Dekalpar^® (Capsules) Instructions for Use

Marketing Authorization Holder

R-Pharm JSC (Russia)

Manufactured By

R-OPRA LLC (Russia)

ATC Code

H05BX02 (Paricalcitol)

Active Substance

Paricalcitol (Rec.INN registered by WHO)

Dosage Form

Dekalpar®

Capsules 1 mcg

Dosage Form, Packaging, and Composition

Capsules

10 pcs. – blister packs (3 pcs.) – cardboard packs (30 pcs.) – By prescription

Clinical-Pharmacological Group

Drug regulating calcium and phosphorus metabolism

Pharmacotherapeutic Group

Drugs regulating calcium metabolism; antiparathyroid drugs, other antiparathyroid drugs

Pharmacological Action

A drug that regulates calcium and phosphorus metabolism, a synthetic analogue of calcitriol (biologically active vitamin D). Paricalcitol exerts its biological effect by interacting with vitamin D receptors, leading to selective activation of the response mediated by this vitamin. Vitamin D and Paricalcitol reduce the level of parathyroid hormone by inhibiting its synthesis and secretion. In the early stages of chronic kidney disease, a decrease in calcitriol levels is observed.

Secondary hyperparathyroidism is characterized by an increase in parathyroid hormone (PTH) levels, which is associated with inadequate levels of active vitamin D. This vitamin is synthesized in the skin and enters the body with food. Vitamin D is sequentially hydroxylated in the liver and kidneys and converted into an active form that interacts with vitamin D receptors.

Calcitriol [1,25(OH)2 D3] is an endogenous hormone that activates vitamin D receptors in the parathyroid glands, intestines, kidneys, and bone tissue (thereby maintaining parathyroid function and calcium and phosphorus homeostasis), as well as in many other tissues, including the prostate, endothelium, and immune cells. Receptor activation is necessary for normal bone formation. In kidney disease, the activation of vitamin D is suppressed, leading to increased PTH levels, the development of secondary hyperparathyroidism, and disruption of calcium and phosphorus homeostasis.

The decrease in calcitriol levels and the increase in PTH activity, which often precede changes in plasma calcium and phosphorus levels, cause changes in the rate of bone turnover and can lead to the development of renal osteodystrophy. In patients with chronic kidney disease, a decrease in PTH levels has a beneficial effect on bone alkaline phosphatase activity, bone metabolic processes, and bone tissue fibrosis. Therapy with active vitamin D not only reduces PTH levels and improves bone metabolic processes but also helps prevent or eliminate other consequences of vitamin D deficiency.

Pharmacokinetics

After IV bolus administration of paricalcitol in doses from 0.04 mcg/kg to 0.24 mcg/kg, the drug concentration decreases rapidly within 2 hours, subsequently the drug concentration decreases linearly, with a mean T_1/2 of about 15 hours. With repeated use of paricalcitol, no signs of accumulation were noted.

Plasma protein binding is high – more than 99%. In healthy individuals, the V_d at steady state is about 23.8 L. In patients with end-stage chronic kidney disease receiving hemodialysis or peritoneal dialysis, the V_d of paricalcitol at a dose of 0.24 mcg/kg averages 31-35 L.

Several metabolites of paricalcitol are detected in urine and feces. Unchanged Paricalcitol was not found in urine. Paricalcitol is metabolized by hepatic and extrahepatic enzymes, including mitochondrial CYP24, as well as CYP3A4 and UGT1A4. Identified metabolites include products of 24(R)-hydroxylation (present in plasma in low concentrations), as well as 24,26- and 24,28-dihydroxylation and direct glucuronidation. Paricalcitol does not have an inhibitory effect on CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A at concentrations up to 50 nM (21 ng/mL). At similar concentrations of paricalcitol, the activity of CYP2B6, CYP2C9, and CYP3A4 increases by less than 2 times.

