Drug information of Doxercalciferol

Doxercalciferol is metabolized to the active form of vitamin D. The active form of vitamin D controls the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidneys, and in conjunction with PTH, the mobilization of calcium from the skeleton.

Metabolism

Hepatic via CYP27 to active metabolites, 1α,25-(OH)₂D₂ (major) and 1α,24-dihydroxyvitamin D₂ (minor).

Time to Peak

Major metabolite: 8 hours (injection); 11 to 12 hours (oral).

Half-Life Elimination

Major metabolite: ~32 to 37 hours (range: up to 96 hours)

Labeled Indications

Secondary hyperparathyroidism (patients on dialysis): Injection, oral: Treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis

Secondary hyperparathyroidism (patients not on dialysis): Oral: Treatment of secondary hyperparathyroidism in patients with stage 3 or 4 CKD

Secondary hyperparathyroidism:

Chronic kidney disease (CKD) patients on dialysis:

Note: KDIGO guidelines recommend maintaining intact parathyroid hormone (PTH) levels in the range of ~2 to 9 times the upper normal limit for the assay. Caution is advised to avoid hypercalcemia or elevated phosphate levels (KDIGO 2017)

Initial:

Oral: 10 mcg 3 times/week at dialysis (no more frequently than every other day)

IV: 4 mcg 3 times/week at the end of dialysis (no more frequently than every other day)

Dose titration: Ensure serum calcium is within normal limits prior to increasing the dose.

Oral: Titrate the dose by 2.5 mcg/dose at 8-week intervals to achieve target plasma PTH level. Maximum: 20 mcg 3 times/week at dialysis (60 mcg weekly). Hold therapy or decrease dose if PTH is persistently and abnormally low or if corrected serum calcium is consistently above normal range; if doxercalciferol is held, may restart 1 week later at a dose that is at least 2.5 mcg lower than the previous dose.

IV: Titrate the dose by 1 to 2 mcg/dose at 8-week intervals if plasma PTH is not lowered by 50% and to achieve target plasma PTH level. Maximum: 18 mcg weekly. Hold therapy or decrease dose if PTH is persistently and abnormally low or if corrected serum calcium is consistently above normal range; if doxercalciferol is held, may restart 1 week later at a dose that is at least 1 mcg lower than the previous dose.

CKD patients not on dialysis (CKD stage ≥G3):

Note: KDIGO guidelines do not recommend routine use of vitamin D analogs (eg, doxercalciferol) in patients not on dialysis with CKD stages G3 to G5; it may be reasonable to reserve use for patients with CKD stages G4 or G5 and with severe and progressive hyperparathyroidism. Caution is advised to avoid hypercalcemia or elevated phosphate levels (KDIGO 2017).

Initial: Oral: 1 mcg once daily

Dose titration: Oral: Titrate the dose by 0.5 mcg/dose at 2-week intervals to achieve target plasma PTH level. Maximum: 3.5 mcg once daily. Ensure serum calcium is within normal limits prior to increasing the dose. Hold therapy or decrease dose if PTH is persistently and abnormally low or if corrected serum calcium is consistently above normal range; if doxercalciferol is held, may restart 1 week later at a dose that is at least 0.5 mcg lower than the previous dose.

Hypersensitivity to doxercalciferol or any component of the formulation; hypercalcemia; vitamin D toxicity

Documentation of allergenic cross-reactivity for vitamin D analogues is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Get emergency medical help if you have signs of an allergic reaction: hives; chest discomfort, difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using doxercalciferol and call your doctor at once if you have:

• chest pain, slow heartbeats;
• high calcium levels-nausea, vomiting, constipation, increased thirst or urination, confusion, lack of energy, weight loss, tiredness;
• signs of infection--fever, chills, flu-like symptoms, warmth, redness, vomiting, diarrhea, pain or burning when you urinate;
• low red blood cells (anemia)--pale skin, feeling light-headed or short of breath, cold hands and feet; or
• dehydration symptoms--feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin.

Common side effects may include:

• numbness, tingling, burning pain;
• infections, not feeling well;
• cold symptoms such as stuffy nose, sneezing, cough;
• itching;
• headache, dizziness, weakness;
• depressed mood, trouble sleeping;
• upset stomach, nausea, vomiting, constipation;
• feeling short of breath;
• swelling; or
• muscle stiffness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Some medicines can make doxercalciferol much less effective when taken at the same time. If you take any of the following medicines, take your oral doxercalciferol dose 1 hour before or 4 to 6 hours after you take the other medicine:

• cholestyramine; or
• mineral oil.

Tell your doctor about all your other medicines, especially:

• digoxin;
• an antacid;
• an antibiotic or antifungal medicine;
• a calcium or a vitamin D supplement;
• a diuretic or "water pill"; or
• seizure medicine.

You should not use doxercalciferol if you are allergic to it, or if you have high levels of vitamin D or calcium in your body.

Tell your doctor if you have ever had:

• liver disease;
• a vitamin D deficiency; or
• high levels of calcium in your blood (hypercalcemia).

Tell your doctor if you are pregnant or breast-feeding.

If you breast-feed while receiving doxercalciferol injection, watch for signs of hypercalcemia in your baby (such as feeding problems, vomiting, constipation, or seizure).

Doxercalciferol is not approved for use by anyone younger than 18 years old.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Doxercalciferol is usually given either once daily or 3 times per week. Follow your doctor's dosing instructions very carefully.

Doxercalciferol oral is taken by mouth.

Doxercalciferol injection is given as an infusion into a vein at the end of dialysis. A healthcare provider will give you this injection.

Your blood will need to be tested often. Your doses may be delayed based on the results.

Even if you have no symptoms, tests can help your doctor determine if doxercalciferol is effective.

Store at room temperature away from moisture and heat.

Call your doctor for instructions if you miss a dose of doxercalciferol. 

Storage

Capsules: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Injection, single use vial: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from light.

Injection, multi-dose use vial: Store intact vial at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). After initial entry, unused portion may be stored at 2°C to 8°C (36°F to 46°F) for up to 3 days. Protect from light.

The manufacturer makes no recommendation regarding use during pregnancy.

US FDA pregnancy category: Not assigned

Comments:
-The limited data on use in pregnant women are insufficient to identify a risk for major birth defects, miscarriage, or other adverse effects with this drug.
-The risk of maternal hypertension, preeclampsia, miscarriage, premature birth polyhydramnios, stillbirth, and low birth weight are increased in patients with chronic kidney disease.