Action and Spectrum

Mechanism of action and Spectrum

The mechanism of action is primarily through activation of the vitamin D receptor (VDR), which is found in many tissues, including bone, intestine, and kidney

When calcitriol binds to the VDR, it forms a complex with the retinoid X receptor (RXR). This complex then binds to specific DNA sequences (vitamin D response elements) in target genes to regulate gene expression. This regulation of gene expression leads to a variety of biological effects, including:

Regulation of calcium and phosphorus homeostasis: calcitriol is crucial in maintaining adequate calcium and phosphorus levels in the blood. It increases the absorption of calcium and phosphorus from the intestine and decreases the excretion of calcium by the kidneys.

Bone metabolism: calcitriol regulates bone metabolism by promoting the formation and maturation of osteoclasts, which are responsible for the resorption of bone, and by promoting the formation and differentiation of osteoblasts, which are responsible for the formation of new bone.

Immune system regulation: calcitriol has been shown to play a role in regulating the immune system. It has been shown to have anti-inflammatory effects and enhance specific immune cells’ activity, including T cells and natural killer cells

Drug Interaction

Adverse Reaction

Frequency undefined:

apathy

cardiac arrythmia

dry mouth

growth suppression

hyperthermia

hypercholesterolemia

hyperphosphatemia

decreased libido

bone or muscle pain

nocturia

psychosis

somnolence

abdominal pain

constipation

dehydration

headache

hypercalcemia

hypermagnesemia

hypertension

metallic taste

pruritis

weakness

Black Box Warning

Contraindication / Caution

Contraindications

• Hypercalcemia, or elevated levels of calcium in the blood, can result from excessive vitamin D supplementation
• Hypersensitivity reactions, including skin rashes and itching, are also possible with calcitriol use

Caution

There are several cautions associated with the use of calcitriol, including:

• Monitoring of blood calcium levels: It can affect the levels of calcium and other minerals in the blood, so it’s essential to regularly monitor these levels to ensure they remain within a safe range
• Monitoring of kidney function: It is primarily metabolized by the kidneys, so it’s important to monitor kidney function in patients taking calcitriol, particularly in those with kidney disease or a history of kidney problems.
• Drug interactions: It can interact with other medications, including thiazide diuretics, glucocorticoids, and phenobarbital.
• Use in pregnancy and breastfeeding: It has not been studied in pregnant or breastfeeding women, so it should be used with caution in these populations.
• Vitamin D supplementation: It is a form of vitamin D, and excessive vitamin D supplementation can lead to hypercalcemia (elevated levels of calcium in the blood). It’s important to avoid taking additional vitamin D supplements while taking calcitriol unless directed by a healthcare provider.
• Bone health: It can affect bone metabolism, and long-term use may increase the risk of osteoporosis (bone weakening) and fractures. It’s essential to monitor bone health in patients taking calcitriol, especially in older adults and those with bone problems.
• Sun exposure: It can increase the skin’s sensitivity to the sun, so it’s important to limit sun exposure and use sun protection measures, such as wearing protective clothing and sunblock, while taking calcitriol.

Pregnancy / Lactation

Pregnancy consideration: C

Lactation: Excretion of the drug in human breast milk is known

Pregnancy category

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology

calcitriol (1,25-dihydroxy vitamin D3) is the active form of vitamin D and is involved in regulating calcium and phosphorus metabolism

Pharmacodynamics

The pharmacodynamics of calcitriol can be described as follows:

• Regulation of calcium and phosphorus metabolism: It regulates calcium and phosphorus levels in the blood. It acts on the small intestine to increase calcium and phosphorus absorption and on the bones to release calcium and phosphorus into the blood. Calcitriol also stimulates the kidneys to produce 1,25-dihydroxycalcidiol, which helps regulate calcium levels in the blood
• Bone metabolism: It regulates bone metabolism by promoting bone formation and decreasing bone resorption. It stimulates the differentiation and proliferation of osteoblasts (bone-forming cells) and suppresses the activity of osteoclasts (bone-resorbing cells)
• Immune system regulation: It has been shown to have immune-modulating effects, particularly in treating autoimmune diseases. It has been shown to suppress T-cell activation, reduce inflammation, and increase the production of natural killer cells
• Cell growth and differentiation: It has been shown to regulate cell growth and differentiation in various tissues, including the skin, prostate, and breast. It has been studied for its potential to prevent or treat certain types of cancer, but more research is needed in this area
• Vitamin D receptor activation: It binds to the vitamin D receptor (VDR), found in many tissues, including bone, intestine, and kidney. When calcitriol binds to the VDR, it forms a complex with the retinoid X receptor (RXR). This complex then binds to specific DNA sequences (vitamin D response elements) in target genes to regulate gene expression

Pharmacokinetics

Absorption

It is not absorbed orally, so it must be given by injection or topically. The onset of action: 2-6 hours after oral administration

Peak plasma time: 3-6 hours after oral administration

Duration: 3-5 days after oral or intravenous administration

Distribution

It is highly protein bound, with 99.9% of the drug bound to proteins in the blood

Metabolism

It is primarily metabolized by the kidneys and, to a lesser extent, by the liver. It is metabolized by 24-hydroxylation to calcitroic acid and stepwise hydroxylation to the vitamin D3 lactone ring

Elimination/Excretion

The half-life of calcitriol in the blood is about 5-8 hours in adults and 27 hours in children. It is primarily excreted in the feces (50%) and, to a lesser extent, in the urine (16%)

Adminstartion

Administration

Intravenous administration

Injection through a catheter at the end of hemodialysis is a standard method of administering calcitriol in patients with kidney disease. This method helps to restore normal calcium and phosphorus levels in the blood quickly

A single daily dose of calcitriol is usually sufficient, although the specific dose and frequency will depend on the patient’s needs and medical condition

Patient Information Leaflet

Patient information leaflet

Generic Name: calcitriol

Pronounced: [ kal-si-TRYE-ol ]

Why do we use calcitriol?

calcitriol is a form of vitamin D that is used for several medical purposes, including:

• Management of hypocalcemia: calcitriol is used to treat hypocalcemia, a condition in which the calcium level in the blood is too low. This can occur due to various medical conditions, including kidney disease, malabsorption, and certain medications.
• Treatment of osteoporosis: calcitriol is used to help prevent bone loss and fractures in patients with osteoporosis, a condition in which the bones become weak and brittle.
• Treatment of secondary hyperparathyroidism: calcitriol is used to treat secondary hyperparathyroidism. This condition occurs in patients with kidney disease and is characterized by elevated levels of parathyroid hormone in the blood.
• Treatment of rickets: calcitriol is used to treat rickets, a condition in which the bones become soft and bend easily. This can occur due to a deficiency of vitamin D or calcium