Paricalcitol is eliminated by biliary excretion. In healthy individuals, approximately 63% of the active substance is excreted through the intestine and 19% by the kidneys. When used in doses from 0.04 to 0.16 mcg/kg, the T_1/2 of paricalcitol in healthy volunteers averages 5-7 hours. In patients with end-stage chronic kidney disease, a decrease in clearance and an increase in T_1/2 were found compared to healthy individuals.

Indications

Prevention and treatment of secondary hyperparathyroidism developing in chronic renal failure (end-stage chronic kidney disease).

ICD codes

Dosage Regimen

Determine the initial dose based on the patient’s body weight or the baseline intact parathyroid hormone (iPTH) level.

For weight-based dosing, administer an initial dose of 0.04 mcg/kg to 0.1 mcg/kg (2.8-7 mcg) as a bolus injection no more than every other day during dialysis.

For iPTH-based dosing, use an initial dose of 0.24 mcg for iPTH levels less than 500 pg/mL, 0.36 mcg for levels 500-1000 pg/mL, and 0.48 mcg for levels greater than 1000 pg/mL.

Do not exceed the maximum single dose of 0.48 mcg.

Adjust the dose based on the iPTH response, targeting a reduction of 30% to 60% from baseline.

Increase the dose by 2-4 mcg at 2-4 week intervals if the iPTH level is not adequately suppressed.

Withhold the dose if the iPTH level falls below 100 pg/mL.

Resume therapy at a reduced dose when the iPTH level rises above 150 pg/mL.

Monitor serum calcium and phosphorus levels at least once monthly during dose titration.

Monitor iPTH levels every 3 months once a stable dose is established.

Adverse Reactions

Cardiovascular system frequently – tachycardia.

Digestive system dry mouth, gastrointestinal bleeding, nausea, vomiting, taste perversion.

CNS dizziness, headache.

Respiratory system pneumonia.

Allergic reactions rarely – urticaria, angioedema, laryngeal edema.

Dermatological reactions rash, itching.

Other edema, chills, malaise, fever, influenza, sepsis.

Contraindications

Hypervitaminosis D; concomitant use with phosphates or vitamin D derivatives; hypercalcemia; children under 18 years of age; lactation period (breastfeeding); hypersensitivity to paricalcitol.

Use in Pregnancy and Lactation

Adequate and strictly controlled clinical studies on the safety of the drug during pregnancy have not been conducted. Paricalcitol can be used during pregnancy only if the potential benefit to the mother outweighs the possible risk to the fetus.

It is not known whether Paricalcitol is excreted in human breast milk. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Pediatric Use

Contraindicated in children under 18 years of age (clinical studies have not been conducted).

Geriatric Use

No differences in the efficacy or safety of the drug were identified in patients under 65 years of age and over 65 years of age.

Special Precautions

Should be used with caution concomitantly with cardiac glycosides.

When titrating the dose of paricalcitol, more frequent laboratory tests may be required. When the dose is selected, serum calcium and phosphorus levels should be measured at least once a month. Serum or plasma PTH levels are recommended to be monitored every 3 months. For reliable analysis of biologically active PTH in patients with stage 5 chronic kidney disease, it is recommended to use a second or subsequent generation method.

No differences in the efficacy or safety of the drug were identified in patients under 65 years of age and over 65 years of age.

Experience with the use of paricalcitol in children and adolescents under 18 years of age is limited.

Drug Interactions

In a study of the interaction between ketoconazole and paricalcitol upon oral administration, it was shown that ketoconazole causes an approximately 2-fold increase in the AUC of paricalcitol. Paricalcitol is partially metabolized by the CYP3A isoenzyme, and ketoconazole is a potent inhibitor of this isoenzyme, so caution is required when using paricalcitol concomitantly with ketoconazole and other potent inhibitors of the CYP3A isoenzyme.

Hypercalcemia of any origin enhances the intoxication with cardiac glycosides (caution is required when used concomitantly).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.