TYMLOS- abaloparatide injection, solution
Radius Health, Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use TYMLOS safely and effectively. See full prescribing information for TYMLOS.
TYMLOS ® (abaloparatide) injection, for subcutaneous use
Initial U.S. Approval: 2017
WARNING: RISK OF OSTEOSARCOMA
See full prescribing information for complete boxed warning.
RECENT MAJOR CHANGES
Contraindications, Hypersensitivity (4) 10/2020
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. ( 1)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Injection: 3120 mcg/1.56 mL (2000 mcg/mL) in a single-patient-use prefilled pen. The prefilled pen delivers 30 daily doses of 80 mcg abaloparatide in 40 mcL of sterile, clear, colorless solution. ( 3)
Known hypersensitivity to TYMLOS ( 4)
WARNINGS AND PRECAUTIONS
The most common adverse reactions (incidence ≥2%) are hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain and vertigo. ( 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.
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
FULL PRESCRIBING INFORMATION: CONTENTS*
TYMLOS is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture defined as a history of osteoporotic fracture, 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 [see Clinical Studies ( 14)] .
Limitations of Use
Because of the unknown relevance of the rodent osteosarcoma findings to humans, cumulative use of TYMLOS and parathyroid hormone analogs (e.g., teriparatide) for more than 2 years during a patient’s lifetime is not recommended [see Warnings and Precautions ( 5.1)].
Injection: 3120 mcg/1.56 mL (2000 mcg/mL) in a single-patient-use prefilled pen. The prefilled pen delivers 30 doses of TYMLOS, each containing 80 mcg of abaloparatide in 40 mcL of a sterile, clear, colorless solution.
TYMLOS is contraindicated in patients with a history of systemic hypersensitivity to abaloparatide or to any component of the product formulation. Reactions have included anaphylaxis, dyspnea and urticaria [see Adverse Reactions (6.3)].
Abaloparatide caused a dose-dependent increase in the incidence of osteosarcoma in male and female rats after subcutaneous administration at exposures 4 to 28 times the human exposure at the clinical dose of 80 mcg [see Nonclinical Toxicology ( 13.1)]. It is unknown whether TYMLOS will cause osteosarcoma in humans.
The use of TYMLOS is not recommended in patients at increased risk of osteosarcoma including those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, bone metastases or skeletal malignancies, hereditary disorders predisposing to osteosarcoma, or prior external beam or implant radiation therapy involving the skeleton.
Cumulative use of TYMLOS and parathyroid hormone analogs (e.g., teriparatide) for more than 2 years during a patient’s lifetime is not recommended.
Orthostatic hypotension may occur with TYMLOS, typically within 4 hours of injection. Associated symptoms may include dizziness, palpitations, tachycardia or nausea, and may resolve by having the patient lie down. For the first several doses, TYMLOS should be administered where the patient can sit or lie down if necessary [see Adverse Reactions ( 6.1)].
TYMLOS may cause hypercalcemia. TYMLOS is not recommended in patients with pre-existing hypercalcemia or in patients who have an underlying hypercalcemic disorder, such as primary hyperparathyroidism, because of the possibility of exacerbating hypercalcemia [see Adverse Reactions ( 6.1)].
TYMLOS may cause hypercalciuria. It is unknown whether TYMLOS may exacerbate urolithiasis in patients with active or a history of urolithiasis. If active urolithiasis or pre-existing hypercalciuria is suspected, measurement of urinary calcium excretion should be considered [see Adverse Reactions ( 6.1)].
The following adverse reactions are described in greater detail in other sections:
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.
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)] .
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.
|*Adverse reactions reported in ≥2% of TYMLOS-treated patients.|
|Abdominal pain upper||3||2|
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)].
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 (10% vs. 3%) and pain (9% vs. 7%). Severe redness, severe edema, and severe pain were reported among 2.9%, 0.4%, and 0.4% of the TYMLOS-treated patients.
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)] .
