| Revision as of 12:34, 10 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 447577475 of page Tetracosactide for the Chem/Drugbox validation project (updated: 'StdInChI', 'StdInChIKey'). |
Latest revision as of 22:23, 11 November 2024 edit Cbare (talk | contribs)104 editsm Add DrugBank accession |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{cs1 config|name-list-style=vanc}} |
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<includeonly></includeonly>{{About|Adrenocorticotropic hormone as a medication and diagnostic agent|as a natural hormone|Adrenocorticotropic hormone}} |
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{{Drugbox |
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{{Drugbox |
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| IUPAC_name = |
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| Watchedfields = |
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| verifiedrevid = |
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| drug_name = Adrenocorticotropic hormone |
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| IUPAC_name = H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-Lys-Val-Tyr-Pro-Asn-Gly-Ala-Glu-Asp-Glu-Ser-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH |
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| image = |
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| image2 = |
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| width2 = |
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<!--Clinical data--> |
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| pronounce = |
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| tradename = Acortan, Acthar, Acton, Cortigel, Trofocortina |
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| Drugs.com = {{drugs.com|international|corticotropin }} |
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| MedlinePlus = |
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| pregnancy_US = |
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| legal_US = |
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| licence_EU = |
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| legal_status = Rx-only |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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| elimination_half-life = |
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| excretion = |
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<!--Identifiers--> |
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| CAS_number_Ref = |
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| CAS_supplemental = |
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| ATC_prefix = |
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| ATC_suffix = |
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| ChEBI_Ref = |
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| ChEBI = |
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| PubChem =16132265 |
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| IUPHAR_ligand = |
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| DrugBank_Ref = |
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| DrugBank = DB01285 |
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| ChemSpiderID_Ref = |
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| ChemSpiderID = none |
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| UNII_Ref = |
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| KEGG_Ref = |
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| KEGG = |
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| ChEMBL_Ref = |
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| ChEMBL = |
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<!-- Chemical and physical data --> |
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| C=207 | H=308 | N=56 | O=58 | S=1 |
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}} |
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{{Drugbox |
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| drug_name = Tetracosactide |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 470603578 |
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| IUPAC_name = <small>L</small>-seryl-<small>L</small>-tyrosyl-<small>L</small>-seryl-<small>L</small>-methionyl-<small>L</small>-α-glutamyl-<small>L</small>-histidyl-<small>L</small>-phenylalanyl-<small>L</small>-arginyl-<small>L</small>-tryptophylglycyl-<small>L</small>-lysyl-<small>L</small>-prolyl-<small>L</small>-valylglycyl-<small>L</small>-lysyl-<small>L</small>-lysyl-<small>L</small>-arginyl-<small>L</small>-arginyl-<small>L</small>-prolyl-<small>L</small>-valyl-<small>L</small>-lysyl-<small>L</small>-valyl-<small>L</small>-tyrosyl-<small>L</small>-proline |
