Danazol - Indications, Contraindications, Warnings, and Precautions

Overview

Danazol is a medication that is extensively employed for treating endometriosis. The usage of Danazol for endometriosis is endorsed by the drug regulatory body of the United States - the Food and Drug Administration (FDA). In addition to endometriosis, Danazol is also advised for certain gynecological troubles. It is a synthetically made hormonal derivative that potentially revises the hormone level in the female body. It is marketed in the form of pills, which are meant to be taken orally.

How Does Danazol Work?

Danazol falls under the category of androgenic hormones, which are artificial male hormonal derivatives. Danazol is obtained from Ethisterone. It works by collapsing the female hormone level, particularly estrogen. It acts on the ovaries by directly checking the steroidogenesis process by which ovarian hormones are produced. Once estrogen production is dropped to a considerable level, it reflects potential beneficial impacts on the female body.

Available Doses and Dosage Forms:

Danazol is available in distinct dosages and is a prescription medicine that cannot be purchased without a doctor’s prescription. Danazol is advised for oral administration and is hence made available as pills. Doctors determine the dosage by taking into account the condition and its severity. The marketed doses of Danazol are as follows;

• Available Doses: 50 milligrams (mg), 100 mg, and 200 mg.

• Dosage Forms: Capsule form.

Warnings:

• Fetal Injury: Danazol is known for its negative impact on the developing female fetus in the womb. If Danazol is consumed by pregnant women, it can impact the fetus. It holds the risk of developing female genital defects, both structural and functional defects like labial fusion, clitoral hypertrophy, vaginal atresia, and many more in the female fetus. Hence it is strictly warned not to take Danazol if planning for pregnancy or has already tested positive. In addition, it is instructed to use non-hormonal contraceptives to check pregnancy while undergoing therapy using Danazol.

• Lethal Strokes: Intake of Danazol, at times, trigger lethal strokes in the form of thromboembolism (the blood flow hampered by an atypical clot that is formed within the vessel).

• Liver Disease: Danazol, when taken for a longer period, remarkably harms liver functions. It triggers the development of certain liver diseases like benign hepatic adenoma (tumor within the liver) and peliosis hepatis (forming blood-gathering spaces within the liver).

• Intracranial Hypertension: Danazol is known for its potency to raise the pressure within the skull giving rise to drug-induced benign intracranial hypertension. In this condition, the brain cells are subjected to exaggerated pressure, which eventually impairs brain functions.

• Risk of Coronary Artery Diseases: Certain studies reported that Danazol intake for an extended period amends the lipid profile in the body. The low-density lipoproteins (bad cholesterol) level rises at the same time, and the high-density lipoprotein (good cholesterol) collapses. This lipid revision enhances the probability of developing coronary artery disease (cholesterol gathering within the coronary arteries). Close monitoring of the lipid profile is mandatory to keep track of coronary arterial disorders.

• Androgenic Effects: As Danazol belongs to the androgenic hormone category, at times, long-run consumption of Danazol precipitates androgenic effects like male pattern hair growth and pimple breakouts. As soon as androgenic effects are reflected, patients are instructed to withdraw the drug and immediately report it to the concerned doctor.

For Patients:

What Is Endometriosis?

The female uterus is coated with a specific layer of cells - the endometrium. It is this layer that enhances the process called implantation. Implantation is the technical term that denotes the attachment of fertilized eggs (egg after union with sperm) into the womb (uterus). Normally, the endometrium develops only in the womb. But in endometriosis, the endometrial layer develops in other areas, like the fallopian tube (bridging the womb and ovary), outside the womb, cervix (links vagina and womb), and vagina, where it is not intended to develop. The exact causative mechanism that triggers the development of endometriosis is still unfigured. Women with endometriosis are encountered with infertility issues and atypical menstrual pain. Blood spots are often encountered in between a period. At times, the pain is elicited even during intercourse, defecation, and urination. Endometriosis negatively impacts the quality of one’s life. Pain and infertility sometimes lead to mental distress and depression. The symptoms associated with endometriosis can be effectively tackled with appropriate medications.

When and Why Is Danazol Prescribed?

