Doxercalciferol

If you experience any of the following serious side effects, stop taking doxercalciferol and seek emergency medical attention or contact your doctor immediately:

• an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives);
• an irregular heartbeat;
• increased nighttime urination; or
• abdominal pain.

Contact your doctor if you experience any of the following side effects:

• nausea, vomiting, or decreased appetite;
• dry mouth;
• constipation;
• weakness;
• headache;
• dizziness;
• a metallic taste;
• muscle or bone pain;
• increased thirst or urination;
• shortness of breath; or
• itching.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Take doxercalciferol exactly as directed by your doctor. If you do not understand the directions on your prescription bottle, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with water.

Doxercalciferol is usually taken three times a week during dialysis. Follow your doctor's instructions.

Store doxercalciferol at room temperature away from moisture, light, and heat.

Seek emergency medical attention.

Symptoms of a doxercalciferol overdose are not known but may include irregular heartbeats, abdominal pain, nausea, vomiting, dry mouth, decreased appetite, constipation, weakness, muscle pain, bone pain, tiredness, headache, and a metallic taste in the mouth.

Notify your doctor if you miss a dose of doxercalciferol.

Pregnancy Category: B

Lactation: excretion in milk unknown/not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Administration

IV bolus

You should not take doxercalciferol if you have high levels of vitamin D or calcium in your body.

To make sure doxercalciferol is safe for you, tell your doctor if you have:

• liver disease;

• a vitamin D deficiency; or

• high levels of calcium in your blood (hypercalcemia).

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. Your dose needs may be different during pregnancy.

It is not known whether doxercalciferol passes into breast milk. However, other forms of vitamin D can pass into breast milk and could harm a nursing baby. You should not breast-feed while taking doxercalciferol.

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

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Doxercalciferol is usually taken 3 times per week during dialysis. Follow your doctor's instructions.

While using doxercalciferol, you may need frequent blood tests.

Call your doctor if your symptoms do not improve, or if they get worse.

Doxercalciferol is only part of a complete treatment program that may also include special instructions about the foods you eat and vitamins or mineral supplements you take. Follow your doctor's instructions very closely.

Store at room temperature away from moisture, light, and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Early signs of overdose may include weakness, muscle or bone pain, constipation, nausea, vomiting, weight loss, or a metallic taste in your mouth.

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

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

• nausea, vomiting, constipation, loss of appetite, weight loss;

• increased thirst or urination, or urinating less than usual;

• dryness or metallic taste in your mouth;

• itching, warmth, redness, tingly feeling;

• weakness, drowsiness, lack of energy, tired feeling;

• headache, dizziness, confusion, ringing in your ears;

• muscle weakness, bone pain; or

• irregular heartbeats, feeling nervous or irritable.

Common side effects may include:

• headache, dizziness;

• nausea, vomiting;

• feeling short of breath;

• swelling; or

• general ill feeling.

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.

Drugs Affecting Hepatic Microsomal Enzymes

Possible pharmacokinetic interaction with hepatic enzyme inducers (e.g., glutethimide, phenobarbital) or inhibitors (e.g., erythromycin, ketoconazole) affecting hepatic hydroxylation (activation) of doxercalciferol.1 7

Specific Drugs

Importance of diet and calcium supplementation regimen adherence.1 7

Importance of a combined dietary calcium and calcium-containing phosphate binder intake of 1.5–2 g of calcium daily.1

Importance of serum iPTH, calcium, phosphorus, and alkaline phosphatase monitoring prior to initiation of therapy and periodically thereafter.1 7

Importance of immediate reporting of potential manifestations of hypercalcemia.1 7

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 7

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 7

Importance of informing patients of other precautionary information.1 7 (See Cautions.)

Secondary hyperparathyroidism:

Oral:

Dialysis patients:

Initial dose: iPTH >400 pg/mL: 10 mcg 3 times/week at dialysis for 8 weeks

Dose titration:

iPTH level >300 pg/mL (dose should be titrated to lower iPTH to within the range of 150 to 300 pg/mL): Increase to 12.5 mcg 3 times/week at dialysis for 8 more weeks; this titration process can continue at 8-week intervals in 2.5 mcg/dose increments (maximum: 20 mcg 3 times/week).

iPTH level 150 to 300 pg/mL: Maintain current dose

iPTH level <100 pg/mL: Suspend doxercalciferol for 1 week; resume at a reduced dose; decrease each dose (not weekly dose) by at least 2.5 mcg

Hypercalcemia, hyperphosphatemia, or serum calcium times serum phosphorus product >55 mg2/dL2: Decrease or suspend dose and/or adjust dose of phosphate binders; if dose is suspended, resume at a reduced dose; decrease each dose (not weekly dose) by at least 2.5 mcg.

