Identification
- Summary
Hydroxyprogesterone caproate is a synthetic progestin used for the prevention of spontaneous preterm births in singleton pregnancies in women who have previously had a spontaneous preterm birth.
- Brand Names
- Makena
- Generic Name
- Hydroxyprogesterone caproate
- DrugBank Accession Number
- DB06789
- Background
Hydroxyprogesterone caproate is a synthetic steroid hormone that is similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone formed from caproic acid (hexanoic acid). Hydroxyprogesterone caproate was previously marketed under the trade name Delalutin by Squibb, which was approved by the U.S. Food and Drug Administration (FDA) in 1956 and withdrawn from marketing in 1999. The U.S. FDA approved Makena from KV Pharmaceutical (previously named as Gestiva) on February 4, 2011 for prevention of preterm delivery in women with a history of preterm delivery, sparking a pricing controversy.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Hydroxyprogesterone caproate (DB06789)
- Weight
- Average: 428.6041
Monoisotopic: 428.292659768 - Chemical Formula
- C27H40O4
- Synonyms
- 17-alpha-hydroxy-progesterone caproate
- 17alpha-Caproyloxypregn-4-ene-3,20-dione
- 17alpha-Hydroxyprogesterone hexanoate
- Caproate d'hydroxyprogesterone
- Caproato de hidroxiprogesterona
- Hydroxyprogesterone caproate
- Hydroxyprogesterone hexanoate
- External IDs
- NSC-17592
Pharmacology
- Indication
Hydroxyprogesterone caproate is indicated for the prevention of spontaneous preterm births in singleton pregnancies in women who have previously had a spontaneous preterm birth. (1)
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
No specific pharmacodynamic studies have been performed to assess hydroxyprogesterone caproate injections. (4) However, the mechanism of action is likely related to increased interaction between progesterone and progesterone receptors. (5)
- Mechanism of action
The mechanism by which progesterone prevents preterm birth is not well understood, but many pathways are likely involved. (1) Progesterone plays a vital role in regulation of the female reproductive system and is important for successful implantation of the embryo and maintenance of pregnancy. It acts by binding to progesterone receptors in the uterus, ovaries, breasts and in the central nervous system. These receptors exist in 2 isoforms, PR-A and PR-B. Progesterone binding to these receptors ultimately leads to regulation of gene transcription. (2) This results in an anti-inflammatory effect which blunts the proinflammatory state that occurs with initiation of labor, and maintains uterine queiscence by stabilizing progesterone acting on the myometrium. (2)
Target Actions Organism UProgesterone receptor agonistHumans - Absorption
Absorption of 17-hydroxyprogesteron caproate is slow, occurring over a long period of time. (3)
- Volume of distribution
Hydroxyprogesterone caproate has a high volume of distribution. (3)
- Protein binding
Hydroxyprogesterone caproate is extensively protein bound in the plasma. (3)
- Metabolism
The main enzymes involved in metabolism of hydroxyprogesterone caproate are cytochrome P450 (CYP) 3A4 and to a lesser extent CYP3A5. (3)
- Route of elimination
Following intramuscular injection, approximately 50% of hydroxyprogesterone caproate metabolites are eliminated in the feces, while approximately 30% of metabolites are eliminated in the urine. (3)
- Half-life
Half-life = 16 days (±6 days). (3)
- Clearance
Clearance is highly variable from patient to patient. (3)
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Injection site pain is the most common adverse effect associated with hydroxyprogesterone caproate. Other commonly reported adverse effects include: injection site swelling, urticaria, pruritus, injection site pruritus, nausea, injection site nodule, and diarrhea. (4)
