Paricalcitol

Paricalcitol
Clinical data
Trade names Zemplar
Synonyms (1R,3S)-5-[2-[(1R,3aR,7aS)-1-[(2R,5S)-6-hydroxy-5,6-dimethyl-3E-hepten-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-cyclohexane-1,3-diol
AHFS/Drugs.com Monograph
MedlinePlus a682335
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    administration    		 Oral, Intravenous
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 72%[1]
    Protein binding 99.8%[1]
    Metabolism Hepatic[1]
    Elimination half-life 14-20 hours[1]
    Excretion Faeces (74%), urine (16%)[1]
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    ECHA InfoCard 100.184.862 Edit this at Wikidata
    Chemical and physical data
    Formula C27H44O3
    Molar mass 416.636 g/mol
     ☒N☑Y (what is this?)  (verify)

    Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. Marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid hormone) associated with chronic renal failure. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol).

    Medical uses

    Its primary use in medicine is in the treatment of secondary hyperparathyroidism associated with chronic kidney disease.[2] In three placebo-controlled studies, chronic renal failure patients treated with paricalcitol achieved a mean parathyroid hormone (PTH) reduction of 30% in six weeks. Additionally there was no difference in incidence of hypercalcemia or hyperphosphatemia when compared to placebo.[3] A double-blind randomised study with 263 dialysis patients showed a significant advantage over calcitriol (also known as activated vitamin D3; a similar molecule to 1,25-dihydroxyergocalciferol, adding a methyl group on C24 and lacking a double-bond in the C22 position). After 18 weeks, all patients in the paricalcitol group had reached the target parathormone level of 100 to 300 pg/ml, versus none in the calcitriol group.[4] Combination therapy with paricalcitol and trandolapril has been found to reduce fibrosis in obstructive uropathy.[5] Forty-eight-week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in 227 patients with chronic kidney disease.[6]

    Adverse effects

    Adverse effects by frequency:[1][2][7][8]
    Very common (>10% frequency):

    • Nausea

    Common (1-10% frequency):

    Uncommon (0.1-1% frequency):

    ‡ These are adverse effects only seen in patients with grade 3 or 4 chronic kidney disease. † These are adverse effects only seen in patients with grade 5 chronic kidney disease.

    Contraindications

    Contraindications include:[8]

    whereas cautions include:[1]

    • Impaired liver function
    • It is also advised that physicians regularly monitor their patients' calcium and phosphorus levels.

    Interactions

    Drugs that may interact with paricalcitol include:[1][8]

    Overdose

    Electrolyte abnormalities (e.g. hypercalcaemia and hyperphosphataemia) are common overdose symptoms.[8] Treatment is mostly supportive, with particular attention being paid to correcting electrolyte anomalies and reducing intake of calcium in both the form of supplementation and diet.[8] As it is so heavily bound to plasma proteins haemodialysis is unlikely to be helpful in cases of overdose.[8]

    Early symptoms of overdose can include:[8]

    • Weakness
    • Headache
    • Somnolence
    • Nausea
    • Vomiting
    • Dry mouth
    • Constipation
    • Muscle pain
    • Bone pain
    • Metallic taste in the mouth.

    It is worth noting, however, that may of these symptoms are also indicative of kidney failure and hence may be masked by the patient's condition.[8]

    Late symptoms of overdose include:

    • Loss of appetite
    • Weight loss
    • Conjunctivitis (calcific)
    • Pancreatitis
    • Photophobia
    • Rhinorrhoea
    • Pruritus
    • Hyperthermia
    • Decreased libido
    • Elevated BUN
    • Hypercholesterolaemia
    • Elevated AST and ALT
    • Ectopic calcification
    • Hypertension
    • Cardiac arrhythmias
    • Somnolence
    • Death
    • Psychosis (rare)

    Mechanism of action

    3D structure of paricalcitol

    Like 1,25-dihydroxyergocalciferol, paricalcitol acts as an agonist at the vitamin D receptor and thereby lowers parathyroid hormone levels in the blood.[1]

    Pharmacokinetics

    The plasma concentration of paricalcitol decreases rapidly and log-linearly within two hours after initial intravenous administration. Therefore, it is not expected to accumulate with multiple dosing, since paricalcitol is usually given no more frequently than every other day (3 times per week).[9][10]

    References

    1. 1 2 3 4 5 6 7 8 9 "Zemplar (paricalcitol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 26 January 2014.
    2. 1 2 Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
    3. ↑ "Zemplar: Drug Information"
    4. ↑ Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2005/2006 (in German).
    5. ↑ Tan, X; He, W; Liu, Y (2009). "Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in obstructive nephropathy". Kidney International. 76 (12): 1248–57. doi:10.1038/ki.2009.346. PMID 19759524.
    6. ↑ Thadhani, R; Appelbaum, E; Pritchett, Y; Chang, Y; Wenger, J; Tamez, H; Bhan, I; Agarwal, R; et al. (2012). "Vitamin D Therapy and Cardiac Structure and Function in Patients With Chronic Kidney Disease - The PRIMO Randomized Controlled Trial". JAMA. 307 (7): 674–684. doi:10.1001/jama.2012.120. PMID 22337679.
    7. ↑ "PARICALCITOL capsule, liquid filled [Teva Pharmaceuticals USA Inc]" (PDF). DailyMed. Teva Pharmaceuticals USA Inc. September 2013. Retrieved 26 January 2014.
    8. 1 2 3 4 5 6 7 8 "Zemplar Soft Capsules 1 mcg - Summary of Product Characteristics". electronic Medicines Compendium. AbbVie Limited. 15 April 2013. Retrieved 26 January 2014.
    9. ↑ Rxlist: Zemplar
    10. ↑ Zemplar (paricalcitol) [prescribing information]. North Chicago, IL: AbbVie Inc. October 1, 2015. |access-date= requires |url= (help)
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