INTERACTIONS Digoxin: Monitor serum calcium more frequently when using NATPARA in patients receiving digoxin. ( 5.5 , 7.2 )
7.1 Alendronate Co-administration of alendronate and NATPARA leads to reduction in the calcium-sparing effect, which can interfere with the normalization of serum calcium. Concomitant use of NATPARA with alendronate is not recommended.
7.2 Digoxin NATPARA causes transient increase in calcium and therefore, concomitant use of NATPARA and cardiac glycosides (e.g., digoxin) may predispose patients to digitalis toxicity if hypercalcemia develops. Digoxin efficacy is reduced if hypocalcemia is present. In patients using NATPARA concomitantly with digoxin, carefully monitor serum calcium and digoxin levels, and patients for signs and symptoms of digoxin toxicity. Adjustment of digoxin and/or NATPARA may be needed. No drug-drug interaction study has been conducted with digoxin and NATPARA.
NATPARA is contraindicated in patients with a known hypersensitivity to any component of this product. Hypersensitivity reactions (e.g., anaphylaxis, angioedema, and urticaria) have occurred with NATPARA [see Warnings and Precautions (5.6) , Adverse Reactions (6.3) ] . Hypersensitivity to any component of this product. ( 4 )
AND PRECAUTIONS Potential Risk of Osteosarcoma: Prescribe NATPARA only to patients who cannot be well-controlled on calcium and active vitamin D. Avoid use of NATPARA in patients who are at increased risk for osteosarcoma. ( 5.1 )
Severe
Hypercalcemia : Monitor serum calcium when starting or adjusting NATPARA dose and when making changes to co-administered drugs known to raise serum calcium. ( 2.4 , 5.3 , 6.1 )
Severe
Hypocalcemia: Can occur with interruption or discontinuation of NATPARA treatment. Monitor serum calcium and replace calcium and vitamin D. ( 2.4 , 5.4 , 6.1 )
Digoxin
Toxicity: Hypercalcemia increases the risk of digoxin toxicity. In patients using NATPARA concomitantly with digoxin, monitor serum calcium more frequently and increase monitoring when initiating or adjusting NATPARA dose. ( 5.5 ) Hypersensitivity: Hypersensitivity reactions (anaphylaxis, dyspnea, angioedema, urticaria, rash) have been reported. If signs or symptoms of a serious hypersensitivity reaction occur, discontinue treatment with NATPARA and treat patient according to the standard of care ( 2.6 , 4 , 5.6 , 6.3 )
5.1 Potential Risk of Osteosarcoma In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor). The occurrence of osteosarcoma was observed to be dependent on parathyroid hormone dose and treatment duration. This effect was observed at parathyroid hormone exposure levels ranging from 3 to 71 times the exposure levels for humans receiving a 100 mcg dose of NATPARA. These data could not exclude a risk to humans <span class="opacity-50 text-xs">[see Nonclinical Toxicology (13.1) ]</span> . Because of a potential risk of osteosarcoma, use NATPARA only in patients who cannot be well-controlled on calcium supplements and active forms of vitamin D alone and for whom the potential benefits are considered to outweigh this potential risk <span class="opacity-50 text-xs">[see Limitations of Use (1) ]</span> . To further mitigate the potential risk of osteosarcoma, avoid use of NATPARA in patients who are at increased risk for osteosarcoma, such as patients with Paget's disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, patients with hereditary disorders predisposing to osteosarcoma, or patients with a prior history of external beam or implant radiation therapy involving the skeleton. Instruct patients to promptly report clinical symptoms (e.g., persistent localized pain) and signs (e.g., soft tissue mass tender to palpation) that could be consistent with osteosarcoma. NATPARA is available only through a restricted program under a REMS <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span> .
5.2 NATPARA REMS Program Because of the potential risk of osteosarcoma associated with NATPARA therapy, NATPARA is available only through a restricted REMS program called the NATPARA REMS Program. Under the NATPARA REMS Program, only certified healthcare providers can prescribe and only certified pharmacies can dispense NATPARA. Further information is available at www.NATPARAREMS.com or by telephone at 1-855-NATPARA (1-855-628-7272).
5.3 Hypercalcemia Severe hypercalcemia has been reported with NATPARA. In the pivotal trial, 3 patients randomized to NATPARA required administration of IV fluids to correct hypercalcemia during treatment with NATPARA. The risk is highest when starting or increasing the dose of NATPARA, but can occur at any time. Monitor serum calcium and patients for signs and symptoms of hypercalcemia. Treat hypercalcemia per standard practice and consider holding and/or lowering the dose of NATPARA if severe hypercalcemia occurs <span class="opacity-50 text-xs">[see Dosage and Administration (2) , Adverse Reactions (6.1) ]</span>.
5.4 Hypocalcemia Severe hypocalcemia has been reported in patients taking NATPARA, including cases of hypocalcemia that resulted in seizures. The risk is highest when NATPARA is withheld, missed or abruptly discontinued, but can occur at any time. Monitor serum calcium and patients for signs and symptoms of hypocalcemia. Resume treatment with, or increase the dose of, an active form of vitamin D or calcium supplements or both if indicated in patients interrupting or discontinuing NATPARA to prevent severe hypocalcemia <span class="opacity-50 text-xs">[see Dosage and Administration (2.6) , Adverse Reactions (6.1) ]</span>.
5.5 Risk of Digoxin Toxicity with Concomitant Use of Digitalis Compounds The inotropic effects of digoxin are affected by serum calcium levels. Hypercalcemia of any cause may predispose to digoxin toxicity. In patients using NATPARA concomitantly with digitalis compounds, monitor serum calcium and digoxin levels and patients for signs and symptoms of digitalis toxicity. Adjustment of digoxin and/or NATPARA may be needed. No drug-drug interaction study has been conducted with digoxin and NATPARA <span class="opacity-50 text-xs">[see Drug Interactions (7) , Adverse Reactions (6.1) ]</span>.
5.6 Hypersensitivity There have been reports of hypersensitivity reactions in patients taking NATPARA. Reactions included anaphylaxis, dyspnea, angioedema, urticaria, and rash. If signs or symptoms of a serious hypersensitivity reaction occur, discontinue treatment with NATPARA, treat hypersensitivity reaction according to the standard of care, and monitor until signs and symptoms resolve <span class="opacity-50 text-xs">[see Contraindications (4) , Adverse Reactions (6.3) ]</span> . Monitor for hypocalcemia if NATPARA is discontinued <span class="opacity-50 text-xs">[see Dosage and Administration (2.6) ]</span>.