Tymlos
Generic: ABALOPARATIDE
Basic Information
Manufacturer
Radius Health, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
712143d9-e21e-4013-bb3b-3426a21060a8
Indications & Usage
1 INDICATIONS AND USAGE TYMLOS is a human parathyroid hormone related peptide [PTHrP(1-34)] analog indicated for the: Treatment of postmenopausal women with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy.
( 1.1 ) Treatment to increase bone density in men with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy.
( 1.2 ) 1.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture TYMLOS is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy.
In postmenopausal women with osteoporosis, TYMLOS reduces the risk of vertebral fractures and nonvertebral fractures.
1.2 Treatment to Increase Bone Density in Men with Osteoporosis at High Risk for Fracture TYMLOS is indicated to increase bone density in men with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy.
( 1.1 ) Treatment to increase bone density in men with osteoporosis at high risk for fracture or patients who have failed or are intolerant to other available osteoporosis therapy.
( 1.2 ) 1.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture TYMLOS is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy.
In postmenopausal women with osteoporosis, TYMLOS reduces the risk of vertebral fractures and nonvertebral fractures.
1.2 Treatment to Increase Bone Density in Men with Osteoporosis at High Risk for Fracture TYMLOS is indicated to increase bone density in men with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy.
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Orthostatic Hypotension [see Warnings and Precautions ( 5.2 )] Hypercalcemia [see Warnings and Precautions ( 5.3 )] Hypercalciuria and Urolithiasis [see Warnings and Precautions ( 5.4 )] Osteoporosis in postmenopausal women: The most common adverse reactions (incidence ≥2%) are hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain, and vertigo.
( 6.1 ) Osteoporosis in men: The most common adverse reactions (incidence ≥2%) are injection site erythema, dizziness, arthralgia, injection site swelling, injection site pain, contusion, nausea, diarrhea, abdominal distension, abdominal pain, and bone pain.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Radius Health, Inc.
at 1-855-672-3487 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.
Adverse Reactions from Clinical Trial in Postmenopausal Women with Osteoporosis The safety of TYMLOS was evaluated in a randomized, multicenter, double-blind, placebo-controlled clinical trial in postmenopausal women with osteoporosis aged 49 to 86 years (mean age 69 years) who were randomized to receive 80 mcg of TYMLOS (N = 824) or placebo (N = 821), given subcutaneously once daily for 18 months [see Clinical Studies ( 14.1 )] .
In this study, the incidence of all-cause mortality was 0.4% in the TYMLOS group and 0.6% in the placebo group.
The incidence of serious adverse events was 10% in the TYMLOS group and 11% in the placebo group.
The percentage of patients who discontinued study drug due to adverse events was 10% in the TYMLOS group and 6% in the placebo group.
The most common adverse reactions leading to study drug discontinuation in the TYMLOS group were nausea (2%), dizziness (1%), headache (1%), and palpitations (1%).
Table 1 shows the most common adverse reactions in the trial.
These adverse reactions were generally not present at baseline, occurred more commonly with TYMLOS than with placebo, and occurred in at least 2% of the patients treated with TYMLOS.
Table 1: Common Adverse Reactions Reported in Postmenopausal Women with Osteoporosis * * Adverse reactions reported in ≥2% of TYMLOS-treated patients.
Preferred term TYMLOS (N=822) (%) Placebo (N=820) (%) Hypercalciuria 11 9 Dizziness 10 6 Nausea 8 3 Headache 8 6 Palpitations 5 0.4 Fatigue 3 2 Abdominal pain upper 3 2 Vertigo 2 2 Orthostatic Hypotension In the clinical trial of women with postmenopausal osteoporosis, the incidence of orthostatic blood pressure decline ≥20 mmHg systolic or ≥10 mmHg diastolic at 1 hour after the first injection was 4% in the TYMLOS group and 3% in the placebo group.
At later time points the incidence was generally similar between the treatment groups.
Adverse reactions of orthostatic hypotension were reported in 1% of patients receiving TYMLOS and 0.5% of patients receiving placebo.
Dizziness was reported by more TYMLOS-treated patients (10%) compared to placebo (6%) [see Warnings and Precautions ( 5.2 )] .
