Abaloparatide (Monograph)

Brand name: Tymlos
Drug class: Parathyroid Agents
Chemical name: l-Alanyl-l-valyl-l-seryl-l-α-glutamyl-l-histidyl-l-glutaminyl-l-leucyl-l-leucyl-l-histidyl-l-α-aspartyl-l-lysylglycyl-l-lysyl-l-seryl-l-isoleucyl-l-glutaminyl-l-α-aspartyl-l-leucyl-l-arginyl-l-arginyl-l-arginyl-l-α-glutamyl-l-leucyl-l-leucyl-l-α-glutamyl-l-lysyl-l-leucyl-l-leucyl-2-methylalanyl-l-lysyl-l-leucyl-l-histidyl-l-threonyl-l-alaninamide
Molecular formula: C₁₇₄H₃₀₀N₅₆O₄₉
CAS number: 247062-33-5

Medically reviewed by Drugs.com on Apr 20, 2023. Written by ASHP.

Introduction

Synthetic human parathyroid hormone (parathormone, PTH)-related peptide analog; an osteoanabolic agent.

Uses for Abaloparatide

Osteoporosis in Postmenopausal Women

Treatment of osteoporosis in postmenopausal women at high risk for fractures (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or those intolerant of or failing to respond to other osteoporosis therapy. Has been shown to reduce the risk of vertebral fractures and nonvertebral fractures in these patients.

Because of possible risk of osteosarcoma, treatment duration of more than 2 years during a patient's lifetime is not recommended.

In addition to adequate intake of calcium/vitamin D and other lifestyle modifications (e.g., exercise, avoidance of excessive alcohol and tobacco use), experts recommend pharmacologic therapy for osteoporosis in postmenopausal women at high risk of fractures. Choice of therapy should be individualized based on potential benefits (with respect to fracture risk reduction) and adverse effects of therapy as well as patient preferences, comorbidities, drug availability, and costs.

Clinical practice guidelines generally recommend parathyroid hormone and parathyroid hormone–related protein analogs (e.g., teriparatide, abaloparatide) in postmenopausal women with osteoporosis who are at very high risk of fracture (e.g., those with several or multiple vertebral fractures). Treatment duration should be limited to 2 years. In such women who have completed a course of teriparatide or abaloparatide, treatment with antiresorptive osteoporosis therapies is recommended to maintain bone density gains.

Osteoporosis in Men

Treatment of osteoporosis in men at high risk for fractures (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or those intolerant of or failing to respond to other osteoporosis therapy.

Because of possible risk of osteosarcoma, treatment duration of more than 2 years during a patient's lifetime is not recommended.

In addition to adequate intake of calcium/vitamin D and other lifestyle modifications (e.g., exercise, avoidance of excessive alcohol and tobacco use), the Endocrine Society guidelines recommend that men at high risk of fracture be treated with an approved pharmacologic agent. Selection of therapy should be individualized based on factors such as fracture history, severity of osteoporosis (T-scores), risk of hip fracture, patterns of bone mineral density (BMD), comorbid conditions, and cost.

Abaloparatide Dosage and Administration

General

Pretreatment Screening

Evaluate patient's risk of osteosarcoma. Avoid use of abaloparatide in patients at increased baseline risk (e.g., patients with open epiphyses, metabolic bone diseases other than osteoporosis including Paget's disease of the bone, bone metastases or history of skeletal malignancies, or hereditary disorders predisposing to osteosarcoma).
Evaluate patients for hypercalcemia; abaloparatide is not recommended in patients with preexisting hypercalcemia or in patients who have an underlying hypercalcemic disorder.

Patient Monitoring

Monitor urine calcium if pre-existing hypercalciuria or active urolithiasis is suspected.

Other General Considerations

Patients should receive supplemental calcium and vitamin D while receiving abaloparatide if dietary intake is inadequate.

Administration

Administer by sub-Q injection. Do not administer IV or IM.

Sub-Q Administration

Administer sub-Q into the periumbilical region of the abdomen (avoid the 2-inch area around the navel) at the same time every day. Rotate injection site with each administration.

Commercially available as a clear, colorless solution in a prefilled single-patient-use injection pen that delivers 80 mcg of abaloparatide per actuation.

Use each injection pen for up to 30 days after the first injection and then dispose of properly, even if the pen contains unused solution.

Administer initially in a setting in which the patient can assume a supine or sitting position if symptoms of orthostatic hypotension occur.

Dosage

Adults

Postmenopausal Women with Osteoporosis

Sub-Q

80 mcg once daily.

Use for more than 2 years during a patient's lifetime is not recommended.

Men with Osteoporosis

Sub-Q

80 mcg once daily.

Use for more than 2 years during a patient's lifetime is not recommended.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

No dosage adjustment necessary in mild, moderate, or severe renal impairment.

Cautions for Abaloparatide

Contraindications

Known hypersensitivity to abaloparatide or any component of the formulation.

Warnings/Precautions

Osteosarcoma

Increased incidence of osteosarcoma in male and female rats; effect was dose dependent. Not known if drug causes osteosarcoma in humans.

Avoid use of abaloparatide in patients with increased baseline risk of osteosarcoma (e.g., patients with open epiphyses, metabolic bone diseases other than osteoporosis including Paget's disease of the bone, bone metastases or history of skeletal malignancies, or hereditary disorders predisposing to osteosarcoma).

