Rocaltrol - Calcitriol capsule, Gelatin Coated
(Calcitriol)Rocaltrol - Calcitriol capsule, Gelatin Coated Prescribing Information
Predialysis Patients
Rocaltrol is indicated in the management of secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe chronic renal failure (Ccr 15 to 55 mL/min) not yet on dialysis. In children, the creatinine clearance value must be corrected for a surface area of 1.73 square meters. A serum iPTH level of ≥ 100 pg/mL is strongly suggestive of secondary hyperparathyroidism.
Dialysis Patients
Rocaltrol is indicated in the management of hypocalcemia and the resultant metabolic bone disease in patients undergoing chronic renal dialysis. In these patients, Rocaltrol administration enhances calcium absorption, reduces serum alkaline phosphatase levels, and may reduce elevated parathyroid hormone levels and the histological manifestations of osteitis fibrosa cystica and defective mineralization.
Hypoparathyroidism Patients
Rocaltrol is also indicated in the management of hypocalcemia and its clinical manifestations in patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, and pseudohypoparathyroidism.
The optimal daily dose of Rocaltrol must be carefully determined for each patient. Rocaltrol can be administered orally either as a capsule (0.25 mcg or 0.50 mcg) or as an oral solution (1 mcg/mL). Rocaltrol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of serum calcium.
The effectiveness of Rocaltrol therapy is predicated on the assumption that each patient is receiving an adequate but not excessive daily intake of calcium. Patients are advised to have a dietary intake of calcium at a minimum of 600 mg daily. The U.S. RDA for calcium in adults is 800 mg to 1200 mg. To ensure that each patient receives an adequate daily intake of calcium, the physician should either prescribe a calcium supplement or instruct the patient in proper dietary measures.
Because of improved calcium absorption from the gastrointestinal tract, some patients on Rocaltrol may be maintained on a lower calcium intake. Patients who tend to develop hypercalcemia may require only low doses of calcium or no supplementation at all.
During the titration period of treatment with Rocaltrol, serum calcium levels should be checked at least twice weekly. When the optimal dosage of Rocaltrol has been determined, serum calcium levels should be checked every month (or as given below for individual indications). Samples for serum calcium estimation should be taken without a tourniquet.
Pediatric Pharmacokinetics
The steady-state pharmacokinetics of oral Rocaltrol were determined in a small group of pediatric patients (age range: 1.8 to 16 years) undergoing peritoneal dialysis. Rocaltrol was administered for 2 months at an average dose of 10.2 ng/kg (SD 5.5 ng/kg). In this pediatric population, mean Cmax was 116 pmol/L, mean serum half-life was 27.4 hours, and mean clearance was 15.3 mL/hr/kg.1
Geriatric
No studies have examined the pharmacokinetics of calcitriol in geriatric patients.
Gender
Controlled studies examining the influence of gender on calcitriol have not been conducted.
Hepatic Insufficiency
Controlled studies examining the influence of hepatic disease on calcitriol have not been conducted.
Renal Insufficiency
Lower predose and peak calcitriol levels in serum were observed in patients with nephrotic syndrome and in patients undergoing hemodialysis compared with healthy subjects. The elimination half-life of calcitriol increased by at least twofold in chronic renal failure and hemodialysis patients compared with healthy subjects. Peak serum levels in patients with nephrotic syndrome were reached in 4 hours. For patients requiring hemodialysis peak serum levels were reached in 8 to 12 hours; half-lives were estimated to be 16.2 and 21.9 hours, respectively.
Rocaltrol should not be given to patients with hypercalcemia or evidence of vitamin D toxicity. Use of Rocaltrol in patients with known hypersensitivity to Rocaltrol (or drugs of the same class) or any of the inactive ingredients is contraindicated.
