Calcijex

Contraindications

Hypercalcemia or evidence of vitamin D toxicity

Hypersensitivity to calcitriol, other vitamin D analogues, or other ingredients

Cautions

Excessive vitamin D may suppress parathyroid hormone

Risk of hyperphosphatemia, hypercalciuria

Efficacy may be unpredictable in patients with malabsorption syndrome

Adequate dietary calcium supplementation necessary for clinical response to vitamin D

Use caution in malabsorption syndrome, renal/hepatic impairment,

Calcijex is part of the drug class:

• Other antipsoriatics for topical use

Calcijex will work only if you get the right amount of calcium from the foods you eat. If you get too much calcium from foods, you may experience serious side effects of Calcijex, and if you do not get enough calcium from foods, Calcijex will not control your condition. Your doctor will tell you which foods are good sources of these nutrients and how many servings you need each day. If you find it difficult to eat enough of these foods, tell your doctor. In that case, your doctor can prescribe or recommend a supplement.

If you are being treated with dialysis (process of cleaning the blood by passing it through a machine), your doctor may also prescribe a low-phosphate diet. Follow these directions carefully.

If you do not have kidney disease, you should drink plenty of fluids while taking Calcijex. If you have kidney disease, talk to your doctor about how much fluid you should drink each day.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

• It is advised to have a dietary intake of calcium at a minimum of 600 mg daily. The U.S. recommended daily allowance (RDA) for calcium in adults is 800 mg to 1200 mg.
• Keep all appointments with your doctor and the laboratory. 

• It is used to control low blood calcium levels in certain patients.
• It is used to treat high parathyroid hormone levels in certain patients.
• It may be given to you for other reasons. Talk with the doctor.

Use Calcijex as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

General

Excessive dosage of Calcijex (calcitriol injection) induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium and phosphorus should be determined at least twice weekly. Should hypercalcemia develop, the drug should be discontinued immediately.

Calcijex should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias.

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).

Essential Laboratory Tests

Serum calcium, phosphorus, magnesium and alkaline phosphatase and 24-hour urinary calcium and phosphorus should be determined periodically. During the initial phase of the medication, serum calcium and phosphorus should be determined more frequently (twice weekly).

Adynamic bone disease may develop if PTH levels are suppressed to abnormal levels. If biopsy is not being done for other (diagnostic) reasons, PTH levels may be used to indicate the rate of bone turnover. If PTH levels fall below recommended target range (1.5 to 3 times the upper limit of normal), in patients treated with Calcijex, the Calcijex dose should be reduced or therapy discontinued. Discontinuation of Calcijex therapy may result in rebound effect, therefore, appropriate titration downward to a maintenance dose is recommended.

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of Calcijex (calcitriol injection). Calcitriol was not mutagenic in vitro in the Ames Test nor was oral calcitriol genotoxic in vivo in the Mouse Micronucleus Test. No significant effects on fertility and/or general reproductive performances were observed in a Segment I study in rats using oral calcitriol at doses of up to 0.3 mcg/kg.

Pregnancy

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

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.

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.

Pediatric Use

The safety and effectiveness of Calcijex were examined in a 12-week randomized, double-blind, placebo-controlled study of 35 pediatric patients, aged 13-18 years, with end-stage renal disease on hemodialysis. Sixty-six percent of the patients were male, 57% were African-American, and nearly all had received some form of vitamin D therapy prior to the study. The initial dose of Calcijex was 0.5 mcg, 1.0 mcg, or 1.5 mcg, 3 times per week, based on baseline iPTH level of less than 500 pg/mL, 500-1000 pg/mL, or greater than 1000 pg/mL, respectively. The dose of Calcijex was adjusted in 0.25 mcg increments based on the levels of serum iPTH, calcium, and Ca x P. The mean baseline levels of iPTH were 769 pg/mL for the 16 Calcijex-treated patients and 897 pg/mL for the 19 placebo-treated subjects. The mean weekly dose of Calcijex ranged from 1.0 mcg to 1.4 mcg. In the primary efficacy analysis, 7 of 16 (44%) subjects in the Calcijex group had 2 consecutive 30% decreases from baseline iPTH compared with 3 of 19 (16%) patients in the placebo group (95% CI for the difference between groups -6%, 62%). One Calcijex-treated patient experienced transient hypercalcemia (> 11.0 mg/dL), while 6 of 16 (38%) Calcijex-treated patients vs. 2 of 19 (11%) placebo-treated patients experienced Ca x P > 75.

Geriatric Use

Clinical studies of Calcijex 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.

Administration of Calcijex (calcitriol injection) to patients in excess of their requirements can cause hypercalcemia, hypercalciuria and hyperphosphatemia. High intake of calcium and phosphate concomitant with Calcijex 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 Calcijex 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, Calcijex 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 Calcijex 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.