Danazol is routinely prescribed to deal with the symptoms of endometriosis and, thereby, enhances the patient’s quality of life. In addition to endometriosis, Danazol is also employed for the treatment of an inborn condition called hereditary angioedema (recurrent pronounced swelling) and fibrocystic breast disease (fluid-filled spaces forms inside the breast). Danazol modifies the hormonal level in the body, and that is how it aids in providing relief from the symptoms associated with endometriosis and fibrocystic breast disease. It is advised to check the repeated occurrence of angioedema. Hence it is proposed for a preventive role rather than treatment.

Things to Inform the Doctor Before Taking Danazol:

Proper communication with the doctor is essential before initiating treatment therapy using Danazol. Some of the critical information to be shared with the doctor include the following:

• If the patient had encountered an exaggerated reaction upon intake of Danazol or other medicine containing any of the constituents in Danazol ever before, it should be priorly informed so that an allergy test can be initiated before advising the treatment dose to clear off suspicion of allergy towards Danazol.

• The patient’s medical history, including details of other disease conditions, should be shared with the doctor. Pre-existing disease conditions like blood disorders (porphyria), heart disease, epilepsy (seizure), kidney disease, boosted blood pressure, vaginal bleeding, and many more, at times elevate the risk of developing lethal complications associated with Danazol.

• A list of all the concomitant medications should be provided to the concerned doctor to make sure that none of the already undertaking medicines react with the Danazol. Occasionally, certain drug-drug associations influence the effectiveness of either or both drugs.

• Pregnant patients are advised to refrain from consuming Danazol as it induces fetal harm. If the woman is planning for conception shortly, it should be discussed with the doctor before initiating the treatment therapy. Furthermore, women in the active sexual phase should discuss with the doctor regarding appropriate contraceptive options to check unplanned pregnancy.

• If the patient is a lactating mother, Danazol can reach the breastfed child’s body through breast milk and can bring about negative hormonal impacts on the baby.

Things to Consider While Taking Danazol:

Danazol therapy should be cautiously monitored for unpleasant reactions. Certain factors need to be taken into account while consuming Danazol. Some of those factors include the following:

• In case the patient got tested positive for pregnancy while undergoing therapy using Danazol, it should be reported to the concerned doctor at the earliest. It is strictly advised to withdraw further Danazol intake.

• Any form of unpleasant event in the body that happens following Danazol intake should be reported as soon as possible. At times, it can be signs of allergic reactions or exaggerated sensitivity towards Danazol.

• If facial puffiness or puffiness involving other body areas develops after initiating Danazol therapy, it should be withdrawn abruptly to check the progression of complications.

• Any signs of stroke (hindered blood flow to the brain) entail immediate medical assistance as it can threaten one’s life.

What Are the Instructions to Be Followed While on Danazol?

• Danazol should be taken only if prescribed by the doctor. Self-medication of Danazol can have lethal impacts on the body.

• Danazol should be taken only in the specified dose that is advised by the concerned physician. Dose modification can either end up in overdose or underdose issues when done without medical advice and consultation.

• It is instructed to consume the pill at the same time every day so that the hormone level gets regularized.

• Before consuming the Danazol pill, make sure that the pills are within the usage period.

• Appropriate contraceptive options need to be implemented to check unintentional conception during Danazol therapy.

What Are the Possible Side Effects of Danazol?

Danazol potentially brings about diverse side effects. Some of the routinely reported side effects of Danazol include the following:

• Danazol intake over a significant period can give rise to the development of androgenic effects on the female body. Male pattern hair loss, acne (pimples), pronounced rise in the bodyweight, the voice becomes harsh and throaty, hirsutism (male pattern hair growth), and seborrheic lesions (dandruff-like flaky patches) are the frequently encountered androgenic side effects of Danazol.

• Various menstrual irregularities in the form of change in the period cycle, abnormal bleeding in between periods (when bleeding is not intended), and occasional missing out of periods are often encountered with Danazol administration.

• Vaginal dryness, abnormal sweating, face turning red and flamed (flushing), emotional outbursts, depleted breast size, and severe irritability are some of the unpleasant effects of Danazol that arise due to diminished estrogen levels in the body.

• Daily intake of a considerably high dose of Danazol precipitates troubles in liver functions.

• Less frequently, certain skin reactions in the form of rashes, blisters, and occasional skin peeling and flaking are encountered following long-term therapy using Danazol.