Since Rocaltrol is believed to be the active hormone which exerts vitamin D activity in the body, adverse effects are, in general, similar to those encountered with excessive vitamin D intake, i.e., hypercalcemia syndrome or calcium intoxication, depending on the severity and duration of hypercalcemia
Overdosage of any form of vitamin D is dangerous
Rocaltrol is the most potent metabolite of vitamin D available. The administration of Rocaltrol to patients in excess of their daily requirements can cause hypercalcemia, hypercalciuria, and hyperphosphatemia. Therefore, pharmacologic doses of vitamin D and its derivatives should be withheld during Rocaltrol treatment to avoid possible additive effects and hypercalcemia. If treatment is switched from ergocalciferol (vitamin D2) to calcitriol, it may take several months for the ergocalciferol level in the blood to return to the baseline value
Calcitriol increases inorganic phosphate levels in serum. While this is desirable in patients with hypophosphatemia, caution is called for in patients with renal failure because of the danger of ectopic calcification. A nonaluminum phosphate-binding compound and a low-phosphate diet should be used to control serum phosphorus levels in patients undergoing dialysis.
Magnesium-containing preparations (e.g., antacids) and Rocaltrol should not be used concomitantly in patients on chronic renal dialysis because such use may lead to the development of hypermagnesemia.
Studies in dogs and rats given calcitriol for up to 26 weeks have shown that small increases of calcitriol above endogenous levels can lead to abnormalities of calcium metabolism with the potential for calcification of many tissues in the body.
The early and late signs and symptoms of vitamin D intoxication associated with hypercalcemia include:
In clinical studies on hypoparathyroidism and pseudohypoparathyroidism, hypercalcemia was noted on at least one occasion in about 1 in 3 patients and hypercalciuria in about 1 in 7 patients. Elevated serum creatinine levels were observed in about 1 in 6 patients (approximately one half of whom had normal levels at baseline).
In concurrent hypercalcemia and hyperphosphatemia, soft-tissue calcification may occur; this can be seen radiographically
Overdosage of any form of vitamin D is dangerous
Rocaltrol is the most potent metabolite of vitamin D available. The administration of Rocaltrol to patients in excess of their daily requirements can cause hypercalcemia, hypercalciuria, and hyperphosphatemia. Therefore, pharmacologic doses of vitamin D and its derivatives should be withheld during Rocaltrol treatment to avoid possible additive effects and hypercalcemia. If treatment is switched from ergocalciferol (vitamin D2) to calcitriol, it may take several months for the ergocalciferol level in the blood to return to the baseline value
Calcitriol increases inorganic phosphate levels in serum. While this is desirable in patients with hypophosphatemia, caution is called for in patients with renal failure because of the danger of ectopic calcification. A nonaluminum phosphate-binding compound and a low-phosphate diet should be used to control serum phosphorus levels in patients undergoing dialysis.
Magnesium-containing preparations (e.g., antacids) and Rocaltrol should not be used concomitantly in patients on chronic renal dialysis because such use may lead to the development of hypermagnesemia.
Studies in dogs and rats given calcitriol for up to 26 weeks have shown that small increases of calcitriol above endogenous levels can lead to abnormalities of calcium metabolism with the potential for calcification of many tissues in the body.
In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine
Excessive dosage of Rocaltrol induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium should be determined twice weekly. In dialysis patients, a fall in serum alkaline phosphatase levels usually antedates the appearance of hypercalcemia and may be an indication of impending hypercalcemia. An abrupt increase in calcium intake as a result of changes in diet (e.g., increased consumption of dairy products) or uncontrolled intake of calcium preparations may trigger hypercalcemia.
Should hypercalcemia develop, treatment with Rocaltrol should be stopped immediately. During periods of hypercalcemia, serum calcium and phosphate levels must be determined daily. When normal levels have been attained, treatment with Rocaltrol can be continued, at a daily dose 0.25 mcg lower than that previously used. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated. Rocaltrol should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias.
Immobilized patients, e.g., those who have undergone surgery, are particularly exposed to the risk of hypercalcemia.
In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine. While this is usually reversible, it is important in such patients to pay careful attention to those factors which may lead to hypercalcemia. Rocaltrol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of the serum calcium. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated.
Patients with normal renal function taking Rocaltrol should avoid dehydration. Adequate fluid intake should be maintained.