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| image = Tetracosactide.png |
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| image = Tetracosactide.png |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = |
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| tradename = Cortrosyn, Synacthen, Nuvacthen |
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| Drugs.com = {{drugs.com|international|tetracosactide}} |
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| Drugs.com = {{drugs.com|international|tetracosactide}} |
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| MedlinePlus = a605020 |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category = |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = |
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| routes_of_administration = |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| metabolism = |
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| metabolism = |
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| elimination_half-life = |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 16960-16-0 |
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| CAS_number = 16960-16-0 |
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| ATC_prefix = H01 |
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| ATC_prefix = H01 |
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| ATC_suffix = AA02 |
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| ATC_suffix = AA02 |
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| PubChem = 16129617 |
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| PubChem = 16129617 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank = |
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| DrugBank = DB01284 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 10481947 |
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| ChemSpiderID = 10481947 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 72YY86EA29 |
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| UNII = 72YY86EA29 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00284 |
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| KEGG = D00284 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 3901 |
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| ChEBI = 3901 |
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| IUPHAR_ligand = 6965 |
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| synonyms = Ba 30920<br />α<sup>1–24</sup> corticotrophin<br /><small>Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-Lys-Val-Tyr-Pro</small> |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=136 | H=210 | N=40 | O=31 | S=1 |
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| C=136 | H=210 | N=40 | O=31 | S=1 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| molecular_weight = 2933.44 g/mol |
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| InChI = 1S/C136H210N40O31S/c1-75(2)109(127(200)154-71-106(181)156-88(31-13-17-52-137)114(187)158-89(32-14-18-53-138)115(188)159-91(35-21-56-149-134(142)143)116(189)164-96(37-23-58-151-136(146)147)131(204)175-60-25-39-104(175)126(199)173-111(77(5)6)128(201)163-90(33-15-19-54-139)120(193)171-110(76(3)4)129(202)169-101(65-80-43-47-84(180)48-44-80)132(205)176-61-26-40-105(176)133(206)207)172-125(198)103-38-24-59-174(103)130(203)95(34-16-20-55-140)157-107(182)70-153-113(186)99(66-81-68-152-87-30-12-11-29-85(81)87)167-117(190)92(36-22-57-150-135(144)145)160-121(194)98(63-78-27-9-8-10-28-78)166-123(196)100(67-82-69-148-74-155-82)168-118(191)93(49-50-108(183)184)161-119(192)94(51-62-208-7)162-124(197)102(73-178)170-122(195)97(165-112(185)86(141)72-177)64-79-41-45-83(179)46-42-79/h8-12,27-30,41-48,68-69,74-77,86,88-105,109-111,152,177-180H,13-26,31-40,49-67,70-73,137-141H2,1-7H3,(H,148,155)(H,153,186)(H,154,200)(H,156,181)(H,157,182)(H,158,187)(H,159,188)(H,160,194)(H,161,192)(H,162,197)(H,163,201)(H,164,189)(H,165,185)(H,166,196)(H,167,190)(H,168,191)(H,169,202)(H,170,195)(H,171,193)(H,172,198)(H,173,199)(H,183,184)(H,206,207)(H4,142,143,149)(H4,144,145,150)(H4,146,147,151)/t86-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,109-,110-,111-/m0/s1 |