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Hydroxyprogesterone caproate can be increased when it is combined with Abametapir. Abatacept The metabolism of Hydroxyprogesterone caproate can be increased when combined with Abatacept. Abciximab The therapeutic efficacy of Abciximab can be decreased when used in combination with Hydroxyprogesterone caproate. Acalabrutinib The metabolism of Hydroxyprogesterone caproate can be decreased when combined with Acalabrutinib. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Hydroxyprogesterone caproate. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Hydroxyprogesterone caproate. Acetaminophen The metabolism of Hydroxyprogesterone caproate can be increased when combined with Acetaminophen. Acetazolamide The metabolism of Hydroxyprogesterone caproate can be increased when combined with Acetazolamide. Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Hydroxyprogesterone caproate. Acitretin The therapeutic efficacy of Hydroxyprogesterone caproate can be decreased when used in combination with Acitretin. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Delalutin (Bristol-Myers Squibb) / Gestiva (Cytyc) / Hormofort (Kobanyai) / ldrogestene (Farmila)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Makena Injection 250 mg/1mL Intramuscular AMAG Pharmaceuticals, Inc. 2011-02-03 Not applicable US 
Makena Injection 250 mg/1mL Subcutaneous AMAG Pharmaceuticals, Inc. 2018-02-14 Not applicable US Makena Injection 250 mg/1mL Intramuscular AMAG Pharmaceuticals, Inc. 2011-02-03 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Hydroxyprogesterone Caproate Injection 250 mg/1mL Intramuscular McGuff Pharmaceuticals, Inc. 2016-12-02 2016-12-02 US Hydroxyprogesterone Caproate Liquid 250 mg/1mL Intramuscular LSNE-LEON SLU 2019-08-23 Not applicable US Hydroxyprogesterone Caproate Injection 250 mg/1mL Intramuscular AMERICAN REGENT, INC. 2019-03-01 Not applicable US Hydroxyprogesterone caproate Injection 250 mg/1mL Intramuscular Slayback Pharma LLC 2019-03-25 Not applicable US Hydroxyprogesterone Caproate Injection 250 mg/1mL Intramuscular Slayback Pharma LLC 2018-12-28 Not applicable US Hydroxyprogesterone Caproate Injection 250 mg/1mL Intramuscular Prasco Laboratories 2018-07-02 Not applicable US Hydroxyprogesterone Caproate Injection 1250 mg/5mL Intramuscular AuroMedics Pharma LLC 2019-04-16 Not applicable US Hydroxyprogesterone Caproate Injection 250 mg/1mL Intramuscular Mylan Institutional LLC 2019-08-23 Not applicable US Hydroxyprogesterone Caproate Injection 250 mg/1mL Intramuscular AMERICAN REGENT, INC. 2018-06-28 Not applicable US Hydroxyprogesterone caproate Injection 250 mg/1mL Intramuscular GP PHARM SA 2019-03-01 Not applicable US
Categories
- Drug Categories
- Adrenal Cortex Hormones
- Antineoplastic Agents
- Combination Contraceptives (with Estrogen and derivatives)
- Contraceptive Agents, Female
- Cytochrome P-450 CYP2C19 Inducers
- Cytochrome P-450 CYP2C19 Inducers (strength unknown)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Substrates
- Estrogen Antagonists
- Fused-Ring Compounds
- Gonadal Hormones
- Gonadal Steroid Hormones
- Hormonal Contraceptives for Systemic Use
- Hormone Antagonists
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hydroxyprogesterones
- Hyperglycemia-Associated Agents
- Pregnanes
- Pregnenediones
- Pregnenes
- Progesterone and Derivatives
- Progesterone Congeners
- Progestin Contraceptives
- Progestins
- Steroids
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Pregnane steroids
- Direct Parent
- Gluco/mineralocorticoids, progestogins and derivatives
- Alternative Parents
- Steroid esters / 20-oxosteroids / 3-oxo delta-4-steroids / Delta-4-steroids / Cyclohexenones / Alpha-acyloxy ketones / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives
- Substituents
- 20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / Aliphatic homopolycyclic compound / Alpha-acyloxy ketone / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Cyclic ketone / Cyclohexenone
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- corticosteroid hormone (CHEBI:5812)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 276F2O42F5
- CAS number
- 630-56-8
- InChI Key
- DOMWKUIIPQCAJU-LJHIYBGHSA-N
- 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
- IUPAC Name
- (1R,3aS,3bR,9aR,9bS,11aS)-1-acetyl-9a,11a-dimethyl-7-oxo-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-1-yl hexanoate
- SMILES
- [H][C@@]12CC[C@](OC(=O)CCCCC)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
References
- Synthesis Reference
U.S. Patent 2,753,360.
