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  • CLASSES

    Parathyroid Hormone Analogs and Modifiers

    DEA CLASS

    Rx

    DESCRIPTION

    An analog of human parathyroid hormone related peptide [PTHrP(1-34)]
    Used for the treatment of postmenopausal women with osteoporosis at high risk for fracture
    Cumulative use for more than 2 years during a patient's lifetime is not recommended

    COMMON BRAND NAMES

    TYMLOS

    HOW SUPPLIED

    TYMLOS Subcutaneous Inj Sol: 1mL, 2000mcg

    DOSAGE & INDICATIONS

    For the treatment of postmenopausal women with osteoporosis at high risk for fracture.
    Subcutaneous dosage
    Adult postmenopausal females

    80 mcg subcutaneously once daily. Use should be reserved for postmenopausal women at high risk for fracture, including a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Supplement calcium and vitamin D if dietary intake is inadequate. Cumulative use of abaloparatide for more than 2 years during a patient's lifetime is not recommended. Follow abaloparatide treatment with a bisphosphonate or denosumab to prevent decline of bone density and loss of efficacy against fracture. The North American Menopause Society (NAMS) recommends that use of parathyroid analogs in postmenopausal women be reserved for those patients with a high risk of fracture who do not have hypercalcemia, bone metastases, any bone tumor-predisposing disorder, or a history of skeletal irradiation.

    MAXIMUM DOSAGE

    Adults

    80 mcg/day subcutaneously.

    Geriatric

    80 mcg/day subcutaneously.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Subcutaneous Administration

    General Information
    For subcutaneous use only. Do not administer intravenously or intramuscularly.
    Abaloparatide is available as a prefilled pen (TYMLOS pen) containing 30 doses of abaloparatide (each dose contains 80 mcg in 40 mcL).
    Needles are NOT included with the pen. The patient will need a separate prescription for the needles. The correct needles to use with the pen are 5 mm to 8 mm, 31-gauge. Compatible needles include Clickfine, BD Ultra-Fine, MedtFine, Easy Comfort, Clever Choice, Comfort EZ, and SureComfort.
    Abaloparatide pens should never be shared among patients. Even if the disposable needle is changed, sharing may result in transmission of hepatitis viruses, HIV, or other blood-borne pathogens. Do not share pens among multiple patients in an inpatient setting. Reserve the use of any pen for 1 patient only.
    Storage: Prior to the first use, store the pen in the refrigerator (do not freeze). After the first use, store the pen for up to 30 days at room temperature between 68 to 77 degrees F (20 to 25 degrees C); do not freeze the pen or expose it to heat. Keep the pen cap on the pen when not in use. Do not store the pen with a needle attached. Use the pen only for 30 days. Properly dispose of the pen 30 days after first opening it even if it still contains unused medicine.
     
    Subcutaneous Administration (TYMLOS Pen)
    Patients and caregivers should receive proper training and instruction on the proper use of the abaloparatide pen.
    Pull off the pen cap from the pen. Keep the pen cap for storage between injections. Check the pen cartridge. The liquid should be clear, colorless, and free of particles; if not, do not use.
    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.
    Pull off the outer pen needle cap from the pen needle and keep it to re-cap the needle after the injection.
    Carefully pull off the inner pen needle cap and dispose of it.
    Each new pen must be primed prior to the first use only. This step removes air bubbles from the pen.
    Turn the dose knob on the pen away from you (clockwise) until it stops. You will see "80” lined up in the dose display window.
    Hold the 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.
    Press the green injection button until it will not go any further. You will see "0" lined up in the dose display window. A drop of liquid should come out of the needle tip. If not, repeat the priming steps.
    Set the patient's dose on the pen by turning the dose knob on the pen away from you (clockwise) until the dose knob stops and "80" is lined up in the dose display window.
    Choose and clean an injection site in the periumbilical region of the abdomen. Avoid the 2-inch area around the navel. Do not inject into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks.
    Insert the pen needle straight into the patient's skin.
    Press the green injection button on the pen until it cannot go any further and "0" is in the dose display window. Do not move the pen after inserting the needle.
    Continue to press the green injection button while counting to 10. Counting to 10 will allow the full dose to be given.
    After counting to 10, release the green injection button and slowly remove the pen from the injection site by pulling the pen needle straight out.
    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.
    Unscrew the used, capped needle from the pen. 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. Properly dispose of the used needle.
    Firmly replace the pen cap onto the pen. Keep the pen cap on the pen for storage between injections.
    Rotate site of injection daily and administer at approximately the same time every day.
    The first several doses should be administered with the patient laying down in case symptoms of orthostatic hypotension occur.

    STORAGE

    TYMLOS:
    - Avoid exposure to heat
    - Do not freeze
    - May be stored at temperatures up to 77 degrees F if used within 1 month
    - See package insert for detailed storage information
    - Store between 36 to 46 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Abaloparatide is contraindicated in patients with abaloparatide hypersensitivity. Anaphylaxis, dyspnea, and urticaria have occurred during treatment.

    Orthostatic hypotension

    Use abaloparatide cautiously in patients with pre-existing orthostatic hypotension. Orthostatic hypotension may occur with the administration of abaloparatide, usually within 4 hours of injection. Symptoms include dizziness, palpitations, tachycardia or nausea. These symptoms may resolve if the patient lies down. Therefore, the first several daily doses should be administered at a location where the patient can sit or lie down if needed.

    Hypercalcemia, hyperparathyroidism

    Abaloparatide may cause hypercalcemia and is not recommended in patients with pre-existing hypercalcemia or in patients who have an underlying hypercalcemic disorder (e.g., primary hyperparathyroidism) due to the possibility of exacerbating the condition. Measure serum calcium at least 16 hours after drug administration if indicated.