Tachycardia In women with postmenopausal osteoporosis, adverse reactions of tachycardia, including sinus tachycardia, were reported in 2% of patients receiving TYMLOS and 1% of patients in the placebo group.
In 5 of the 13 patients receiving TYMLOS who experienced tachycardia, symptoms occurred within 1 hour of administration.
TYMLOS has been associated with a dose-dependent increase in heart rate which developed within 15 minutes after injection and resolved in about 6 hours [see Clinical Pharmacology ( 12.2 )] .
Injection Site Reactions During the first month of the trial, injection site reactions were assessed daily one-hour after injection.
TYMLOS had a higher incidence than placebo of injection site redness (58% vs.
28%), edema (11% vs.
3%), and pain (10% vs.
7%).
Severe redness, severe edema, and severe pain were reported among 2.9%, 0.4%, and 0.4% of the TYMLOS-treated patients.
Laboratory Abnormalities Hypercalcemia In the clinical trial of women with postmenopausal osteoporosis, TYMLOS caused increases in serum calcium concentrations [see Warnings and Precautions ( 5.3 )] .
The incidence of hypercalcemia, defined as albumin-corrected serum calcium ≥10.7 mg/dL at 4 hours following injection at any visit, was 3% in TYMLOS-treated patients and 0.1% with placebo.
Pre-dose serum calcium was similar to baseline in both groups.
There were 2 (0.2%) TYMLOS-treated patients and no placebo-treated patients who discontinued from the study due to hypercalcemia.
The incidence of hypercalcemia with TYMLOS was higher in patients with mild or moderate renal impairment (4%) compared to patients with normal renal function (1%).
Increases in Serum Uric Acid TYMLOS increased serum uric acid concentrations.
In the postmenopausal osteoporosis trial, among patients with normal baseline uric acid concentrations, 25% of patients in the TYMLOS group and 6% of patients in the placebo group had at least one post-baseline concentration above the normal range.
The hyperuricemia observed in TYMLOS-treated patients was not associated with an increase in adverse reactions of gout or arthralgia over that observed with placebo.
Hypercalciuria and Urolithiasis In the clinical trial of women with postmenopausal osteoporosis, the overall incidence of urine calcium:creatinine ratio >400 mg/g was higher with TYMLOS than with placebo (20% vs 15%, respectively).
Urolithiases were reported in 2.1% of TYMLOS-treated patients and 1.7% of placebo-treated patients.
Adverse Reactions from the Extension Study in Postmenopausal Women with Osteoporosis Following 18 months of treatment with TYMLOS or placebo, 1139 women transitioned to treatment with alendronate 70 mg administered orally once weekly.
The incidence of adverse events occurring during alendronate treatment was similar in patients with prior placebo or TYMLOS therapy [see Clinical Studies ( 14.1 )] .
Adverse Reactions from Clinical Trial in Men with Osteoporosis The safety of TYMLOS was evaluated in a randomized, multicenter, double-blind, placebo-controlled clinical trial in men with osteoporosis aged 42 to 85 years (mean age 68 years) who were randomized to receive 80 mcg of TYMLOS (N = 149) or placebo (N = 79), given subcutaneously once daily for 12 months [see Clinical Studies ( 14.2 )] .
In this study, no patient from either treatment group had an adverse reaction with a fatal outcome during the trial.
Serious adverse reactions were reported by 5.4% of subjects treated with TYMLOS and 5.1% of subjects in the placebo group.
Adverse reactions leading to study drug discontinuation were reported for 6.7% of patients treated with TYMLOS and 5.1% of patients receiving placebo.
The most common adverse reaction leading to study drug discontinuation in the TYMLOS group was dizziness (2%).
Table 2 shows the most common adverse reactions in the trial.
These adverse reactions were generally not present at baseline, occurred more commonly with TYMLOS than with placebo and occurred in at least 2% of the patients treated with TYMLOS.
Table 2: Common Adverse Reactions Reported in Men with Osteoporosis Adverse reactions reported in ≥2% of TYMLOS-treated patients.