- General References
- Goodnight W: Clinical Application of Progesterone for the Prevention of Preterm Birth, 2016. Am J Perinatol. 2016 Feb;33(3):253-7. doi: 10.1055/s-0035-1570378. Epub 2016 Jan 20. [Article]
- Ruan X, Mueck AO: Systemic progesterone therapy--oral, vaginal, injections and even transdermal? Maturitas. 2014 Nov;79(3):248-55. doi: 10.1016/j.maturitas.2014.07.009. Epub 2014 Jul 22. [Article]
- Feghali M, Venkataramanan R, Caritis S: Prevention of preterm delivery with 17-hydroxyprogesterone caproate: pharmacologic considerations. Semin Perinatol. 2014 Dec;38(8):516-22. doi: 10.1053/j.semperi.2014.08.013. Epub 2014 Sep 23. [Article]
- O'Brien JM, Lewis DF: Prevention of preterm birth with vaginal progesterone or 17-alpha-hydroxyprogesterone caproate: a critical examination of efficacy and safety. Am J Obstet Gynecol. 2016 Jan;214(1):45-56. doi: 10.1016/j.ajog.2015.10.934. Epub 2015 Nov 10. [Article]
- External Links
- KEGG Drug
- D00949
- KEGG Compound
- C08148
- PubChem Compound
- 169870
- PubChem Substance
- 310264886
- ChemSpider
- 148552
- BindingDB
- 70293
- 12488
- ChEBI
- 5812
- ChEMBL
- CHEMBL1200848
- ZINC
- ZINC000004083606
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Hydroxyprogesterone_caproate
- FDA label
- Download (383 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Prevention Premature Births 1 4 Recruiting Treatment Ovarian Hyper Stimulation Syndrome (OHSS) / Pregnancy Early / Spontaneous Abortions 1 3 Completed Prevention Human Immunodeficiency Virus Type 1 (HIV-1) Infection / Premature Births 1 3 Completed Prevention Neonatal Complications / Preterm Delivery 1 3 Completed Prevention Premature Births 1 3 Terminated Treatment Assessing Injection Pain of Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) in Healthy Post-menopausal Women 1 3 Terminated Treatment Locally Advanced Breast Cancer and Large Operable Breast Cancer 1 3 Unknown Status Prevention Obstetric Labour, Premature / Premature Births 1 3 Unknown Status Prevention Pregnancy 1 2 Completed Not Available Preterm Delivery 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Parenteral Injection Intramuscular 250 MG Injection Intramuscular 1250 mg/5mL Injection Intramuscular 250 mg/1mL Liquid Intramuscular 250 mg/1mL Powder Not applicable 1 kg/1kg Injection, solution Injection, solution Intramuscular 250 mg Injection, solution Parenteral 341 MG/2ML Injection Subcutaneous 250 mg/1mL Solution Parenteral 250 mg Injection, suspension, extended release Intramuscular; Parenteral 250 MG/ML Injection, emulsion Intramuscular 250 mg/ml Injection Intramuscular Solution Intramuscular 500 mg Injection Intramuscular 0.250 g/ml Solution Intramuscular 250 mg Solution 250 mg/1ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region USRE44846 No 2014-04-15 2019-08-10 US US8021335 No 2011-09-20 2026-10-04 US US8562564 No 2013-10-22 2026-01-24 US US9533102 No 2017-01-03 2026-01-24 US US9629959 No 2017-04-25 2026-01-24 US US9844558 No 2017-12-19 2036-05-02 US US9180259 No 2015-11-10 2026-01-24 US US9789257 No 2017-10-17 2034-02-11 US US10471075 No 2019-11-12 2036-05-02 US US11154562 No 2021-10-26 2036-05-02 US US11304962 No 2016-05-02 2036-05-02 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 119-121 U.S. Patent 2,753,360. - Predicted Properties
Property Value Source Water Solubility 0.000866 mg/mL ALOGPS logP 4.81 ALOGPS logP 5.88 Chemaxon logS -5.7 ALOGPS pKa (Strongest Acidic) 17.75 Chemaxon pKa (Strongest Basic) -4.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 60.44 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 121.69 m3·mol-1 Chemaxon Polarizability 50.28 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-0aba-3940000000-835c32531e48d578d8ee
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Zinc ion binding
- Specific Function
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
- Gene Name
- PGR
- Uniprot ID
- P06401
- Uniprot Name
- Progesterone receptor
- Molecular Weight
- 98979.96 Da
References
- O'Brien JM, Lewis DF: Prevention of preterm birth with vaginal progesterone or 17-alpha-hydroxyprogesterone caproate: a critical examination of efficacy and safety. Am J Obstet Gynecol. 2016 Jan;214(1):45-56. doi: 10.1016/j.ajog.2015.10.934. Epub 2015 Nov 10. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Feghali M, Venkataramanan R, Caritis S: Prevention of preterm delivery with 17-hydroxyprogesterone caproate: pharmacologic considerations. Semin Perinatol. 2014 Dec;38(8):516-22. doi: 10.1053/j.semperi.2014.08.013. Epub 2014 Sep 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Feghali M, Venkataramanan R, Caritis S: Prevention of preterm delivery with 17-hydroxyprogesterone caproate: pharmacologic considerations. Semin Perinatol. 2014 Dec;38(8):516-22. doi: 10.1053/j.semperi.2014.08.013. Epub 2014 Sep 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- Curator comments
- The data supporting CYP2C19 enzyme induction currently available is limited to in vitro studies.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Zhao Y, Alshabi AM, Caritis S, Venkataramanan R: Impact of 17-alpha-hydroxyprogesterone caproate on cytochrome P450s in primary cultures of human hepatocytes. Am J Obstet Gynecol. 2014 Oct;211(4):412.e1-6. doi: 10.1016/j.ajog.2014.03.048. Epub 2014 Mar 26. [Article]
Drug created at September 14, 2010 16:21 / Updated at February 21, 2021 18:52