As with all therapeutic proteins, 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 to TYMLOS in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
Of the patients receiving TYMLOS for 18 months, 49% (300/610) developed anti-abaloparatide antibodies, of these, 68% (201/297) developed neutralizing antibodies to abaloparatide. Of the patients with anti-abaloparatide antibodies tested for cross-reactivity, 2.3% (7/298) developed cross-reactivity to PTHrP, 43% (3/7) developed neutralizing antibodies to PTHrP, and 0% (0/298) developed cross-reactive antibodies to PTH. Antibody formation did not appear to have any clinically significant impact on safety or efficacy endpoints, including bone mineral density (BMD) response, fracture reduction, immune-related hypersensitivity or allergic reactions, or other adverse events.
Most of the patients with anti-abaloparatide antibodies during treatment with TYMLOS, 85% (256/300), had follow-up antibody measurements six months after completion of TYMLOS therapy. Among these patients, 56% (143/256) remained antibody positive.
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.
No specific drug-drug interaction studies have been performed [see Clinical Pharmacology ( 12.3)].
TYMLOS is not indicated for use in females of reproductive potential. There are no human data with TYMLOS use in pregnant women to inform any drug associated risks. Animal reproduction studies with abaloparatide have not been conducted.
TYMLOS is not indicated for use in females of reproductive potential. There is no information on the presence of abaloparatide in human milk, the effects on the breastfed infant, or the effects on milk production.
Safety and effectiveness of TYMLOS have not been established in pediatric patients. TYMLOS is not recommended for use in pediatric patients with open epiphyses or hereditary disorders predisposing to osteosarcoma because of an increased baseline risk of osteosarcoma [see Warnings and Precautions ( 5.1)].
Of the total number of patients in the postmenopausal osteoporosis clinical studies of TYMLOS, 82% were age 65 years and over, and 19% were age 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.
No dosage adjustment is required for patients with mild, moderate, or severe renal impairment. A study of a single dose of TYMLOS 80 mcg given subcutaneously was conducted in subjects with normal renal function or mild, moderate, or severe renal impairment. The maximal concentration (C max) and area under the concentration-time curve (AUC) of abaloparatide increased 1.4- and 2.1-fold, respectively, in subjects with severe renal impairment, compared to subjects with normal renal function. Patients with severe renal impairment may have increased abaloparatide exposure that may increase the risk of adverse reactions; therefore, monitor for adverse reactions [see Clinical Pharmacology ( 12.3)].
In a clinical study, accidental overdose was reported in a patient who received 400 mcg in one day (5 times the recommended clinical dose); dosing was temporarily interrupted. The patient experienced asthenia, headache, nausea, and vertigo. Serum calcium was not assessed on the day of the overdose, but on the following day the patient’s serum calcium was within the normal range. The effects of overdose may include hypercalcemia, nausea, vomiting, dizziness, tachycardia, orthostatic hypotension, and headache.
There is no specific antidote for TYMLOS. Treatment of suspected overdose should include discontinuation of TYMLOS, monitoring of serum calcium and phosphorus, and implementation of appropriate supportive measures, such as hydration. Based on the molecular weight, plasma protein binding and volume of distribution, abaloparatide is not expected to be dialyzable.
TYMLOS injection for subcutaneous administration contains abaloparatide, a synthetic 34 amino acid peptide. Abaloparatide is an analog of human parathyroid hormone related peptide, PTHrP(1-34). It has 41% homology to hPTH(1-34) (human parathyroid hormone 1-34) and 76% homology to hPTHrP(1-34) (human parathyroid hormone-related peptide 1-34).
Abaloparatide has a molecular formula of C 174 H 300 N 56 O 49 and a molecular weight of 3961 daltons with the amino acid sequence shown below:
TYMLOS injection is supplied as a sterile, colorless, clear solution in a glass cartridge which is pre-assembled into a disposable single-patient-use pen. The pen is intended to deliver 30 once daily abaloparatide doses of 80 mcg in 40 mcL. Each cartridge contains 1.56 mL of TYMLOS solution. Each mL contains 2000 mcg abaloparatide and the following inactive ingredients: 5 mg phenol, 5.08 mg sodium acetate trihydrate, 6.38 mg acetic acid, and water for injection.
Abaloparatide is a PTHrP(1-34) analog which acts as an agonist at the PTH1 receptor (PTH1R). This results in activation of the cAMP signaling pathway in target cells. In rats and monkeys, abaloparatide had an anabolic effect on bone, demonstrated by increases in BMD and bone mineral content (BMC) that correlated with increases in bone strength at vertebral and/or nonvertebral sites [see Nonclinical Toxicology ( 13.2)].
