Usage
Calcitriol is a synthetic, active form of vitamin D3. It is primarily prescribed for:
- Hypocalcemia in patients with chronic kidney disease: This includes patients undergoing dialysis and those with secondary hyperparathyroidism.
- Hypoparathyroidism: This condition involves decreased function of the parathyroid glands, leading to low calcium levels.
- Vitamin D-dependent rickets (off-label): A rare genetic disorder impacting vitamin D metabolism.
- Postmenopausal osteoporosis and corticosteroid-induced osteoporosis: Calcitriol may be used as an adjunct to calcium supplementation in preventing bone loss.
Calcitriol’s pharmacological classification is as a vitamin D analog or a calcium regulator.
Mechanism of Action: Calcitriol functions as a hormone, regulating calcium and phosphorus homeostasis. It promotes intestinal calcium absorption, increases renal tubular reabsorption of calcium, and mobilizes calcium from bone. This leads to an increase in serum calcium levels.
Alternate Names
- 1,25-dihydroxyvitamin D3
- 1,25(OH)2D3
Brand Names:
How It Works
Pharmacodynamics: Calcitriol primarily acts by binding to the vitamin D receptor (VDR), a nuclear receptor present in target tissues like the intestine, kidneys, and bone. This receptor complex then interacts with specific DNA sequences, modulating gene expression and regulating calcium and phosphorus transport proteins. Calcitriol increases intestinal calcium absorption, decreases renal excretion of calcium, and increases bone resorption. It also suppresses parathyroid hormone (PTH) synthesis and secretion.
Pharmacokinetics: Calcitriol can be administered orally or intravenously. Oral absorption can be variable and may be reduced by food. It is metabolized in the liver by CYP3A4 and other enzymes. Elimination occurs primarily through the biliary route, with some renal excretion.
Receptor Binding: Calcitriol exerts its effects primarily by binding to the VDR.
Enzyme Inhibition/Neurotransmitter Modulation: No significant direct enzyme inhibition or neurotransmitter modulation has been described for calcitriol.
Elimination Pathways: Primarily biliary excretion, with some renal excretion.
Dosage
Standard Dosage
Adults:
- Oral: Initial dose of 0.25 mcg/day, titrated based on serum calcium levels, up to a maintenance dose of 0.5-2 mcg/day.
- Intravenous: Initial dose of 0.5 mcg three times a week, titrated based on serum calcium levels, up to a maintenance dose of 0.5-4 mcg three times a week.
Children:
Dosing in children varies depending on age and indication, ranging from 0.01 mcg/kg/day to 0.5 mcg/day, and should be carefully titrated based on the child’s weight, age, and clinical response.
Special Cases:
- Elderly Patients: Close monitoring of serum calcium levels is recommended, but no specific dosage adjustments are typically required.
- Patients with Renal Impairment: Dosing should be individualized based on serum calcium and phosphorus levels.
- Patients with Hepatic Dysfunction: Close monitoring is recommended, and dose adjustment may be needed.
- Patients with Comorbid Conditions: Careful monitoring is required, especially in patients with cardiovascular disease or conditions affecting calcium metabolism.
Clinical Use Cases
Dosing for specific clinical situations such as intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations should be individualized based on patient needs and serum calcium monitoring. There are no standard recommendations for Calcitriol specific to these situations. The use of calcitriol in these situations may be determined if hypocalcaemia is observed.
Dosage Adjustments
Dose modifications may be necessary based on renal or hepatic function, metabolic disorders, or concomitant medications that interact with calcitriol.
Side Effects
Common Side Effects
- Hypercalcemia (high blood calcium) symptoms: nausea, vomiting, constipation, increased thirst, increased urination, weakness, confusion
- Headache
- Weakness
- Dry mouth
- Constipation
Rare but Serious Side Effects
- Cardiac arrhythmias
- Acute kidney injury
- Severe hypercalcemia
Long-Term Effects
- Nephrocalcinosis (calcium deposits in the kidneys)
- Soft tissue calcification
Adverse Drug Reactions (ADR)
Severe hypercalcemia requiring immediate medical intervention.
