Danazol (Danocrine) is a synthetic androgen like testosterone. It is used in the treatment of endometriosis, hereditary angioedema, and fibrocystic disease of the breast.

Danazol Uses:

• Endometriosis:

  • For treating endometriosis susceptible to hormonal therapy.

• Hereditary angioedema (HAE), prophylaxis:

  • Prophylaxis against all kinds of angioedema including, cutaneous abdominal, laryngeal in all genders.
  • Guideline recommendations:   Guidelines do not recommend treating HAE acute attacks. However, it may be used instead of CI inhibitor for long time prevention of HAE and temporary use against before procedure.

• Off Label Use of Danazol in Adults:

  • Cyclic mastalgia secondary to benign breast disorders
  • Refractory immune thrombocytopenia.

Danazol (Danocrine) Dose in Adults

Note: start therapy during menstruation in women.

Danazol (Danocrine) Dose in the treatment of Cyclic breast pain (mastalgia) associated with benign breast disorders (off-label):

• Use orally. Start with 100 mg twice daily on day 1 of menstruation.
• Dosing range: 100 to 400 mg per day.
• Duration of therapy: 3 to 6 months.
• The dose was tapered before ending in a few research studies.

Danazol (Danocrine) Dose in the treatment of Endometriosis (females): Oral:

• Mild disease:

  • Initial: 200 to 400 mg/day in 2 divided doses slowly down titrate while maintaining use for 3 -6 months straight, may continue till 9 months.
  • If symptoms develop again treatment can be started once more.

• Moderate to severe disease or infertility:

  • Initial: 800 mg/day in 2 divided doses slowly down titrate while maintaining use for 3 -6 months straight, may continue till 9 months.
  • If symptoms develop again treatment can be started once more.

Danazol (Danocrine) Dose in the treatment of Hereditary angioedema (prophylaxis): Oral:

Note: Because of the adverse effect profile use the smallest possible dose. Multiple short spurts of therapy may lead to side effect frequency comparable to long-duration treatment.

• Short-term/ preprocedural prophylaxis (off-label dose):

  • 5 to 10 mg/kg/day;
  • The dose can be adjusted according to feedback. (maximum: 600 mg/day).
  • Given 5 days prior to the procedure and 2 to 3 days post-procedure.

• Long-term prophylaxis:

  • 100 mg on an alternate day up to 200 mg 2 to 3 times daily.
  • After achieving a positive response dose is reduced by half every 4 to 12 weeks or more based on attack timing
  •  >200 mg/day for an extended period of time is not recommended because of adverse effects.

Danazol (Danocrine) Dose in the treatment of refractory immune thrombocytopenia (off-label):

• Oral: 200 mg 2 to 4 times/day (10 to 15 mg/kg/day in divided doses);
• The response is seen in anywhere from 2 weeks to few months may take up to 6 months or 600 mg once daily for 6 months or more than 400 mg once daily for 3 months, later if remission maintained 200 mg once daily.

Danazol (Danocrine) Dose in Childrens

Danazol (Danocrine) Dose in the treatment of Hereditary angioedema: 

• Adolescents ≥16 years:

  • Short-term prophylaxis (for patient-specific triggers, medical and dental procedures):
    • Oral: 2.5 to 10 mg/kg/day divided into 3 doses;
    • The maximum daily dose: 600 mg/day;
    • begin 5 days prior and continued for 2 to 5 days post procedure.
  • Long-term prophylaxis:
    • Oral: Initial: 2.5 mg/kg/day;
    • The maximum initial daily dose: 50 mg/day;
    • The dose is up titrated gradually every 2 weeks until the maximum tolerated or maximum recommended dose is reached or symptoms resolved.
  • The maximum daily dose: 5 mg/kg/day up to 200 mg/day.
  • After symptoms are improved down-titrate dose ;
  • The maximum dose: 100 mg/dose.

Danazol (Danocrine) Pregnancy Category: X

• [US Boxed Warning]Pregnancy is not a good time to use Danazol.
• Danazol exposure in utero can cause androgenic effects for the female fetus.
• There have been reports of clitoral hypertrophy and labial fusion as well as urogenital sinus defect and vaginal atresia.
• Before treatment, it is important to get rid of any pregnancy. Non-hormonal contraception can be used for the duration of the therapy.
• If the patient becomes pregnant during treatment, discontinue immediately.
• There are very few case reports that show pregnancy with danazol for non-responsive HAE.