Effects on Markers of Bone Turnover
A dose-finding study of abaloparatide administered once daily for 24 weeks demonstrated a dose-response relationship for BMD and bone formation markers.
Daily administration of TYMLOS to postmenopausal women with osteoporosis in clinical studies increased the bone formation marker serum procollagen type I N-propeptide (PINP). The increase in PINP levels peaked at Month 1 at 93% above baseline then decreased slowly over time. The increase in PINP was maintained above baseline throughout the treatment duration. At Month 18, PINP concentrations were approximately 45% above baseline. The increase in the bone resorption marker serum collagen type I cross-linked C-telopeptide (sCTX) peaked at Month 3 at 43% above baseline then decreased to 20% above baseline by Month 18.
A 4-way cross-over thorough QT/QTc study was conducted in 55 healthy subjects who received single doses of placebo, subcutaneous doses of abaloparatide at 80 mcg and 240 mcg (three times the recommended dose), and moxifloxacin 400 mg orally. Abaloparatide increased heart rate, with a mean peak increase of 15 beats per minute (bpm) and 20 bpm at the first time point (15 minutes) after dosing with 80 mcg and 240 mcg, respectively. There were no clinically meaningful effects of abaloparatide on QTcI (individually corrected QT intervals) or cardiac electrophysiology.
Following seven days of subcutaneous administration of abaloparatide 80 mcg, the mean (SD) abaloparatide exposure was 812 (118) pg/mL for C max and 1622 (641) pg·hr/mL for AUC 0-24.
Figure 1 below shows the mean (SD) abaloparatide pharmacokinetic profile in postmenopausal women (N = 8) on Day 7.
The median (range) time to peak concentration of abaloparatide 80 mcg was 0.51 hr (0.25 to 0.52 hr) following subcutaneous administration. The absolute bioavailability of abaloparatide in healthy women after subcutaneous administration of an 80 mcg dose was 36%.
The in vitro plasma protein binding of abaloparatide was approximately 70%. The volume of distribution was approximately 50 L.
The mean (SD) half-life of abaloparatide is 1.7 (0.7) hrs. The peptide fragments are primarily eliminated through renal excretion.
No specific metabolism or excretion studies have been performed with TYMLOS. The metabolism of abaloparatide is consistent with non-specific proteolytic degradation into smaller peptide fragments, followed by elimination by renal clearance.
No age-related differences in abaloparatide pharmacokinetics were observed in postmenopausal women ranging from 49 to 86 years of age.
No differences in abaloparatide pharmacokinetics based on race were observed in clinical trials.
Patients with Renal Impairment
A single 80 mcg subcutaneous dose of abaloparatide was administered to male and female patients with renal impairment: 8 patients with mild renal impairment (CLCr 60 to 89 mL/min), 7 patients with moderate renal impairment (CLCr 30 to 59 mL/min), 8 patients with severe renal impairment (CLCr 15 to 29 mL/min), and 8 healthy subjects with normal renal function (CLCr 90 or greater mL/min) matched by sex, age, and body mass index (BMI). Abaloparatide C max increased 1.0-, 1.3-, and 1.4-fold in patients with mild, moderate, and severe renal impairment, compared to the healthy subjects with normal renal function. Abaloparatide AUC increased 1.2-, 1.7-, and 2.1-fold in patients with mild, moderate, and severe renal impairment, compared to the healthy subjects with normal renal function. Patients undergoing dialysis were not included in the study.
In vitro studies showed that abaloparatide, at therapeutic concentrations, does not inhibit or induce Cytochrome P450 enzymes.
In a 2-year carcinogenicity study, abaloparatide was administered once daily to male and female Fischer rats by subcutaneous injection at doses of 10, 25, and 50 mcg/kg. These doses resulted in systemic exposures to abaloparatide that were 4, 16, and 28 times, respectively, the systemic exposure observed in humans following the recommended subcutaneous dose of 80 mcg (based on AUC comparisons). Neoplastic changes related to treatment with abaloparatide consisted of marked dose-dependent increases in osteosarcoma and osteoblastoma incidence in all male and female dose groups. The incidence of osteosarcoma was 0-2% in untreated controls and reached 87% and 62% in male and female high-dose groups, respectively. The bone neoplasms were accompanied by marked increases in bone mass.
