Hydroxyprogesterone caproate

Not to be confused with 17α-Hydroxyprogesterone or Medroxyprogesterone acetate.

Hydroxyprogesterone caproate
Clinical data
Trade namesDelalutin, Proluton, Makena, others
Other namesOHPC; Hydroxyprogesterone capronate; Hydroxyprogesterone hexanoate; 17α-Hydroxyprogesterone caproate; 17α-OHPC; 17-Hydroxyprogesterone caproate; 17-OHPC; 17-HPC; 17α-HPC; HPC; LPCN-1107; 17α-Hydroxypregn-4-ene-3,20-dione 17α-hexanoate
Routes of
administration		Intramuscular injection,[1] subcutaneous autoinjection[2][3]
Drug classProgestogen; Progestin; Progestogen ester; Antigonadotropin
ATC code
Legal status
Legal status
  • US: withdrawn
Pharmacokinetic data
BioavailabilityOral: Very low (~3% in rats)[4]
Intramuscular: 100% (in rats)[4]
Protein bindingExtensive (to albumin, not to CBGTooltip corticosteroid-binding globulin or (likely) SHBGTooltip sex hormone-binding globulin)[1][5][6]
MetabolismReduction and hydroxylation (via CYP3A4, CYP3A5, CYP3A7) and conjugation (glucuronidation, sulfation, acetylation)[1]
Elimination half-lifeNon-pregnant: 7.8 days[7][8]
Singlet: 16–17 days[1][9]
Twins: 10 days[9]
ExcretionFeces: 50%[1]
Urine: 30%[1]
Identifiers
IUPAC name
  • [(8R,9S,10R,13S,14S,17R)-17-acetyl-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] hexanoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.010.127
Chemical and physical data
FormulaC27H40O4
Molar mass428.613 g·mol−1
3D model (JSmol)
SMILES
  • O=C4\C=C2/[C@]([C@H]1CC[C@@]3([C@@](OC(=O)CCCCC)(C(=O)C)CC[C@H]3[C@@H]1CC2)C)(C)CC4
InChI
  • InChI=1S/C27H40O4/c1-5-6-7-8-24(30)31-27(18(2)28)16-13-23-21-10-9-19-17-20(29)11-14-25(19,3)22(21)12-15-26(23,27)4/h17,21-23H,5-16H2,1-4H3/t21-,22+,23+,25+,26+,27+/m1/s1 Y
  • Key:DOMWKUIIPQCAJU-LJHIYBGHSA-N Y
  (verify)

Hydroxyprogesterone caproate, sold under the brand name Delalutin among others, is a medication used to reduce the risk of preterm birth in women pregnant with one baby who have a history of spontaneous preterm birth.[10] In March 2023, the manufacturer, Covis Pharma, agreed to withdraw the drug from the US market.[11][12][13] The approval of this drug substance was withdrawn by the US Food and Drug Administration (FDA) in April 2023.[10] In May 2024, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency recommended suspending the marketing authorizations of medications containing 17-hydroxyprogesterone caproate in the European Union.[14]

Hydroxyprogesterone caproate is a progestin medication which was used to prevent preterm birth in pregnant women with a history of the condition and to treat gynecological disorders.[1][8][9][15][3] It has also been formulated in combination with estrogens for various indications (brand names Gravibinon and Primosiston) and as a form of long-lasting injectable birth control (brand name Chinese Injectable No. 1).[16] It is not used by mouth and is instead given by injection into muscle or fat.[1][4][3]

Hydroxyprogesterone caproate is generally well tolerated and produces few side effects.[1] Injection site reactions such as pain and swelling are the most common side effect of hydroxyprogesterone caproate.[1] The medication may increase the risk of gestational diabetes when used in pregnant women.[1][17] Hydroxyprogesterone caproate is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[17] It has some antimineralocorticoid activity and no other important hormonal activity.[18][19][20][21][22] The medication shows a number of differences from natural progesterone.[17][23]

Hydroxyprogesterone caproate was discovered in 1953 and was introduced for medical use in 1954 or 1955.[24] It was marketed in the United States under the brand name Delalutin and throughout Europe under the brand name Proluton.[25] The medication was discontinued in the United States in 1999.[26] However, hydroxyprogesterone caproate was subsequently reintroduced in the United States under the brand name Makena for the treatment of preterm birth in 2011 until the FDA banned 17α-OHPC in 2023.[27]

