Common Adverse Reactions in Phase 3 Placebo-Controlled Trials Reported in ≥1.4% of Rayaldee-Treated Subjects1
|Blood creatinine increased|
|Cardiac failure congestive|
|Chronic obstructive pulmonary disease|
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Hypercalcemia: Excessive administration of vitamin D compounds, including Rayaldee, can cause hypercalcemia and hypercalciuria. Severe hypercalcemia due to substantial overdosage of vitamin D and its metabolites may require emergency attention. Patients should be informed about the symptoms of elevated calcium. • Digitalis toxicity: Potentiated by hypercalcemia of any cause.
1,25D = 1,25-dihydroxyvitamin D
25D = 25-hydroxyvitamin D
CKD = chronic kidney disease
CV = cardiovascular
iPTH = intact parathyroid hormone
SHPT = secondary hyperparathyroidism
KDIGO states, “Calcitriol and vitamin D (1-alpha hydroxylated) analogs are not suggested for routine use in adult patients with SHPT and CKD stages 3a–5. It is reasonable to reserve the use of these agents for patients with CKD stage 4 or 5 with severe and progressive hyperparathyroidism.”1
Nutritional vitamin D (cholecalciferol and ergocalciferol) remains unproven in the treatment of SHPT, due to a lack of studies with sufficient duration1
KDIGO describes Rayaldee® (calcifediol) extended-release as a novel vitamin D prohormone that both increases 25D and 1,25D levels and lowers iPTH; however, it notes no patient-level outcome studies have been conducted1
Rayaldee® (calcifediol) extended-release 30 mcg capsules is indicated for the treatment of secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Rayaldee is not indicated in patients with stage 5 chronic kidney disease or end-stage renal disease on dialysis.
• Hypercalcemia: Excessive administration of vitamin D compounds, including Rayaldee, can cause hypercalcemia and hypercalciuria. Severe hypercalcemia due to substantial overdosage of vitamin D and its metabolites may require emergency attention. Patients should be informed about the symptoms of elevated calcium. • Digitalis toxicity: Potentiated by hypercalcemia of any cause. Monitor serum calcium and signs and symptoms of digitalis toxicity more frequently when initiating or adjusting the dose of Rayaldee. • Adynamic Bone Disease: Monitor for abnormally low levels of intact parathyroid hormone (iPTH) levels when using Rayaldee, and adjust dose if needed. • The most common adverse reactions (≥3% and more frequent than placebo) were anemia, nasopharyngitis, increased blood creatinine, dyspnea, cough, congestive heart failure and constipation. • Care should be taken while dosing Rayaldee with cytochrome P450 inhibitors, thiazides, cholestyramine or drugs stimulating microsomal hydroxylation due to the potential for drug interactions. • Serum calcium should be below 9.8 mg/dL before initiating treatment. • Monitor serum calcium, phosphorus, 25-hydroxyvitamin D and iPTH 3 months after starting therapy or changing dose.
Reference: 1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD–MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease—Mineral and Bone Disorder (CKD–MBD). http://kdigo.org/wp-content/uploads/2017/03/KDIGO-2017-CKD-MBD-Guideline-English.pdf. Accessed June 21, 2017
Phase 3 Study Design