The relevance of the rat findings to humans is uncertain. The use of TYMLOS is not recommended in patients at increased risk of osteosarcoma [see Warnings and Precautions ( 5.1)].
Abaloparatide was not genotoxic or mutagenic in a standard battery of tests including the Ames test for bacterial mutagenesis, the chromosome aberration test using human peripheral lymphocytes, and the mouse micronucleus test.
In toxicity studies in rats and monkeys of up to 26-week and 39-week duration, respectively, findings included vasodilation, increases in serum calcium, decreases in serum phosphorus, and soft tissue mineralization at doses ≥10 mcg/kg/day. The 10 mcg/kg/day dose resulted in systemic exposures to abaloparatide in rats and monkeys that were 2 and 3 times, respectively, the exposure in humans at daily subcutaneous doses of 80 mcg.
Pharmacologic effects of abaloparatide on the skeleton were assessed in 12- and 16-month studies in ovariectomized (OVX) rats and monkeys, at doses up to 11 and 1 times human exposure at the recommended subcutaneous dose of 80 mcg, respectively (based on AUC comparisons). In these animal models of postmenopausal osteoporosis, treatment with abaloparatide resulted in dose-dependent increases in bone mass at vertebral and/or nonvertebral sites, correlating with increases in bone strength. The anabolic effect of abaloparatide was due to the predominant increase in osteoblastic bone formation and was evidenced by increases in trabecular thickness and/or cortical thickness due to endosteal bone apposition. Abaloparatide maintained or improved bone quality at all skeletal sites evaluated and did not cause any mineralization defects.
Efficacy Study in Women with Postmenopausal Osteoporosis
The efficacy of TYMLOS for the treatment of postmenopausal osteoporosis was evaluated in Study 003 (NCT 01343004), an 18-month, randomized, multicenter, double-blind, placebo-controlled clinical trial in postmenopausal women aged 49 to 86 years (mean age of 69) who were randomized to receive TYMLOS 80 mcg (N = 824) or placebo (N = 821) given subcutaneously once daily. Approximately 80% of patients were Caucasian, 16% were Asian, and 3% were Black; 24% were Hispanic. At baseline, the mean T-scores were -2.9 at the lumbar spine, -2.1 at the femoral neck, and -1.9 at the total hip. At baseline, 24% of patients had at least one prevalent vertebral fracture and 48% had at least one prior nonvertebral fracture. Patients took daily supplemental calcium (500 to 1000 mg) and vitamin D (400 to 800 IU).
The efficacy study was extended as Study 005 (NCT 01657162), an open-label study where patients were no longer receiving TYMLOS or placebo but were maintained in their original randomized treatment group and received 70 mg alendronate weekly, with calcium and vitamin D supplements for 6 months. Study 005 enrolled 1139 patients, representing 92% of patients who completed Study 003. This included 558 patients who had previously received TYMLOS and 581 patients who had previously received placebo. The cumulative 25-month efficacy dataset included 18 months of exposure to TYMLOS or placebo in Study 003, 1 month of no treatment, followed by 6 months of alendronate therapy in Study 005. Study 005 was then continued to complete 18 months of additional alendronate exposure during which time patients were no longer blinded to their original Study 003 treatment group
Effect on New Vertebral Fractures
The primary endpoint was the incidence of new vertebral fractures in patients treated with TYMLOS compared to placebo. TYMLOS resulted in a significant reduction in the incidence of new vertebral fractures compared to placebo at 18 months (0.6% TYMLOS compared to 4.2% placebo, p ˂0.0001). The absolute risk reduction in new vertebral fractures was 3.6% at 18 months and the relative risk reduction was 86% for TYMLOS compared to placebo ( Table 2). The incidence of new vertebral fractures at 25 months was 0.6% in patients treated with TYMLOS then alendronate, compared to 4.4% in patients treated with placebo then alendronate (p ˂0.0001). The relative risk reduction in new vertebral fractures at 25 months was 87% for patients treated with TYMLOS then alendronate, compared to patients treated with placebo then alendronate, and the absolute risk reduction was 3.9% ( Table 2). After 24 months of open-label alendronate therapy, the vertebral fracture risk reduction achieved with TYMLOS therapy was maintained.