  1. ^ a b c d e f g h i j k Deeks ED (October 2011). "17 α-Hydroxyprogesterone caproate (Makena): in the prevention of preterm birth". Paediatric Drugs. 13 (5): 337–45. doi:10.2165/11208140-000000000-00000. PMID 21888448. S2CID 207297651.
  2. ^ Cite error: The named reference pmid29191450 was invoked but never defined (see the help page).
  3. ^ a b c "Makena- hydroxyprogesterone caproate injection". DailyMed. 19 December 2022. Archived from the original on 13 March 2023. Retrieved 13 March 2023.
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  7. ^ Onsrud M, Paus E, Haug E, Kjørstad K (1985). "Intramuscular administration of hydroxyprogesterone caproate in patients with endometrial carcinoma. Pharmacokinetics and effects on adrenal function". Acta Obstetricia et Gynecologica Scandinavica. 64 (6): 519–23. doi:10.3109/00016348509156732. PMID 2932883. S2CID 12007439.
  8. ^ a b Hines M, Lyseng-Williamson KA, Deeks ED (March 2013). "17 α-hydroxyprogesterone caproate (Makena): a guide to its use in the prevention of preterm birth". Clinical Drug Investigation. 33 (3): 223–7. doi:10.1007/s40261-013-0060-6. PMID 23413110. S2CID 23221264.
  9. ^ a b c Cite error: The named reference pmid25256193 was invoked but never defined (see the help page).
  10. ^ a b "FDA Commissioner and Chief Scientist Announce Decision to Withdraw Approval of Makena". U.S. Food and Drug Administration (Press release). 6 April 2023. Archived from the original on 6 April 2023. Retrieved 7 April 2023. This article incorporates text from this source, which is in the public domain.
  11. ^ Jewett C (8 March 2023). "Preterm Birth Drug Withdrawn After 12 Years". The New York Times. Archived from the original on 10 March 2023. Retrieved 10 March 2023.
  12. ^ Dillinger K (8 March 2023). "Maker of preterm birth drug Makena to withdraw it from market". CNN. Archived from the original on 10 March 2023. Retrieved 10 March 2023.
  13. ^ "Covis Pharma Responds to Presiding Officer's Report Summarizing FDA Advisory Committee Hearing" (Press release). Covis Pharma. 7 March 2023. Archived from the original on 13 March 2023. Retrieved 13 March 2023 – via GlobeNewswire.
  14. ^ "Hydroxyprogesterone caproate medicines to be suspended from the EU market". European Medicines Agency (EMA). 17 May 2024. Retrieved 18 May 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  15. ^ Manuck TA (December 2017). "17-alpha hydroxyprogesterone caproate for preterm birth prevention: Where have we been, how did we get here, and where are we going?". Seminars in Perinatology. 41 (8): 461–467. doi:10.1053/j.semperi.2017.08.004. PMID 28947068. S2CID 36945947. Archived from the original on 12 December 2020. Retrieved 2 November 2021.
  16. ^ Newton JR, D'arcangues C, Hall PE (1994). "A review of "once-a-month" combined injectable contraceptives". Journal of Obstetrics and Gynaecology. 4 (Suppl 1): S1-34. doi:10.3109/01443619409027641. PMID 12290848.
  17. ^ a b c Cite error: The named reference pmid23643669 was invoked but never defined (see the help page).
  18. ^ Horsky J, Presl J (6 December 2012). Ovarian Function and its Disorders: Diagnosis and Therapy. Springer Science & Business Media. pp. 95–. ISBN 978-94-009-8195-9. Archived from the original on 8 March 2023. Retrieved 16 September 2018.
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  24. ^ Cite error: The named reference Cancer1979 was invoked but never defined (see the help page).
  25. ^ Cite error: The named reference IndexNominum2000 was invoked but never defined (see the help page).
  26. ^ Kim S. "The Orphan Drug Act: How the FDA Unlawfully Usurped Market Exclusivity". Northwestern Journal of Technology and Intellectual Property. 11. Heinonline: &#91, v&#93. Archived from the original on 8 March 2023. Retrieved 18 July 2016.
  27. ^ Cite error: The named reference pmid21410391 was invoked but never defined (see the help page).
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