Hypersensitivity reactions (pruritus, rash, urticaria, and very rarely severe erythematous skin disorders) may occur in susceptible individuals. One case of erythema multiforme and one case of allergic reaction (swelling of lips and hives all over the body) were confirmed by rechallenge.
To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals LLC at 1-866-982-5438 (1-866-9VALIDUS) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Cholestyramine
Cholestyramine has been reported to reduce intestinal absorption of fat-soluble vitamins; as such it may impair intestinal absorption of Rocaltrol
Overdosage of any form of vitamin D is dangerous
Rocaltrol is the most potent metabolite of vitamin D available. The administration of Rocaltrol to patients in excess of their daily requirements can cause hypercalcemia, hypercalciuria, and hyperphosphatemia. Therefore, pharmacologic doses of vitamin D and its derivatives should be withheld during Rocaltrol treatment to avoid possible additive effects and hypercalcemia. If treatment is switched from ergocalciferol (vitamin D2) to calcitriol, it may take several months for the ergocalciferol level in the blood to return to the baseline value
Calcitriol increases inorganic phosphate levels in serum. While this is desirable in patients with hypophosphatemia, caution is called for in patients with renal failure because of the danger of ectopic calcification. A nonaluminum phosphate-binding compound and a low-phosphate diet should be used to control serum phosphorus levels in patients undergoing dialysis.
Magnesium-containing preparations (e.g., antacids) and Rocaltrol should not be used concomitantly in patients on chronic renal dialysis because such use may lead to the development of hypermagnesemia.
Studies in dogs and rats given calcitriol for up to 26 weeks have shown that small increases of calcitriol above endogenous levels can lead to abnormalities of calcium metabolism with the potential for calcification of many tissues in the body.
Excessive dosage of Rocaltrol induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium should be determined twice weekly. In dialysis patients, a fall in serum alkaline phosphatase levels usually antedates the appearance of hypercalcemia and may be an indication of impending hypercalcemia. An abrupt increase in calcium intake as a result of changes in diet (e.g., increased consumption of dairy products) or uncontrolled intake of calcium preparations may trigger hypercalcemia.
Should hypercalcemia develop, treatment with Rocaltrol should be stopped immediately. During periods of hypercalcemia, serum calcium and phosphate levels must be determined daily. When normal levels have been attained, treatment with Rocaltrol can be continued, at a daily dose 0.25 mcg lower than that previously used. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated. Rocaltrol should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias.
Immobilized patients, e.g., those who have undergone surgery, are particularly exposed to the risk of hypercalcemia.
In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine. While this is usually reversible, it is important in such patients to pay careful attention to those factors which may lead to hypercalcemia. Rocaltrol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of the serum calcium. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated.
Patients with normal renal function taking Rocaltrol should avoid dehydration. Adequate fluid intake should be maintained.
Phenytoin/Phenobarbital
The coadministration of phenytoin or phenobarbital will not affect plasma concentrations of calcitriol, but may reduce endogenous plasma levels of 25(OH)D3 by accelerating metabolism. Since blood level of calcitriol will be reduced, higher doses of Rocaltrol may be necessary if these drugs are administered simultaneously.
Thiazides
Thiazides are known to induce hypercalcemia by the reduction of calcium excretion in urine. Some reports have shown that the concomitant administration of thiazides with Rocaltrol causes hypercalcemia. Therefore, precaution should be taken when coadministration is necessary.
Digitalis
Calcitriol dosage must be determined with care in patients undergoing treatment with digitalis, as hypercalcemia in such patients may precipitate cardiac arrhythmias
Excessive dosage of Rocaltrol induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium should be determined twice weekly. In dialysis patients, a fall in serum alkaline phosphatase levels usually antedates the appearance of hypercalcemia and may be an indication of impending hypercalcemia. An abrupt increase in calcium intake as a result of changes in diet (e.g., increased consumption of dairy products) or uncontrolled intake of calcium preparations may trigger hypercalcemia.
