| Revision as of 22:13, 10 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit |
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{{Short description|Chemical compound}} |
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{{Use dmy dates|date=June 2024}} |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 413090405 |
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| verifiedrevid = 460037495 |
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| IUPAC_name = (''R'')-''N''--3-<br>propan-1-amine |
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| image = Cinacalcet Structural Formulae.png |
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| image = Cinacalcet Structural Formulae.png |
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| width = |
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| alt = |
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| image2 = Cinacalcet ball-and-stick.png |
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| width2 = |
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| alt2 = |
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| caption = |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| tradename = |
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| pronounce = |
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| tradename = Sensipar, Mimpara |
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| Drugs.com = {{drugs.com|monograph|cinacalcet}} |
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| Drugs.com = {{drugs.com|monograph|cinacalcet}} |
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| MedlinePlus = a605004 |
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| MedlinePlus = a605004 |
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| licence_EU = Mimpara |
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| licence_US = Cinacalcet |
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| DailyMedID = Cinacalcet |
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| pregnancy_AU = B3 |
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| pregnancy_AU = B3 |
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| pregnancy_AU_comment = <ref name="Drugs.com Pregnancy">{{cite web | title=Cinacalcet (Sensipar) Use During Pregnancy | website=Drugs.com | date=19 July 2019 | url=https://www.drugs.com/pregnancy/cinacalcet.html | access-date=24 December 2019}}</ref> |
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| pregnancy_US = C |
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| pregnancy_category= |
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| routes_of_administration = ] |
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| class = |
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| ATC_prefix = H05 |
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| ATC_suffix = BX01 |
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| ATC_supplemental = |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = <ref name="NPS Sensipar">{{cite web | title=Sensipar Tablets | website=NPS MedicineWise | date=1 May 2018 | url=https://www.nps.org.au/medicine-finder/sensipar-tablets | archive-url=https://web.archive.org/web/20191207201258/https://www.nps.org.au/medicine-finder/sensipar-tablets | archive-date=7 December 2019 | url-status=live | access-date=7 December 2019}}</ref> |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F--> |
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| legal_BR_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled--> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = POM |
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| legal_UK_comment = <ref name="Mimpara SmPC">{{cite web | title=Mimpara 30 mg Film-coated Tablets - Summary of Product Characteristics (SmPC) | website=electronic medicines compendium (emc) | date=8 July 2019 | url=https://www.medicines.org.uk/emc/product/5599/smpc | archive-url=https://web.archive.org/web/20191207194300/https://www.medicines.org.uk/emc/product/5599/smpc | archive-date=7 December 2019 | url-status=live | access-date=7 December 2019}}</ref> |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Sensipar FDA label" /> |
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| legal_EU = Rx-only |
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| legal_EU_comment = <ref name="Mimpara EPAR" /> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV--> |
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| legal_UN_comment = |
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| legal_status = Rx-only |
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| legal_status = Rx-only |
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| routes_of_administration = Oral |
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<!--Pharmacokinetic data--> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = 20 to 25%<br>Increases if taken with food |
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| bioavailability = 20 to 25%<br />increases if taken with food |
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| protein_bound = 93 to 97% |
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| protein_bound = 93 to 97% |
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| metabolism = ] (]-, ]- and ]-mediated) |
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| metabolism = ] (]-, ]- and ]-mediated) |
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| metabolites = |
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| onset = |
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| elimination_half-life = 30 to 40 hours |
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| elimination_half-life = 30 to 40 hours |
