FDA label 442fbcd2-0765-39d6-e054-00144ff88e88

WARNINGS Overdosage of any form of vitamin D, including Hectorol, is dangerous (see OVERDOSAGE). Progressive hypercalcemia due to overdosage of vitamin D and its metabolites may be so severe as to require emergency attention. Acute hypercalcemia may exacerbate tendencies for cardiac arrhythmias and seizures and may potentiate the action of digitalis drugs. Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. The serum calcium times serum phosphorus (Ca X P) product should be maintained at < 55 mg2/dL2 in patients with chronic kidney disease. Radiographic evaluation of suspect anatomical regions may be useful in the early detection of this condition. Since doxercalciferol is a precursor for 1a potent metabolite of vitamin D2, pharmacologic doses of vitamin D and its derivatives should be withheld during Hectorol treatment to avoid possible additive effects and hypercalcemia. Oral calcium-based or other non-aluminum-containing phosphate binders and a low phosphate diet should be used to control serum phosphorus levels in patients with chronic kidney disease. Uncontrolled serum phosphorus exacerbates secondary hyperparathyroidism and can lessen the effectiveness of Hectorol in reducing blood PTH levels. If hypercalcemia occurs after initiating Hectorol therapy, the dose of Hectorol and/or calcium-containing phosphate binders should be decreased. If hyperphosphatemia occurs after initiating Hectorol, the dose of Hectorol should be decreased and/or the dose of phosphate binders increased. (See dosing recommendations for Hectorol under DOSAGE AND ADMINISTRATIONsection.) Magnesium-containing antacids and Hectorol should not be used concomitantly in patients on chronic renal dialysis because such use may lead to the development of hypermagnesemia.

ADVERSE REACTIONS Dialysis: Hectorol has been evaluated for safety in clinical studies in 165 patients with chronic kidney disease on hemodialysis. In two placebo-controlled, double-blind, multicenter studies, discontinuation of therapy due to any adverse event occurred in 2.9% of 138 patients treated with Hectorol for four to six months (dosage titrated to achieve target iPTH levels, see CLINICAL PHARMACOLOGY/Clinical Studies) and in 3.3% of 61 patients treated with placebo for two months. Adverse events occurring in the Hectorol group at a frequency of 2% or greater and more frequently than in the placebo group are presented in Table 3below: Table 3: Adverse Events Reported by2% of HectorolTreated Patients and More Frequently Than Placebo During the Double-blind Phase of Two Clinical Studies Adverse Event Hectorol(n=61) % Placebo (n=61) % Body as a Whole Abscess3.30.0Headache27.918.0Malaise27.919.7 Cardiovascular System Bradycardia6.64.9 Digestive System Anorexia4.93.3Constipation3.33.3Dyspepsia4.91.6Nausea/Vomiting21.319.7 Musculoskeletal System Arthralgia4.90.0 Metabolic and Nutritional Edema34.421.3Weight increase4.90.0 Nervous System Dizziness11.59.8Sleep disorder3.30.0 Respiratory System Dyspnea11.56.6 Skin Pruritus8.26.6A patient who reported the same medical term more than once was counted only once for that medical term. Pre-dialysis: Hectorol has been evaluated for safety in clinical studies in 55 patients (27 active and 28 placebo) with chronic kidney disease, Stages 3 or 4. In two placebo-controlled, double-blind, multicenter studies, discontinuation of therapy due to any adverse event occurred in one (3.7%) of 27 patients treated with Hectorol for 24 weeks (dosage titrated to achieve target iPTH levels, see CLINICAL PHARMACOLOGY/Clinical Studies) and in three (10.7%) of 28 patients treated with placebo for 24 weeks. Adverse events occurring in the Hectorol group at a frequency of 5% or greater and more frequently than in the placebo group are as follows: Body as a Whole Digestive System Hematologic and Lymphatic Metabolic and Nutritional Nervous System Respiratory SystemCough increased, Dyspnea, Rhinitis. Potential adverse effects of Hectorol 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, and anorexia. Late Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated blood urea nitrogen (BUN), albuminuria, hypercholesterolemia, elevated serum aspartate transaminase (AST) and alanine transaminase (ALT), ectopic calcification, hypertension, cardiac arrhythmias, sensory disturbances, dehydration, apathy, arrested growth, urinary tract infections, and, rarely, overt psychosis.