TERIPARATIDE Drug Interactions: What You Need to Know

INTERACTIONS Digoxin: Transient hypercalcemia may predispose patients to digitalis toxicity ( 5.5 , 7.1 )

7.1 Digoxin Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Teriparatide injection may transiently increase serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when Teriparatide injection is used in patients receiving digoxin [ see Warnings and Precaution ( 5.5 ) and Clinical Pharmacology ( 12.3 ) ].

Teriparatide injection is contraindicated in patients with hypersensitivity to teriparatide or to any of its excipients. Hypersensitivity reactions have included angioedema and anaphylaxis [ see Adverse Reactions ( 6.3 ) ]. Patients with hypersensitivity to teriparatide or to any of its excipients ( 4 )

AND PRECAUTIONS Osteosarcoma : Avoid use in patients with increased risk of osteosarcoma including patients with open epiphyses, metabolic bone diseases including Paget’s disease, bone metastases or history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma. ( 5.1 ) Hypercalcemia and Cutaneous Calcification : Avoid in patients known to have an underlying hypercalcemic disorder. Discontinue in patients developing worsening of previously stable cutaneous calcification. ( 5.2 ) Risk of Urolithiasis : Consider the risk/benefit in patients with active or recent urolithiasis because of risk of exacerbation ( 5.3 )

Orthostatic

Hypotension : Transient orthostatic hypotension may occur with initial doses of Teriparatide injection ( 5.4 )

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 injection 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 injection use [ see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.3 ), and Nonclinical Toxicology ( 13.1 ) ] .

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) [ see Use in Specific Populations ( 8.4 ) ]. 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 injection has not been studied in patients with pre-existing hypercalcemia. Teriparatide injection may cause hypercalcemia and may exacerbate hypercalcemia in patients with pre-existing hypercalcemia [ see Adverse Reactions ( 6.1 , 6.3 ) ] .

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 postmarketing setting in patients taking Teriparatide injection. 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 injection and patients treated with placebo. However, Teriparatide injection 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 should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur. In short-term clinical pharmacology studies of Teriparatide injection in healthy volunteers, transient episodes of symptomatic orthostatic hypotension were observed in 5% of volunteers. Typically, these events began within 4 hours of dosing and resolved (without treatment) within a few minutes to a few hours. When transient orthostatic hypotension occurred, it happened within the first several doses, it was relieved by placing the person in a reclining position, and it did not preclude continued treatment.

5.5 Risk of Digoxin Toxicity Hypercalcemia may predispose patients to digitalis toxicity because Teriparatide injection transiently increases serum calcium. Consider the potential onset of signs and symptoms of digitalis toxicity when Teriparatide injection is used in patients receiving digoxin [ see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 ) ] .