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| duration_of_action = |
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| excretion = ] (80%) and fecal (15%) |
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| excretion = ] (80%) and fecal (15%) |
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<!-- Identifiers --> |
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<!--Identifiers--> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 226256-56-0 |
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| CAS_number = 226256-56-0 |
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| CAS_supplemental = |
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| ATC_prefix = H05 |
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| ATC_suffix = BX01 |
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| ATC_supplemental = |
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| PubChem = 156419 |
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| PubChem = 156419 |
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| PubChemSubstance = 46506315 |
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| IUPHAR_ligand = 3308 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB01012 |
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| DrugBank = DB01012 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D03504 |
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| KEGG = D03504 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| KEGG2_Ref = {{keggcite|correct|kegg}} |
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| KEGG2 = D03505 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 48390 |
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| ChEBI = 48390 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = <!-- blanked - oldvalue: 1201284 --> |
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| ChEMBL = 1201284 |
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| C=22 | H=22 | F=3 | N=1 |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| molecular_weight = 357.412 g/mol |
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| synonyms = |
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| smiles = FC(F)(F)c1cccc(c1)CCCN(c3c2ccccc2ccc3)C |
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<!-- Chemical and physical data --> |
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| InChI = 1/C22H22F3N/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3/t16-/m1/s1 |
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| IUPAC_name = (''R'')-''N''--3-<br />propan-1-amine |
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| InChIKey = VDHAWDNDOKGFTD-MRXNPFEDBJ |
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| chemical_formula = |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| C=22 | H=22 | F=3 | N=1 |
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| StdInChI = 1S/C22H22F3N/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3/t16-/m1/s1 |
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| SMILES = CC(C1=CC=CC2=CC=CC=C21)NCCCC3=CC(=CC=C3)C(F)(F)F |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| Jmol = |
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| StdInChIKey = VDHAWDNDOKGFTD-MRXNPFEDSA-N |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C22H22F3N/c1-16(20-13-5-10-18-9-2-3-12-21(18)20)26-14-6-8-17-7-4-11-19(15-17)22(23,24)25/h2-5,7,9-13,15-16,26H,6,8,14H2,1H3/t16-/m1/s1 |
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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = VDHAWDNDOKGFTD-MRXNPFEDSA-N |
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| density = |
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| density_notes = |
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| melting_point = |
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| melting_high = |
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| boiling_notes = |
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| solubility = |
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| sol_units = |
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| specific_rotation = |
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}} |
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}} |
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<!-- Definition and medical use--> |
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'''Cinacalcet''' (]) is a ] that acts as a calcimimetic (i.e. it mimics the action of ] on ]s) by allosteric activation of the ] that is expressed in various human organ tissues. It is sold by ] under the trade name '''Sensipar''' in North America and Australia and as '''Mimpara''' in Europe. Cinacalcet is used to treat secondary ] (elevated ] levels), a consequence of having end-stage renal disease.<ref name="pmid16825031">{{cite journal | author = Torres PU | title = Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism caused by chronic kidney disease | journal = Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation | volume = 16 | issue = 3 | pages = 253–8 | year = 2006 | pmid = 16825031 | doi = 10.1053/j.jrn.2006.04.010 }}</ref>. Cinacalcet is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma.<ref name="Sensipar for patients with parathyroid carincoma">{{cite news|url=http://www.sensipar.com/Sensipar_for_HPC.html|title=Sensipar for Parathyroid Carcinoma|date=2009|publisher=Amgen|accessdate=25 September 2009}}</ref> |