Cumulative use of abaloparatide for >2 years during a patient's lifetime not recommended.

Orthostatic Hypotension

Orthostatic hypotension may occur, generally within 4 hours of administration. Symptoms may include dizziness, palpitations, tachycardia, or nausea, and may resolve by having the patient recline. Administer the first several doses in a setting in which the patient can sit or recline if necessary.

Hypercalcemia

Hypercalcemia reported; occurred at higher rate in patients with impaired renal function. Not recommended in patients with preexisting hypercalcemia or in those with underlying hypercalcemic disorder (e.g., primary hyperparathyroidism) because of possibility of exacerbating hypercalcemia.

Hypercalciuria and Urolithiasis

May cause hypercalciuria. Not known whether drug may exacerbate urolithiasis in patients with active urolithiasis or a history of this condition.

Consider measurement of urinary calcium excretion if active urolithiasis or preexisting hypercalciuria is suspected.

Immunogenicity

Potential for immunogenicity with all therapeutic proteins, including abaloparatide. Development of antibodies (including neutralizing antibodies) to the drug reported; clinically important effects not observed.

Specific Populations

Pregnancy

Do not use in females of reproductive potential. No data regarding use of drug in pregnant women to inform any drug-associated risks. Animal reproduction studies with abaloparatide not performed.

Lactation

Not known whether abaloparatide is distributed into milk in humans or has any effects on milk production or the breast-fed infant.

Pediatric Use

Safety and efficacy not established. Not recommended in pediatric patients with open epiphyses or hereditary disorders predisposing to osteosarcoma because of increased baseline risk of osteosarcoma.

Geriatric Use

No overall differences in safety or efficacy observed between geriatric patients and younger adults, but increased sensitivity of some older patients cannot be ruled out.

Hepatic Impairment

Information lacking regarding exposure of abaloparatide in patients with hepatic impairment; no specific dosage recommendations available for this patient population.

Renal Impairment

Possible increased exposure of abaloparatide in patients with severe renal impairment; no dosage adjustment required, but monitor such patients for potential adverse effects.

Common Adverse Effects

Osteoporosis in postmenopausal women (≥2%): hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain, and vertigo.

Osteoporosis in men (≥2%): injection site erythema, dizziness, arthralgia, injection site swelling, injection site pain, confusion, nausea, diarrhea, abdominal distension, abdominal pain, and bone pain.

Drug Interactions

No formal drug interaction studies to date.

Does not inhibit or induce CYP isoenzymes at therapeutic concentrations based on in vitro studies. Not a substrate of organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)2, multidrug and toxin extrusion (MATE)1, or MATE2K.

Abaloparatide Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is 36% following sub-Q administration in healthy women.

Median time to peak plasma concentrations: 0.51 hours.

Exhibits a dose-response relationship for bone mineral density (BMD) and bone formation markers when administered once daily for 24 weeks.

Special Populations

In patients with mild, moderate, or severe renal impairment, AUC increased by 1.2-, 1.7-, or 2.1-fold, respectively. Peak plasma concentrations increased by 1.3- or 1.4-fold in those with moderate or severe renal impairment; not increased in those with mild renal impairment.

In postmenopausal women and men, age and race do not appear to affect pharmacokinetics.

Distribution

Plasma Protein Binding

Approximately 70% in vitro.

Not known if abaloparatide is distributed into human milk.

Elimination

Metabolism

Metabolism thought to be mediated by proteolytic enzymes.

Elimination Route

Principally excreted in urine as peptide fragments.

Half-life

Approximately 1 hour.

Stability

Storage

Parenteral

Prefilled Injection Pen

2–8°C prior to first use; 20–25°C after first use for up to 30 days, then discard.

Do not freeze; do not expose to heat.

Actions

Synthetic human PTH-related peptide analog containing 34 amino acids.
Exhibits agonist activity at the PTH receptor type 1 resulting in activation of cyclic adenosine-3′,5′-monophosphate (cAMP) signaling pathway target cells.
Exhibits anabolic effect on bone (demonstrated by elevations in BMD and bone mineral content) correlating with increases in bone strength at vertebral and/or nonvertebral sites in animals.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Inform patients about the increased incidence of osteosarcoma in rats receiving abaloparatide; clinical relevance of this effect in humans unknown. Advise patients to immediately report signs and symptoms of potential osteosarcoma (e.g., persistent localized pain, new soft tissue mass tender to palpation).
Inform patients that abaloparatide may cause hypercalcemia and instruct patients to immediately report symptoms of hypercalcemia (e.g., nausea, vomiting, constipation, lethargy, muscle weakness).
Risk of orthostatic hypotension; advise patients to sit or recline until symptoms resolve if lightheadedness or palpitations occur following administration of abaloparatide and to contact a clinician prior to continuing therapy if such symptoms persist or worsen.
Advise patients to seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction including anaphylaxis, dyspnea, or urticaria.
Instruct patients and caregivers on the proper use and disposal of the injection pen. Importance of advising patients to not share the injection pen with others and to not transfer contents of the pen to a syringe. Inform patients that each injection pen may be used for up to 30 days and then the pen should be discarded, even if it contains unused solution.
Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Inform patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.