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| StdInChI = 1S/C136H210N40O31S/c1-75(2)109(127(200)154-71-106(181)156-88(31-13-17-52-137)114(187)158-89(32-14-18-53-138)115(188)159-91(35-21-56-149-134(142)143)116(189)164-96(37-23-58-151-136(146)147)131(204)175-60-25-39-104(175)126(199)173-111(77(5)6)128(201)163-90(33-15-19-54-139)120(193)171-110(76(3)4)129(202)169-101(65-80-43-47-84(180)48-44-80)132(205)176-61-26-40-105(176)133(206)207)172-125(198)103-38-24-59-174(103)130(203)95(34-16-20-55-140)157-107(182)70-153-113(186)99(66-81-68-152-87-30-12-11-29-85(81)87)167-117(190)92(36-22-57-150-135(144)145)160-121(194)98(63-78-27-9-8-10-28-78)166-123(196)100(67-82-69-148-74-155-82)168-118(191)93(49-50-108(183)184)161-119(192)94(51-62-208-7)162-124(197)102(73-178)170-122(195)97(165-112(185)86(141)72-177)64-79-41-45-83(179)46-42-79/h8-12,27-30,41-48,68-69,74-77,86,88-105,109-111,152,177-180H,13-26,31-40,49-67,70-73,137-141H2,1-7H3,(H,148,155)(H,153,186)(H,154,200)(H,156,181)(H,157,182)(H,158,187)(H,159,188)(H,160,194)(H,161,192)(H,162,197)(H,163,201)(H,164,189)(H,165,185)(H,166,196)(H,167,190)(H,168,191)(H,169,202)(H,170,195)(H,171,193)(H,172,198)(H,173,199)(H,183,184)(H,206,207)(H4,142,143,149)(H4,144,145,150)(H4,146,147,151)/t86?,88-,89-,90+,91-,92+,93+,94+,95+,96-,97+,98+,99+,100+,101+,102+,103+,104+,105+,109+,110+,111+/m1/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| InChIKey = ZOEFCCMDUURGSE-SQKVDDBVSA-N |
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| StdInChIKey = ZOEFCCMDUURGSE-CQVUSSRSSA-N |
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| StdInChI = 1S/C136H210N40O31S/c1-75(2)109(127(200)154-71-106(181)156-88(31-13-17-52-137)114(187)158-89(32-14-18-53-138)115(188)159-91(35-21-56-149-134(142)143)116(189)164-96(37-23-58-151-136(146)147)131(204)175-60-25-39-104(175)126(199)173-111(77(5)6)128(201)163-90(33-15-19-54-139)120(193)171-110(76(3)4)129(202)169-101(65-80-43-47-84(180)48-44-80)132(205)176-61-26-40-105(176)133(206)207)172-125(198)103-38-24-59-174(103)130(203)95(34-16-20-55-140)157-107(182)70-153-113(186)99(66-81-68-152-87-30-12-11-29-85(81)87)167-117(190)92(36-22-57-150-135(144)145)160-121(194)98(63-78-27-9-8-10-28-78)166-123(196)100(67-82-69-148-74-155-82)168-118(191)93(49-50-108(183)184)161-119(192)94(51-62-208-7)162-124(197)102(73-178)170-122(195)97(165-112(185)86(141)72-177)64-79-41-45-83(179)46-42-79/h8-12,27-30,41-48,68-69,74-77,86,88-105,109-111,152,177-180H,13-26,31-40,49-67,70-73,137-141H2,1-7H3,(H,148,155)(H,153,186)(H,154,200)(H,156,181)(H,157,182)(H,158,187)(H,159,188)(H,160,194)(H,161,192)(H,162,197)(H,163,201)(H,164,189)(H,165,185)(H,166,196)(H,167,190)(H,168,191)(H,169,202)(H,170,195)(H,171,193)(H,172,198)(H,173,199)(H,183,184)(H,206,207)(H4,142,143,149)(H4,144,145,150)(H4,146,147,151)/t86-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,109-,110-,111-/m0/s1 |
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| StdInChIKey = ZOEFCCMDUURGSE-SQKVDDBVSA-N |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Adrenocorticotropic hormone''' is used as a medication and as ] in the ].<ref name="IndexNominum2000" /><ref name=Elks2014/>{{rp|316,1165}}<ref name="MortonHall2012" />{{rp|84,271}} |
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The form that is purified from pig ]s is known as '''corticotropin'''<ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA275|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=275–}}</ref><ref name=Elks2014>{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3}}</ref>{{rp|316}} is a medication and naturally occurring ] ] produced and secreted by the ].<ref name=MortonHall2012>{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=84–}}</ref>{{rp|84}} |
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The form that is made synthetically is '''tetracosactide''', also known as '''synacthen''',<ref>{{cite web|url=https://bnf.nice.org.uk/medicinal-forms/tetracosactide.html|title=BNF|website=NICE}}</ref> '''tetracosactrin''' and '''cosyntropin'''.<ref name="Elks2014"/>{{rp|1165}}<ref name="MortonHall2012"/>{{rp|271}}<ref>{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA1005|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=1005–}}</ref> It consists of the first 24 (of a total of 39) ]s of ACTH and retains full function of the parent peptide.<ref name="Elks2014"/>{{rp|1165}} Tetracosactide stimulates the release of ]s such as ] from the ]s, and is used for the ] to assess ] function.<ref name="MortonHall2012" />{{rp|271}} |
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== Medical uses == |
