RAYALDEE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RAYALDEE (RAYALDEE).
Rayaldee (calcifediol) is a vitamin D3 analog that is converted to the active hormone calcitriol by 1-alpha-hydroxylase in the kidney. It acts as a vitamin D receptor agonist, increasing intestinal absorption of calcium and phosphate, promoting renal tubular reabsorption of calcium, and suppressing parathyroid hormone (PTH) secretion. In CKD patients, it lowers elevated PTH levels.
| Metabolism | Prodrug; converted to calcitriol (1,25-dihydroxyvitamin D) by 1-alpha-hydroxylase (CYP27B1) primarily in the kidney. Additionally, it may be metabolized by CYP24A1 to inactive metabolites. |
| Excretion | Primarily fecal via biliary excretion (70-80%); renal excretion accounts for <10% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 14-19 hours, reflecting the extended-release formulation designed for once-daily dosing. |
| Protein binding | Approximately 99% bound to vitamin D-binding protein (DBP) and albumin. |
| Volume of Distribution | Approximately 0.6-0.8 L/kg, indicating distribution primarily into extracellular fluid and tissues. |
| Bioavailability | Orally administered extended-release formulation has a bioavailability of approximately 70-80% relative to immediate-release calcifediol. |
| Onset of Action | Therapeutic effect (increase in serum 25-hydroxyvitamin D) observed within 7-14 days of initiating daily dosing. |
| Duration of Action | Duration of action (maintained serum 25-hydroxyvitamin D levels above baseline) persists throughout the 24-hour dosing interval with once-daily administration. |
30 mcg orally once daily at bedtime.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for any degree of renal impairment, including end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use cautiously. |
| Pediatric use | Safety and efficacy not established in pediatric patients below 18 years of age; no dosing recommendations available. |
| Geriatric use | No specific dose adjustment required; use standard adult dosing. Monitor serum calcium and phosphate levels due to potential age-related renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RAYALDEE (RAYALDEE).
| Breastfeeding | Calcifediol is excreted into human breast milk; the M/P ratio is not specifically available for calcifediol, but vitamin D metabolites are present. Breastfeeding during maternal vitamin D deficiency is not recommended due to risk of infant deficiency. However, maternal supplementation with recommended doses may not pose significant risk. Monitor infant for signs of hypercalcemia or vitamin D toxicity if maternal doses are high. No specific M/P ratio reported. |
| Teratogenic Risk | Rayaldee (calcifediol) is a vitamin D analog. Inadequate vitamin D during pregnancy is associated with adverse fetal outcomes including skeletal abnormalities and impaired growth. However, excessive vitamin D intake is also potentially teratogenic, with animal studies showing fetal anomalies at high doses. The specific risk profile for calcifediol in pregnancy is not well-established; use only if clearly needed. First trimester: theoretical risk of hypercalcemia-induced teratogenicity with excessive doses. Second and third trimesters: avoid hypercalcemia as it may lead to fetal supravalvular aortic stenosis, elfin facies, and mental retardation. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to calcifediol or any product components","hypercalcemia","vitamin D toxicity","hypervitaminosis D"]
| Precautions | ["Hypercalcemia","Hypercalciuria","hyperphosphatemia","digitalis toxicity risk if hypercalcemia occurs","adynamic bone disease risk with oversuppression of PTH","drug interactions with strong CYP3A4 inhibitors/inducers","monitor serum calcium, phosphate, and PTH regularly"] |
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| Fetal Monitoring | Monitor maternal serum calcium, phosphate, and 25-hydroxyvitamin D levels periodically. Assess renal function and urinary calcium excretion if high doses used. Fetal monitoring includes ultrasound for skeletal development and growth if maternal calcium levels are elevated. Monitor infant for hypercalcemia after birth if maternal doses exceed recommended dietary allowances. |
| Fertility Effects | No specific data on Rayaldee; vitamin D insufficiency is associated with impaired fertility in both genders. Correction of deficiency may improve fertility outcomes. No known direct negative effect on fertility at therapeutic doses. |