Abaloparatide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Pen-injector, Subcutaneous:

Tymlos: 3120 mcg/1.56 mL (1.56 mL) [contains phenol]

Pharmacology

Mechanism of Action

Abaloparatide is an analog of human parathyroid hormone related peptide (PTHrP[1-34]), which acts as an agonist at the PTH1 receptor (PTH1R). This results in stimulation of osteoblast function and increased bone mass (Harslof 2016; Leder 2017).

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: ~50 L

Metabolism

Hepatic (nonspecific proteolysis)

Excretion

Urine (as peptide fragments)

Time to Peak

0.51 hours (range: 0.25 to 0.52 hours)

Half-Life Elimination

1.7 hours

Protein Binding

~70%

Use in Specific Populations

Special Populations: Renal Function Impairment

Maximum serum concentration increased 1-, 1.3- and 1.4-fold in patients with mild, moderate and severe renal impairment, respectively. AUC increased 1.2-, 1.7- and 2.1-fold in patients with mild, moderate and severe renal impairment, respectively.

Use: Labeled Indications

Osteoporosis: Treatment of postmenopausal females with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture). May also be used in patients who have failed or are intolerant to other available osteoporosis therapy.

Limitations of use: Cumulative lifetime duration of abaloparatide and any other parathyroid hormone therapy (eg, teriparatide) should not exceed 2 years.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosage and Administration

Dosing: Adult

Note: Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate; however, use caution to avoid hypercalcemia. Assess serum calcium prior to initiation; avoid use in patients with preexisting hypercalcemia or hypercalcemic disorder.

Osteoporosis, treatment (postmenopausal females): Note: Use typically reserved for reduction of vertebral and nonvertebral fractures in patients with very high fracture risk (eg, previous severe or multiple vertebral fractures), or as an alternative agent in patients for whom first-line therapies are not tolerated or ineffective (ES [Eastell 2019]).

SubQ: 80 mcg once daily.

Discontinuation/interruption of therapy: Because the benefits of anabolic therapy are quickly lost after discontinuation, it is generally recommended to initiate a bisphosphonate to maintain bone density gains following a course of abaloparatide (Bone 2018; ES [Eastell 2019]).

Duration of therapy: Fracture reduction efficacy has been demonstrated over a period of 18 months. Cumulative lifetime duration of abaloparatide and any other parathyroid hormone therapy (eg, teriparatide) should not exceed 2 years.

Dosing: Geriatric

Refer to adult dosing.

Administration

SubQ: Inject subcutaneously into the periumbilical region of the abdomen. Rotate the site of the injection every day and administer at approximately the same time every day. Do not administer intravenously or intramuscularly. Initial doses should occur under circumstances in which the patient may sit or lie down, in the event of orthostasis.

Dietary Considerations

Ensure adequate calcium and vitamin D intake; if dietary intake is inadequate, dietary supplementation is recommended. Females and males should consume:

Calcium: 1,000 mg/day (males: 50 to 70 years) or 1,200 mg/day (females ≥51 years and males ≥71 years) (IOM 2011; NOF [Cosman 2014]).

Vitamin D: 800 to 1,000 int. units/day (males and females ≥50 years) (NOF [Cosman 2014]). Recommended Dietary Allowance (RDA): 600 int. units/day (males and females ≤70 years) or 800 int. units/day (males and females ≥71 years) (IOM 2011).

Storage

Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze or heat. After first use, store for up to 30 days at 20°C to 25°C (68°F to 77°F).

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>10%:

Endocrine & metabolic: Increased uric acid (25%)

Genitourinary: Hypercalciuria (11% to 20%)

Immunologic: Antibody development (49%; neutralizing antibodies: 68%; antibody formation was not found to have any clinical significance)

Local: Erythema at injection site (58%)

1% to 10%:

Cardiovascular: Palpitations (5%), orthostatic hypotension (1% to 4%), sinus tachycardia (≤2%), tachycardia (≤2%)

Central nervous system: Dizziness (10%), headache (8%), fatigue (3%)

Endocrine & metabolic: Hypercalcemia (3%)

Gastrointestinal: Nausea (8%), upper abdominal pain (3%)

Local: Swelling at injection site (10%), pain at injection site (9%)

Warnings/Precautions

Concerns related to adverse effects:

• Hypercalcemia: May cause or exacerbate hypercalcemia; use is not recommended in patients with preexisting hypercalcemia or with an underlying hypercalcemic disorder (eg, primary hyperparathyroidism).
• Orthostatic hypotension: May cause orthostatic hypotension. Transient orthostatic hypotension usually occurs within 4 hours of dosing.
• Osteosarcoma: [US Boxed Warning]: In animal studies, abaloparatide has been associated with an increase in osteosarcoma; risk was dependent on both dose and duration. Avoid use in patients with an increased risk of osteosarcoma (including Paget disease, bone metastases or skeletal malignancies, hereditary disorders predisposing to osteosarcoma, unexplained elevation of alkaline phosphatase, prior external beam or implant radiation therapy involving the skeleton, or in patients with open epiphyses).

Disease-related concerns:

• Urolithiasis: Use may cause hypercalciuria; use with caution in patients with active or recent urolithiasis because of risk of exacerbation.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Use for >2 years during a patient's lifetime is not recommended.

Monitoring Parameters

Orthostatic hypotension; serum calcium; urinary calcium (patients with suspected active urolithiasis or preexisting hypercalciuria).

Bone mineral density (BMD) should be evaluated at baseline and ~1 to 2 years following initiation of therapy (AACE/ACE [Camacho 2016]; ES [Eastell 2019]; NOF [Cosman 2014]); may consider monitoring biochemical markers of bone turnover (eg, serum P1NP) at baseline, 3 months, and 6 months, to assess treatment response (ES [Eastell 2019]; Miller 2016).

Pregnancy

Pregnancy Considerations

Abaloparatide is not indicated for use in women of reproductive potential. Animal reproduction studies have not been conducted.

Patient Education

What is this drug used for?

• It is used to put off soft, brittle bones (osteoporosis) in women after change of life.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea
• Headache
• Loss of strength and energy
• Abdominal pain
• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High calcium like weakness, confusion, fatigue, headache, nausea and vomiting, constipation, or bone pain.
• Kidney stone like back pain, abdominal pain, or blood in the urine.
• Bone pain
• Skin swelling
• Lump
• Persistent pain
• Severe dizziness
• Passing out
• Fast heartbeat
• Abnormal heartbeat
• Muscle weakness
• Painful urination
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.