Preferred Term TYMLOS (N=149) (%) Placebo (N=79) (%) Injection site erythema 13 5 Dizziness 9 1 Arthralgia 7 1 Injection site swelling 7 0 Injection site pain 6 0 Contusion 3 0 Abdominal distention 3 0 Diarrhea 3 0 Nausea 3 0 Abdominal Pain 2 0 Bone Pain 2 0 Orthostatic Hypotension In the clinical trial of men with osteoporosis, the incidence of orthostatic blood pressure declines of ≥20 mmHg systolic or ≥10 mmHg diastolic at 1 hour after the first injection was 6% in the TYMLOS group and 3% in the placebo group.
Adverse reactions of orthostatic hypotension were reported in 1% of patients receiving TYMLOS and 0 patients receiving placebo.
Dizziness was reported by more TYMLOS-treated patients (9%) compared to placebo (1%) [see Warnings and Precautions ( 5.2 )] .
Laboratory Abnormalities Hypercalcemia In the clinical trial of men with osteoporosis, TYMLOS caused increases in serum calcium concentrations [see Warnings and Precautions ( 5.3 )] .
The incidence of hypercalcemia, defined as albumin-corrected serum calcium ≥10.8 mg/dL at 4 hours following injection at any visit, was 3% in TYMLOS-treated patients and 0% with placebo.
Pre-dose serum calcium was similar to baseline in both groups.
The incidence of hypercalcemia, defined as albumin-corrected serum calcium ≥10.8 mg/dL at 4 hours following injection, with TYMLOS was higher in patients with mild or moderate renal impairment (4%) compared to patients with normal renal function (0%).
Increases in Serum Uric Acid TYMLOS increased serum uric acid concentrations.
In the male osteoporosis trial, among patients with normal baseline uric acid concentrations, 7% of patients in the TYMLOS group and 6% of patients in the placebo group had at least one post-baseline concentration above the normal range.
The hyperuricemia observed in TYMLOS-treated patients was not associated with an increase in adverse reactions of gout or arthralgia over that observed with placebo.
Hypercalciuria and Urolithiasis In the clinical trial of men with osteoporosis, the overall incidence of urine calcium: creatinine ratio >400 mg/g was not greater with TYMLOS than with placebo.
Urolithiases were reported in 2% of TYMLOS-treated patients and 1% of placebo-treated patients.
6.2 Postmarketing Experience The following adverse reactions have been identified during the post-approval use of TYMLOS.
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.
Abdominal distension, abdominal pain, abdominal discomfort Constipation, diarrhea, vomiting, decreased appetite Asthenia, lethargy, malaise, feeling abnormal, hot flush Insomnia Hypersensitivity and anaphylactic reactions, dyspnea (in the context of allergic reactions) Pruritus, rash Generalized pain and pain in bone, joint, back, and extremity Blood pressure increased Muscle spasms of the leg and back Injection site reactions including bruising, hemorrhage, pruritus, and rash
( 6.1 ) Osteoporosis in men: The most common adverse reactions (incidence ≥2%) are injection site erythema, dizziness, arthralgia, injection site swelling, injection site pain, contusion, nausea, diarrhea, abdominal distension, abdominal pain, and bone pain.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Radius Health, Inc.
at 1-855-672-3487 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.
Adverse Reactions from Clinical Trial in Postmenopausal Women with Osteoporosis The safety of TYMLOS was evaluated in a randomized, multicenter, double-blind, placebo-controlled clinical trial in postmenopausal women with osteoporosis aged 49 to 86 years (mean age 69 years) who were randomized to receive 80 mcg of TYMLOS (N = 824) or placebo (N = 821), given subcutaneously once daily for 18 months [see Clinical Studies ( 14.1 )] .
In this study, the incidence of all-cause mortality was 0.4% in the TYMLOS group and 0.6% in the placebo group.
The incidence of serious adverse events was 10% in the TYMLOS group and 11% in the placebo group.
The percentage of patients who discontinued study drug due to adverse events was 10% in the TYMLOS group and 6% in the placebo group.
The most common adverse reactions leading to study drug discontinuation in the TYMLOS group were nausea (2%), dizziness (1%), headache (1%), and palpitations (1%).