• Nausea, bloating (gas-filled belly), diarrhea, and vomiting are the widely reported gastrointestinal effects of Danazol.

• Long-term consumption of Danazol reflects atypical puffiness, particularly in the arms and feet. The person encounters pain in the joints and muscle region.

• The person always experiences worn-out and exhausted sensations while undergoing therapy using Danazol.

What Should Be Done if a Dose Is Missed?

Generally, Danazol pills are advised to be taken twice a day. In case the person forgets to take the pill on time and remembers it later, it is advised to take the forgotten dose only after ensuring that there is sufficient time for the next dose. In case the person recognizes the missed dose only at the time of the subsequent dose, it is recommended to ignore the forgotten dose and move ahead with the next dose. It is strictly warned not to consume an extra pill in case of missed doses, as it would end up in toxicity and other issues.

How to Treat Danazol Overdose?

Patients are always schooled to consume only the dose prescribed by the doctor. Taking more than the prescribed quantity of Danazol precipitates lethal impacts on the person’s health. Concerning symptoms like dark-colored urine, intense stomach ache, skin eliciting yellow tint, collapse, and breathing troubles demand instant medical care to safeguard the person’s life. There is no specific medicine that can counter the effect of Danazol.

How to Store Danazol?

• Danazol capsules are marketed in blister packages, and it is intended to be stored in that package itself till consumption.

• Moisture contamination impacts the constituents in the pills. Likewise, exposure to extreme temperatures damages the pill. The ideal temperature range for the storage of Danazol is reported to be 20 to 30 degrees Celsius.

• Make sure that the medicines are not accessible to kids to check the unintentional self-intake of pills by small kids.

For Doctors:

Indications

Danazol is indicated for:

• Endometriosis (responsive to hormonal therapy).

• Fibrocystic breast disease (with nodularity and tenderness).

• Hereditary angioedema (as prophylactic to check further episodes of angioedema).

Contraindications

Danazol is not supposed to be taken under certain conditions. Some of the potential contraindications for Danazol include the following:

• Pregnancy is a critical contraindication for Danazol. The consumption of Danazol induces virilization in the developing female child in the uterus. Consequently, the female fetus exhibits genital malformations in the form of the urogenital sinus, merged labia, and clitoromegaly. These abnormalities are more pronounced when Danazol is consumed in the eighth week of pregnancy or later.

• Danazol is advised not to be taken if the person is suffering from vaginal bleeding, which is not diagnosed.

• Danazol should never be given to a person with porphyria. The enzyme ALA (delta-aminolevulinic acid) synthase is concerned with the breakdown of porphyrins. Danazol enhances the breakdown of porphyrin by stimulating the ALA synthase enzyme, thereby worsening porphyria.

• Compromised heart, kidney, and liver functions are contraindications for Danazol as the medicine further deteriorates the condition.

• Danazol should never be prescribed for individuals with androgen-dependent tumors. Danozol being an androgen derivative, facilitates tumor development.

• Patients with known allergies or pronounced sensitivities toward Danazol or any of its components should refrain from taking Danazol. Further intake of Danazol activates an intense allergic reaction in the body which can be lethal.

• Patients who give a definite history of thromboembolic events should refrain from taking Danazol. The medicine potentially raises the likelihood of developing thrombosis and other related vascular complications.

Dosage and Administration

Dosing: The dosage of Danazol depends on the condition for which it is prescribed and the severity of the condition.

1. Endometriosis: Mild cases are advised to take an inceptive dose of 100 milligrams (mg) to 200 mg capsules two times a day routinely for six months. However, the duration of treatment varies considerably and, at times, may stretch out to nine months. Severe cases require an inceptive dose of 400 mg two times a day. Patients' responses are taken into account while reducing the dose.

2. Fibrocystic Breast Disease: For fibrocystic breast disease, 100 mg of Danazol pills are advised to be taken two times a day.

3. Hereditary Angioedema: 200 mg Danazol pills two times a day are advised for checking angioedema attacks. However, slight alterations in the dosage are made considering the response of the patient toward Danazol therapy.

Administration:

Danazol capsules should be swallowed orally with a glass of water. The pill administration should be initiated during periods to preclude the risk of pregnancy.

Food Interaction:

No reports suggest Danazol interaction with food, and hence, it can be taken either before or after meals.