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Both corticotropin and tetracosactide have been used for diagnostic purposes to determine ], particularly in ], via the ].<ref name=Gettig2009rev/><ref name=USlabelCosyntropin/><ref name=UKSynacthenDiagnostic/> However, as of 2015 the US label for corticotropin does not include diagnostic use.<ref name=USlabelCorticotropin/> |
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Both corticotropin and tetracosactide have been used for therapeutic purposes.<ref name=USlabelCorticotropin/><ref name=UKSynacthenTherapeutic/> In the US the tetracosactide label is limited to diagnosis<ref name=Gettig2009rev/><ref name=USlabelCosyntropin/> but the UK label provides for therapeutic uses.<ref name=UKSynacthenTherapeutic/> |
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In the US corticotropin is used to treat ] in infants, acute exacerbations of ] in adults; acute episodes of ] and ] and ]; in acute exacerbations or as maintenance therapy for collagen disorders like ] and systemic ]; for skin conditions like severe ] and ]; for ]; for severe acute and chronic allergic and inflammatory processes involving the eye such as ], ] and ], diffuse posterior ], ], ], ], and anterior segment inflammation; ] in the lungs; and to treat ] in certain ]s.<ref name=USlabelCorticotropin/> |
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In the UK tetracosactide is used for short-term therapy in conditions for which ] are usually used but for some reason should not be; some uses include use for people who do not respond to glucocorticoids or cannot tolerate them who have ], ], ], ], or ].<ref name=UKSynacthenTherapeutic/> |
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== Contraindications == |
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In the US the only contraindication for tetracosactide for diagnostic use is hypersensitivity to ACTH<ref name=USlabelCosyntropin/> but in the UK, regulators placed contraindications for hypersensitivity to ACTH and additionally, for people with allergic disorders including asthma, acute psychosis, infectious diseases, peptic ulcer, refractory heart failure, ], treatment of primary adrenocortical insufficiency and adrenocongenital syndrome.<ref name=UKSynacthenDiagnostic/> |
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The same contraindications that were applied in the UK for diagnostic use of tetracosactide, apply for therapeutic use of both tetracosactide and corticotropin in the US and UK.<ref name=USlabelCorticotropin/><ref name=UKSynacthenTherapeutic/> |
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In addition, the US label for corticotropin for therapeutic uses includes contraindications for people who have recently had surgery, and people with scleroderma, osteoporosis, uncontrolled hypertension, or sensitivity to proteins of porcine origin; in addition the infection diseases systemic fungal infection, ocular herpes simplex, and infants who have congenital infections are specified. The label also notes that people taking corticotropin for immunosuppression should not be given live vaccines.<ref name=USlabelCorticotropin/> |
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== Adverse effects == |
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People taking corticotropin or tetracosactide are more likely to get infections, and are at risk of hypothalamic-pituitary-axis (HPA) suppression and ].<ref name=USlabelCorticotropin/><ref name=UKSynacthenTherapeutic/> |
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== Pharmacology == |
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In the normal situation, ACTH is released from the ] at the base of the brain. It acts on the adrenal glands to stimulate the production of steroid hormones (]s). If the adrenal glands are healthy, a single injection of tetracosactide results in a rise in blood ] concentrations in 30 minutes. If the adrenal glands appear not to be working then tetracosactide injection can be given to check whether the problem is due to diseased or damaged adrenals or due to lack of pituitary ACTH. |
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Tetracosactide stimulates the release of ]s such as ] from the ]s, and is used for the ] to assess ] function.<ref name="MortonHall2012" />{{rp|271}} |
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== Chemistry == |
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The synthetic form consists of the first 24 (of a total of 39) ]s of ACTH and retains full function of the parent peptide.<ref name="Elks2014"/>{{rp|1165}} |
