Orkedia Special Precautions

Precautions Concerning Dosage and Administration: Secondary hyperparathyroidism in patients on maintenance dialysis: Since evocalcet decreases blood calcium levels, the physician must confirm that the patient's serum calcium level is not low (>=8.4 mg/dL, as a guide) before starting administration.
If the dose needs to be increased, the dose should be increased in 1 mg increments at intervals of at least 2 weeks.
If the patient has a high PTH level (an intact PTH level of ≥ 500 pg/mL, as a guide) and a serum calcium level of ≥ 9.0 mg/dL, the physician should consider the starting dose with 2 mg of evocalcet once daily [see Pharmacology: Pharmacodynamics: Phase III long-term treatment study in Japan (Hemodialysis) and Phase III general study in Japan (Peritoneal Dialysis) under Actions].
Measure serum calcium levels at least once a week at the start of treatment and at the time of dose adjustment and at least once every 2 weeks during the maintenance period. Take actions, as shown in the following table, when the serum calcium level decreases to < 8.4 mg/dL (see Important Precautions as follows; Precautions Concerning Patients with Specific Backgrounds: Patients with Complication or History of Diseases, etc.: Patients with hypocalcemia as follows; and Clinically Significant Adverse Reactions: Hypocalcemia (16.2%) under Adverse Reactions). (See Table 7.)

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It is desirable to measure a serum calcium level before an oral dose to appropriately evaluate the efficacy and safety of this drug. In the case of hypoalbuminemia (i.e., serum albumin level of < 4.0 g/dL), it is desirable to use a corrected calcium level^Note as an indicator.
Measure PTH levels periodically to maintain PTH levels within the target range. Measure PTH levels twice monthly at the start of treatment and at the time of dose adjustment (about 3 months after the start of treatment as a guide). It is desirable to measure PTH levels once monthly after confirming that the PTH level has become almost stable. It is desirable to measure a PTH level before an oral dose in order to appropriately evaluate the efficacy and safety of this drug.
Hypercalcaemia in patients with parathyroid carcinoma and hypercalcaemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy or patients with recurrent primary hyperparathyroidism after parathyroidectomy: It is desirable to measure serum calcium levels twice a week as a guide at the start of treatment and at the time of dose adjustment, and periodically during the maintenance period.
In the case of serum calcium level exceeding 12.5 mg/dL, consider the initial dose of 2 mg/dose twice daily.
In the case requiring dose adjustment, increase/decrease doses by referring to the following table. As a general rule, increase doses step by step with intervals of at least two weeks. If the serum calcium level is difficult to control, the dose may be increased or decreased by 1 mg. (See Table 8.)

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Interrupt the treatment immediately if a serum calcium level decreases to 7.5 mg/dL or lower. In addition, consider administrating calcium and/or vitamin D preparations if required (see Important Precautions as follows; Precautions Concerning Patients with Specific Backgrounds: Patients with Complication or History of Diseases, etc.: Patients with hypocalcemia as follows; and Clinically Significant Adverse Reactions: Hypocalcemia (16.2%) under Adverse Reactions).
In the case of hypoalbuminemia (i.e., serum albumin level of < 4.0 g/dL), it is desirable to use a corrected calcium level^Note as an indicator.
^Note)How to calculate a corrected calcium level: Corrected calcium level (mg/dL) = Serum calcium level (mg/dL) - Serum albumin level (g/dL) + 4.0.
Important Precautions: Measure serum calcium levels periodically and pay careful attention to prevent the occurrence of hypocalcemia during treatment with ORKEDIA. When hypocalcemia has occurred or may possibly occur, the physician should consider reducing the dose of ORKEDIA, etc., as well as the need to administer calcium and/or vitamin D preparations. When the patient discontinued using calcium or vitamin D preparation during treatment with ORKEDIA, the physician should pay attention to the occurrence of hypocalcemia (see Precautions Concerning Dosage and Administration: Secondary hyperparathyroidism in patients on maintenance dialysis and Hypercalcaemia in patients with parathyroid carcinoma and hypercalcaemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy or patients with recurrent primary hyperparathyroidism after parathyroidectomy as previously mentioned; Precautions Concerning Patients with Specific Backgrounds: Patients with Complication or History of Diseases, etc.: Patients with hypocalcemia as follows; and Clinically Significant Adverse Reactions: Hypocalcemia (16.2%) under Adverse Reactions).
Observe the patient's condition frequently at the start of treatment and at the time of dose adjustment of ORKEDIA, and pay attention to the occurrence of adverse reactions.
Precautions Concerning Patients with Specific Backgrounds: Patients with Complication or History of Diseases, etc.: Patients with hypocalcemia: ORKEDIA may aggravate hypocalcemia (see Precautions Concerning Dosage and Administration: Secondary hyperparathyroidism in patients on maintenance dialysis and Hypercalcaemia in patients with parathyroid carcinoma and hypercalcaemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy or patients with recurrent primary hyperparathyroidism after parathyroidectomy as previously mentioned; Important Precautions as previously mentioned ; and Clinically Significant Adverse Reactions: Hypocalcemia (16.2%) under Adverse Reactions).
Patients with Hepatic Impairment: Blood evocalcet concentrations may increase (see Pharmacology: Pharmacokinetics: Patients with Specific Backgrounds: Patients with hepatic impairment under Actions). In addition, since the safety and efficacy have not been established in patients with severe hepatic impairment, administration of this drug is not recommended.
Precaution Concerning Use: Precautions Concerning the Dispensing of the Drug: Instruct the patient to remove an ORKEDIA tablet from the blister before taking the tablet. It has been reported that, after accidental swallowing of a blister, the sharp hard edges of the blister pierced and penetrated the esophageal mucosa, resulting in serious complications, such as mediastinitis.
Other Precautions: Information Based on Clinical Use: In foreign countries, it was reported that patients developed adynamic bone disease due to an excessive decrease in PTH induced by calcium receptor agonists.
In foreign countries, it was reported that patients developed hungry bone syndrome with hypocalcemia and hypophosphatemia due to a rapid decrease in PTH after administration of calcium receptor agonists.
Use in Children: Clinical studies with the efficacy and safety in pediatric subjects have not been conducted.
Use in the Elderly: If any adverse reaction occurs in an elderly patient, the physician must take appropriate measures, such as dose reduction. In general, the elderly have decreased physiological function.