Table 1 shows the most common adverse reactions in the trial.
These adverse reactions were generally not present at baseline, occurred more commonly with TYMLOS than with placebo, and occurred in at least 2% of the patients treated with TYMLOS.
Table 1: Common Adverse Reactions Reported in Postmenopausal Women with Osteoporosis * * Adverse reactions reported in ≥2% of TYMLOS-treated patients.
Preferred term TYMLOS (N=822) (%) Placebo (N=820) (%) Hypercalciuria 11 9 Dizziness 10 6 Nausea 8 3 Headache 8 6 Palpitations 5 0.4 Fatigue 3 2 Abdominal pain upper 3 2 Vertigo 2 2 Orthostatic Hypotension In the clinical trial of women with postmenopausal osteoporosis, the incidence of orthostatic blood pressure decline ≥20 mmHg systolic or ≥10 mmHg diastolic at 1 hour after the first injection was 4% in the TYMLOS group and 3% in the placebo group.
At later time points the incidence was generally similar between the treatment groups.
Adverse reactions of orthostatic hypotension were reported in 1% of patients receiving TYMLOS and 0.5% of patients receiving placebo.
Dizziness was reported by more TYMLOS-treated patients (10%) compared to placebo (6%) [see Warnings and Precautions ( 5.2 )] .
Tachycardia In women with postmenopausal osteoporosis, adverse reactions of tachycardia, including sinus tachycardia, were reported in 2% of patients receiving TYMLOS and 1% of patients in the placebo group.
In 5 of the 13 patients receiving TYMLOS who experienced tachycardia, symptoms occurred within 1 hour of administration.
TYMLOS has been associated with a dose-dependent increase in heart rate which developed within 15 minutes after injection and resolved in about 6 hours [see Clinical Pharmacology ( 12.2 )] .
Injection Site Reactions During the first month of the trial, injection site reactions were assessed daily one-hour after injection.
TYMLOS had a higher incidence than placebo of injection site redness (58% vs.
28%), edema (11% vs.
3%), and pain (10% vs.
7%).
Severe redness, severe edema, and severe pain were reported among 2.9%, 0.4%, and 0.4% of the TYMLOS-treated patients.
Laboratory Abnormalities Hypercalcemia In the clinical trial of women with postmenopausal osteoporosis, TYMLOS caused increases in serum calcium concentrations [see Warnings and Precautions ( 5.3 )] .
The incidence of hypercalcemia, defined as albumin-corrected serum calcium ≥10.7 mg/dL at 4 hours following injection at any visit, was 3% in TYMLOS-treated patients and 0.1% with placebo.
Pre-dose serum calcium was similar to baseline in both groups.
There were 2 (0.2%) TYMLOS-treated patients and no placebo-treated patients who discontinued from the study due to hypercalcemia.
The incidence of hypercalcemia with TYMLOS was higher in patients with mild or moderate renal impairment (4%) compared to patients with normal renal function (1%).
Increases in Serum Uric Acid TYMLOS increased serum uric acid concentrations.
In the postmenopausal osteoporosis trial, among patients with normal baseline uric acid concentrations, 25% of patients in the TYMLOS group and 6% of patients in the placebo group had at least one post-baseline concentration above the normal range.
The hyperuricemia observed in TYMLOS-treated patients was not associated with an increase in adverse reactions of gout or arthralgia over that observed with placebo.
Hypercalciuria and Urolithiasis In the clinical trial of women with postmenopausal osteoporosis, the overall incidence of urine calcium:creatinine ratio >400 mg/g was higher with TYMLOS than with placebo (20% vs 15%, respectively).
Urolithiases were reported in 2.1% of TYMLOS-treated patients and 1.7% of placebo-treated patients.
Adverse Reactions from the Extension Study in Postmenopausal Women with Osteoporosis Following 18 months of treatment with TYMLOS or placebo, 1139 women transitioned to treatment with alendronate 70 mg administered orally once weekly.
The incidence of adverse events occurring during alendronate treatment was similar in patients with prior placebo or TYMLOS therapy [see Clinical Studies ( 14.1 )] .
