Intravenous Secondary hyperparathyroidism in patients with chronic kidney disease on dialysis
Adult: For prevention and treatment of cases associated with stage 5 CKD on dialysis: Initial dose in mcg is calculated based on baseline intact parathyroid hormone (iPTH) levels in picograms per mL (pg/mL) divided by 80. Doses are administered no more frequently than every other day via IV bolus inj through the haemodialysis access at any time during dialysis. Max initial dose: 40 mcg. Individualise and titrate the dose at 2-4 weeks intervals based on iPTH relative to baseline and serum Ca and phosphorus levels. If iPTH is the same, increased, or decreased by <30%: Increase initial dose by 2-4 mcg. If iPTH decreased by ≥30% and ≤60%: Maintain initial dose. If iPTH is <150 pg/mL or decreased by >60%: Decrease initial dose by 2-4 mcg. Dose reduction or dosing interruption may be required according to iPTH and serum Ca and phosphorus levels. Dosage recommendations may vary among individual products or between countries (refer to detailed product or local guidelines).
Oral Secondary hyperparathyroidism in patients with chronic kidney disease on dialysis
Adult: For prevention and treatment of cases associated with stage 5 CKD on haemodialysis or peritoneal dialysis: Initial dose in mcg is calculated based on baseline intact parathyroid hormone (iPTH) levels in picograms per mL (pg/mL) divided by 60 or 80. Doses are administered 3 times weekly, no more frequently than every other day. Max initial dose: 32 mcg. Individualise and titrate the dose based on iPTH and serum Ca and phosphorus levels. Titration dose in mcg is calculated based on the most recent iPTH level in pg/mL divided by 60 or 80. Dose reduction or dosing interruption may be required according to iPTH and serum Ca and phosphorus levels. Dosage formula recommendations may vary among individual products or between countries (refer to detailed product or local guidelines).
Oral Secondary hyperparathyroidism in chronic kidney disease
Adult: For prevention and treatment of cases associated with stages 3 and 4 CKD: Initial dose is based on baseline intact parathyroid hormone (iPTH) levels in picograms per mL (pg/mL). iPTH ≤500 pg/mL: 1 mcg once daily or 2 mcg 3 times weekly (no more frequently than every other day); iPTH >500 pg/mL: 2 mcg once daily or 4 mcg 3 times weekly (no more frequently than every other day). Individualise and titrate the dose at 2-4 weeks intervals based on iPTH relative to baseline and serum Ca and phosphorus levels. If iPTH is the same, increased, or decreased by <30%: Increase initial dose by 1 mcg (if taken daily) or 2 mcg (if taken 3 times weekly, no more frequently than every other day). If iPTH decreased by ≥30% and ≤60%: Maintain initial dose. If iPTH is <60 pg/mL or decreased by >60%: Decrease initial dose by 1 mcg (if taken daily) or 2 mcg (if taken 3 times weekly, no more frequently than every other day). Further dose reduction or dosing interruption may be required according to iPTH and serum Ca and phosphorus levels (refer to detailed product guidelines). Child: For prevention and treatment of cases associated with stages 3 and 4 CKD: ≥10-16 years Initially, 1 mcg 3 times weekly, no more frequently than every other day. Individualise and titrate the dose based on iPTH and serum Ca and phosphorus levels to maintain an iPTH level within the target range. Dose may be increased in 1 mcg increments at intervals of every 4 weeks, maintaining the 3 times weekly regimen. Dose reduction, dosing interruption or discontinuation may be required according to iPTH and serum Ca and phosphorus levels (refer to detailed product guidelines).
Special Patient Group
Patient who starts or discontinues concomitant therapy with strong CYP3A inhibitors (e.g. ketoconazole, ritonavir, clarithromycin): Dose adjustment may be needed.
Administration
May be taken with or without food.
Contraindications
Hypercalcaemia, vitamin D toxicity.
Special Precautions
Patient who starts or discontinues concomitant therapy with strong CYP3A inhibitors; those receiving digitalis therapy. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Progressive or acute hypercalcaemia which may increase the risk of cardiac arrhythmias and seizures; chronic hypercalcaemia which may lead to generalised vascular and soft tissue calcification; over suppression of PTH, hypercalciuria, hyperphosphataemia, adynamic bone disease. Cardiac disorders: Palpitations, chest pain. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, abdominal pain or discomfort, dysgeusia, dry mouth, GERD. General disorders and administration site conditions: Chills, malaise, asthenia, pyrexia. Infections and infestations: Viral, fungal or bacterial infection. Immune system disorders: Hypersensitivity reactions, angioedema. Metabolism and nutrition disorders: Hyperkalaemia, hypoparathyroidism, oedema, dehydration, decreased appetite. Musculoskeletal and connective tissue disorders: Muscle spasm, myalgia, back pain, arthritis. Nervous system disorders: Headache, dizziness. Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, cough, pneumonia, oropharyngeal pain; rhinitis (oral in children). Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus, acne. Vascular disorders: Hypertension, hypotension.