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'''Cinacalcet''', sold under the brand name '''Sensipar''' among others, is a medication used to treat ], ] and ].<ref name="Sensipar FDA label" /><ref name="FDA Pediatric" /><ref name="Mimpara EPAR">{{cite web | title=Mimpara EPAR | website=] (EMA) | date=22 August 2019 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/mimpara | access-date=23 December 2019}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Cinacalcet acts as a ] (i.e., it mimics the action of ] on ]s) by ] activation of the ] that is expressed in various human organ tissues. |
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==Clinical uses== |
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Cinacalcet is indicated for the treatment of ] in patients with chronic kidney disease on dialysis and hypercalcemia in patients with ]. |
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The most common side effects include ] and ].<ref name="Mimpara EPAR" /> |
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==Synthesis== |
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] |
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Cinacalcet was approved in the United States in March 2004,<ref name="Sensipar FDA label">{{cite web | title=Sensipar- cinacalcet hydrochloride tablet, coated | website=] | date=5 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=45028573-13c4-4c8b-ae62-6c75bba97c81 | access-date=24 December 2019}}</ref><ref name="FDA Approval">{{cite web | title=Drug Approval Package: Sensipar (Cinacalcet HCI) NDA #021688 | website=U.S. ] (FDA) | date=7 December 2019 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-688_Sensipar.cfm | archive-url=https://web.archive.org/web/20191207192407/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-688_Sensipar.cfm | archive-date=7 December 2019 | url-status=live | access-date=7 December 2019}} {{PD-notice}}</ref><ref>{{cite web | title=Sensipar | website=U.S. ] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021688 | archive-url=https://web.archive.org/web/20191207195449/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021688 | archive-date=7 December 2019 | url-status=live | access-date=7 December 2019}} {{PD-notice}}</ref> and in the European Union in October 2004.<ref name="Mimpara EPAR" /><ref name="Mimpara SmPC" /> It was the first allosteric G protein-coupled receptor modulator to enter the pharmaceutical market.<ref name=pmid17266540>{{cite journal |vauthors=Bräuner-Osborne H, Wellendorph P, Jensen AA |title=Structure, pharmacology and therapeutic prospects of family C G-protein coupled receptors |journal=Current Drug Targets |volume=8 |issue=1 |pages=169–84 |year=2007 |pmid=17266540 |doi=10.2174/138945007779315614}}</ref> In 2013, cinacalcet was the 76th most prescribed medicine in the United States.<ref>{{cite web | title=U.S. Pharmaceutical Statistics | website=Drugs.com | date=February 2014 | url=https://www.drugs.com/stats/top100/sales | access-date=13 July 2020}}</ref><ref>{{cite web | title=Sales Statistics for Sensipar Prescriptions | website=Drugs.com | date=2 September 2020 | url=https://www.drugs.com/stats/sensipar | access-date=8 September 2020}}</ref> |
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==Medical uses== |
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In the United States, cinacalcet is indicated for the treatment of ] in people with chronic kidney disease on dialysis and ] in people with parathyroid carcinoma.<ref name="Sensipar FDA label" /><ref name="jones and bartlett">{{cite book|title=2014 Nurses Drug Handbook|date=2014|publisher=Jones & Bartlett Learning|location=Burlington, MA|isbn=978-1-284-03115-7|pages=|edition=13th|url=https://archive.org/details/2014nursesdrugha0000unse/page/245}}</ref> Cinacalcet can also be used to treat severe hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo ].<ref name="Sensipar FDA label" /><ref name="Cinacalet: MedlinePlus Drug Information">{{cite web|publisher=U.S. National Library of Medicine|title=Cinacalcet|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a605004.html|accessdate=29 October 2014}}</ref> |
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In the European Union cinacalcet is indicated for: |
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* the treatment of secondary hyperparathyroidism (HPT) in adults with end stage renal disease (ESRD) on maintenance dialysis therapy.<ref name="Mimpara EPAR" /> |
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* the treatment of secondary hyperparathyroidism (HPT) in children aged three years and older with end stage renal disease (ESRD) on maintenance dialysis therapy in whom secondary HPT is not adequately controlled with standard of care therapy.<ref name="Mimpara EPAR" /> |
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* part of a therapeutic regimen including phosphate binders and/or vitamin D sterols, as appropriate.<ref name="Mimpara EPAR" /> |
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* the treatment of parathyroid carcinoma and primary hyperparathyroidism in adults.<ref name="Mimpara EPAR" /> |
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* the reduction of hypercalcaemia in adults with: |
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** parathyroid carcinoma;<ref name="Mimpara EPAR" /> |
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** primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels (as defined by relevant treatment guidelines), but in whom parathyroidectomy is not clinically appropriate or is contraindicated.<ref name="Mimpara EPAR" /> |
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===Pregnancy and lactation=== |
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Cinacalcet has pregnancy category C in the US, meaning that adequate and well-controlled studies involving cinacalcet in pregnant women have not been done.<ref name="Sensipar FDA label"/><ref name="Drugs.com Pregnancy" /> |
