What are the adverse effects of Tymlos (abaloparatide) and how should they be managed?

Tymlos Side Effects and Management

Tymlos (abaloparatide) commonly causes injection site reactions, dizziness, nausea, headache, palpitations, and orthostatic hypotension, with most adverse effects being mild to moderate in severity. 1

Common Adverse Effects

Most Frequent Side Effects

• Injection site reactions (bruising, hemorrhage, pruritus, rash) are among the most commonly reported adverse events 1
• Dizziness and vertigo occur frequently and may be related to orthostatic hypotension 2, 1
• Gastrointestinal symptoms including nausea, upper abdominal pain, diarrhea, vomiting, constipation, and abdominal distension 2, 1
• Headache and fatigue are commonly reported 2, 1
• Palpitations and increased heart rate occur more frequently with abaloparatide than with teriparatide 2, 3

Musculoskeletal Effects

• Bone pain, arthralgia, and joint pain are reported in both men and women 4, 2, 1
• Muscle spasms particularly affecting the leg and back 1
• Generalized pain in extremities 1

Metabolic and Laboratory Abnormalities

Calcium-Related Effects

• Hypercalciuria is a recognized adverse effect that warrants monitoring, particularly in patients with active urolithiasis or pre-existing hypercalciuria 4, 2
• Hypercalcemia occurs but at significantly lower rates compared to teriparatide 3, 5, 6
• Urolithiasis was reported in 2% of Tymlos-treated patients versus 1% of placebo-treated patients 1

Uric Acid Effects

• Hyperuricemia was observed in clinical trials but was not associated with increased adverse reactions of gout or arthralgia over placebo 1
• This is a particular concern in patients with chronic kidney disease 4

Cardiovascular Effects

Cardiovascular adverse effects including palpitations, tachycardia, and increased heart rate occur more frequently with abaloparatide than with teriparatide and require clinical awareness. 2, 3

• Orthostatic hypotension is a recognized risk, particularly with initial dosing 1
• Patients should be advised to administer Tymlos in a position where they can sit or lie down if dizziness occurs 1

Serious Adverse Events and Postmarketing Reports

Allergic Reactions

• Hypersensitivity and anaphylactic reactions have been reported in postmarketing surveillance 1
• Dyspnea in the context of allergic reactions 1
• Pruritus and rash (both generalized and at injection sites) 1

Other Serious Concerns

• Asthenia, lethargy, and malaise have been reported 1
• Insomnia is documented in postmarketing experience 1

Special Population Considerations

Renal Impairment

• Patients with severe renal impairment may have 1.4-fold increase in Cmax and 2.1-fold increase in AUC, potentially increasing the risk of adverse reactions 1
• No dosage adjustment is required, but closer monitoring for adverse reactions is recommended in severe renal impairment 1
• Both hypercalcemia and hyperuricemia are particular concerns in CKD patients 4

Geriatric Patients

• No overall differences in safety were observed between older and younger patients, though greater sensitivity in some older individuals cannot be ruled out 1
• In clinical studies, 82% of postmenopausal women were ≥65 years and 19% were ≥75 years 1

Management Strategies

Monitoring Requirements

• Monitor for orthostatic hypotension, especially during initial administration 1
• Consider measuring urinary calcium excretion if active urolithiasis or pre-existing hypercalciuria is suspected 4
• Monitor for adverse reactions more closely in patients with severe renal impairment due to increased drug exposure 1
• Assess serum calcium and phosphorus if overdose is suspected 1

Overdose Management

• In case of overdose (one reported case of 400 mcg in one day), effects may include hypercalcemia, nausea, vomiting, dizziness, tachycardia, orthostatic hypotension, and headache 1
• Discontinue Tymlos immediately, monitor serum calcium and phosphorus, and implement supportive measures such as hydration 1
• No specific antidote exists, and abaloparatide is not expected to be dialyzable 1

Patient Education

• Advise patients to administer Tymlos while in a position where they can sit or lie down if dizziness occurs 1
• Inform patients about common injection site reactions and how to rotate injection sites 1
• Counsel on recognizing signs of hypersensitivity reactions 1

Critical Safety Consideration

All patients must transition to an antiresorptive agent (bisphosphonate or denosumab) immediately after completing Tymlos therapy to prevent rapid bone loss and rebound vertebral fractures. 4, 2 This is not optional—discontinuation without sequential antiresorptive therapy causes serious risk of multiple vertebral fractures occurring as soon as 7-9 months after the last dose 7, 4.

Withdrawal Due to Adverse Events

• Teriparatide (a similar anabolic agent) probably increases withdrawal due to adverse events, and similar considerations apply to abaloparatide 4
• The overall tolerability profile is considered good, with most adverse effects being mild to moderate 3, 5, 6
• Discontinuation rates due to adverse effects are somewhat higher compared to teriparatide, particularly related to palpitations and increased heart rate 3