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== Manufacturing == |
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{{Empty section|date=January 2017}} |
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== History == |
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{{Empty section|date=January 2017}} |
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== Society and culture == |
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===Approved forms=== |
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In the US, available forms of animal-derived corticotrophin have included: |
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* Corticotrophin derived from ]s from pigs, in a ] formulation as well as in a zinc hydrochloride formulation, each first approved in the US in 1955 and subsequently discontinued.<ref name=NDA009854>{{cite web|title=NDA 009854: Purified corticotropin-zinc hydrochloride|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=009854|publisher=FDA|access-date=22 January 2017}}</ref><ref name=NDA008975>{{cite web|title=NDA 008975: Purified corticotrophin gel|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=008975|publisher=FDA|access-date=22 January 2017}}</ref> In September 2015 ANI Pharmaceuticals and ] agreed that ANI would purchase NDA 009854 and NDA 008975 and related trademarks and other assets related to these two versions of corticotrophin from Merck for $75M and ongoing royalties; the transaction closed in January 2016.<ref name=ANI2015>{{cite web|title=Form 8K, Exhibit 99.1: Press release: ANI Pharmaceuticals to Acquire Two NDAs from Merck for $75 Million|url=https://www.sec.gov/Archives/edgar/data/1023024/000114420415055677/v420588_ex99-1.htm|publisher=ANI Pharmaceuticals via SEC Edgar|date=September 21, 2015}} See </ref> As of November 2016 ANI was preparing its supplemental NDA to get approval to re-introduce this formulation;<ref>{{cite web|title=Form 8-K Exhibit 99.1: ANI Pharmaceuticals Reports Record Third Quarter Results and Year-To-Date 2016 Highlights and Narrows Full-year Guidance|url=https://www.sec.gov/Archives/edgar/data/1023024/000114420416131250/v452042_ex99-1.htm|publisher=ANI Pharmaceuticals via SEC Edgar|date=November 3, 2016}} See </ref> in 2015 ANI estimated that the US market for these products was about $1 billion per year, based on sales of Acthar gel.<ref name=ANI2015/> |
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* Corticotrophin, first approved in 1952 and subsequently discontinued; as of January 2017 this NDA was under control of Parkedale, a subsidiary of ] which is in turn a subsidiary of ].<ref name=NDA008317>{{cite web|title=NDA 008317: ACTH (Corticotropin)|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=008317|publisher=FDA|access-date=22 January 2017}}</ref><ref>{{cite web|title=King Pharmaceuticals, Inc. Form 10-K, Annual report for the fiscal year ended December 31, 2007|url=https://www.sec.gov/Archives/edgar/data/1047699/000095014408001506/g11456e10vk.htm|publisher=SEC Edgar}}</ref> |
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* Corticotrophin branded as "Acthar", was first approved in 1950 and was subsequently discontinued; as of January 2017 this NDA was under control of ].<ref name=NDA007504>{{cite web|title=NDA 007504: Acthar (Corticotropin)|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=007504|publisher=FDA|access-date=22 January 2017}}</ref> |
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* A corticotrophin was approved in 1957 under NDA 010831, was subsequently discontinued, and as of January 2017 was under control of Organics/Lagrange, a subsidiary of ] via Abbott's acquisition of ]'s drug business.<ref name=NDA010831>{{cite web|title=NDA 010831: Corticotropin|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=010831|publisher=FDA|access-date=22 January 2017}}</ref><ref>{{cite news| vauthors = Whalen J, Cimilluca D, McCracken J | title=Abbott to Buy Solvay Drug Unit for $7 Billion|url=https://www.wsj.com/articles/SB125405897500043951|work=Wall Street Journal|date=28 September 2009}}</ref><ref>{{cite web|title=Press Release - Lincoln International|url=http://www.lincolninternational.com/transactions/organics/|publisher=Lincoln International|access-date=23 January 2017|date=14 August 2013|archive-url=https://web.archive.org/web/20170202093905/http://www.lincolninternational.com/transactions/organics/|archive-date=2 February 2017|url-status=dead}}</ref> A ] version under this NDA was approved under ANDA 088772 and was subsequently discontinued, and as of January 2017 was under the control of ].<ref name=ANDA088772>{{cite web|title=ANDA 088772: Corticotropin|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=088772|publisher=FDA|access-date=22 January 2017}}</ref> |