Should hypercalcemia develop, treatment with Rocaltrol should be stopped immediately. During periods of hypercalcemia, serum calcium and phosphate levels must be determined daily. When normal levels have been attained, treatment with Rocaltrol can be continued, at a daily dose 0.25 mcg lower than that previously used. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated. Rocaltrol should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias.
Immobilized patients, e.g., those who have undergone surgery, are particularly exposed to the risk of hypercalcemia.
In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine. While this is usually reversible, it is important in such patients to pay careful attention to those factors which may lead to hypercalcemia. Rocaltrol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of the serum calcium. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated.
Patients with normal renal function taking Rocaltrol should avoid dehydration. Adequate fluid intake should be maintained.
Ketoconazole
Ketoconazole may inhibit both synthetic and catabolic enzymes of calcitriol. Reductions in serum endogenous calcitriol concentrations have been observed following the administration of 300 mg/day to 1200 mg/day ketoconazole for a week to healthy men. However,
Corticosteroids
A relationship of functional antagonism exists between vitamin D analogues, which promote calcium absorption, and corticosteroids, which inhibit calcium absorption.
Phosphate-Binding Agents
Since Rocaltrol also has an effect on phosphate transport in the intestine, kidneys and bones, the dosage of phosphate-binding agents must be adjusted in accordance with the serum phosphate concentration.
Vitamin D
Since calcitriol is the most potent active metabolite of vitamin D3, pharmacological doses of vitamin D and its derivatives should be withheld during treatment with Rocaltrol to avoid possible additive effects and hypercalcemia
Overdosage of any form of vitamin D is dangerous
Rocaltrol is the most potent metabolite of vitamin D available. The administration of Rocaltrol to patients in excess of their daily requirements can cause hypercalcemia, hypercalciuria, and hyperphosphatemia. Therefore, pharmacologic doses of vitamin D and its derivatives should be withheld during Rocaltrol treatment to avoid possible additive effects and hypercalcemia. If treatment is switched from ergocalciferol (vitamin D2) to calcitriol, it may take several months for the ergocalciferol level in the blood to return to the baseline value
Calcitriol increases inorganic phosphate levels in serum. While this is desirable in patients with hypophosphatemia, caution is called for in patients with renal failure because of the danger of ectopic calcification. A nonaluminum phosphate-binding compound and a low-phosphate diet should be used to control serum phosphorus levels in patients undergoing dialysis.
Magnesium-containing preparations (e.g., antacids) and Rocaltrol should not be used concomitantly in patients on chronic renal dialysis because such use may lead to the development of hypermagnesemia.
Studies in dogs and rats given calcitriol for up to 26 weeks have shown that small increases of calcitriol above endogenous levels can lead to abnormalities of calcium metabolism with the potential for calcification of many tissues in the body.
Calcium Supplements
Uncontrolled intake of additional calcium-containing preparations should be avoided
Excessive dosage of Rocaltrol induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium should be determined twice weekly. In dialysis patients, a fall in serum alkaline phosphatase levels usually antedates the appearance of hypercalcemia and may be an indication of impending hypercalcemia. An abrupt increase in calcium intake as a result of changes in diet (e.g., increased consumption of dairy products) or uncontrolled intake of calcium preparations may trigger hypercalcemia.
Should hypercalcemia develop, treatment with Rocaltrol should be stopped immediately. During periods of hypercalcemia, serum calcium and phosphate levels must be determined daily. When normal levels have been attained, treatment with Rocaltrol can be continued, at a daily dose 0.25 mcg lower than that previously used. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated. Rocaltrol should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias.
Immobilized patients, e.g., those who have undergone surgery, are particularly exposed to the risk of hypercalcemia.
In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine. While this is usually reversible, it is important in such patients to pay careful attention to those factors which may lead to hypercalcemia. Rocaltrol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of the serum calcium. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated.
Patients with normal renal function taking Rocaltrol should avoid dehydration. Adequate fluid intake should be maintained.
Magnesium
Magnesium-containing preparations (e.g., antacids) may cause hypermagnesemia and should therefore not be taken during therapy with Rocaltrol by patients on chronic renal dialysis.