|* Includes patients who had both pre- and post-treatment spine radiographs in Study 003
† Includes patients who had both pre- and post-treatment spine radiographs in Study 005
‡ Confidence Interval
|Percentage of Postmenopausal
Women With Fractures
Effect on Nonvertebral Fractures
TYMLOS resulted in a significant reduction in the incidence of nonvertebral fractures at the end of the 18 months of treatment plus 1 month follow-up where no drug was administered (2.7% for TYMLOS-treated patients compared to 4.7% for placebo-treated patients). The relative risk reduction in nonvertebral fractures for TYMLOS compared to placebo was 43% (logrank test p = 0.049) and the absolute risk reduction was 2.0%.
Following 6 months of alendronate treatment in Study 005, the cumulative incidence of nonvertebral fractures at 25 months was 2.7% for women in the prior TYMLOS group compared to 5.6% for women in the prior placebo group ( Figure 2). At 25 months, the relative risk reduction in nonvertebral fractures was 52% (logrank test p = 0.017) and the absolute risk reduction was 2.9%.
* Excludes fractures of the sternum, patella, toes, fingers, skull and face and those associated with high trauma.
† Includes patients randomized in Study 003
TYMLOS demonstrated consistent reductions in the risk of vertebral and nonvertebral fractures regardless of age, years since menopause, presence or absence of prior fracture (vertebral, nonvertebral) and BMD at baseline.
Effect on Bone Mineral Density (BMD)
Treatment with TYMLOS for 18 months in Study 003 resulted in significant increases in BMD compared to placebo at the lumbar spine, total hip and femoral neck, each with p<0.0001 ( Table 3). Similar findings were seen following 6 months of alendronate treatment in Study 005 ( Table 3).
|* Includes patients randomized in Study 003
† Includes patients enrolled in Study 005
|Treatment Difference (%)
(95% CI §)
|Lumbar Spine||9.2||0.5||8.8 (8.2, 9.3)|
|Total Hip||3.4||-0.1||3.5 (3.3, 3.8)|
|Femoral Neck||2.9||-0.4||3.3 (3.0, 3.7)|
|TYMLOS/ Alendronate (N=558 †) (%)||Placebo/ Alendronate (N=581 †) (%)|
|Lumbar Spine||12.8||3.5||9.3 (8.6, 10.1)|
|Total Hip||5.5||1.4||4.1 (3.7, 4.5)|
|Femoral Neck||4.5||0.5||4.1 (3.6, 4.6)|
TYMLOS demonstrated consistent increases in BMD regardless of age, years since menopause, race, ethnicity, geographic region, presence or absence of prior fracture (vertebral, nonvertebral), and BMD at baseline.
Effect on Bone Histology
Bone biopsy specimens were obtained from 71 patients with osteoporosis after 12 – 18 months of treatment (36 in the TYMLOS group and 35 in the placebo group). Of the biopsies obtained, 55 were adequate for quantitative histomorphometry assessment (27 in the TYMLOS group and 28 in the placebo group). Qualitative and quantitative histology assessment showed normal bone architecture and no evidence of woven bone, marrow fibrosis, or mineralization defects.
TYMLOS injection is supplied as a pre-assembled single-patient-use disposable pen (NDC 70539-001-01) packaged in a cardboard carton (NDC 70539-001-02) with the Instructions for Use and Medication Guide. Each disposable pen embodies a glass cartridge that contains 3120 mcg of abaloparatide in 1.56 mL (2000 mcg/mL) of sterilized, clear, colorless fluid. Each pen provides a 30-day supply for once daily injection of 80 mcg abaloparatide in 40 mcL.
Sterile needles are not included.
Risk of Osteosarcoma
Advise patients that the active ingredient in TYMLOS, abaloparatide, caused a dose-dependent increase in the incidence of osteosarcoma in male and female rats and that it is unknown whether TYMLOS will cause osteosarcoma in humans [see Warnings and Precautions ( 5.1)].