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* A corticotrophin called H.P. Acthar Gel was approved in 1952 and as of January 2017 was under the control of ].<ref name=NDA008372>{{cite web|title=NDA 008372: H.P. Acthar Gel (Corticotropin)|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=008372|publisher=FDA|access-date=22 January 2017}}</ref> A repository version of H.P. Acthar gel was approved in 2010 and as of January 2017 was also under the control of Mallinkrodt.<ref name=NDA022432>{{cite web|title=NDA022432: H.P. Acthar Gel (Repository Corticotropin)|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022432|publisher=FDA|access-date=22 January 2017}}</ref><ref name=USlabelCorticotropin>{{cite web|title=US Label: H.P. Acthar Gel (repository corticotropin) and (corticotropin)|url=http://www.acthar.com/pdf/Acthar-PI.pdf|publisher=Mallinckrodt|format=First approved 1952|date=February 2015}}</ref> |
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Synthetic forms were created as a replacement for the animal-derived products.<ref name=Gettig2009rev>{{cite journal | vauthors = Gettig J, Cummings JP, Matuszewski K | title = H.p. Acthar gel and cosyntropin review: clinical and financial implications | journal = P & T | volume = 34 | issue = 5 | pages = 250–257 | date = May 2009 | pmid = 19561871 | pmc = 2697107 }}</ref> |
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In the US, available forms of tetracosactide/cosyntropin, the synthetic form of corticotrophin, have been approved only for diagnostic uses,<ref name=Gettig2009rev/> and have included: |
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*A branded version called Cortrosyn, which was created and developed by ] and was approved by the FDA in 1970, and as of January 2017 was under the control of ],<ref name=NDA016750>{{cite web|title=NDA016750: Cortrosyn (Cosyntropin)|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=016750|publisher=FDA|access-date=22 January 2017}}</ref><ref>Organon sold the rights to Cortrosyn to Amphastar in 2003, per {{cite web|title=Amphastar Pharmaceuticals S-1, Amendment 5|url=https://www.sec.gov/Archives/edgar/data/1297184/000104746905025331/a2152635zs-1a.htm|publisher=SEC Edgar|date=October 27, 2005}}</ref> and there were three generic versions under ANDAs, one for ] approved in 2009,<ref name=ANDA090574>{{cite web|title=ANDA 090574: Cosyntropin|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=090574|publisher=FDA|access-date=22 January 2017}}</ref> one for Sandoz/], approved in 2012,<ref name=ANDA202147>{{cite web|title=ANDA 202147:Cosyntropin |url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=202147|publisher=FDA|access-date=22 January 2017}}</ref> and another for Amphastar under ANDA 016750.<ref name=NDA016750/> This version is a powder that is reconstituted before use.<ref name=NDA022028SummaryReview/><ref name=USlabelCosyntropin>{{cite web|title=US Cortrosyn (cosyntropin) label|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022028s005lbl.pdf|publisher=FDA|access-date=28 January 2021}}</ref> |
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* A version of cosyntropin in solution (as opposed to powder) was developed by Sandoz/] and was approved under the 505b(2) pathway in 2008; as of January 2017 it had been discontinued.<ref name=NDA022028SummaryReview>{{cite web|title=NDA 022028: Summary review|url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022028s000_SumR.pdf|publisher=FDA|date=February 21, 2008}}</ref><ref name=NDA022028>{{cite web|title=NDA 022028: Cosyntropin solution|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022028|publisher=FDA|access-date=22 January 2017}}</ref><ref name=USlabelCosyntropinSolution>{{cite web|title=US Label: Cosyntropin Injection|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022028lbl.pdf|publisher=FDA|date=February 2008}}</ref> |
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In the UK, available forms of tetracosactide/cosyntropin, the synthetic form of corticotrophin, have been approved for both therapeutic and diagnostic uses, and have included: |
