Calcitriol

Pronunciation

Pronunciation: KAL-si-TRYE-ole
Class: Fat-soluble vitamin

Trade Names

Calcijex
- Injection 1 mcg/mL

Calcitriol Injection
- Injection 2 mcg/mL

Rocaltrol
- Capsules 0.25 mcg
- Capsules 0.5 mcg
- Solution, oral 1 mcg/mL

Vetical
- Ointment 3 mcg/g

Pharmacology

Supply of vitamin D depends mainly on exposure to UV rays of the sun for conversion of 7-dehydrocholesterol in the skin to vitamin D 3 (cholecalciferol). Vitamin D 3 is activated in the liver and kidney before fully active as a regulator of calcium and phosphorus metabolism at target tissues. The mechanism of action in the treatment of psoriasis has not been established.

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Pharmacokinetics

Absorption

Oral

Rapidly absorbed from the intestine. T max is 3 to 6 h.

Distribution

Approximately 99.9% protein bound.

Metabolism

The first pathway involves 24-hydroxylase to produce calcitroic acid; the second pathway involves hydroxylation and cyclization.

Elimination

The half-life is about 5 to 8 h. About 27% is excreted in the feces and 7% in the urine within 24 h.

Special Populations

Renal Function Impairment

The half-life is increased by at least 2-fold.

Hepatic Function Impairment

Studies have not been conducted.

Elderly

Studies have not been conducted.

Children

The half-life is prolonged.

Gender

Studies have not been conducted.

Indications and Usage

Dialysis (Oral, IV)

Hypocalcemia and resultant metabolic bone disease in patients on chronic renal dialysis.

Predialysis (Oral)

Secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe chronic renal failure (CrCl 15 to 55 mL/min) not yet on dialysis.

Hypoparathyroidism (Oral)

Hypocalcemia in patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, and pseudohypoparathyroidism.

Psoriasis (Topical)

Treatment of mild to moderate plaque psoriasis.

Unlabeled Uses

Management of psoriatic lesions.

Contraindications

Hypercalcemia or patients with vitamin D toxicity; hypersensitivity to any component of this product.

Dosage and Administration

Dialysis

PO 0.25 mcg/day. If all unsatisfactory response, increase dose by 0.25 mcg/day at 4- to 8-wk intervals. Obtain serum calcium levels at least twice weekly during this titration. If hypercalcemia occurs, immediately discontinue treatment until normocalemia is obtained. Normal or only slightly reduced calcium levels may respond to dosages of 0.25 mcg every other day.

IV 0.02 mcg/kg (1 to 2 mcg) 3 times/wk, every other day. May increase 0.5 to 1 mcg, every 2 to 4 wk. During this titration, obtain serum calcium levels twice weekly.

Predialysis
Adults and Children (older than 3 years of age)

PO Initial dosage is 0.25 mcg/day in adults and children older than 3 yr of age. Dosage may be increased up to 0.5 mcg/day.

Children younger than 3 years of age

PO 10 to 15 mg/kg/day.

Hypoparathyroidism

PO Initial dosage is 0.25 mcg/day in the morning. If unsatisfactory response, increase dose at 2- to 4-wk intervals. During this titration, obtain serum calcium levels 2 times/wk. If hypercalcemia occurs, immediately discontinue treatment until normocalemia is obtained.

Adults and children (6 yr of age and older)

PO 0.5 to 2 mcg daily.

Children (1 to 5 yr of age)

PO Usually given 0.25 to 0.75 mcg daily.

Psoriasis
Adults

Topical Apply to affected areas twice daily, morning and evening (max, 200 g/week).

General Advice

  • Oral
  • Administer prescribed dose without regard to meals, but administer with food if GI upset occurs.
  • Administer dose in the morning to patient with hypoparathyroidism.
  • Administer prescribed dose of oral solution using disposable graduated oral dispensers supplied with medication.
  • Injection
  • For IV bolus injection only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
  • Do not administer if particulate matter, cloudiness, or discoloration noted.
  • Discard any unused solution. Do not save for future use.
  • Ointment
  • The topical ointment should not be applied to the eyes, lips, or face.
  • Not for oral, opthalmic, or intravaginal use.

Storage/Stability

Store at 59° to 86°F. Protect from light. Do not freeze or refrigerate ointment.

Drug Interactions

Calcium supplements

Avoid uncontrolled intake of additional calcium-containing preparations.

Cholestyramine

May reduce intestinal absorption of fat-soluble vitamins.

Corticosteroids

Calcium absorption–promoting effects of calcitriol may be antagonized by corticosteroids, which inhibit calcium absorption.

Digitalis

Use with caution; may precipitate cardiac arrhythmias.

Ketoconazole

May reduce endogenous calcitriol concentrations.

Magnesium

Magnesium-containing products may cause hypermagnesemia and should be avoided during calcitriol administration to patients on chronic renal dialysis.