Pharmacology of Danazol

Mechanism of Action:

Danazol brings about its effect through diverse mechanisms. Danazol interacts with the sex hormones and clamps down the hypothalamic-pituitary-ovarian axis. It directly influences the steroidogenesis process and thereby brings down the hormone synthesis in the ovaries, testes, and adrenals. It diminishes the impact of both follicle-stimulating hormone and luteinizing hormone. Danazol hampers progesterone production from the ovary. In addition, Danazol interacts with certain hormone receptors and globulins like corticosteroid-binding globulin and sex hormone-binding globulin and interrupts the interaction of globulin with the concerned hormone receptors. Furthermore, it modifies the endometrial tissue and makes it degenerative and inactive; thus, it aids in dealing with the symptoms of endometriosis.

Pharmacodynamics:

As a result of the repression of the hypothalamic-pituitary-ovarian axis induced by Danazol, the female hormone level drops considerably. The menstrual cycle rhythm also gets disrupted by Danazol.

Pharmacokinetics:

• Absorption: Following oral intake, Danazol is effectively taken up from the intestine. Within a period of two to eight hours, Danazol attains its utmost concentration in the blood.

• Distribution: As Danazol is soluble in lipids, it can infiltrate into the deeper cellular compartment making it available for deeper sites.

• Metabolism: Danazol undergoes considerable breakdown within the body. The metabolic products encompass two primary metabolites and almost ten secondary metabolites.

• Elimination: The products formed by Danazol metabolism are expelled via urine or feces. Urine is the chief route of Danazol elimination that flushes out the primary metabolites while the remaining smaller proportion of metabolites is expelled through feces.

Drug Interactions

Danazol interacts with a few other drugs to produce some unwanted health impacts. Some of the widely reported drug interactions of Danazol include:

• Danazol administration to a person under Warfarin therapy precipitates the lengthening of prothrombin time.

• Danazol is capable of enhancing insulin resistance, and hence simultaneous administration of Danazol and antidiabetic drugs necessitates thorough glucose monitoring.

• Concurrent intake of both Carbamazepine and Danazol reflects an obvious peaking of Carbamazepine concentration in the blood. In addition to Carbamazepine, Tacrolimus, and Cyclosporine also precipitate pronounced hikes in concentration in the serum, eventually leading to toxicity issues and impacting renal functions.

• Simultaneous intake of Danazol and cholesterol-lowering medicines (statins) like Atorvastatin elevates the likelihood of rhabdomyolysis and myopathy.

• Simultaneous intake of Danazol and glucocorticoids hampers liver function to a great extent.

Warnings and Precautions Before Prescribing Danazol

• Harm to Fetus: Danazol is potentially capable of precipitating defects in the fetus if consumed during pregnancy. Androgenic properties of Danazol induce genital issues in the female fetus in utero.

• Fatal Strokes: Danazol intake at times trigger the development of thromboembolic events and other vascular complications.

• Impaired Liver Function: Consumption of Danazol consistently for a longer period impairs the functions of the liver. It even ends up in liver conditions like benign hepatic adenoma and peliosis hepatis. Hence, periodic assessments should be carried out to keep an eye on liver function.

• Androgenic Effects: Danazol brings in certain androgenic effects on the female body and needs to be monitored closely because those effects cannot be rectified.

• Atherosclerosis: Danazol intake modifies the lipid profile in the body and eventually makes it favorable for the development of coronary artery diseases and atherosclerosis.

• Fluid Retention: Danazol induces fluid gathering in the body, and hence it is advised to monitor when given for patients with a known history of migraine, epilepsy, hypertension, polycythemia, kidney, and heart diseases. Diabetic patients should be prescribed Danazol only after considering their medical needs.

Other Specifications

• Danazol During Pregnancy: Danazol is capable of inducing harmful effects on the fetus, and hence it is strictly not advised for pregnant women. Studies reported genital malformations in the female fetus in response to maternal Danazol intake.

• Danazol During Breastfeeding: Breastfeeding women should refrain from taking Danazol, as it gets into the baby through breastmilk, which can bring in undesirable androgenic effects on the baby’s body.

• Danazol in Pediatric Patients: Data concerning the pediatric use of Danazol is inadequate to establish its efficacy and safety. Hence it is not preferred for the pediatric population.