Contraindications
- Hypercalcemia
- Vitamin D toxicity
- Hypersensitivity to calcitriol or any component of the formulation.
Drug Interactions
- Thiazide diuretics: Can increase the risk of hypercalcemia.
- Cardiac glycosides (e.g., digoxin): Hypercalcemia can exacerbate digitalis toxicity.
- Magnesium-containing antacids: Can decrease calcitriol absorption.
- Phosphate binders: Can affect calcium and phosphorus balance.
- CYP3A4 inducers/inhibitors: Can affect calcitriol metabolism (e.g., ketoconazole, rifampin).
- Cholestyramine: Can decrease calcitriol absorption.
Pregnancy and Breastfeeding
Calcitriol is classified as Pregnancy Category C. Its use during pregnancy should be limited to situations where the benefits clearly outweigh the risks. Calcitriol is excreted in breast milk, and its use during breastfeeding is generally not recommended. Close monitoring of infant calcium levels is essential if calcitriol is used during lactation.
Drug Profile Summary
- Mechanism of Action: Binds to VDR, regulating calcium and phosphorus homeostasis.
- Side Effects: Hypercalcemia, headache, weakness, dry mouth, constipation. Serious side effects include cardiac arrhythmias and acute kidney injury.
- Contraindications: Hypercalcemia, vitamin D toxicity, hypersensitivity.
- Drug Interactions: Thiazide diuretics, digoxin, magnesium antacids, phosphate binders, CYP3A4 inducers/inhibitors, cholestyramine.
- Pregnancy & Breastfeeding: Category C; use with caution. Not recommended during breastfeeding.
- Dosage: Adults: 0.25-2 mcg/day orally or 0.5-4 mcg three times a week IV. Pediatric dosing varies with age and indication.
- Monitoring Parameters: Serum calcium, phosphorus, creatinine, and 24-hour urinary calcium.
Popular Combinations
Calcitriol is often used in combination with calcium supplements to treat hypocalcemia and prevent or treat osteoporosis.
Precautions
- Monitor serum calcium, phosphorus, creatinine, and urinary calcium regularly.
- Monitor for signs and symptoms of hypercalcemia.
- Adjust dosage in patients with renal or hepatic impairment.
- Consider dietary calcium intake.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Calcitriol?
A: The recommended initial dose for adults is 0.25 mcg daily, titrated up to 0.5-2 mcg/day based on serum calcium levels. Pediatric and special population dosing varies and should be carefully determined based on individual patient factors.
Q2: How should Calcitriol be administered?
A: Calcitriol can be administered orally or intravenously.
Q3: What are the common side effects of Calcitriol?
A: Common side effects include hypercalcemia (with associated symptoms), headache, weakness, dry mouth, and constipation.
Q4: What are the serious side effects of Calcitriol?
A: Serious side effects include cardiac arrhythmias, acute kidney injury, and severe hypercalcemia.
Q5: What are the contraindications to using Calcitriol?
A: Contraindications include hypercalcemia, vitamin D toxicity, and hypersensitivity to calcitriol or any component of the formulation.
Q6: What are the key drug interactions with Calcitriol?
A: Significant drug interactions include thiazide diuretics, digoxin, magnesium-containing antacids, phosphate binders, and CYP3A4 inducers/inhibitors.
Q7: Can Calcitriol be used during pregnancy or breastfeeding?
A: Calcitriol is Pregnancy Category C and should be used with caution during pregnancy. It is generally not recommended during breastfeeding due to excretion in breast milk.
Q8: What parameters should be monitored during Calcitriol therapy?
A: Serum calcium, phosphorus, creatinine, and 24-hour urinary calcium should be monitored regularly.
Q9: How does Calcitriol work in the body?
A: It binds to the vitamin D receptor, promoting intestinal calcium absorption, reducing renal calcium excretion, and mobilizing calcium from bone.
