General Since ROCALTROL (calcitriol) is a potent cholecalciferol derivative with profound effects on intestinal absorption of dietary calcium and inorganic phosphate, it should not be used concomitantly with other vitamin D products or its derivatives.
The desired therapeutic margin of ROCALTROL is narrow, therefore, the optimal daily dose must be carefully determined for each patient by dose titration to obtain satisfactory response in the biochemical parameters and clinical manifestations (see DOSAGE AND ADMINISTRATION section).
Cardiovascular In patients on digitalis, hypercalcemia may precipitate cardiac arrhythmias; in such patients ROCALTROL should be used with extreme caution. Carcinogenesis and mutagenesis See TOXICOLOGY section Endocrine and Metabolism Chronic hypercalcemia can lead to generalized vascular calcification, nephrocalcinosis, calcifications of the cornea or other soft tissues.
During treatment with ROCALTROL the serum total calcium (mg/dL) times serum inorganic phosphate product (Ca x P) should not exceed 70 mg2/dl2. Dialysate calcium level of 7 mg% or above in addition to excessive dietary calcium supplements may lead to frequent episodes of hypercalcemia.
Patients need to adhere to prescribed calcium intake, dietary and supplementary, and avoid unapproved non-prescription drugs or medications. Patients should also be made aware of the symptoms of hypercalcemia and should seek medical attention if such symptoms are noted (see ADVERSE REACTIONS).
Patients with vitamin D resistant rickets (familial hypophosphatemia) should pursue their oral phosphate therapy. However, the possible stimulation of intestinal phosphate absorption by ROCALTROL should be taken into account since this effect may modify the requirement for phosphate supplements (see DRUG INTERACTIONS).
Renal In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine. While the elevation of serum creatinine 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 increased with Page 5 of 25 careful monitoring of serum calcium concentrations. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated.
Patients taking ROCALTROL should avoid dehydration. Adequate fluid intake should be maintained.
Special Populations Pregnant Women:
The safety of ROCALTROL in women who are or may become pregnant has not been established; use of ROCALTROL in these cases may be considered only when the potential benefits have been weighed against possible hazards to mother and fetus.
Nursing Women:
ROCALTROL may be excreted in human milk. In view of the potential for hypercalcemia in the mother and for adverse reactions from ROCALTROL in nursing infants, mothers may breastfeed while taking ROCALTROL, provided that the serum calcium levels of the mother and infant are monitored.
Geriatrics (>65 years of age):
Limited data are available in patients 65 years of age or older. Caution should be used when treating elderly patients.
Pediatrics (<18 years of age):
The safety and efficacy of calcitriol capsules in children have not been sufficiently investigated. Use is not recommended in this patient population. Monitoring and Laboratory Tests Serum calcium, inorganic phosphorus, magnesium, alkaline phosphatase as well as 24-hour urinary calcium and phosphorus should be determined periodically during maintenance therapy with ROCALTROL.
During the initial phase of the medication (dosage adjustment), serum calcium should be determined at least twice weekly. A fall in serum alkaline phosphatase values may indicate impending hypercalcemia. Should hypercalcemia develop, the drug should be discontinued immediately until the serum calcium level has normalized.
This may take several days to a week. Therapy with ROCALTROL should only be considered when adequate laboratory facilities for monitoring of blood and urine chemistries are available. During treatment progressive hypercalcemia either due to hyper-responsiveness or overdosage may become so severe as to require emergency treatment.
Periodic ophthalmological examinations and radiological evaluation of suspected anatomical regions for early detection of ectopic calcifications are advisable. ADVERSE REACTIONS Adverse Drug Reaction Overview Hypersensitivity reactions (pruritis, rash, urticaria, and very rarely severe erythematous skin Page 6 of 25 disorders) may occur.
The adverse effects of ROCALTROL (calcitriol) are similar to those encountered with excessive vitamin D intake. The early signs and symptoms associated with vitamin D intoxication and hypercalcemia are weakness, headache, somnolence, nausea, cardiac arrhythmias, excessive thirst, vomiting, dry mouth, constipation, muscle pain, bone pain, metallic taste, abdominal pain or stomach ache.
The late signs and symptoms are polyuria, polydipsia, urinary tract infections, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, elevated AST and/or ALT, albuminuria, hypercholesterolemia, ectopic calcification, hypertension, cardiac arrhythmias, and rarely, overt psychosis.
Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The following adverse reactions, based on clinical studies and post-market experience in various indications, have been reported in association with ROCALTROL treatment.
Where data are derived from spontaneous […]