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* A version branded Synacthen and provided in solution 250 mcg ampoules, for diagnostic uses, approved in 2008 and as of January 2017 controlled by Mallinckrodt.<ref name=UKSynacthenDiagnostic>{{cite web|title=Synacthen Ampoules 250 micrograms per ml - Summary of Product Characteristics|url=https://www.medicines.org.uk/emc/product/10823|publisher=UK Electronic Medicines Compendium|access-date=23 January 2017|language=en|format=First approved 25 June 1998 under PL 43357/0001|date=June 8, 2016}}</ref> |
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* A version branded Synacthen, absorbed on to zinc phosphate, provided in milky white suspension, approved in 2008 and as of January 2017 controlled by Mallinckrodt.<ref name=UKSynacthenTherapeutic>{{cite web|title=Synacthen Depot Ampoules 1mg/ml - Summary of Product Characteristics|url=https://www.medicines.org.uk/emc/product/10823 |publisher=Electronic Medicines Compendium|access-date=28 January 2021|language=en|format=First approved 25 June 1998 under PL43357/0002|date=June 8, 2016|website=medicines.org.uk}}</ref> |
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===Doping=== |
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As of 2007, it was widely reported that tetracosactide had been used as an illegal performance-enhancing drug by professional cyclists.<ref name="isbn0-224-08017-2">{{cite book | vauthors = Kimmage P | title = Rough Ride | publisher = Yellow Jersey Press | year = 2007 | page = 125 | chapter = tour 87 stage 14 | isbn = 978-0-224-08017-0 }}</ref> It is known to be used as a doping agent to increase the secretion of glucocorticoids by adrenal glands.<ref name="pmid21170520">{{cite journal | vauthors = Chaabo A, de Ceaurriz J, Buisson C, Tabet JC, Lasne F | title = Simultaneous quantification and qualification of synacthen in plasma | journal = Analytical and Bioanalytical Chemistry | volume = 399 | issue = 5 | pages = 1835–1843 | date = February 2011 | pmid = 21170520 | doi = 10.1007/s00216-010-4565-z | s2cid = 28664950 }}</ref> |
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===Pricing=== |
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Mallinckrodt acquired the US rights to the animal-derived form via its acquisition of Questcor Pharmaceuticals in 2014.<ref name=WaPo2017/> When Questcor acquired the drug in 2001 it sold for $40 a vial; within a year of the acquisition Questcor raised the price of the drug to $1,500 per vial and to $28,000 by 2013.<ref name=NYTprice2012>{{cite news | url = https://www.nytimes.com/2012/12/30/business/questcor-finds-profit-for-acthar-drug-at-28000-a-vial.html | title = Questcor Finds Profits, at $28,000 a Vial | vauthors = Pollack A | date = 2012-12-29 | work = New York Times }}</ref><ref name=FierceSuit>{{cite news| vauthors = Staton T |title=Questcor's Acthar maneuvers land Mallinckrodt in hot water with FTC, state AGs|url=http://www.fiercepharma.com/pharma/questcor-s-acthar-maneuvers-land-mallinckrodt-hot-water-ftc-state-ags|work=FiercePharma|date=June 18, 2015|language=en}}</ref> In 2013, Questcor acquired the US rights to a competing product, Synacthen Depot, from Novartis.<ref name=FierceSuit/> In 2014 Mallinckrodt raised the price of Acthar further to $34,000.<ref>{{cite web |title=Pharma corp. hikes infant epilepsy drug price by 2,000%, from $33.05 per vial to $680 per vial |date=16 November 2015 |url=http://www.zmescience.com/medicine/infant-epilepsy-drug-hike-04234/ |access-date=16 November 2015 }}</ref><ref>{{cite news| vauthors = Galeon D |title=Company Raises the Price of a Drug That Fights Infant Epilepsy by 85,000%|url=https://futurism.com/company-raises-the-price-of-a-drug-that-fights-infant-epilepsy-by-85000/|work=Futurism|date=21 January 2017}}</ref> The ] and attorneys general from five states sued Mallinckrodt for anti-competitive behavior with regard to the acquisition of Synacthen Depot and the monopolistic pricing of Acthar, and in January 2017 the company settled, agreeing to pay $100 million and to license Synacthen Depot to a competitor.<ref name=WaPo2017>{{cite news| vauthors = Johnson CY |title=Maker of $34,000-a-vial drug to pay $100 million for allegedly preventing competition|url=https://www.washingtonpost.com/news/wonk/wp/2017/01/18/maker-of-34000-a-vial-drug-to-pay-100-million-for-allegedly-preventing-competition/|newspaper=Washington Post|date=January 18, 2017}}</ref> According to Kaiser Health News, Mallinckrodt responded by increasing its Congressional lobbying to $610,000, and its contributions to Congress members to $44,000, in the first quarter of 2017.<ref>, By Jay Hancock and Elizabeth Lucas and Sydney Lupkin, Kaiser Health News, July 24, 2017</ref> |
