kal-si-fe-DYE-ol

Therapeutic Classification: vitamins

Pharmacologic Classification: fat soluble vitamins

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

• 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.

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

Absorption: Absorption increased with high-fat meals.

Distribution: Well distributed to extravascular tissues.

Protein Binding: >98%.

Metabolism/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.

(reduction in plasma intact PTH concentrations)

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.

CV: HF, arrhythmias.

F and E: HYPERCALCEMIA, hyperkalemia, hyperphosphatemia, polydipsia.

GI: constipation, nausea, vomiting.

GU: ↑serum creatinine, polyuria.

Hemat: anemia.

Metab: ↓appetite, ↓ weight.

MS: adynamic bone disease, fractures.

Neuro: SEIZURES, confusion.

Resp: bronchitis, cough, dyspnea.

Misc: fatigue.

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 Appendix M) and foods high in phosphate content may lead to hypercalcemia and hyperphosphatemia.

• 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.

• Extended-release capsules: 30 mcg;

• 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.

• 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.

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

• 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.

• 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.

Rayaldee

• Risk for injury (Adverse Reactions).

NDC Code^*

• 70301- OPKO Pharmaceuticals LLC
  • 70301-1001- Rayaldee
    • 70301-1001-1- 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (70301-1001-1)

• 70301- OPKO Pharmaceuticals LLC
  • 70301-1001- Rayaldee
    • 70301-1001-2- 60 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (70301-1001-2)