General

Pronunciation:
kal-si-fe-dye-ol

Trade Name(s)

• Rayaldee

Ther. Class.

vitamins

Pharm. Class.

fat soluble vitamins

Indications

Secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels <30 ng/mL.

Action

Calcifediol is a prohormone of the active form of vitamin D₃ , calcitriol. Promotes the absorption of calcium and phosphorus and decreases intact parathyroid hormone (PTH) concentrations.

Therapeutic Effect(s):

Reduction in intact PTH concentrations with improved calcium and phosphorous homeostasis.

Pharmacokinetics

Absorption: Absorption increased with high-fat meals.

Distribution: Well distributed to extravascular tissues.

Protein Binding: >98%.

Metabolism and Excretion: Converted to calcitriol by the 1-alpha-hydroxylase enzyme, CYP27B1, in kidney; also metabolized by CYP24A1 to inactive metabolites. Primarily excreted in feces.

Half-life: 25 days.

TIME/ACTION PROFILE (reduction in plasma intact PTH concentrations)

Contraindication/Precautions

Contraindicated in:

• Hypercalcemia.

Use Cautiously in:

• OB:  Safety not established;
•  Lactation: Use while breastfeeding only if potential maternal benefits justify potential risks to infant;
• Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: HF, arrhythmias

F and E: HYPERCALCEMIA, hyperkalemia, hyperphosphatemia, polydipsia

GI: constipation, nausea, vomiting

GU: ↑ serum creatinine, polyuria

Hemat: anemia

Metabolic: ↓ appetite, ↓ weight

MS: adynamic bone disease, fractures

Neuro: SEIZURES, confusion

Resp: bronchitis, cough, dyspnea

Misc: fatigue

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• May potentiate effects of  digoxin  on heart, including ↑ risk of arrhythmias.
•  Calcium-containing drugs,  thiazide diuretics, and other  vitamin D analogs may ↑ risk of hypercalcemia.
•  CYP450 inhibitors, including  atazanavir,  clarithromycin,  indinavir,  itraconazole,  ketoconazole,  nefazodone,  nelfinavir,  ritonavir,  saquinavir, and  voriconazole  may ↑ levels and risk of hypercalcemia.
•  Carbamazepine,  phenobarbital,  phenytoin, and  rifampin  may ↓ levels and effectiveness.
•  Cholestyramine  may ↓ absorption and effectiveness.

Drug-Food:

Ingestion of foods high in calcium content (see food sources for specific nutrients) and foods high in phosphate contentmay lead to hypercalcemia and hyperphosphatemia.

Route/Dosage

PO (Adults): 30 mcg once daily at bedtime; if desired intact PTH level remains elevated after 3 mo, ↑ to 60 mcg once daily at bedtime. Maintenance dose should target total 25-hydroxyvitamin D levels of 30–100 ng/mL, intact PTH levels within desired therapeutic range, serum calcium <9.8 mg/dL, and serum phosphorus ≤5.5 mg/dL.

Availability

Extended-release capsules: 30 mcg

Assessment

• Monitor for signs and symptoms of hypercalcemia (feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, weight loss) during therapy. May increase risk of cardiac arrhythmias and seizures. May require frequent monitoring and change in dose.
• Monitor serum and signs and symptoms of digitalis toxicity (abdominal pain, anorexia, nausea, vomiting, visual disturbances, bradycardia, other arrhythmias) during therapy in patients taking concomitant digoxin. Hypercalcemia may increase risk of digitalis toxicity in patients taking digoxin.
• Monitor for signs and symptoms of adynamic bone disease (fractures) during therapy. May develop if intact PTH levels are abnormally low due to suppression by calcifediol.

Lab Test Considerations:

Ensure serum calcium is <9.8 mg/dL before starting therapy.

• Monitor serum calcium, phosphorus, total 25-hydroxyvitamin D and intact PTH levels at least every 3 mo after starting therapy or dose adjustment, and then at least every 6 to 12 mo.

Potential Diagnoses

• Risk for injury (Adverse Reaction) 

Implementation

• PO Administer at bedtime; swallow capsules whole, do not open, crush, or chew.

Patient/Family Teaching

• Instruct patient to take calcifediol as directed. If a dose is missed, omit and take next dose at the next regularly scheduled time; do not double doses.
• Advise patient to notify health care professional if signs and symptoms of hypercalcemia occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
• Emphasize importance of routine lab tests.
• Rep:  Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Monitor infants exposed to calcifediol through breast milk for signs and symptoms of hypercalcemia, including seizures, vomiting, constipation and weight loss. Consider monitoring of serum calcium in the infant.

Evaluation/Desired Outcomes

Serum total hydroxyvitamin D levels between 30 and 100 ng/mL, intact PTH levels within therapeutic range, serum calcium (corrected for low albumin) within normal range and serum phosphorus <5.5 mg/dL.