Generic Name: Abaloparatide
Brand Names: Various around the world
What is Abaloparatide?
Abaloparatide is a synthetic peptide analogue of human parathyroid hormone-related protein (PTHrP), designed for the treatment of postmenopausal osteoporosis. Some popular brand names of drugs containing abaloparatide include Tymlos and Eladynos. In this article, we will analyse several studies on abaloparatide, including works by Gonnelli and Caffarelli (2016), Brent (2021), and Leder et al. (2015), to provide a comprehensive overview of this medication’s therapeutic category, chemical structure, mechanism of action, and indications for use.
Therapeutic category
Abaloparatide belongs to the class of anabolic agents used in the treatment of osteoporosis. It is a bone-forming medication that stimulates the activity of osteoblasts, the cells responsible for the synthesis and mineralization of bone matrix (Gonnelli and Caffarelli, 2016, “Clinical Cases in Mineral and Bone Metabolism”).
Chemical structure and properties
Abaloparatide is a 34-amino acid peptide with a molecular weight of 3961 Da. Its amino acid sequence is similar to that of the N-terminal part of human PTHrP, but at positions 22, 23, 24, 26, 27, 30, and 31 there are changes that make it more effective at building bone while lowering the risk of hypercalcemia (Brent, 2021, “European Journal of Pharmacology”).
Mechanism of action
It works by attaching to and turning on the parathyroid hormone type 1 receptor (PTH1R) on osteoblasts and osteocytes. Osteoblast differentiation, function, and longevity are all boosted by this activity, which leads to more bone growth. Abaloparatide also stops osteoclasts from breaking down bone, which makes bones stronger and more dense (Leder et al., 2015, “The Journal of Clinical Endocrinology & Metabolism”).
Indications for use
Abaloparatide is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. This includes women with a history of osteoporotic fracture, multiple risk factors for fracture, or those who have failed or are intolerant to other available osteoporosis therapy (Gonnelli and Caffarelli, 2016, “Clinical Cases in Mineral and Bone Metabolism”). The medication is administered as a daily subcutaneous injection, with a recommended dosage of 80 µg per day for up to 18 months (Brent, 2021, “European Journal of Pharmacology”).
Warnings
Precautions before taking the drug Abaloparatide
Before starting abaloparatide treatment, doctors should check to see if the patient already has any conditions that could make the drug less safe or less effective. Patients with a history of high calcium levels, Paget’s disease of the bone, high alkaline phosphatase levels for no clear reason, or previous external beam or implant radiation treatment should be carefully looked at (Gonnelli and Caffarelli, 2016). Also, people who have serious renal failure or end-stage renal disease should be closely watched to make sure they don’t develop hypercalcemia while taking abaloparatide.
Contraindications
Abaloparatide is contraindicated in patients with a history of hypersensitivity to the active substance or any of the excipients in the formulation. It should not be used in patients with pre-existing hypercalcemia, as the medication may exacerbate this condition. Pregnant and lactating women should also avoid using abaloparatide, as the safety and efficacy of the drug have not been established in these populations (Brent).
What you should avoid
During treatment with abaloparatide, patients should avoid excessive calcium intake, either through diet or supplementation, as this may increase the risk of hypercalcemia. Patients should also avoid smoking and excessive alcohol consumption, as these habits can negatively impact bone health and reduce the effectiveness of the medication.
Dosage and administration of the drug Abaloparatide
The recommended dosage of abaloparatide is 80 µg administered once daily as a subcutaneous injection in the periumbilical region of the abdomen. The duration of treatment should not exceed 18 months, as the safety and efficacy of the medication beyond this period have not been established (Leder et al.). Patients should be trained on proper injection techniques and should rotate injection sites to minimise the risk of local reactions.
Routes and methods of administration
Abaloparatide is available as a pre-filled pen device containing 30 doses of the medication. Each dose is delivered in a volume of 40 µL. Patients should be instructed to remove the pen from the refrigerator at least 30 minutes before administration to allow the medication to reach room temperature. The injection site should be cleaned with an alcohol swab before administration, and the pen should be held perpendicular to the skin during injection. After use, the pen should be stored in the refrigerator to maintain the stability of the medication.
What should I do if I miss a dose of the drug Abaloparatide?
If a patient misses a dose of abaloparatide, they should take the missed dose as soon as they remember, provided that the next scheduled dose is not due within the next 12 hours. If the next dose is due within 12 hours, the patient should skip the missed dose and continue with the regular dosing schedule. Patients should not take two doses at once to compensate for a missed dose, as this may increase the risk of adverse effects.
Overdose
In the event of an overdose with abaloparatide, patients may experience symptoms of hypercalcemia, such as nausea, vomiting, constipation, fatigue, and confusion. In severe cases, cardiac arrhythmias and renal impairment may occur. Treatment of abaloparatide overdose involves supportive care and the management of hypercalcemia through hydration, diuresis, and the use of calcitonin or bisphosphonates if necessary (Gonnelli and Caffarelli).
Side Effects of the drug Abaloparatide
The most common side effects associated with abaloparatide treatment include injection site reactions, such as redness, swelling, and pain. These reactions are typically mild and transient, resolving within a few days of onset. Other common adverse effects include hypercalciuria, dizziness, nausea, headache, and palpitations (Leder et al.).
Less frequent but more serious side effects may include hypercalcemia, orthostatic hypotension, and tachycardia. Patients should be monitored for signs and symptoms of these conditions during treatment, and the medication should be discontinued if severe or persistent adverse effects occur (Brent).
