Danazol

Synonyms :
Cyclomen, Danazolum, Danocrine

Status : approved

Therapeutic Classification

OTHER SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM

GENITO URINARY SYSTEM AND SEX HORMONES
SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
OTHER SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM

Description

A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [PubChem]

Used

For the treatment of endometriosis and fibrocystic breast disease (in patients unresponsive to simple measures). Also used for the prophylactic treatment of all types of hereditary angioedema in males and females.

Mechanism Of Action

As a gonadotropin inhibitor, danazol suppresses the pituitary-ovarian axis possibly by inhibiting the output of pituitary gonadotropins. Danazol also depresses the preovulatory surge in output of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby reducing ovarian estrogen production. Danazol may also directly inhibits ovarian steroidogenesis; bind to androgen, progesterone, and glucocorticoid receptors; bind to sex-hormone-binding globulin and corticosteroid-binding globulin; and increases the metabolic clearance rate of progesterone. Another mechanism of action by which danazol may use to facilitate regression of endometriosis is by decreasing IgG, IgM, and IgA concentrations, as well as phospholipid and IgG isotope autoantibodies. In the treatment of endometriosis, as a consequence of suppression of ovarian function, danazol causes both normal and ectopic endometrial tissues to become inactive and atrophic. This leads to anovulation and associated amenorrhea. In fibrocystic breast disease, the exact mechanism of action of danazol is unknown, but may be related to suppressed estrogenic stimulation as a result of decreased ovarian production of estrogen. A direct effect on steroid receptor sites in breast tissue is also possible. This leads to a disappearance of nodularity, relief of pain and tenderness, and possibly changes in the menstrual pattern. In terms of hereditary angioedema, danazol corrects the underlying biochemical deficiency by increasing serum concentrations of the deficient C1 esterase inhibitor, resulting in increased serum concentrations of the C4 component of the complement system. (Source: PharmGKB)

Dosage

Form Route Strength
Capsule oral 100 mg
Capsule oral 200 mg
Capsule oral 50 mg

Pharmacodynamics

Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. It was approved by the U.S. Food and Drug Administration (FDA) as the first drug to specifically treat endometriosis, but its role as a treatment for endometriosis has been largely replaced by the gonadotropin-releasing hormone (GnRH) agonists. Danazol has antigonadotropic and anti-estrogenic activities. Danazol acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties.

Metabolism

Hepatic, to principal metabolites, ethisterone and 17-hydroxymethylethisterone.

Half Life

Approximately 24 hours.

Chemical Classification

This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.

Estrane steroids

Organic compounds

Lipids and lipid-like molecules

Steroids and steroid derivatives

Estrane steroids

Chemical Name

Cyclomen

Brands

name Dosage form Country
Cyclomen capsule Canada
Cyclomen capsule Canada
Cyclomen capsule Canada
Danazol capsule US
Danazol capsule US
Danazol capsule US
Danazol capsule US
Danazol capsule US
Danazol capsule US
Danazol capsule US
Danazol capsule US

Drug Drug Interactions

  •  Acetohexamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Alfacalcidol  : May enhance the hypercalcemic effect of Vitamin D Analogs.
  •  Alogliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Aripiprazole  : CYP3A4 Inhibitors (Weak) may increase the serum concentration of Aripiprazole.
  •  Atorvastatin  : May increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Calcitriol  : May enhance the hypercalcemic effect of Vitamin D Analogs.
  •  Canagliflozin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Carbamazepine  : Danazol may decrease the metabolism of Carbamazepine.
  •  Chlorpropamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Cholecalciferol  : May enhance the hypercalcemic effect of Vitamin D Analogs.
  •  Dofetilide  : CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide.
  •  Doxercalciferol  : May enhance the hypercalcemic effect of Vitamin D Analogs.
  •  Ergocalciferol  : May enhance the hypercalcemic effect of Vitamin D Analogs.
  •  Flibanserin  : CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin.
  •  Gliclazide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Glimepiride  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Gliquidone  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Glyburide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Hydrocodone  : CYP3A4 Inhibitors (Weak) may increase the serum concentration of Hydrocodone.
  •  Insulin Aspart  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Detemir  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Glargine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Glulisine  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Lispro  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Regular  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin, isophane  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Linagliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Lomitapide  : CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide.
  •  Lovastatin  : May increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Metformin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Nimodipine  : CYP3A4 Inhibitors (Weak) may increase the serum concentration of Nimodipine.
  •  Paricalcitol  : May enhance the hypercalcemic effect of Vitamin D Analogs.
  •  Pimozide  : CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide.
  •  Pitavastatin  : May increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Repaglinide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Saxagliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Simvastatin  : Danazol may increase the serum concentration of Simvastatin.
  •  Tacrolimus  : May increase the serum concentration of Tacrolimus (Systemic).
  •  Tolbutamide  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
  •  Vildagliptin  : Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.

Food Interactions

  • Take without regard to meals.

Calculated Property

kind Value Source
logP 3.62 ALOGPS
logS -4.3 ALOGPS
Water Solubility 1.76e-02 g/l ALOGPS
logP 3.46 ChemAxon
IUPAC Name (1S,2R,13R,14S,17R,18S)-17-ethynyl-2,18-dimethyl-7-oxa-6-azapentacyclo[11.7.0.0²,¹⁰.0⁴,⁸.0¹⁴,¹⁸]icosa-4(8),5,9-trien-17-ol ChemAxon
Traditional IUPAC Name danazol ChemAxon
Molecular Weight 337.4553 ChemAxon
Monoisotopic Weight 337.204179113 ChemAxon
SMILES [H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC3=C(C[C@]12C)C=NO3 ChemAxon
Molecular Formula C22H27NO2 ChemAxon
InChI InChI=1S/C22H27NO2/c1-4-22(24)10-8-18-16-6-5-15-11-19-14(13-23-25-19)12-20(15,2)17(16)7-9-21(18,22)3/h1,11,13,16-18,24H,5-10,12H2,2-3H3/t16-,17+,18+,20+,21+,22+/m1/s1 ChemAxon
InChIKey InChIKey=POZRVZJJTULAOH-LHZXLZLDSA-N ChemAxon
Polar Surface Area (PSA) 46.26 ChemAxon
Refractivity 98.54 ChemAxon
Polarizability 38.56 ChemAxon
Rotatable Bond Count 0 ChemAxon
H Bond Acceptor Count 2 ChemAxon
H Bond Donor Count 1 ChemAxon
pKa (strongest acidic) 17.59 ChemAxon
pKa (strongest basic) 0.25 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 5 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Estrogen receptor : in Human
  • Androgen receptor : in Human
  • Progesterone receptor : in Human
  • Gonadotropin-releasing hormone receptor : in Human
  • Putative gonadotropin-releasing hormone II receptor : in Human
  • C-C motif chemokine 2 : in Human