Calcitriol

INDICATIONS AND USAGE Calcitriol injection is indicated in the management of hypocalcemia in patients undergoing chronic renal dialysis. It has been shown to significantly reduce elevated parathyroid hormone levels. Reduction of PTH has been shown to result in an improvement in renal osteodystrophy.

DOSAGE AND ADMINISTRATION Calcitriol injection is for intravenous injection only. The optimal dose of calcitriol injection must be carefully determined for each patient. The effectiveness of calcitriol injection therapy is predicated on the assumption that each patient is receiving an adequate and appropriate daily intake of calcium. The RDA for calcium in adults is 800 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. The recommended initial dose of Calcitriol Injection, depending on the severity of the hypocalcemia and/or secondary hyperparathyroidism, is 1 mcg (0.02 mcg/kg) to 2 mcg administered intravenously three times weekly, approximately every other day. Doses as small as 0.5 mcg and as large as 4 mcg three times weekly have been used as an initial dose. If a satisfactory response is not observed, the dose may be increased by 0.5 to 1 mcg at two to four week intervals. During this titration period, serum calcium and phosphorus levels should be obtained at least twice weekly. If hypercalcemia or a serum calcium times phosphate product greater than 70 is noted, the drug should be immediately discontinued until these parameters are appropriate. Then, the calcitriol injection dose should be reinitiated at a lower dose. Doses may need to be reduced as the PTH levels decrease in response to the therapy. Thus, incremental dosing must be individualized and commensurate with PTH, serum calcium and phosphorus levels. The following is a suggested approach in dose titration: PTH Levels Calcitriol Injection Dose the same or increasing increase decreasing by 30%, 60% decrease one and one-half to three times the upper limit of normal maintain Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard unused portion.

CONTRAINDICATIONS Calcitriol injection should not be given to patients with hypercalcemia or evidence of vitamin D toxicity. Calcitriol injection is contraindicated in patients with previous hypersensitivity to calcitriol or any of its excipients.

ADVERSE REACTIONS Adverse effects of calcitriol injection are, in general, similar to those encountered with excessive vitamin D intake. The early and late signs and symptoms of vitamin D intoxication associated with hypercalcemia include: Early Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain, metallic taste, anorexia, abdominal pain and epigastric discomfort. Late Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis (calcific) pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated SGOT and SGPT, ectopic calcification, hypertension, cardiac arrhythmias, nephrocalcinosis, sensory disturbance, dehydration, apathy, and, rarely, overt psychosis. Occasional mild pain on injection has been observed. Post-Marketing Experience Rare cases of hypersensitivity reactions have been reported, including anaphylaxis. To report SUSPECTED ADVERSE REACTIONS, contact Fosun Pharma USA Inc. at 1-866-611-3762 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions Concomitant use of magnesium-containing preparations should be used with caution or avoided since such use may lead to the development of hypermagnesemia. Corticosteroids with glucocorticoid activity may counteract the bone and mineral metabolism effects of vitamin D analogues. Cytochrome P450 enzyme-inducing anticonvulsants such as carbamazepine, phenobarbital and phenytoin may reduce the effects of vitamin D because they increase vitamin D catabolism.

DESCRIPTION Calcitriol injection is synthetically manufactured calcitriol and is available as a sterile, isotonic, clear, colorless to yellow, aqueous solution for intravenous injection. Calcitriol Injection, USP is available in 1 mL vials. Each 1 mL contains: Active: Calcitriol, 1 mcg. Inactives: Polysorbate 20, 4 mg; Dibasic Sodium Phosphate, Anhydrous 7.6 mg; Edetate Disodium, Dihydrate 1.1 mg; Monobasic Sodium Phosphate, Monohydrate 1.8 mg; Butylated hydroxyltoluene 0.02 mg; Butylated hydroxyl anisole 0.003 mg; Sodium Chloride 1.5 mg; pH Range is from 6.5 to 8.0 and Water for Injection. Calcitriol is a crystalline compound which occurs naturally in humans. It is soluble in organic solvents but relatively insoluble in water. Calcitriol is chemically designated (5Z,7E)-9,10 secocholesta-5,7,10(19)-triene-1α,3β,25-triol and has the following structural formula: The other names frequently used for calcitriol are 1α,25-dihydroxycholecalciferol,1α,25- dihydroxyvitamin D 3 ,1,25-DHCC,1,25(OH) 2 D 3 and 1,25-diOHC. Calcitriol-SPL-Structure

OVERDOSAGE Administration of calcitriol injection to patients in excess of their requirements can cause hypercalcemia, hypercalciuria and hyperphosphatemia. High intake of calcium and phosphate concomitant with calcitriol injection may lead to similar abnormalities (see WARNINGS, PRECAUTIONS and ADVERSE REACTIONS). Treatment of Hypercalcemia and Overdosage in Patients on Hemodialysis General treatment of hypercalcemia (greater than 1 mg/dL above the upper limit of normal range) consists of immediate discontinuation of calcitriol injection therapy, institution of a low calcium diet and withdrawal of calcium supplements. Serum calcium levels should be determined daily until normocalcemia ensues. Hypercalcemia usually resolves in two to seven days. When serum calcium levels have returned to within normal limits, Calcitriol Injection therapy may be reinstituted at a dose 0.5 mcg less than prior therapy. Serum calcium levels should be obtained at least twice weekly after all dosage changes. Persistent or markedly elevated serum calcium levels may be corrected by dialysis against a calciumfree dialysate. Treatment of Accidental Overdosage of Calcitriol Injection The treatment of acute accidental overdosage of calcitriol injection should consist of general supportive measures. Serial serum electrolyte determinations (especially calcium), rate of urinary calcium excretion and assessment of electrocardiographic abnormalities due to the hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis. Discontinuation of supplemental calcium and low calcium diet are also indicated in accidental overdosage. Due to the relatively short duration of the pharmacological action of calcitriol, further measures are probably unnecessary. Should, however, persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives which may be considered, depending on the patients' underlying condition. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce an appropriate forced diuresis. The use of peritoneal dialysis against a calcium-free dialysate has also been reported.

How Supplied Calcitriol Injection, USP is supplied in 1 mL fill in 2 mL vials containing 1 mcg. NDC 72266-251-10 10 Single Dose Vials in one carton Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Distributed by: Fosun Pharma USA Inc. Princeton, NJ 08540 Made in India May 2023 1313000926-00