RAYALDEE

8 mg/dL) before initiating treatment (see Warnings and Precautions). Recommended Dose and Dosage Adjustment The initial dose of RAYALDEE is 30 mcg administered orally once daily at bedtime. 5 mg/dL). Monitor serum calcium, serum phosphorus, serum total 25-hydroxyvitamin D and intact PTH levels at a minimum of 3 months after initiation of therapy or dose adjustment, and subsequently at least every 6 to 12 months.

Increase the dose to 60 mcg orally once daily at bedtime after approximately 3 months, if intact PTH remains above the desired therapeutic range. 5 mg/dL) and serum total 25-hydroxyvitamin D is below 250 nmol/L (100 ng/mL). Suspend dosing if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease (see Warnings and Precautions), if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia (see Warnings and Precautions) or if serum total 25-hydroxyvitamin D is consistently above 250 nmol/L (100 ng/mL).

Restart at a reduced dose after these laboratory values have normalized. There are no special dosing recommendations for pediatrics as Health Canada has not authorized the use of RAYALDEE in this patient population. Administration RAYALDEE capsules should be swallowed whole.

RAYALDEE should be taken once a day at bedtime. Missed Dose Patients should be instructed to skip a missed dose and resume taking the medicine at the next regularly scheduled time. An extra dose should not be administered to make up for a missed dose.

Page 6 of 26

Adverse Reaction Overview The clinical safety of RAYALDEE was evaluated in a 6-week Phase 2 study, two identical Phase 3 placebo-controlled pivotal studies performed in patients with either Stage 3 or 4 chronic kidney Page 9 of 26 disease and serum total 25-hydroxyvitamin D levels less than 75 nmol/L (30 ng/mL), and a long- term safety study.

Comparable proportions of subjects in both treatment groups and in both CKD stage 3 and 4 groups experienced at least one serious treatment emergent adverse event. A greater proportion of RAYALDEE treated subjects experienced a serious treatment emergent adverse event of congestive cardiac failure or increased blood creatinine.

The majority of these events resolved while continuing treatment. Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. These data reflect exposure of a total of 285 subjects to either RAYALDEE 30 or 60 mcg daily or placebo for up to 6 months (mean 24 weeks, range 1 to 31 weeks).

The mean age of the pooled pivotal study population was 66 years (range 25-85 years). Half of the subjects were male, 65% were White, and 32% were African-American or Black. 73m2 without macroalbuminuria and serum total 25-hydroxyvitamin D levels less than 30 ng/mL (75 nmol/L).

Table 2 shows common adverse reactions associated with the use of RAYALDEE in the pooled placebo-controlled trials. 4% of patients treated with RAYALDEE. 1 mg/dL) on placebo from baseline to trial end. 3 mg/dL). 5 mg/dL). e. 1 mg/dL) on placebo from baseline to trial end.

Endocrine and Metabolism:

Hypercalcemia Hypercalcemia may occur during RAYALDEE treatment (see Adverse Reactions). 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, Digitalis Toxicity ).

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.

Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients oral Capsule, 30 mcg [micrograms]/ calcifediol Butylated hydroxytoluene, carrageenan, dehydrated alcohol, dibasic sodium phosphate, FD&C blue #1, hypromellose, lauroyl polyoxylglycerides, medium chain triglycerides, mineral oil, modified corn starch, mono- and di-glycerides, paraffin, propylene glycol, sorbitol sorbitan solution, titanium dioxide and water.

Page 8 of 26 Digitalis Toxicity Hypercalcemia of any cause, including RAYALDEE ( See Warnings and Precautions, Hypercalcemia), 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).

RAYALDEE is contraindicated  in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.

 in patients with hypercalcemia or evidence of vitamin D toxicity Page 5 of 26