calcitriol 1 MCG in 1 ML Injection

Details

WARNINGS

Since calcitriol is the most potent metabolite of vitamin D available, vitamin D and its derivatives should be withheld during treatment.A non-aluminum phosphate-binding compound should be used to control serum phosphorus levels in patients undergoing dialysis.Overdosage of any form of vitamin D is dangerous (see also OVERDOSAGE).

Progressive hypercalcemia due to overdosage of vitamin D and its metabolites may be so severe as to require emergency attention.

Chronic hypercalcemia can lead to generalized vascular calcification, nephrocalcinosis and other soft-tissue calcification.

The serum calcium times phosphate (Ca x P) product should not be allowed to exceed 70.

Radiographic evaluation of suspect anatomical regions may be useful in the early detection of this condition.

DRUG INTERACTIONS

Drug Interactions Magnesium-containing antacid and Calcitriol Injection should not be used concomitantly, because such use may lead to the development of hypermagnesemia.

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.

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 calcium-free 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 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.

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 is available in 1 mL ampuls.

Each 1 mL contains calcitriol, 1 mcg; Polysorbate 20, 4 mg; sodium chloride 1.5 mg; sodium ascorbate 10 mg added; dibasic sodium phosphate, anhydrous 7.6 mg; monobasic sodium phosphate, dihydrate 2.0 mg; edetate disodium, dihydrate 1.1 mg added.

pH 7.2 (6.5 to 8.0).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 D3, 1,25-DHCC, 1,25(OH)2D3, and 1,25-diOHC.

HOW SUPPLIED

Calcitriol Injection is supplied as follows: ListContainerConcentrationFill 3198Ampul1 mcg/mL1 mL PROTECT FROM LIGHT.Store at controlled room temperature 15o to 30oC (59o to 86oF).Rx Only Printed in USANEPHRX 2007 Distributed by: NEPHRX, LLC, Brockton, MA 02301, USAR5-10/07

GERIATRIC USE

Geriatric Use Clinical studies of Calcitriol Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosage range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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.

PEDIATRIC USE

Pediatric Use Pediatric use information is approved for Abbott Laboratories’ calcitriol injection.

However, due to Abbott Laboratories’ marketing exclusivity rights, this drug product is not labeled for pediatric use.

PREGNANCY

Pregnancy: Teratogenic Effects: Pregnancy Category C: Calcitriol has been found to be teratogenic in rabbits when given orally at doses of 0.08 and 0.3 mcg/kg.

All 15 fetuses in 3 litters at these doses showed external and skeletal abnormalities.

However, none of the other 23 litters (156 fetuses) showed external and skeletal abnormalities compared with controls.

Teratogenicity studies in rats at doses up to 0.45 mcg/kg orally showed no evidence of teratogenic potential.

There are no adequate and well-controlled studies in pregnant women.

Calcitriol Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects: In the rabbit, oral dosages of 0.3 mcg/kg/day administered on days 7 to 18 of gestation resulted in 19% maternal mortality, a decrease in mean fetal body weight and a reduced number of newborns surviving to 24 hours.

A study of the effects on orally administered calcitriol on peri- and postnatal development in rats resulted in hypercalcemia in the offspring of dams given calcitriol at doses of 0.08 or 0.3 mcg/kg/day, hypercalcemia and hypophosphatemia in dams given calcitriol at a dose of 0.08 or 0.3 mcg/kg/day and increased serum urea nitrogen in dams given calcitriol at a dose of 0.3 mcg/kg/day.

In another study in rats, maternal weight gain was slightly reduced at an oral dose of 0.3 mcg/kg/day administered on days 7 to 15 of gestation.The offspring of a woman administered oral calcitriol at 17 to 36 mcg/day during pregnancy manifested mild hypercalcemia in the first 2 days of life which returned to normal at day 3.

NUSRING MOTHERS

Nursing Mothers It is not known whether this drug is excreted in human milk.

Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from calcitriol, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

INFORMATION FOR PATIENTS

Information for the Patient The patient and his or her parents should be informed about adherence to instructions about diet and calcium supplementation and avoidance of the use of unapproved non-prescription drugs, including magnesium-containing antacids.

Patients should also be carefully informed about the symptoms of hypercalcemia (see ADVERSE REACTIONS).

DOSAGE AND ADMINISTRATION

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 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 LevelsCalcitriol Injection Dose the same or increasingincrease decreasing by 30%, 60%decrease one and one-half to three times the upper limit of normalmaintain Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Discard unused portion.