Cinaca

Cinacalcet hydrochloride.

Composition: See Table 1.

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Secondary hyperparathyroidism in patients undergoing maintenance dialysis.

The starting dosage for adults is 25 mg of cinacalcet once daily, to be orally administered. With careful management of the patient's serum parathyroid hormone (PTH) and calcium levels, the dose may then be adjusted within a range of 25-75 mg once daily. If no improvement is found in PTH, the dose may be increased up to 100 mg once daily. If dose increase is required, dose should be increased by 25 mg at a time, at intervals of at least 3 weeks.

Overdosage of Cinaca is considered to cause hypocalcaemia. In the case of overdosage, the patient should be monitored for any signs or symptoms of hypocalcaemia. If hypocalcaemia occurs or may occur, drip infusion of calcium preparations should be taken into consideration. As Cinaca is highly protein-bound, hemodialysis is not an effective treatment for overdosage.

Cinaca is contraindicated in patients with a history of hypersensitivity to any of the ingredients in Cinaca.

Cinacalcet lowers serum calcium, and therefore patients should be carefully monitored for the occurrence of hypocalcaemia. Decreases in serum calcium can also prolong the QT interval, potentially resulting in ventricular arrhythmia. Caution is advised in patients with other risk factors for QT prolongation such as patients with known congenital long QT syndrome or patients receiving drugs known to cause QT prolongation. For patients treated with cinacalcet for chronic kidney disease and receiving dialysis, reduce dose or stop use if low blood calcium, signs of QT prolongation, or arrhythmia continue. For these patients, cinacalcet should not be started if they have severe hypocalcaemia.

Careful Administration: Cinaca should be administered with care in the following patients.
Patients with hypocalcaemia: Hypocalcaemia may be aggravated. (See Important Precautions as follows.)
Patients with seizure or a history of seizure: It has been reported in overseas studies that seizure occurred in patients with a history of seizure.
Patients with hepatic function disorder: The exposure amount will be increased since cinacalcet is metabolized in the liver.
Patients with gastrointestinal hemorrhage and/or gastrointestinal ulcer or a history of gastrointestinal hemorrhage and/or gastrointestinal ulcer: The symptoms may worsen or recur.
Important Precautions: During treatment with Cinaca, sufficient caution should be exercised to avoid hypocalcaemia by periodical measurement of the serum calcium level. If hypocalcaemia occurs or may occur, it should be taken into account to use calcium or vitamin D preparations, as well as to reduce the dose of Cinaca. (See Precautions related to dosage and administration as follows.) If administration of calcium or vitamin D preparations is discontinued during treatment with Cinaca, caution should be exercised for possible occurrence of hypocalcaemia. Symptoms likely to be associated with hypocalcaemia such as prolonged QT interval, paresthesia, cramping, feeling unwell, arrhythmia, decreased blood pressure, and seizure, etc. have been reported in clinical studies on the drug.
At the start of administration and during the dose adjustment period, the patient's symptoms should be frequently monitored and caution should be exercised for possible occurrence of adverse reactions.
Precautions related to dosage and administration: Secondary hyperparathyroidism in patients undergoing maintenance dialysis: Cinaca has an effect of decreasing calcium in blood. Therefore, it should be confirmed that the patient's serum calcium level is not low (9.0 mg/dL or more) prior to administration.
The serum calcium level should be determined once a week at the start of administration and during the dose adjustment period, and at least once every two weeks during the maintenance period. If serum calcium level decreases to 8.4 mg/dL or less, the following measures should be taken. If it is difficult to control serum calcium and PTH, dose decreased by 12.5 mg at a time should be considered. (See Table 2.)