Predialysis patients:

Initial dose: iPTH >70 pg/mL with stage 3 disease or >110 pg/mL with stage 4 disease: 1 mcg/day for 2 weeks

Dose titration:

iPTH level >70 pg/mL with stage 3 disease or >110 pg/mL with stage 4 disease (dose should be titrated to lower iPTH to 35 to 70 pg/mL with stage 3 disease or to 70 to 110 pg/mL with stage 4 disease): Increase dose by 0.5 mcg per day every 2 weeks as necessary (maximum dose: 3.5 mcg/day)

iPTH level 35 to 70 pg/mL with stage 3 disease or 70 to 110 pg/mL with stage 4 disease: Maintain current dose

iPTH level is <35 pg/mL with stage 3 disease or <70 pg/mL with stage 4 disease: Suspend doxercalciferol for 1 week, then resume at a reduced dose (at least 0.5 mcg per day lower)

Hypercalcemia, hyperphosphatemia, or serum calcium times serum phosphorus product >55 mg2/dL2: Decrease or suspend dose and/or adjust dose of phosphate binders; if dose is suspended, resume at a reduced dose (at least 0.5 mcg per day lower).

IV:

Dialysis patients:

Initial dose: iPTH level >400 pg/mL: 4 mcg 3 times/week at the end of dialysis; adjust as needed to lower iPTH into a range of 150 to 300 pg/mL

Dose titration (increase dose at 8-week intervals):

iPTH level decreased by <50% and >300 pg/mL (dose should be titrated to lower iPTH to within a range of 150 to 300 pg/mL): Increase by 1 to 2 mcg at 8-week intervals, as necessary (doses >18 mcg/week have not been studied).

iPTH level decreased by >50% and >300 pg/mL: Maintain current dose

iPTH level 150 to 300 pg/mL: Maintain current dose

iPTH level <100 pg/mL: Suspend doxercalciferol for 1 week; resume at a reduced dose (at least 1 mcg lower)

Hypercalcemia, hyperphosphatemia, or serum calcium times serum phosphorus product >55 mg2/dL2: Decrease or suspend dose and/or adjust dose of phosphate binders; if dose is suspended, resume at a reduced dose (at least 1 mcg lower)

Applies to doxercalciferol: injectable solution, oral capsule

Metabolic

Early signs and symptoms of hypercalcemia have included weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain, metallic taste, and anorexia.

Prolonged hypercalcemia may result in polyuria, polydipsia, anorexia, weight loss, nocturia conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated blood urea nitrogen (BUN), albuminuria, hypercholesterolemia, elevated serum aspartate transaminase (AST) and alanine transaminase (ALT), ectopic calcification, hypertension, cardiac arrhythmias, sensory disturbances, dehydration, apathy, arrested growth, urinary tract infections, and, rarely, overt psychosis.

Hyperphosphatemia may exacerbate hyperparathyroidism.

Hypercalciuria may accelerate the onset of renal failure.[Ref]

Very common (10% or more): Edema (34.4%)
Common (1% to 10%): Anorexia, weight increase, dehydration
Frequency not reported: Hypercalcemia, hyperphosphatemia, hypercalciuria[Ref]

Endocrine

Oversuppression of iPTH may result in adynamic bone syndrome.[Ref]

Frequency not reported: Oversuppression of parathyroid hormone[Ref]

Cardiovascular

Common (1% to 10%): Bradycardia, chest pain[Ref]

Gastrointestinal

Very common (10% or more): Nausea/vomiting (21.3%)
Common (1% to 10%): Dyspepsia, constipation[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia[Ref]

Nervous system

Very common (10% or more): Headache (27.9%), dizziness (11.5%)
Common (1% to 10%): Hypertonia, paresthesia[Ref]

Dermatologic

Common (1% to 10%): Pruritus[Ref]

Respiratory

Very common (10% or more): Dyspnea (11.5%)
Common (1% to 10%): Cough increased, rhinitis[Ref]

Other

Very common (10% or more): Malaise (27.9%)
Common (1% to 10%): Abscess[Ref]

Psychiatric

Common (1% to 10%): Sleep disorder, depression
Uncommon (0.1% to 1%): Insomnia[Ref]

Immunologic

Common (1% to 10%): Infection

Hypersensitivity

Hypersensitivity reactions include anaphylaxis with symptoms of angioedema (involving face, lips, tongue, and airway), hypotension, unresponsiveness, chest discomfort, shortness of breath, cardiopulmonary arrest, pruritus, and skin burning sensation. These reactions may occur separately or together.

Postmarketing reports: Hypersensitivity reactions (including fatal outcome)

Hematologic

Common (1% to 10%): Anemia[Ref]

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

See Usual Adult Dose