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Studies have not been done in lactating women; therefore, it is not known whether cinacalcet is excreted into human milk.<ref name="Sensipar FDA label"/><ref name="Drugs.com Pregnancy" /> |
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==Contraindications== |
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] (decreased calcium levels) is a contraindication to the use of cinacalcet. Those who have serum calcium levels less than 7.5 mg/dL should not be started on cinacalcet. Hypocalcemia symptoms include ]s, ]s, muscle cramping, ], and ]s. Cinacalcet should not be administered until serum calcium levels are above 8.0 mg/dL and/or hypocalcemia symptoms are resolved.<ref name="Sensipar FDA label"/> Cinacalcet is not approved for pediatric use in the United States.<ref name="FDA Pediatric">{{cite web | title=FDA Drug Safety Communication: Pediatric clinical studies of Sensipar (cinacalcet hydrochloride) suspended after report of death | website=U.S. ] (FDA) | date=15 January 2016 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-pediatric-clinical-studies-sensipar-cinacalcet-hydrochloride-suspended | archive-url=https://web.archive.org/web/20191224070532/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-pediatric-clinical-studies-sensipar-cinacalcet-hydrochloride-suspended | archive-date=24 December 2019 | url-status=live | access-date=23 December 2019}} {{PD-notice}}</ref><ref name="Sensipar FDA label"/><ref name="Mimpara EPAR" /> |
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==Adverse effects== |
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Common side effects of cinacalcet include upset stomach, vomiting, diarrhea, dizziness, nausea, weakness, and chest pain.<ref name ="Cinacalet: MedlinePlus Drug Information" /> |
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Clinical trials conducted in the United States by Amgen to determine whether the drug is safe in children were halted by the U.S. ] (FDA) in February 2013, following the death of a 14-year-old participant.<ref name="FDA Pediatric" /><ref>{{cite news|last=Edney|first=Anna|title=Amgen Pediatric Trials of Sensipar Halted by FDA After Death|url=http://www.businessweek.com/news/2013-02-26/amgen-pediatric-trials-of-sensipar-halted-by-fda-after-death|newspaper=]|date=26 February 2013|access-date=26 February 2013|archive-url=https://web.archive.org/web/20130302020425/http://www.businessweek.com/news/2013-02-26/amgen-pediatric-trials-of-sensipar-halted-by-fda-after-death|archive-date=2 March 2013|url-status=dead}}</ref> |
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==Overdose== |
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Serious side effects, including overdose symptoms, of cinacalcet include:<ref name ="Cinacalet: MedlinePlus Drug Information" /> |
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* burning |
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* ] |
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* unusual feelings of the ], ], ], or ] |
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* muscle aches or ] |
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* sudden tightening of muscles in ], feet, ], or ] |
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* ] |
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==Interactions== |
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Cinacalcet is a strong inhibitor of the liver enzyme ] and is partially metabolized by ] and ]. Dose adjustments may be necessary if people are treated with CYP3A4 and CYP1A2 inhibitors and medications that are metabolized by CYP2D6.<ref name="Sensipar FDA label"/><ref name="Mimpara SmPC" /> |
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==Pharmacology== |
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B.C. Van Wagenen, S.T. Moe, M.F. Balandrin, E.G. DelMar, E.F. Nemeth, {{US Patent|6,211,244}} (2001). |
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===Mechanism of action=== |
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Cinacalcet is a drug that acts as a ]<ref name="Sensipar FDA label"/><ref name="Mimpara EPAR" /> (i.e. it mimics the action of calcium on tissues) by ] of the ] that is expressed in various human organ tissues. The calcium-sensing receptors on the surface of the chief cell of the ] is the principal negative regulator of parathyroid hormone secretion.<ref>{{Cite web | url=http://www.drugbank.ca/drugs/DB01012 | title=Cinacalcet}}</ref> Cinacalcet increases the sensitivity of calcium receptors on parathyroid cells to reduce parathyroid hormone (PTH) levels and thus decrease serum calcium levels.<ref name="jones and bartlett" /> |
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==References== |
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==References== |
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{{Reflist|2}} |
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{{reflist}} |
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==External links== |
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* run by ] |
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* |
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* - Medlineplus.org |
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* - Drug Digest. |
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{{Calcium homeostasis}} |
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{{Calcium homeostasis}} |
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{{Portal bar | Medicine}} |
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] |
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{{Authority control}} |
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