    New primary malignancy, osteogenic sarcoma, Paget's disease, radiation therapy

    Avoid the use of abaloparatide in patients at increased risk of osteogenic sarcoma (osteosarcoma), including those with open epiphyses (e.g., pediatric patients), metabolic bone diseases other than osteoporosis (e.g., Paget's disease of the bone), bone metastases or a history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma. Osteosarcoma, as a new primary malignancy, has been reported in patients with a PTH-analog in the postmarketing setting; however, increased risk has not been observed in observational human trials. There are limited data assessing risk beyond 2 years of therapy. Abaloparatide has been associated with an increased incidence of osteosarcoma in rat studies. This increased incidence was dependent on e.g., dose and duration of treatment; systemic exposure to abaloparatide in the rats ranged from 4 to 28 times the exposure given to humans in an 80-mcg daily dose. The relevance of these animal osteosarcoma findings is uncertain relative to humans; however, the potential risk should be considered. Abaloparatide use has not been evaluated beyond 2 years; use beyond 2 years is not recommended.

    Hypercalciuria, nephrolithiasis

    Use abaloparatide cautiously in patients with active urolithiasis (nephrolithiasis) or pre-existing hypercalciuria. Abaloparatide may cause hypercalciuria. It is unknown if abaloparatide may exacerbate urolithiasis in patients with active urolithiasis or a history or nephrolithiasis. Consider measuring urinary calcium excretion if active urolithiasis or pre-existing hypercalciuria is suspected.

    Renal failure, renal impairment

    Patients with severe renal impairment and renal failure may have increased abaloparatide exposure. Monitor these patients for adverse reactions during abaloparatide therapy.

    Pregnancy

    Abaloparatide is not indicated for women of reproductive potential. There are no human or animal data on the use of abaloparatide during pregnancy to inform any drug associated risks.

    Breast-feeding

    Abaloparatide is not indicated for women of reproductive potential; there is no experience with use of the drug during breast-feeding. There are no data on the presence of abaloparatide in human milk, the effects on the breast-fed infant, or the effects on milk production.

    Children, infants

    Safety and efficacy of abaloparatide has not been established in infants, children, or adolescents. Pediatric patients are more likely to have open epiphyses or hereditary disorders predisposing them to an increased risk for osteosarcoma.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / Incidence not known
    new primary malignancy / Delayed / Incidence not known
    osteogenic sarcoma / Delayed / Incidence not known

    Moderate

    hyperuricemia / Delayed / 25.0-25.0
    hypercalciuria / Delayed / 11.0-11.0
    palpitations / Early / 5.0-5.0
    hypercalcemia / Delayed / 3.0-3.0
    nephrolithiasis / Delayed / 2.1-2.1
    sinus tachycardia / Rapid / 2.0-2.0
    orthostatic hypotension / Delayed / 1.0-1.0
    dyspnea / Early / Incidence not known
    constipation / Delayed / Incidence not known
    bone pain / Delayed / Incidence not known
    antibody formation / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 9.0-58.0
    dizziness / Early / 10.0-10.0
    nausea / Early / 8.0-8.0
    headache / Early / 8.0-8.0
    abdominal pain / Early / 3.0-3.0
    fatigue / Early / 3.0-3.0
    vertigo / Early / 2.0-2.0
    rash / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    diarrhea / Early / Incidence not known
    vomiting / Early / Incidence not known
    lethargy / Early / Incidence not known
    malaise / Early / Incidence not known
    asthenia / Delayed / Incidence not known
    insomnia / Early / Incidence not known
    muscle cramps / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    back pain / Delayed / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Abaloparatide products.

    PREGNANCY AND LACTATION

    Pregnancy

    Abaloparatide is not indicated for women of reproductive potential. There are no human or animal data on the use of abaloparatide during pregnancy to inform any drug associated risks.

    Abaloparatide is not indicated for women of reproductive potential; there is no experience with use of the drug during breast-feeding. There are no data on the presence of abaloparatide in human milk, the effects on the breast-fed infant, or the effects on milk production.

    MECHANISM OF ACTION

    Abaloparatide is a synthetic peptide analog of the parathyroid hormone-related protein (PTHrP 1-34), which acts as an agonist at the PTH1 receptor (PTH1R) with greater selectivity than teriparatide. Binding to the PTH1R results in activation of the cAMP signaling pathway in target cells. New bone formation on trabecular and cortical bone surfaces occurs through stimulation of osteoblastic activity with once-daily administration of abaloparatide. In animal studies, abaloparatide had an anabolic effect on bone, resulting in increased bone mineral density (BMD) and bone mineral content that correlated with increases in bone strength at vertebral and/or nonvertebral sites. When administered once daily for 24 weeks, a dose-response relationship was observed for BMD and bone formation markers.

    PHARMACOKINETICS

    Abaloparatide is administered subcutaneously. Plasma protein binding is approximately 70%, and the volume of distribution is 50 L. The mean (SD) half-life of abaloparatide is 1.7 (0.7) hours. No specific metabolism studies have been performed with abaloparatide. Metabolism is consistent with non-specific proteolytic degradation into smaller peptide fragments. Peptide fragments are primarily eliminated through renal excretion.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
    No metabolism-related drug interactions are expected. No drug-drug interaction studies have been performed with abaloparatide.

    Subcutaneous Route

    Following 7 days of subcutaneous administration of abaloparatide 80 mcg/day, the mean maximal concentration Cmax (SD) was 812 (118) pg/mL and the mean (SD) exposure was 1,622 (641) pg x hour/mL for AUC. The mean time to peak concentration (Tmax) was 0.51 hr (0.25 to 0.52 hour) following subcutaneous administration. The absolute bioavailability of abaloparatide in healthy women after subcutaneous administration of an 80 mcg dose was 36%.