Danazol

Danazol is a synthetic androgen derived from ethisterone belonging to the pharmacological class of pituitary gonadotropin inhibitors.

Danazol is approved for use by the FDA for treating endometriosis, fibrocystic breast disease, and hereditary angioedema.

Danazol is well-absorbed orally, reaching peak plasma levels within hours. It binds extensively to plasma proteins and is distributed throughout the body. Metabolism primarily occurs in the liver, followed by excretion through urine and feces.

The most common side effects of Danazol include irregular menstruation cycles, weight gain, hair loss, voice changes, and acne. Danazol is available in the form of oral capsules.

The molecule is available in India, the United States, Canada, the United Kingdom, Italy, Australia, Germany, France, Japan and Spain.

Danazol is a synthetic androgen derived from ethisterone belonging to the pharmacological class of pituitary gonadotropin inhibitors.

Because it inhibits gonadotropin production in the pituitary, Danazol suppresses the pituitary-ovarian axis. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) preovulatory surge is suppressed, which lowers ovarian estrogen production. Danazol binds to androgen, progesterone, and glucocorticoid receptors and may directly stop ovarian steroidogenesis. Additionally, it interacts with globulins that bind to corticosteroids and sex hormones, increasing the pace at which progesterone is cleared metabolically. In addition, it might reduce phospholipid and IgG isotope autoantibodies and the quantities of IgG, IgM, and IgA to reverse endometriosis. It may inhibit estrogenic stimulation in fibrocystic breast disease, affecting steroid receptor sites in breast tissue and leading to the removal of nodules and alterations in menstruation patterns. Danazol increases serum concentrations of inadequate C1 esterase inhibitor, which raises serum C4 complement levels, in treating hereditary angioedema.

Danazol action's data duration is approximately 24 to 48 hours after administration.

The onset of Danazol action typically occurs within a few days after its initial administration.

The Data of Cmax of Danazol occurs approximately 2 to 8 hours after oral administration.

The Data of Tmax of Danazol has yet to be established.

Danazol is available in the form of oral capsules.

Capsules: To be swallowed whole with water/liquid. Do not chew, crush or break it.

As the physician recommends, take the medication orally twice daily and it can be taken with or without food as directed.

Danazol can be used for the following health conditions:

Danazol effectively manages benign fibrocystic breast disease symptoms, alleviating tenderness and lumps in breast tissue. It accomplishes this by suppressing ovarian activity and reducing estrogen levels, inducing temporary menopause. Additionally, Danazol inhibits the release of hormones that contribute to breast pain and tissue growth outside the uterus, providing relief from bothersome symptoms associated with this non-cancerous condition.

Endometriosis: Danazol is indicated to treat symptoms associated with endometriosis and/or to decrease the number of endometriotic foci. Danazol can be used as the only hormonal therapy in patients who are not responding to other treatments, or it can be used in conjunction with surgery.

Benign Fibrocystic Breast Disease: Danazol is indicated to treat the symptoms of severe breast fibrocystic disease, including pain and tenderness. Patients who do not respond well to other therapeutic approaches or for whom such approaches are not otherwise recommended should be treated with Danazol.

Breast cancer should be diagnosed thoroughly before starting treatment.

The maximum duration of the treatment should be three to six months.

Orally: Danazol is usually administered orally as a tablet, twice daily, with or without food; adjust dosage according to patient response and severity of condition. When an effective response develops, consider reducing the dosage. Start treatment when a woman is menstruating or wait to start Danazol until after the appropriate investigations have confirmed that there has been no pregnancy. Throughout treatment, take consistent non-hormonal contraception. Approximately one-third of patients—especially those taking higher doses—have regular, inconsistent, or nonexistent menstrual cycles. Treat patients for no more than three or six months at a time.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Danazol is available in the form of oral capsules.

Mild: 200-400 mg/day orally divided BID

Moderate-to-severe: 800 mg/day orally divided BID

Reduce the dosage to a level that will maintain amenorrhea.

Typically, therapy lasts six months, although it might increase to nine.

100–400 mg PO divided BID each day

There was maintenance therapy for three to six months.

First, 200 mg PO BID/TID, then

Reduce the dosage by fifty per cent every one to three months.

If an attack happens, gradually up the dosage to 200 mg daily.

It's crucial to incorporate high-fiber foods like vegetables, fruits and whole grains while limiting processed and fried foods. Making better dietary choices is achieved by favoring plant-based proteins over animal proteins. Limiting alcohol and caffeinated beverages is essential for optimal symptom management. Necessary measures include abstaining from smoking and excessive alcohol use, as well as maintaining a healthy weight through moderate exercise.

The dietary restriction should be individualized as per patient requirements.