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The serum calcium level should be determined before administration of Cinaca so that the effect and safety of the drug may be properly evaluated. Furthermore, it is recommended that corrected serum calcium values* should be used as a guide in patients with hypoalbuminemia (serum albumin <4.0 g/dL).
The serum PTH level should be periodically determined so that it may be maintained at the target level for management. It is recommended that the serum PTH level should be determined twice a month at the start of administration and during the dose adjustment period (about 3 months after the start of administration), and at least once a month after the serum PTH level is confirmed to be almost stable. The serum PTH level should be determined before administration of Cinaca so that the effect and safety of the drug may be properly evaluated.
* A corrected serum calcium value is to be calculated as follows: Corrected serum calcium (mg/dL) = Serum calcium (mg/dL) - Serum albumin (g/dL) + 4.0.
Other Precautions: In an overseas clinical study in which cinacalcet hydrochloride was used in patients with chronic renal failure accompanied by secondary hyperthyroidism who had not yet started dialysis, it has been reported that the serum calcium level tended to be lower than the lower limit of the normal range (8.4 mg/dL) compared to that in patients receiving dialysis. Use of the drug in patients with chronic renal failure accompanied by secondary hyperthyroidism who had not yet been on dialysis has not been approved.
It has been reported abroad that adynamic bone disease occurred due to an excessive decrease in PTH following administration of cinacalcet.
It has been reported abroad that hungry bone syndrome accompanied by hypocalcaemia and hypophosphatemia occurred due to a rapid decrease in PTH following administration of cinacalcet.
Use in the Elderly: Caution should be exercised when Cinaca is administered to patients aged 65 years or older, because they have been reported to show higher incidences of adverse reactions (prolonged QT interval in particular) than those younger than 65 years. If any adverse reactions are observed, appropriate measures such as reducing the dose should be taken.
Use in Children: The safety of Cinaca in low birth weight infants, newborns, sucklings, infants and children has not been established. No clinical experience.

It is recommended not to use Cinaca in pregnant women or in women who may possibly be pregnant. The drug should be used in such patients only if the anticipated therapeutic benefits outweigh the potential risks associated with the treatment. The safety of cinacalcet during pregnancy has not been established. Hypocalcaemia, suppressed weight gain and decreased food consumption in mothers, as well as decreased weight in fetuses, were observed in animal studies (using rats and rabbits). Furthermore, cinacalcet was reported to be transferred through the placenta in animal studies (using rats and rabbits).
Treatment with Cinaca should be avoided in nursing mothers. When the use is necessary in such women, breastfeeding should be discontinued. In animal studies (using rats), cinacalcet was reported to be transferred into milk. Furthermore, suppressed weight gain was observed in newborns on breastfeeding.

Secondary hyperparathyroidism in patients undergoing maintenance dialysis: Adverse reactions (including laboratory abnormalities) were observed in 393 (68.6%) of 573 patients evaluated for safety in Japanese clinical studies.
The major adverse reactions included digestive symptoms such as nausea/vomiting (124 events, 21.6%), gastric discomfort (107 events, 18.7%), anorexia (56 events, 9.8%) and abdominal distention (34 events, 5.9%), as well as hypocalcaemia/decreased serum calcium (84 events, 14.7%) and prolonged QT interval (33 events, 5.8%). [Data at the time of approval.]
Clinically significant adverse reactions: Hypocalcaemia/decreased serum calcium (13.7%): Symptoms considered attributable to hypocalcaemia (prolonged QT interval, numbness, cramping, feeling unwell, arrhythmia, decreased blood pressure, seizure, etc.) may occur. Therefore, the serum calcium level should be periodically determined with reference to Precautions related to dosage and administration under Precautions. If any abnormalities are observed, the serum calcium level should be confirmed and administration of calcium or vitamin D preparations should be taken into consideration. Moreover, it should also be considered to reduce the dose of Cinaca or discontinue the treatment as needed.
Prolonged QT interval (5.3%): The QT interval may be prolonged. If any abnormalities are observed, the serum calcium level should be confirmed and administration of calcium or vitamin D preparations should be taken into consideration. Moreover, it should also be considered to reduce the dose of Cinaca or discontinue the treatment as needed.
Gastrointestinal hemorrhage, gastrointestinal ulcer (incidence unknown): Gastrointestinal hemorrhage and/or gastrointestinal ulcer may develop. Patients must therefore be carefully monitored. If any abnormalities are observed, administration should be discontinued and appropriate measures taken.
Decreased level of consciousness (0.2%), temporary loss of consciousness (0.2%): Decreased level of consciousness, temporary loss of consciousness, etc. may occur. If any abnormalities are observed, appropriate measures including discontinuation of the treatment should be taken.
Sudden death (0.3%): Unexplained sudden death has been reported in patients treated with Cinaca.
Other adverse reactions: If any of the following symptoms are observed, appropriate measures such as dosage reduction or discontinuation should be taken. (See Table 3.)

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Precautions for co-administration: Cinaca should be administered with care when co-administered with the following drugs: See Table 4.

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Precautions regarding dispensing: In the case of press-through package (PTP), the patient should be instructed to remove the drug from the package prior to use. It has been reported that, if a PTP sheet is mistakenly swallowed, the sharp corners of the sheet may puncture the esophageal mucosa and thereby cause perforation, leading to serious complications such as mediastinitis.

Store below 25°C.

Other Agents Affecting Metabolism

H05BX01 - cinacalcet ; Belongs to the class of other anti-parathyroid agents. Used in the management of calcium homeostasis.

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