Adverse Reactions from Clinical Trial in Men with Osteoporosis The safety of TYMLOS was evaluated in a randomized, multicenter, double-blind, placebo-controlled clinical trial in men with osteoporosis aged 42 to 85 years (mean age 68 years) who were randomized to receive 80 mcg of TYMLOS (N = 149) or placebo (N = 79), given subcutaneously once daily for 12 months [see Clinical Studies ( 14.2 )] .
In this study, no patient from either treatment group had an adverse reaction with a fatal outcome during the trial.
Serious adverse reactions were reported by 5.4% of subjects treated with TYMLOS and 5.1% of subjects in the placebo group.
Adverse reactions leading to study drug discontinuation were reported for 6.7% of patients treated with TYMLOS and 5.1% of patients receiving placebo.
The most common adverse reaction leading to study drug discontinuation in the TYMLOS group was dizziness (2%).
Table 2 shows the most common adverse reactions in the trial.
These adverse reactions were generally not present at baseline, occurred more commonly with TYMLOS than with placebo and occurred in at least 2% of the patients treated with TYMLOS.
Table 2: Common Adverse Reactions Reported in Men with Osteoporosis Adverse reactions reported in ≥2% of TYMLOS-treated patients.
Preferred Term TYMLOS (N=149) (%) Placebo (N=79) (%) Injection site erythema 13 5 Dizziness 9 1 Arthralgia 7 1 Injection site swelling 7 0 Injection site pain 6 0 Contusion 3 0 Abdominal distention 3 0 Diarrhea 3 0 Nausea 3 0 Abdominal Pain 2 0 Bone Pain 2 0 Orthostatic Hypotension In the clinical trial of men with osteoporosis, the incidence of orthostatic blood pressure declines of ≥20 mmHg systolic or ≥10 mmHg diastolic at 1 hour after the first injection was 6% in the TYMLOS group and 3% in the placebo group.
Adverse reactions of orthostatic hypotension were reported in 1% of patients receiving TYMLOS and 0 patients receiving placebo.
Dizziness was reported by more TYMLOS-treated patients (9%) compared to placebo (1%) [see Warnings and Precautions ( 5.2 )] .
Laboratory Abnormalities Hypercalcemia In the clinical trial of men with osteoporosis, TYMLOS caused increases in serum calcium concentrations [see Warnings and Precautions ( 5.3 )] .
The incidence of hypercalcemia, defined as albumin-corrected serum calcium ≥10.8 mg/dL at 4 hours following injection at any visit, was 3% in TYMLOS-treated patients and 0% with placebo.
Pre-dose serum calcium was similar to baseline in both groups.
The incidence of hypercalcemia, defined as albumin-corrected serum calcium ≥10.8 mg/dL at 4 hours following injection, with TYMLOS was higher in patients with mild or moderate renal impairment (4%) compared to patients with normal renal function (0%).
Increases in Serum Uric Acid TYMLOS increased serum uric acid concentrations.
In the male osteoporosis trial, among patients with normal baseline uric acid concentrations, 7% of patients in the TYMLOS group and 6% of patients in the placebo group had at least one post-baseline concentration above the normal range.
The hyperuricemia observed in TYMLOS-treated patients was not associated with an increase in adverse reactions of gout or arthralgia over that observed with placebo.
Hypercalciuria and Urolithiasis In the clinical trial of men with osteoporosis, the overall incidence of urine calcium: creatinine ratio >400 mg/g was not greater with TYMLOS than with placebo.
Urolithiases were reported in 2% of TYMLOS-treated patients and 1% of placebo-treated patients.
6.2 Postmarketing Experience The following adverse reactions have been identified during the post-approval use of TYMLOS.
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.
Abdominal distension, abdominal pain, abdominal discomfort Constipation, diarrhea, vomiting, decreased appetite Asthenia, lethargy, malaise, feeling abnormal, hot flush Insomnia Hypersensitivity and anaphylactic reactions, dyspnea (in the context of allergic reactions) Pruritus, rash Generalized pain and pain in bone, joint, back, and extremity Blood pressure increased Muscle spasms of the leg and back Injection site reactions including bruising, hemorrhage, pruritus, and rash