danazol

Action and Spectrum

Actions and Spectrum 

danazol is a synthetic steroid derived from ethisterone. It has anti-estrogenic, anti-progestational, and androgenic effects, which make it useful in a variety of medical conditions. 

danazol is primarily used to treat endometriosis, a condition where the tissue that lines the inside of the uterus grows outside of it, causing pain and discomfort. It is also used to treat fibrocystic breast disease, a benign condition where the breast tissue becomes lumpy and painful. 

danazol works by inhibiting the production of gonadotropins, hormones that stimulate the production of estrogen and progesterone in the ovaries. By doing so, it suppresses ovulation and reduces the production of estrogen and progesterone, which helps alleviate the symptoms of endometriosis and fibrocystic breast disease. 

In addition to its anti-estrogenic and anti-progestational effects, danazol also has androgenic effects. It can increase the production of testosterone, which can lead to masculinization in women, including the growth of facial hair, a deeper voice, and an enlarged clitoris. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Intracranial hypertension 

Increased blood pressure 

Thromboembolism 

Anxiety 

Depression 

Dizziness 

Urticaria 

Gastroenteritis 

Nausea 

Vomiting 

Elevated LFTs 

Joint pain 

Muscle spasm 

Black Box Warning

danazol is not at all recommended in pregnant females. If a female gets pregnant during the therapy, immediately discontinue the treatment.  

Long-term therapy is limited, as it can cause various conditions. They may include peliosis, hepatitis, and benign hepatic adenoma. 

danazol has also been associated with major cases of pseudotumor cerebri. 

Contraindication / Caution

Contraindication/Caution 

danazol is contraindicated in patients with a history of thromboembolic events, such as deep vein thrombosis, pulmonary embolism, or stroke. It is also contraindicated in patients with liver disease, especially those with hepatic dysfunction or cholestasis. 

danazol may cause fetal harm and is contraindicated in pregnant women. It is also contraindicated in patients with a history of hypersensitivity to danazol or any of its components. 

danazol can interact with other medications, including cyclosporine, tacrolimus, and oral anticoagulants, such as warfarin. Therefore, caution should be exercised when using danazol in combination with other medications. 

danazol can cause serious side effects, including liver damage, fluid retention, and changes in lipid metabolism. Therefore, it should be used with caution in patients with a history of liver disease, diabetes, or high cholesterol. 

Finally, danazol can have masculinizing effects, such as the growth of facial hair, deepening of the voice, and enlargement of the clitoris, and should not be used in pregnant women or women who are breastfeeding. It should also be used with caution in men, as it can cause testicular atrophy and decreased sperm count. 

Pregnancy / Lactation

Pregnancy consideration:  

danazol inhibits fetal development if administered in pregnant females 

Breastfeeding warnings:  

Danazol is contraindicated in lactating patients 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 

• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women. 

• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a product in humans; Pregnant women must take care of the potential risks. 

• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergency cases for potential benefits. 

• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 

• Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

danazol is a synthetic steroid that has anti-estrogenic, anti-progestational, and androgenic effects. It works by inhibiting the production of gonadotropins, hormones that stimulate the production of estrogen and progesterone in the ovaries. 

danazol suppresses ovulation and reduces the production of estrogen and progesterone, which helps alleviate the symptoms of endometriosis and fibrocystic breast disease. It also has androgenic effects, which can increase the production of testosterone and lead to masculinization in women. 

danazol is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2-3 hours of oral administration. It has a long elimination half-life of approximately 24-26 hours, which allows for once or twice daily dosing. 

danazol is extensively metabolized in the liver and excreted in the urine and feces. It is primarily metabolized by CYP3A4, and its metabolism can be affected by drugs that induce or inhibit this enzyme. Therefore, caution should be exercised when using danazol in combination with other medications that affect CYP3A4. 

Pharmacodynamics: 

The pharmacodynamics of danazol is related to its anti-estrogenic, anti-progestational, and androgenic effects. 

Anti-estrogenic effects: danazol inhibits the production of gonadotropins, which results in the suppression of ovarian estrogen production. This leads to reduced endometrial proliferation and regression of endometrial implants in endometriosis. In addition, it reduces the cyclic hormonal changes associated with fibrocystic breast disease, resulting in reduced breast pain and tenderness. 

Anti-progestational effects: danazol also inhibits the production of progesterone by suppressing the secretion of luteinizing hormone (LH). This results in an atrophic endometrium, which can help reduce the symptoms of endometriosis. 

Androgenic effects: danazol has weak androgenic effects, which can lead to masculinization in women, including the growth of facial hair, a deeper voice, and an enlarged clitoris. 

Pharmacokinetics: 

Absorption 

The half-life is 4.5 hours 

The peak plasma concentration is achieved in 2 hours 

Distribution 

The drug is well bioavailable 

Metabolism 

It is extensively metabolized in the liver to 2-hydroxymethyl ethisterone 

The metabolites formed are 2-hydroxymethyl ethisterone (activity unknown) 

Elimination and Excretion 

The drug is mainly excreted in the urine, and small amounts are removed in feces 

Adminstartion

Administration 

danazol is usually taken orally in capsule form, with or without food. The exact dosing regimen and duration of treatment will depend on the individual patient and the condition being treated. 

For the treatment of endometriosis, the usual starting dose of danazol is 200-400 milligrams per day, divided into two doses. This dose may be increased up to 800 milligrams per day if necessary. Treatment is typically continued for 6-9 months, although it may be extended in some cases. 

For the treatment of fibrocystic breast disease, the usual starting dose of danazol is 100-400 milligrams per day, divided into two doses. Treatment is typically continued for 3-6 months, although it may be extended in some cases. 

danazol should be taken at the same time(s) each day, and it is important to follow the dosing instructions provided by the healthcare provider. If a dose is missed, it should be taken as soon as possible unless it is close to the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule should be resumed. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: danazol 

Pronounced: DAN-a-zol 

Why do we use danazol? 

danazol is used to treat a variety of conditions, including endometriosis, fibrocystic breast disease, and hereditary angioedema. 

Endometriosis is a condition in which tissue that normally lines the inside of the uterus grows outside of it, causing pain, discomfort, and fertility problems. danazol can help alleviate the symptoms of endometriosis by suppressing ovulation, reducing estrogen and progesterone production, and decreasing endometrial proliferation. 

Fibrocystic breast disease is a condition in which the breasts become lumpy, tender, and painful, especially around the time of menstruation. danazol can help alleviate the symptoms of fibrocystic breast disease by reducing the cyclic hormonal changes associated with this condition.