Assess for signs and symptoms of vitamin D intoxication and hypercalcaemia. Closely monitor iPTH and serum Ca and phosphorus levels when concomitantly used with strong CYP3A inhibitors. Oral: Closely monitor serum or plasma iPTH and serum Ca and phosphorus at baseline, every 2 weeks for the 1st 3 months or after dose adjustment, then monthly for 3 months, and every 3 months thereafter. IV: Closely monitor serum Ca twice weekly during initiation, then at least monthly once the dose is established. Obtain serum or plasma iPTH every 2-4 weeks during initiation or after dose adjustment.
Overdosage
Symptoms: Hypercalcaemia (manifested as headache, somnolence, weakness, nausea, vomiting, dry mouth, metallic taste, constipation, muscle or bone pain, anorexia, weight loss, hypertension, and cardiac arrhythmia), hypercalciuria, hyperphosphataemia, over suppression of PTH. Management: Supportive treatment. If ingestion is recent, may induce emesis or perform gastric lavage. For clinically significant hypercalcaemia, reduce or interrupt the paricalcitol dose, discontinue Ca supplements, establish a low Ca diet, and mobilise the patient. Frequently monitor fluid and electrolyte imbalance (especially serum Ca levels), rate of urinary Ca excretion, and ECG abnormalities (particularly in patients on digitalis therapy).
Drug Interactions
Increased exposure with strong CYP3A inhibitors (e.g. ketoconazole, itraconazole, ritonavir, telaprevir, nefazodone, clarithromycin). Paricalcitol may cause hypercalcaemia which may potentiate digitalis toxicity. Increased risk of hypercalcaemia with high doses of Ca-containing agents, phosphate-containing supplements, other vitamin D compounds, and thiazide diuretics. May result in hypermagnesaemia with Mg-containing preparations (e.g. antacids). May increase the serum concentrations of Al and cause bone toxicity with Al-containing preparations (e.g. phosphate binders, antacids). Intestinal absorption may be impaired by bile acid sequestrants (e.g. colestyramine) and mineral oil.
Food Interaction
Increased exposure with grapefruit juice.
Lab Interference
May increase the serum creatinine which may decrease the eGFR (without changing the true GFR) in predialysis patients.
Action
Description: Mechanism of Action: Paricalcitol, a synthetic vitamin D analogue of calcitriol, is a selective vitamin D receptor (VDR) activator. It decreases PTH levels and improves Ca and phosphate homeostasis by binding to and activating the VDR in the kidneys, parathyroid gland, intestines and bones. Additionally, it can directly act on the bone cells to maintain bone volume and improve mineralisation surfaces. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: Oral: 72-86% (healthy individuals). Time to peak plasma concentration: 3 hours. Distribution: Volume of distribution: Oral: 34 L (healthy individuals); 44-46 L (stage 3 and 4 CKD); 38-49 L (stage 5 CKD). IV: 24 L (healthy individuals); 31-35 L (stage 5 CKD). Plasma protein binding: >99%. Metabolism: Extensively metabolised via hydroxylation and glucuronidation by hepatic and nonhepatic enzymes, including mitochondrial CYP24, CYP3A4 and UGT1A4. Excretion: Healthy individuals: Via faeces (oral: 70%; IV: 63%); urine (oral: 18%; IV: 19%). Elimination half-life: Oral: 4-6 hours (healthy individuals); 17-20 hours (stage 3 and 4 CKD); 14-18 hours (stage 5 CKD on haemodialysis or peritoneal dialysis). IV: 5-7 hours (healthy individuals); 14-15 hours (stage 5 CKD on haemodialysis or peritoneal dialysis).
Chemical Structure
Paricalcitol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5281104, Paricalcitol. https://pubchem.ncbi.nlm.nih.gov/compound/Paricalcitol. Accessed Nov. 21, 2023.
Storage
Soft gelatin cap: Store at 25°C. Solution for inj: Store between 15-30°C.
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