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In Canada, Synacthen Depot's pricing increased by 2000% in 2015, causing some provincial single payer authorities to delist the drug from funded medications. The increase in the drug's price came after ] acquired Questcor and its drug portfolio, which included the worldwide rights to Synacthen Depot. Prior to the price increase, Mallinckrodt claims that the drug was manufactured at a loss. Some have claimed that the price increase is abusive.<ref name=CBC-2015-11-16>{{cite news |url= http://www.cbc.ca/news/health/infantile-seizures-drug-1.3318183 |title= 2,000% price hike for infant seizure drug called 'absurd' | vauthors = Crowe K |publisher= CBC News |date= 16 November 2015 }}</ref> The drug had been priced at $33 but rose to $680 per vial. As an off-patent pharmaceutical, a similar drug, differing in formulation, available in Europe, made by a different manufacturer, sells for $8 per vial.<ref>{{cite news |title= Monday November 16th 2015 |date= 16 November 2015 |series= The National |publisher= CBC News }}</ref> |
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== Research == |
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Acthar gel has been proposed as a therapy to treat refractory ]s<ref name=Gettig2009rev/> and refractory ] due to a variety of glomerular diseases.<ref name=Bomback2011rev>{{cite journal | vauthors = Bomback AS, Tumlin JA, Baranski J, Bourdeau JE, Besarab A, Appel AS, Radhakrishnan J, Appel GB | display-authors = 6 | title = Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel | journal = Drug Design, Development and Therapy | volume = 5 | pages = 147–153 | date = March 2011 | pmid = 21448451 | pmc = 3063118 | doi = 10.2147/DDDT.S17521 | doi-access = free }}</ref> |
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==Veterinary medicine== |
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Both versions of the hormone are also used to perform the ] to diagnose ] and sometimes cats.<ref>{{cite journal | vauthors = Lathan P, Moore GE, Zambon S, Scott-Moncrieff JC | title = Use of a low-dose ACTH stimulation test for diagnosis of hypoadrenocorticism in dogs | journal = Journal of Veterinary Internal Medicine | volume = 22 | issue = 4 | pages = 1070–1073 | date = 2008 | pmid = 18537878 | doi = 10.1111/j.1939-1676.2008.0118.x | doi-access = }}</ref><ref>{{cite news | vauthors = Lyman R |title=Consider ACTH stimulation test when you suspect canine hyperadrenocorticism |url= http://veterinarynews.dvm360.com/consider-acth-stimulation-test-when-you-suspect-canine-hyperadrenocorticism|work=dvm360.com |date=November 1, 2008 |access-date=January 23, 2017|archive-date=July 4, 2018|archive-url=https://web.archive.org/web/20180704182712/http://veterinarynews.dvm360.com/consider-acth-stimulation-test-when-you-suspect-canine-hyperadrenocorticism|url-status=dead}}</ref><ref>{{cite web |title=ACTH Stimulation Test |url= http://www.idexx.com.tw/pdf/zh_tw/smallanimal/snap/cortisol/cortisol-acth-stimulation-protocol.pdf |publisher=Idexx|access-date=23 January 2017|archive-url= https://web.archive.org/web/20170202020508/http://www.idexx.com.tw/pdf/zh_tw/smallanimal/snap/cortisol/cortisol-acth-stimulation-protocol.pdf |archive-date=2017-02-02|url-status=dead}}</ref><ref>{{cite news| vauthors = Gallagher A |title=Demystifying Tests for Hyperadrenocorticism |url= http://www.cliniciansbrief.com/sites/default/files/attachments/ASK_Demystifying%20Tests%20for%20HAC.pdf |work=Clinicians' Brief|date=November 2014|access-date=2017-01-23 |archive-url= https://web.archive.org/web/20141222040116/http://www.cliniciansbrief.com/sites/default/files/attachments/ASK_Demystifying%20Tests%20for%20HAC.pdf |archive-date=2014-12-22|url-status=dead}}</ref> |
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== References == |
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{{reflist}} |
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== External links == |
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* {{MeshName|Adrenocorticotropic+Hormone}} |
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* {{MeshName|Cosyntropin}} |
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{{Melanocortin receptor modulators}} |
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] |
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] |
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] |