Paricalcitol

Paricalcitol
Names
Trade namesZemplar
Other names19-nor-1,25-(OH)2-vitamin D2
IUPAC name
  • (1R,3R,7E,17β)-17-[(1R,2E,4S)-5-hydroxy-1,4,5-trimethylhex-2-en-1-yl]-9,10-secoestra-5,7-diene-1,3-diol
Clinical data
Drug classVitamin D[1]
Main usesHyperparathyroidism due to chronic kidney disease[2]
Side effectsDiarrhea, allergic reactions, nausea, headache, trouble sleeping[1]
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth, intravenous
    External links
    AHFS/Drugs.comMonograph
    US NLMParicalcitol
    MedlinePlusa682335
    Legal
    Legal status
    Pharmacokinetics
    Bioavailability72%[3]
    Protein binding99.8%[3]
    MetabolismHepatic[3]
    Elimination half-life14-20 hours[3]
    ExcretionFaeces (74%), urine (16%)[3]
    Chemical and physical data
    FormulaC27H44O3
    Molar mass416.646 g·mol−1
    InChI
    • InChI=1S/C27H44O3/c1-18(8-9-19(2)26(3,4)30)24-12-13-25-21(7-6-14-27(24,25)5)11-10-20-15-22(28)17-23(29)16-20/h8-11,18-19,22-25,28-30H,6-7,12-17H2,1-5H3/b9-8+,21-11+/t18-,19+,22-,23-,24-,25+,27-/m1/s1 checkY
    • Key:BPKAHTKRCLCHEA-UBFJEZKGSA-N checkY

    Paricalcitol, sold under the trade name Zemplar, is a medication used to prevent and treat hyperparathyroidism due to chronic kidney disease.[2] It is taken by mouth.[2]

    Common side effects include diarrhea, allergic reactions, nausea, headache, and trouble sleeping.[1] Other side effects may include high calcium and aluminum toxicity.[1] There are concerns with use in pregancy.[2] It is a form of calcitriol, an active type of vitamin D.[1]

    Paricalcitol was patented in 1989 and approved for medical use in 1998.[4] It is available as a generic medication.[1] In the United Kingdom 28 doses of 1 microgram costs the NHS about £70 as of 2021.[2] This amount in the United States is about 100 USD.[5]

    Medical uses

    Its primary use in medicine is in the treatment of secondary hyperparathyroidism associated with chronic kidney disease.[6] However current evidence is not sufficient to demonstrate an advantage of paricalcitol over non-selective vitamin D derivatives for this indication.[7]

    Dosage

    The dose used is based on the intact parathyroid hormone levels.[1]

    Side effects

    By frequency:[3][6][8][9]
    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:[9]

    whereas cautions include:[3]

    • 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:[3][9]

    • Ketoconazole, as it may interfere with paricalcitol's metabolism in the liver.
    • Digitoxin, hypercalcaemia due to any cause can exacerbate the toxicity of digitoxin.
    • Thiazide diuretics or calcium supplements as hypercalcaemia may be induced by this combination
    • Magnesium-containing products such as antacids may increase the risk of hypermagnesemia.
    • Aluminium-containing products such as antacids may increase the risk of aluminium toxicity.
    • Drugs that interfere with the absorption of fat-soluble vitamins, such as cholestyramine may interfere with the absorption of paricalcitol.

    Overdose

    Electrolyte abnormalities (e.g. hypercalcaemia and hyperphosphataemia) are common overdose symptoms.[9] 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.[9] As it is so heavily bound to plasma proteins haemodialysis is unlikely to be helpful in cases of overdose.[9]

    Early symptoms of overdose can include:[9]

    • 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.[9]

    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.[3]

    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).[10]

    Chemistry

    It may also be known as (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.

    References

    1. 1 2 3 4 5 6 7 "Paricalcitol Monograph for Professionals". Drugs.com. Archived from the original on 27 February 2021. Retrieved 26 October 2021.
    2. 1 2 3 4 5 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1137. ISBN 978-0857114105.
    3. 1 2 3 4 5 6 7 8 9 "Zemplar (paricalcitol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 2 February 2014. Retrieved 26 January 2014.
    4. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 452. ISBN 9783527607495. Archived from the original on 2021-01-22. Retrieved 2021-03-18.
    5. ↑ "Paricalcitol Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 10 August 2020. Retrieved 26 October 2021.
    6. 1 2 Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
    7. ↑ Cai P, Tang X, Qin W, Ji L, Li Z (April 2016). "Comparison between paricalcitol and active non-selective vitamin D receptor activator for secondary hyperparathyroidism in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials". International Urology and Nephrology. 48 (4): 571–84. doi:10.1007/s11255-015-1195-6. PMID 26748501. S2CID 10633197.
    8. ↑ "PARICALCITOL capsule, liquid filled [Teva Pharmaceuticals USA Inc]" (PDF). DailyMed. Teva Pharmaceuticals USA Inc. September 2013. Archived from the original on 2 February 2014. Retrieved 26 January 2014.
    9. 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. Archived from the original on 1 February 2014. Retrieved 26 January 2014.
    10. ↑ Rxlist: Zemplar Archived 2021-01-19 at the Wayback Machine
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