Instruct patients to promptly report signs and symptoms of possible osteosarcoma such as persistent localized pain or occurrence of a new soft tissue mass that is tender to palpation.
Advise patients that TYMLOS may cause hypercalcemia and discuss the symptoms of hypercalcemia (e.g., nausea, vomiting, constipation, lethargy, muscle weakness) [see Warnings and Precautions ( 5.3)].
Instruct patients to promptly report signs and symptoms of hypercalcemia.
Advise patients to sit or lie down if they feel lightheaded or have palpitations after the injection until their symptoms resolve. If these symptoms persist or worsen, advise patients to consult their healthcare provider before continuing treatment [see Dosage and Administration ( 2.2)].
Advise patients to seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction including anaphylaxis, dyspnea or urticaria [see Contraindications (4) and Adverse Reactions (6.3)].
Use of TYMLOS Pen
Instruct patients and caregivers who administer TYMLOS on how to properly use the TYMLOS pen and to follow sharps disposal recommendations [see Dosage and Administration ( 2.2)]. Advise patients not to share their TYMLOS pen or needles with other patients and not to transfer the contents of the pen to a syringe.
Advise patients that each TYMLOS pen can be used for up to 30 days, and after the 30-day use period, to discard the TYMLOS pen, even if it still contains unused solution [see How Supplied/Storage and Handling ( 16.2)] .
Manufactured in Germany for:
Radius Health, Inc.
950 Winter Street
Waltham, MA 02451
TYMLOS is a registered trademark of Radius Health, Inc.
Copyright © 2017, Radius Health, Inc. All rights reserved.
Revised: October 2020
TYMLOS ® (tim lows’)
injection, for subcutaneous use
|What is the most important information I should know about TYMLOS?
TYMLOS may cause serious side effects including:
|What is TYMLOS?
TYMLOS is a prescription medicine used to:
It is not known if TYMLOS is safe and effective for children 18 years and younger.
|Do not take TYMLOS:
|Before you take TYMLOS, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
|How should I use TYMLOS?
|What are the possible side effects of TYMLOS?
TYMLOS may cause serious side effects including:
The most common side effects of TYMLOS include:
These are not all the possible side effects of TYMLOS. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
|How should I store TYMLOS?
Keep TYMLOS and all medicines out of the reach of children.
|General information about the safe and effective use of TYMLOS.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TYMLOS for a condition for which it was not prescribed. Do not give TYMLOS to other people, even if they have the same condition you have. It may harm them.
You can ask your pharmacist or healthcare provider for information about TYMLOS that is written for health professionals.
|What are the ingredients in TYMLOS?
Active ingredient: abaloparatide
Inactive ingredients: phenol, sodium acetate trihydrate, acetic acid, and water for injection.
Radius Health, Inc., 950 Winter St., Waltham, MA 02451
Copyright © 2017, Radius Health, Inc. All rights reserved.
For more information about TYMLOS, visit our website at www.TYMLOS.com or call Radius Health, Inc., at 1-855-672-3487.
TYMLOS is a registered trademark of Radius Health, Inc. US MG 000001 v3.0
This Medication Guide has been approved by the U.S. Food and Drug Administration Issued: 10/2020
INSTRUCTIONS FOR USE
TYMLOS ® (tim lows’)
injection, for subcutaneous use
Instructions for Use
Read and follow this Instructions for Use so that you inject TYMLOS pen the right way. Call your healthcare provider if you have any questions about the right way to inject the TYMLOS pen.
Important information about your TYMLOS pen
Pen needles to use with your TYMLOS pen
Supplies you will need for each injection using your TYMLOS pen
How should I store the TYMLOS pen?
During 30 days of use:
Keep the TYMLOS pen, pen needles and all medicines out of the reach of children.
For more information about the TYMLOS pen
For more information, go to www.TYMLOS.com or call 1-855-672-3487.
Manufactured in Germany.
Radius Health, Inc.
950 Winter Street
Waltham, MA 02451
TYMLOS is a registered trademark of Radius Health, Inc.
Begin the injection.
Check the TYMLOS ® pen
Step 1. Wash and dry your hands.