Phenytoin/Phenobarbital

Inhibits endogenous synthesis of calcitriol; therefore, may require higher doses calcitriol if given simultaneously.

Phosphate-binding agents

Because phosphate transport in the intestine, kidneys, and bones may be affected, the dosage of phosphate-binding agents must be adjusted based on serum phosphate concentration.

Thiazides

Known to induce hypercalcemia by the reduction of calcium excretion.

Verapamil

Therapeutic effects of verapamil may be reduced.

Vitamin D

To avoid possible additive effects and hypercalcemia, withhold pharmacologic doses of vitamin D and its derivatives.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Dermatologic

Topical

Psoriasis (4%); pruritus (3%); acute blistering dermatitis, erythema, skin burning sensations, skin discomfort (postmarketing).

Genitourinary

Elevated serum creatinine levels.

Topical

Urine abnormality (4%); hypercalciuria (3%).

Hypersensitivity

Anaphylaxis (postmarketing).

Lab Tests

Topical

Hypercalcemia (24%); abnormal lab tests (8%).

Local

Topical

Skin discomfort (3%).

Miscellaneous

Hypersensitivity (pruritis, rash, severe erythematous skin disorder, urticaria, [rare]), erythema multiforme, allergic reaction (eg, hives, swelling of the lips); soft tissue calcification.

Precautions

Monitor

Calcium intake

Ensure that patient is receiving an adequate daily intake of calcium. Consider adding a calcium supplement if dietary calcium intake is less than 600 mg/day. Avoid uncontrolled intake.

Dialysis patients

Ensure that serum calcium, phosphorous, magnesium, and alkaline phosphatase are determined periodically.

Hypercalcemia symptoms

Frequently assess patient for signs and symptoms of hypercalcemia (eg, weakness, headache, drowsiness, nausea, vomiting, bone pain, metallic taste, appetite loss, weight loss, polyuria, polydipsia, nocturia, photophobia, mental status change).

Hypercalcemic patients

Ensure that serum calcium and phosphorous are evaluated daily during periods of hypercalcemia.

Hypoparathyroid patients

Ensure that serum calcium, phosphorous, and 24-h urinary calcium are determined periodically.

Predialysis patients

Ensure that serum calcium, phosphorous, alkaline phosphatase, creatinine, and intact parathyroid hormone (iPTH) are determined before starting therapy. Thereafter, serum calcium, phosphorous, alkaline phosphatase, and creatinine should be determined monthly for 6 mo and then periodically thereafter. The iPTH should be determined every 3 to 4 mo.

Serum calcium levels

Ensure that serum calcium is evaluated before starting therapy, twice weekly during dosage adjustment, and then periodically thereafter, and that blood samples are taken without a tourniquet. If hypercalcemia is noted or if the serum calcium times phosphate product (Ca × P) is more than 70, immediately discontinue therapy.


Pregnancy

Category C .

Lactation

Excreted.

Children

Safety and efficacy not established in dialysis patients; dosing guidelines for oral calcitriol have not been established in children younger than 1 year of age with hypoparathyroidism or younger than 6 years of age with pseudohypoparathyroidism.

Ointment

Safety and efficacy not established in children.

Elderly

Dose selection should be cautious, starting at the low end of the dosage range.

Hypersensitivity

May occur.

UV light exposure

With use of the ointment, patients should avoid excessive exposure of treated areas to either natural or artificial sunlight, including sunlamps and tanning booths.

Overdosage

Symptoms

Adverse reactions are associated with excessive intake. The early stage symptoms of toxicity include the following: weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain, metallic taste, anorexia, abdominal pain, stomach ache. The late stage symptoms of toxicity include the following: cardiac arrhythmias, hypertension, pruritus, conjunctivitis (calcific), anorexia, weight loss, pancreatitis, polyuria, polydipsia, nocturia, elevated BUN, nephrocalcinosis, hypercholesterolemia, elevated AST/ALT, albuminia, decreased libido, hyperthermia, photophobia, rhinorrhea, ectopic calcification, overt psychosis, dystrophy, sensory disturbances, dehydration, apathy, arrested growth, UTI, hypercalcemia, hypercalciuria, hyperphosphatemia, overt psychosis (rare).

Patient Information

  • Instruct patient to carefully follow the diet and calcium supplementation instructions supplied by health care provider.
  • Advise patient to take prescribed dose without regard to meals, but to take with food if GI upset occurs.
  • Advise patient or caregiver using oral solution to use disposable graduated oral dispensers supplied with medication.
  • Instruct dialysis patient to avoid using any magnesium-containing products (eg, antacids).
  • Educate patient regarding signs and symptoms of hypercalcemia. Instruct patient to immediately inform health care provider if they occur.

Copyright © 2009 Wolters Kluwer Health.

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