Interactions
Drug-drug interactions
Abaloparatide may interact with other medications that affect calcium metabolism or bone turnover. Concomitant use of abaloparatide with other PTH analogues or PTHrP agonists should be avoided, as this may increase the risk of hypercalcemia and other adverse effects. Patients taking digoxin or other cardiac glycosides should be closely monitored, as abaloparatide may increase the risk of cardiac arrhythmias by inducing hypercalcemia (Gonnelli and Caffarelli, “Clinical Cases in Mineral and Bone Metabolism”).
Drug-food interactions
The absorption and efficacy of abaloparatide are not significantly affected by food intake. However, patients should be advised to maintain a balanced diet with adequate calcium and vitamin D intake to support bone health during treatment. Excessive calcium intake through diet or supplementation should be avoided, as this may increase the risk of hypercalcemia when combined with abaloparatide therapy (Leder et al., “The Journal of Clinical Endocrinology & Metabolism”).
Additional important information
Special warnings for the elderly and children
Abaloparatide should be used with caution in elderly patients, as they may be more susceptible to the adverse effects of the medication, particularly hypercalcemia and orthostatic hypotension. Dose adjustments may be necessary based on renal function and other comorbidities. The safety and efficacy of abaloparatide in children and adolescents have not been established, and the use of the medication is not recommended in these populations (Brent, “European Journal of Pharmacology”).
Development of resistance
The development of resistance to abaloparatide therapy has not been widely reported in clinical studies. However, the long-term efficacy of the medication may be limited by the potential for osteoblasts to become desensitised to the anabolic effects of PTHrP analogues over time. Further research is needed to evaluate the optimal duration of abaloparatide treatment and the potential for resistance to develop with prolonged use.
Clinical studies of the drug Abaloparatide
Several research studies have looked into how well and safely abaloparatide treats osteoporosis in women who have gone through menopause. Over the course of 18 months in the phase 3 ACTIVE study, abaloparatide significantly raised bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck compared to a placebo (Leder et al.). The medicine also lowered the chance of new fractures of the spine and other bones in this group.
The ACTIVExtend trial showed that abaloparatide’s bone-building effects lasted for up to two years after switching to alendronate therapy. This suggests that treating people with severe osteoporosis with an anabolic agent first and then an antiresorptive drug may have long-term benefits for them (Gonnelli and Caffarelli).
Comparative effectiveness
When put up against teriparatide, which is another anabolic drug used to treat osteoporosis, abaloparatide did a better job of raising BMD at the total hip and femoral neck over the course of 6 months (Brent). Both medicines were linked to similar increases in lumbar spine BMD and lower risks of fracture.
Abaloparatide has been shown to increase bone mineral density (BMD) more quickly and more significantly than bisphosphonates like alendronate and zoledronic acid. This is especially true for people with severe osteoporosis or multiple fracture risk factors (Leder et al., “The Journal of Clinical Endocrinology & Metabolism”).
Pharmacological characteristics
Abaloparatide is different from other osteoporosis medicines because of how it works in the body. It has a more specific anabolic effect than teriparatide, which activates both PTH1R and PTH2R because it only activates the PTH1R signalling pathway in bone (Gonnelli and Caffarelli). This selective stimulation may help explain why hypercalcemia and other bad effects are less common with abaloparatide treatment.
For the medicine to keep working, it needs to be injected under the skin every day because its half-life is only about 1.7 hours (Brent). About 70% of abaloparatide is bioavailable, and the drug is mostly removed from the body through the kidneys. It is not broken down much in the liver.
Briefly
Abaloparatide is a man-made peptide that is similar to human phosphate hormone-related protein (PTHrP). It is used to treat osteoporosis in women who have gone through menopause. As an anabolic agent, it raises the activity of osteoblasts, which causes more bone to form and a net gain in bone mass and strength (Leder et al., 2015). Abaloparatide is injected under the skin every day, and the suggested dose is 80 µg per day for up to 18 months (Brent, 2021). Studies have shown that it works to increase bone mineral density and lower the chance of spinal and nonvertebral cracks in osteoporosis-stricken women who are past menopause (Gonnelli and Caffarelli, 2016). Although abaloparatide is typically well taken, it can cause side effects like reactions at the injection site, high calcium levels in the urine, dizziness, and feeling sick. During treatment, patients should be watched for signs of orthostatic hypotension and hypercalcemia. Abaloparatide might not work well with other drugs that alter the way calcium is used or the way the teeth break down. People who already have high calcium levels or are very allergic to the drug should also not take it. Overall, abaloparatide looks like a good treatment choice for people with severe osteoporosis or a lot of risk factors for fractures. It has targeted anabolic benefits and a safer safety record than other osteoporosis drugs.
ATTENTION: It is of vital importance to never take any medication without the supervision and guidance of a specialised doctor. Consult the package insert of each prescribed medicinal product, as each pharmaceutical company accurately describes the specific specifications for the product, which may undergo regular updates. Note that the trade names mentioned in this article correspond to well-known medicinal products that contain the active substances under analysis. However, there may be variations depending on the composition of each drug. This article focuses on the active substance analysis rather than the drug’s trade name. The reference to trade names is made exclusively for the convenience of readers, who should carefully study the instruction leaflet for each commercial preparation they use. It is necessary to have close cooperation with your attending physician and your pharmacist. The self-administration of any medication carries serious health risks and should be strictly avoided.
Bibliography
- Gonnelli, S., & Caffarelli, C. (2016). Abaloparatide. Clinical Cases in Mineral and Bone Metabolism. ncbi.nlm.nih
- Brent, M. B. (2021). Abaloparatide: a review of preclinical and clinical studies. European Journal of Pharmacology. sciencedirect
- Leder, B. Z., O’Dea, L. S. L., Zanchetta, J. R., Kumar, P., Banks, K., McKay, K., Lyttle, C. R., & Hattersley, G. (2015). Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. The Journal of Clinical Endocrinology & Metabolism. academic.oup
