What are the side effects, contraindications, and monitoring recommendations for Tymlos (abaloparatide) in post‑menopausal women and men at high risk for fracture?

Tymlos (Abaloparatide) Side Effects and Safety Profile

Most Common Side Effects

The most frequently reported adverse effects of Tymlos in postmenopausal women include dizziness (11.0%), hypercalciuria (11.5%), fast heartbeat, upper stomach pain, nausea, fatigue, vertigo, and headache. 1, 2 In men with osteoporosis, the most common side effects are injection site reactions (redness, pain, swelling, bruising), nausea, dizziness, abdominal pain and bloating, joint pain, bone pain, and diarrhea. 1, 3

Cardiovascular Effects

• Orthostatic hypotension and tachycardia occur soon after injection in some patients, causing dizziness, lightheaded feeling, or faster heartbeat that typically resolves within a few hours. 1, 4
• Patients should take their first injections in a place where they can sit or lie down immediately if these symptoms develop. 1
• Palpitations and increased heart rate occur more frequently with abaloparatide compared to teriparatide, contributing to higher discontinuation rates. 4

Metabolic Disturbances

• Hypercalcemia can develop during treatment; serum calcium should be checked at 1 month after initiation and as clinically indicated thereafter. 1
• Symptoms of elevated calcium include nausea, vomiting, constipation, low energy, or muscle weakness. 1
• Hypercalciuria (elevated urine calcium) occurs in 11.5% of patients and may lead to kidney stones (urolithiasis). 1, 2
• Patients should report symptoms of kidney stones: lower back or abdominal pain, pain with urination, or blood in urine. 1

Treatment Discontinuation

• Discontinuation due to adverse effects is more common with abaloparatide than placebo, primarily due to dizziness, palpitations, nausea, and headache. 5, 4
• The overall safety profile remains acceptable, with no significant difference in total adverse event incidence between abaloparatide and placebo groups (risk ratio 1.03). 6

Absolute Contraindications

Tymlos is contraindicated in patients with increased baseline risk of osteosarcoma, including: 1

• Paget's disease of bone
• Prior skeletal radiation therapy
• Bone metastases or history of skeletal malignancies
• Unexplained elevations of alkaline phosphatase
• Open epiphyses (pediatric and young adult patients)

Additional contraindications include: 1

• Hypersensitivity to abaloparatide or any component of the formulation
• Patients at increased risk for osteosarcoma (based on animal studies showing dose-dependent osteosarcoma)

Critical Monitoring Requirements

Baseline Assessment

• Serum calcium and 25-hydroxyvitamin D levels 1
• Renal function (creatinine clearance) 5
• Alkaline phosphatase to exclude Paget's disease 1
• Bone mineral density (BMD) at lumbar spine, total hip, and femoral neck 3, 6

During Treatment

• Serum calcium at 1 month, then as clinically indicated; manage hypercalcemia by reducing calcium supplementation or adjusting dosing frequency. 1
• Urine calcium monitoring for hypercalciuria and kidney stone risk. 1
• Monitor for orthostatic symptoms, especially with initial doses. 1
• BMD testing is not routinely required during the 18-month treatment course but may be performed after completion. 1

Post-Treatment

• Mandatory transition to antiresorptive therapy (bisphosphonate or denosumab) immediately after completing Tymlos to prevent rebound bone loss and fractures. 5, 6
• BMD assessment may be performed after sequential antiresorptive therapy is established. 1

Treatment Duration and Lifetime Limits

Tymlos should not be used for more than 2 years over a patient's lifetime due to osteosarcoma risk observed in animal studies. 1 The standard treatment duration is 18 months in clinical trials, with proven efficacy when followed by alendronate for an additional 24 months. 5, 6

Special Populations

Renal Impairment

• Post hoc analyses support the efficacy and safety of abaloparatide in women with renal impairment, though specific dosing adjustments are not established. 5

Elderly Patients (≥80 Years)

• Efficacy and safety are maintained in women aged 80 years and older, with similar BMD gains and fracture risk reduction. 5

Men with Osteoporosis

• The safety profile in men is consistent with that in postmenopausal women, with injection site reactions being more prominent. 3
• Common adverse events in men include injection site reaction, dizziness, nasopharyngitis, arthralgia, bronchitis, hypertension, and headache (all ≥5%). 3

Type 2 Diabetes

• Abaloparatide is effective and well-tolerated in postmenopausal women with type 2 diabetes mellitus. 5

Essential Supplementation

• Calcium: 1,000–1,200 mg daily from diet and supplements. 1
• Vitamin D: 600–800 IU daily to maintain serum 25(OH)D ≥20 ng/mL. 1
• Patients can take calcium and vitamin D supplements while using Tymlos. 1

Administration Precautions

• Inject subcutaneously in the lower abdomen, avoiding the 2-inch area around the navel. 1
• Rotate injection sites with each dose. 1
• Do not inject intravenously or intramuscularly. 1
• Do not transfer medicine from the pen to a syringe, as this causes incorrect dosing. 1
• Use a new pen needle (5–8 mm, 31-gauge) for each injection. 1
• Do not share pens or needles due to infection risk. 1
• Discard the pen after 30 days even if medicine remains. 1

Storage Requirements

• Before first use: Refrigerate at 36°F to 46°F (2°C to 8°C). 1
• After first use: Store at room temperature 68°F to 77°F (20°C to 25°C) for up to 30 days. 1
• Do not freeze or expose to heat. 1
• Discard if solution is cloudy, colored, or contains particles. 1

Key Clinical Pitfalls to Avoid

• Never discontinue Tymlos without immediately starting an antiresorptive agent (bisphosphonate or denosumab), as this causes rebound bone loss and increased fracture risk. 5, 6
• Do not use Tymlos as first-line therapy; bisphosphonates remain first-line for most patients with osteoporosis. 7
• Do not exceed the 2-year lifetime cumulative exposure limit. 1
• Do not prescribe to patients with normal fracture risk; reserve for those at very high risk (recent fracture, T-score ≤-3.0, multiple prior fractures, or bisphosphonate failure). 7, 2
• Do not combine with bisphosphonates during active treatment, as concurrent therapy offers no additional benefit. 7