriparatide were detected in 3% of women (15/541) who received Teriparatide Injection.
Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy.
There was no evidence of hypersensitivity reactions among these patients.
Antibody formation did not appear to have effects on serum calcium, or on bone mineral density (BMD) response.
6.3 Postmarketing Experience Adverse Reactions from Postmarketing Spontaneous Reports The following adverse reactions have been identified during postapproval use of Teriparatide Injection.
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 ( 5.2 )] .
Hypercalcemia greater than 13 mg/dL has been reported with Teriparatide Injection use.
Adverse events reported since market introduction that were temporally related to Teriparatide Injection 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 Injection-treated patients.
In these two studies, three and zero osteosarcoma cases were identified among 379,283 and 153,316 Teriparatide Injection users, respectively.
The study results suggest a similar risk for osteosarcoma between Teriparatide Injection 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.
Men with Primary or Hypogonadal Osteoporosis and Postmenopausal Women with Osteoporosis The safety of Teriparatide Injection 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 Injection 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 Injection group and 1% in the placebo group.
The incidence of serious adverse events was 16% in the Teriparatide Injection group and 19% in the placebo group.
Early discontinuation due to adverse events occurred in 7% in the Teriparatide Injection group and 6% in the placebo group.
Table 1 lists adverse events from these two trials that occurred in ≥2% of Teriparatide Injection-treated and more frequently than placebo-treated patients.
Table 1: Percentage of Patients with Adverse Events Reported by at Least 2% of Teriparatide Injection-Treated Patients and in More Teriparatide Injection-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 Injection 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 Injection 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 Injection administration was 11% of women and 6% of men treated with Teriparatide Injection compared to 2% of women and 0% of the men treated with placebo.
The percentage of patients treated with Teriparatide Injection whose transient hypercalcemia was verified on consecutive measurements was 3% of women and 1% of men.
Urinary Calcium — Teriparatide Injection increased urinary calcium excretion, but the frequency of hypercalciuria in clinical trials was similar for patients treated with Teriparatide Injection and placebo [see Clinical Pharmacology ( 12.2 )] .
Serum Uric Acid — Teriparatide Injection increased serum uric acid concentrations.
In clinical trials, 3% of Teriparatide Injection-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 Injection 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 ≥5mg 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 Injection 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 Injection group compared to the active control group.
The incidence of serious adverse events was 21% in Teriparatide Injection patients and 18% in active control patients, and included pneumonia (3% Teriparatide Injection, 1% active control).
Early discontinuation because of adverse events occurred in 15% of Teriparatide Injection patients and 12% of active control patients, and included dizziness (2% Teriparatide Injection, 0% active control).
Adverse events reported at a higher incidence in the Teriparatide Injection group and with at least a 2% difference in Teriparatide Injection-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 Immunogenicity As with all peptides, there is potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other Teriparatide products may be misleading.
In the clinical trial of postmenopausal women with osteoporosis [see Clinical Studies ( 14.1 )] , antibodies that cross reacted with Teriparatide were detected in 3% of women (15/541) who received Teriparatide Injection.
Generally, antibodies were first detected following 12 months of treatment and diminished after withdrawal of therapy.
There was no evidence of hypersensitivity reactions among these patients.
Antibody formation did not appear to have effects on serum calcium, or on bone mineral density (BMD) response.
6.3 Postmarketing Experience Adverse Reactions from Postmarketing Spontaneous Reports The following adverse reactions have been identified during postapproval use of Teriparatide Injection.
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 ( 5.2 )] .
Hypercalcemia greater than 13 mg/dL has been reported with Teriparatide Injection use.
Adverse events reported since market introduction that were temporally related to Teriparatide Injection 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 Injection-treated patients.
In these two studies, three and zero osteosarcoma cases were identified among 379,283 and 153,316 Teriparatide Injection users, respectively.
The study results suggest a similar risk for osteosarcoma between Teriparatide Injection 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.