Rayaldee

Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• constipation
• decreased appetite
• fatigue
• irritability
• muscle weakness
• vomiting

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• Rayaldee

Available Dosage Forms:

• Capsule, Liquid Filled
• Capsule, Extended Release

Therapeutic Class: Nutritive Agent

Pharmacologic Class: Vitamin D (class)

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• If you are taking digoxin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with Rayaldee.
• If you take cholestyramine, talk with your pharmacist about how to take with this medicine.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Rayaldee while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Hypercalcemia

Hypercalcemia may occur during Rayaldee treatment [see Adverse Reactions (6.1)]. Acute hypercalcemia may increase the risk of cardiac arrhythmias and seizures and may potentiate the effect of digitalis on the heart [see Warnings and Precautions (5.2)]. Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. Severe hypercalcemia may require emergency attention.

Hypercalcemia may be exacerbated by concomitant administration of high doses of calcium containing preparations, thiazide diuretics, or other vitamin D compounds. In addition, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. In these circumstances, frequent serum calcium monitoring and Rayaldee dose adjustments may be required. Patients with a history of hypercalcemia prior to initiating therapy with Rayaldee should be monitored more frequently for possible hypercalcemia during therapy.

Patients should be informed about the symptoms of elevated serum calcium, which include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, and weight loss.

Digitalis Toxicity

Hypercalcemia of any cause, including Rayaldee [See Warnings and Precautions (5.1)], increases the risk of digitalis toxicity. In patients using Rayaldee concomitantly with digitalis compounds, monitor both serum calcium and patients for signs and symptoms of digitalis toxicity and increase the frequency of monitoring when initiating or adjusting the dose of Rayaldee [see Dosage and Administration (2)].

Adynamic Bone Disease

Adynamic bone disease with subsequent increased risk of fractures may develop if intact PTH levels are suppressed by Rayaldee to abnormally low levels. Monitor intact PTH levels and adjust Rayaldee dose, if needed [see Dosage and Administration (2.2)].

Teratogenic Effects - Pregnancy Category C: Calcifediol has been shown to be teratogenic in rabbits when given in doses of 8 to 16 times the human dose of 60 mcg/day, based on body surface area. There are no adequate and well-controlled studies in pregnant women. Rayaldee should be used during pregnancy only if the potential benefit justifies potential risk to the fetus.

When calcifediol was given orally to bred rabbits on the 6th through the 18th day of gestation, gross visceral and skeletal examination of pups indicated that the compound was teratogenic at doses of 25 and 50 mcg/kg/day. A dose of 5 mcg/kg/day was not teratogenic. In a similar study in rats, calcifediol was not teratogenic at doses up to and including 60 mcg/kg/day.

Labor and Delivery: The effect of this drug on the mother and fetus during labor and delivery is not known.

Nursing Mothers

Limited available evidence indicates that calcifediol is poorly excreted in human milk. Caution should be exercised when Rayaldee is administered to a nursing woman.

Pediatric Use

The safety and efficacy of Rayaldee have not been established in pediatric patients.

Geriatric Use

Of the total number of subjects in phase 3 placebo-controlled clinical studies of Rayaldee, 63% were ≥65 years of age and 22% were ≥75 years of age. No overall differences in the safety or efficacy of Rayaldee were observed between subjects older than 65 years and younger subjects.

Renal Impairment

No difference in efficacy was observed between patients with stage 3 chronic kidney disease or those with stage 4 disease in subgroup analysis. Safety outcomes were similar in these subgroups. The safety and efficacy of Rayaldee in the treatment of secondary hyperparathyroidism in patients with stage 2 or stage 5 chronic kidney disease and patients with end-stage renal disease on dialysis have not been established [see Indications and Usage (1)].

Excessive administration of Rayaldee can cause hypercalciuria, hypercalcemia, hyperphosphatemia, or oversuppression of intact PTH. Common symptoms of vitamin D overdosage may include constipation, decreased appetite, dehydration, fatigue, irritability, muscle weakness, or vomiting.

Treatment of acute accidental overdosage with Rayaldee should consist of general supportive measures. If the overdosage is discovered within a short time, induce emesis or perform gastric lavage to prevent further absorption. Obtain serial serum and urine calcium measurements, and assess any electrocardiographic abnormalities due to hypercalcemia. Discontinue supplemental calcium. Treat with standard medical care if persistent and markedly elevated serum calcium levels occur.

Calcifediol is not significantly removed by dialysis.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No neoplastic changes attributable to calcifediol were observed at subcutaneous doses of 3, 10 and 33 mcg/kg/day in a 26-week rasH2 transgenic mouse study.

In vitro or in vivo mutagenicity studies have not been performed with Rayaldee. No genotoxic or mutagenic effects have been reported with calcifediol.

Calcifediol has not been shown to have significant effects on fertility in rats.

Applies to calcifediol: oral capsule, oral capsule extended release

Metabolic

Metabolic side effects have included hypercalcemia, and increased phosphate absorption.[Ref]

Early signs and symptoms of hypercalcemia include headache, anorexia, nausea, vomiting, metallic taste, constipation, abdominal cramps, dry mouth, weakness, fatigue, muscle and bone pain, ataxia, tinnitus, and vertigo. Later hypercalcemia may result in pruritus, mental confusion, coma, hypertension, cardiac arrhythmias, seizures, metastatic calcification, and renal insufficiency manifested by polyuria, nocturia, polydipsia, and proteinuria. Patients with renal failure are more prone to the development of hypercalcemia because the urinary excretion of calcium cannot compensate for increases in serum calcium.

Increased phosphate absorption may be detrimental in patients with chronic renal failure and hyperphosphatemia.

Because of the long half-life of calcifediol, reversal of toxic symptoms may take 7 to 30 days.[Ref]

Some side effects of Rayaldee may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.