What are the warnings and precautions for prescribing Forteo (teriparatide)?

From the Guidelines

Forteo (teriparatide) should be prescribed with caution due to its potential risks, including osteosarcoma, hypercalcemia, and other adverse effects, and should not be used longer than 2 years. The medication has a boxed warning for osteosarcoma risk, as it caused dose-dependent bone tumors in rat studies, so it should be avoided in patients with increased baseline risk for osteosarcoma including those with Paget's disease, unexplained alkaline phosphatase elevations, open epiphyses, or prior radiation therapy involving the skeleton 1. Forteo is contraindicated in patients with hypercalcemia, as it may exacerbate this condition. Caution is needed in patients with active or recent urolithiasis, as the medication can increase urinary calcium excretion. Orthostatic hypotension may occur, especially after initial doses, so patients should be advised to sit or lie down if symptoms develop. Transient hypercalcemia typically occurs 4-6 hours after injection but usually resolves within 24 hours. Patients with bone metastases, metabolic bone diseases other than osteoporosis, or pre-existing hypercalcemic disorders should avoid Forteo.

The most recent and highest quality study, published in 2023, suggests that teriparatide may be used as a treatment option for females with primary osteoporosis at very high risk of fracture, but with low-certainty evidence 1. However, the study also notes that bisphosphonates are the preferred initial treatment due to their more favorable balance of benefits and harms. The 2017 study provides more detailed information on the adverse effects of teriparatide, including mild upper gastrointestinal symptoms, headache, and hypercalcemia 1. The 2009 study highlights the potential increased risk of osteosarcoma with teriparatide use, particularly in patients with a history of malignancy prone to metastasize to bone 1.

Key points to consider when prescribing Forteo include:

• Osteosarcoma risk: avoid in patients with increased baseline risk, including Paget's disease, unexplained alkaline phosphatase elevations, open epiphyses, or prior radiation therapy involving the skeleton
• Hypercalcemia: contraindicated in patients with hypercalcemia, as it may exacerbate this condition
• Urolithiasis: caution needed in patients with active or recent urolithiasis, as the medication can increase urinary calcium excretion
• Orthostatic hypotension: may occur, especially after initial doses, so patients should be advised to sit or lie down if symptoms develop
• Transient hypercalcemia: typically occurs 4-6 hours after injection but usually resolves within 24 hours
• Bone metastases, metabolic bone diseases, or pre-existing hypercalcemic disorders: patients with these conditions should avoid Forteo.

From the FDA Drug Label

5 WARNINGS AND PRECAUTIONS 5. 1 Osteosarcoma An increase in the incidence of osteosarcoma (a malignant bone tumor) was observed in male and female rats treated with teriparatide. Osteosarcoma has been reported in patients treated with teriparatide in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans There are limited data assessing the risk of osteosarcoma beyond 2 years of teriparatide use Avoid teriparatide injection use in patients with (these patients are at increased baseline risk of osteosarcoma): Open epiphyses (pediatric and young adult patients) (teriparatide injection is not approved in pediatric patients) Metabolic bone diseases other than osteoporosis, including Paget's disease of the bone. Bone metastases or a history of skeletal malignancies. Prior external beam or implant radiation therapy involving the skeleton. Hereditary disorders predisposing to osteosarcoma. 5. 2 Hypercalcemia and Cutaneous Calcification Hypercalcemia Teriparatide has not been studied in patients with pre-existing hypercalcemia. Teriparatide may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia Avoid teriparatide injection in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism. Risk of Cutaneous Calcification Including Calciphylaxis Serious reports of calciphylaxis and worsening of previously stable cutaneous calcification have been reported in the post-marketing setting in patients taking teriparatide Risk factors for development of calciphylaxis include underlying autoimmune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use. Discontinue teriparatide injection in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification. 5. 3 Risk of Urolithiasis In clinical trials, the frequency of urolithiasis was similar in patients treated with teriparatide and patients treated with placebo. However, teriparatide has not been studied in patients with active urolithiasis. If teriparatide injection-treated patients have pre-existing hypercalciuria or suspected/known active urolithiasis, consider measuring urinary calcium excretion Consider the risks and benefits of use in patients with active or recent urolithiasis because of the potential to exacerbate this condition. 5. 4 Orthostatic Hypotension Teriparatide injection may cause orthostatic hypotension. Patients should be instructed to sit or lie down if they experience orthostatic hypotension after the injection The most common adverse reactions associated with teriparatide injection are:

• Hypercalcemia
• Hypercalciuria
• Hyperphosphatemia
• Headache
• Nausea
• Dizziness
• Pain in extremity

The warnings and precautions for prescribing Forteo (teriparatide) include:

• Osteosarcoma: Avoid use in patients with increased baseline risk of osteosarcoma, such as those with open epiphyses, metabolic bone diseases, bone metastases, or a history of skeletal malignancies.
• Hypercalcemia and Cutaneous Calcification: Avoid use in patients with pre-existing hypercalcemia or hypercalcemic disorders, and discontinue use if calciphylaxis or worsening cutaneous calcification occurs.
• Risk of Urolithiasis: Consider measuring urinary calcium excretion in patients with pre-existing hypercalciuria or suspected/known active urolithiasis, and weigh the risks and benefits of use in patients with active or recent urolithiasis.
• Orthostatic Hypotension: Instruct patients to sit or lie down if they experience orthostatic hypotension after the injection. These warnings and precautions are based on the information provided in the drug label 2.

From the Research

Warnings and Precautions for Prescribing Forteo (Teriparatide)

The following are warnings and precautions for prescribing Forteo (teriparatide):

• Osteosarcoma: There is a potential risk of osteosarcoma associated with teriparatide use, as evidenced by studies in rats 3. Although the risk in humans is considered low, it is essential to carefully evaluate the benefits and risks of teriparatide therapy, particularly in patients with a history of radiation exposure.
• Hypercalcemia: Teriparatide can cause hypercalcemia, which may be mild and transient or severe and life-threatening 4, 5. Patients should be monitored for symptoms of hypercalcemia, and serum calcium levels should be measured after 1 month of treatment.
• Urinary Calcium Excretion: Teriparatide can increase urinary calcium excretion, which may be a concern in patients with a history of kidney stones or other renal disorders 4.
• Contraindications: Teriparatide is contraindicated in patients with certain conditions, including Paget's disease, bone cancer, or high levels of calcium in the blood 6.
• Duration of Therapy: Teriparatide therapy should not exceed 2 years, due to the potential risk of osteosarcoma and other adverse effects 6.
• Monitoring: Patients receiving teriparatide should be monitored regularly for adverse effects, including hypercalcemia, and for changes in bone mineral density and markers of bone turnover 4, 7.

Special Considerations

The following special considerations should be taken into account when prescribing teriparatide:

• Combination Therapy: Concurrent therapy with antiresorptive agents, such as bisphosphonates, should be avoided, although sequential therapy may be considered to consolidate the beneficial effects of teriparatide on the skeleton 6.
• Patient Selection: Teriparatide should be reserved for patients with severe osteoporosis who are at high risk for fracture, including those who have failed or are intolerant of previous osteoporosis therapy 7, 6.
• Dosing and Administration: Teriparatide should be administered via subcutaneous injection, and the dose should be individualized based on the patient's response to therapy and tolerance 4, 7.