Step 2. Check the expiration date (Exp.) on the TYMLOS pen.
Attach pen needle to your TYMLOS pen
Step 3. Pull off the pen cap from your TYMLOS pen. (See Figure D.)
Step 4. Pull off the protective paper from the outer needle cap of your pen needle. (See Figure E.)
Step 5. Keep the needle straight and screw it onto the pen until fixed; a secure fit is ensured even if there is no noticeable stop. Do not over-tighten. (See Figure F.)
Step 6. Pull off the outer pen needle cap from the pen needle and keep it to use after your injection. (See Figure G.)
Step 7. Carefully pull off the inner pen needle cap and dispose of it. (See Figure H.)
Step 8. If you are using this pen for the first time, go to the “New pen setup - Day 1 Only” section to prime your pen.
New pen setup – Day 1 Only (Priming your TYMLOS pen)
Do not repeat new pen setup on Days 2 through 30.
Step 9. The “New pen setup” removes air bubbles (primes your pen). You only need to prime your pen on Day 1 for each new pen. Otherwise, you will waste medicine.
Step 10. Turn the dose knob on your TYMLOS pen away from you (clockwise) until it stops. (See Figure I.)
Note: You will see “ • 80 ” lined up in the dose display window.
Step 11. Hold the TYMLOS pen with the pen needle pointing up. Tap lightly with your finger on the cartridge holder to move any air bubbles in the cartridge to the top of the cartridge. (See Figure J.)
Note: Do Step 11 even if you do not see air bubbles.
Step 12. Press the green injection button until it will not go any further. (See Figure K).
Note: You should see liquid come out of the needle tip.
Note: You will see “•0” lined up in the dose display window.
What should I do if liquid does not come out of the needle tip?
Set the dose on your TYMLOS pen
Do not push the green injection button while setting your dose.
Step 13. Turn the dose knob on your pen away from you (clockwise) until the dose knob stops and “•80” is lined up in the dose display window. (See Figure L.)
If you set the dose before you are ready to give your injection, turn the dose knob toward you (counter-clockwise) until “•0” is in the dose display window.
If you are not able to set the TYMLOS pen to “•80”, dispose of the pen and use a new TYMLOS pen for your injection, repeating Steps 1 through 13.
Choose and clean your injection site
Step 14. Injections should be given in the lower stomach area (abdomen). (See Figure M.) Avoid the 2-inch area around your belly button (navel).
For each injection, change (rotate) your injection site around your abdomen. Talk to your healthcare provider about how to change (rotate) your injection site for each injection. Do not use the same injection area for each injection. Do not inject into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks.
Step 15. Wipe the injection site with an alcohol swab and allow it to dry. Do not touch, fan, or blow on the injection site after you have cleaned it.
Giving your TYMLOS pen injection
Read Step 16 and Step 17 before you give your injection.
Inject your TYMLOS pen the way your healthcare provider has shown you.
Step 16. (See Figure N.)
Step 17. (See Figure O.)
Step 18. After counting to 10, release your finger from the green injection button and slowly remove the TYMLOS pen from the injection site by pulling the pen needle straight out.
Remove the pen needle
Step 19. Carefully place the outer needle cap back on the pen needle. Press on the outer needle cap until it snaps into place and is secure. (See Figure P.)
Caution: To prevent needle stick injury, carefully follow Step 20.
Step 20. Unscrew the capped needle (like unscrewing a cap from a bottle). To unscrew the capped needle you may need to turn it 8 or more turns and then gently pull until the capped needle comes off. (See Figure Q.)
Note: Do not push on the outer needle cap while unscrewing the needle. You should see a gap widening between the outer needle cap and the pen as you unscrew the needle. (See Figure R.)
Replace pen cap
Step 21. Firmly replace the pen cap onto the TYMLOS pen. (See
Keep the pen cap on your TYMLOS pen between injections.
After your injection
Step 22. Press a cotton ball or gauze pad over the injection site and hold for 10 seconds. Do not rub the injection site. You may have slight bleeding. This is normal.
You may cover the injection site with a small adhesive bandage, if needed.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
abaloparatide injection, solution
|Labeler - Radius Health, Inc. (146676262)|
|Registrant - Radius Health, Inc. (146676262)|
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