Danazol may be contraindicated in the following conditions: -

The adverse reactions related to Danazol can be categorized as:

Common Adverse Effects: Weight gain, acne, oily skin, decreased breast size, and irregular menstruation.

Less Common Adverse Effects: Mood swings, headache or hot flashes.

Rare Adverse Effects: Liver abnormalities, cardiovascular issues, fluid retention, or allergic reactions such as hives or swelling.

The clinically relevant drug interactions of Danazol are briefly summarized here.

Prothrombin time prolongation may occur in patients who are stable on warfarin. Danazol usage concurrently may raise carbamazepine levels. Because Danazol can cause insulin resistance, using antidiabetic drugs with caution is advised. Danazol may cause elevated plasma levels of cyclosporin and tacrolimus, which increases the risk of renal toxicity and necessitates systemic concentration monitoring and dose modifications. Danazol could cause synthetic vitamin D analogues to be more calcemic in people with primary hypoparathyroidism. When Danazol is used concurrently with statins such as atorvastatin, lovastatin, or simvastatin, the risk of myopathy and rhabdomyolysis increases. This should be carefully considered, and the labelling of statin drugs may recommend dose adjustments.

The most common side effects of Danazol include:

Hoarseness of voice

Itchy scalp and hair loss

Weight gain

Stomach pain

Skin rashes

Chest pain

Acne

Abnormal hair growth on a woman's face and body

Swelling

Sore throat

Pregnancy Category X (FDA): The risks outweigh the potential benefits. Safer alternatives exist.

It is contraindicated for women who are pregnant or may become pregnant to use Danazol capsules.

Pregnancy-related drug exposure has been linked to androgenic consequences in female fetuses, including vaginal atresia, urogenital sinus defect, clitoral enlargement, and ambiguous genitalia.

When given orally to pregnant rats between the sixth and the fifteenth day of gestation at dosages as high as 250 mg/kg/day (7–15 times the human dose), the drug did not cause teratogenicity or embryotoxicity, nor did it affect the size, viability, or weight of the offspring when compared to controls.

When this medication was given to rabbits between days 6 and 18 of pregnancy at doses of 60 mg/kg/day and higher (2-4 times the human amount), the development of the fetus was inhibited.

Contraindicated in breastfeeding patients.

As per the FDA, safety and effectiveness in the pediatric population have not been established.

The safety and efficacy of Danazol in geriatric patients haven't been extensively studied. Caution is advised due to the potential risks of prostate hypertrophy, altered lipid profiles, and hepatic complications. Elderly patients should receive the lowest effective dose, with close monitoring for possible complications during treatment.

Renal impairment: Should be used only if the benefits outweigh the risks; Caution.

Patients with liver function disorders should take caution while administering Danazol capsules because the drug is extensively metabolized in the liver.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Danazol.

Overconsumption of Danazol could lead to yellowing eyes/skin, severe stomach/abdominal pain, and dark urine.

There is no specific antidote or treatment for excessive Danazol intake, so treatment typically involves symptomatic and supportive measures. Danazol should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake.

In cases where ingestion occurred recently, gastric lavage may be intended, followed by supportive treatment to manage symptoms. It is essential to monitor vital signs, electrolytes, and organ function. Hospitalization and observation at a medical facility are required in severe cases, especially if extensive drug intake is suspected.

Danazol derives from ethisterone, a modified form of testosterone, which is a synthetic steroid. Although it was the first medication approved by the U.S. Food and Drug Administration (FDA) to treat endometriosis specifically, gonadotropin-releasing hormone (GnRH) agonists have essentially taken its position as an endometriosis treatment. Danazol exhibits both anti-gonadotropic and anti-estrogenic properties. Danazol functions as an anterior pituitary suppressor by preventing the pituitary from producing gonadotropins. It has some androgenic characteristics. Continuous monitoring for any potential complications or adverse effects is essential.

Danazol capsules are taken orally and absorbed well from the gastrointestinal tract. After ingestion, they are efficiently absorbed, reaching peak levels in the bloodstream within 2 to 3 hours, thereby exerting their intended effects.

Due to its lipophilicity and ability to partition into cell membranes, Danazol is likely to be distributed into deep tissue compartments.

The metabolites of Danazol appear to be metabolized down and removed by the kidneys and faeces. In the urine, 2-hydroxymethyl danazol and ethisterone are the two primary metabolites that are eliminated. Products found in faeces included at least ten distinct items.Different studies have shown different elimination half-lives for Danazol. Male healthy subjects have a mean half-life of 9.7 hours for Danazol. In endometriosis patients, the half-life of Danazol was observed to be 23.7 hours after 6 months of 200 mg three times a day therapy.

Metabolism: extensively in the liver to 2-hydroxymethyl ethisterone

Metabolites: 2-hydroxymethyl ethisterone (activity unknown)