Calcifediol

RAYALDEE

What it isCalcitriol precursor that bypasses hepatic vitamin-D hydroxylation; secondary hyperparathyroidism in CKD.

Why it mattersAs the circulating vitamin-D storage form, it raises levels more predictably than cholecalciferol without hepatic activation.

What it changesHypercalcemia and hyperphosphatemia require laboratory monitoring; cost exceeds conventional vitamin D.

FDA-approved for

FDA dosing	Population	Start	Target	Max
Secondary hyperparathyroidism in stage 3/4 CKD with vitamin D insufficiency	Adults	30 mcg QHS	Titrate to PTH/25-OH-D goals	60 mcg QHS

Titration Increase after approximately 3 months

Renal Indicated for stage 3–4 CKD; not established in stage 2, stage 5, or ESRD on dialysis

Hepatic Undefined

Swallow capsules whole
Take once daily at bedtime
Ensure serum calcium <9.8 mg/dL before initiating and before any dose increase
Skip a missed dose; do not take an extra/double dose
Suspend dosing if PTH persistently low, serum calcium consistently above normal, or 25-OH-D >100 ng/mL; restart at reduced dose after normalization

Hypercalcemia (may be exacerbated by calcium preparations, thiazides, or other vitamin D compounds)
Digitalis toxicity potentiated by hypercalcemia — monitor when initiating/adjusting
Adynamic bone disease if PTH suppressed too low

Pregnancy No human data; animal skeletal/soft-tissue malformations at ≥8× the 60 mcg/day dose; CKD itself poses maternal/fetal risks

Lactation No data on presence in human milk; monitor breastfed infants for hypercalcemia

NO BOXED WARNINGS

Principal riskHypercalcemia and hyperphosphatemia

Cost, est. cash$20–$300/month

Generic entry2034 est.

Therapeutic safety burden1 / 4

Overdose danger1 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk1 / 4

Legacy pregnancy categoryUnknown / historical label unavailable

Defining liabilityUsually well tolerated at replacement doses; excessive dosing can cause agent-specific metabolic or organ toxicity.