Danazol use during breastfeeding:

• Breastfeeding is not recommended. Before starting Danazol, you should use other agents or stop breastfeeding.

Dose in Kidney disease:

Contraindicated in severe renal failure.

Dose in Liver disease:

Contraindicated in severe liver dysfunction.

Side effects of Danazol (Danocrine):

• Cardiovascular:

  • Edema
  • Flushing
  • Hypertension
  • Myocardial Infarction
  • Palpitations
  • Syncope
  • Tachycardia

• Central Nervous System:

  • Depression
  • Dizziness
  • Emotional Lability
  • Fatigue
  • Headache
  • Nervousness
  • Paresthesia
  • Sleep Disorder
  • Voice Disorder (Deepening Of The Voice, Hoarseness, Instability, Sore Throat)

• Dermatologic:

  • Acne Vulgaris
  • Alopecia
  • Diaphoresis
  • Maculopapular Rash
  • Papular Rash
  • Pruritus
  • Seborrhea
  • Urticaria
  • Vesicular Eruption

• Endocrine & Metabolic:

  • Amenorrhea (May Continue Post-Therapy)
  • Change In Libido
  • Decreased Glucose Tolerance (And Glucagon Changes)
  • Decreased HDL Cholesterol
  • Decreased Thyroxine Binding Globulin
  • Hirsutism (Mild)
  • Increased LDL Cholesterol
  • Increased Thyroxine Binding Globulin
  • Menstrual Disease (Altered Timing Of Cycle, Spotting)
  • Weight Gain

• Gastrointestinal:

  • Constipation
  • Gastroenteritis
  • Nausea
  • Vomiting

• Genitourinary:

  • Asthenospermia
  • Breast Atrophy
  • Decreased Ejaculate Volume
  • Hematuria
  • Inhibition Of Spermatogenesis
  • Spermatozoa Disorder (Changes In Sperm Count And Semen Viscosity)
  • Vaginal Dryness
  • Vaginal Irritation

• Hematologic & Oncologic:

  • Abnormal Erythrocytes (Increased)
  • Decreased Sex Hormone Binding Globulin
  • Eosinophilia
  • Increased Sex Hormone-Binding Globulin
  • Leukocytosis
  • Leukopenia
  • Malignant Neoplasm (After Prolonged Use)
  • Petechial Rash
  • Polycythemia
  • Purpuric Rash
  • Thrombocythemia
  • Thrombocytopenia

• Hepatic:

  • Cholestatic Jaundice
  • Hepatic Adenoma
  • Hepatic Neoplasm (Malignant; After Prolonged Use)
  • Increased Liver Enzymes
  • Jaundice
  • Peliosis Hepatitis

• Neuromuscular & Skeletal:

  • Ankylosing Spondylitis
  • Arthralgia
  • Back Pain
  • Increased Creatine Phosphokinase
  • Joint Swelling
  • Limb Pain
  • Muscle Cramps
  • Muscle Spasm
  • Neck Pain
  • Tremor
  • Weakness

• Ophthalmic:

  • Visual Disturbance

• Respiratory:

  • Interstitial Pneumonitis

Contraindications to Danazol (Danocrine):

• Hypersensitivity to danazol and any component of the formula
• Undiagnosed abnormal Genital Bleeding.
• pregnancy
• Breastfeeding
• porphyria
• Severe renal, cardiac, or liver failure
• androgen-dependent tumor
• Current or past history of thrombosis/thromboembolic diseases

Canadian labeling: Additional contraindications not in the US labeling

• Genital neoplasia
• Simvastatin may be administered concurrently.

Warnings and precautions

• Androgen effects:

  • It can cause permanent androgenic effects.

• Changes in blood lipids:

  • Atherosclerosis and CAD risk increase due to decreased high-density and increased low-density cholesterol.

• Hepatotoxicity: [US Boxed Warning]

  • When used for a prolonged period, peliosis liveritis and benign hepatic tumors have been reported. 
  • Although initial symptoms may not be apparent, they may lead to serious intraabdominal bleeding. 
  • Use minimum lowest effective dose. Do not delay in reducing the dose.
  • You should monitor your liver function and be on the lookout for potential hepatotoxicity while you are receiving treatment.

• Intracranial hypertension [US Boxed Warning]

  • This condition may be linked to pseudotumor cerebri, which can cause headaches, nausea, vomiting, and visual impairments.
  • If you are experiencing signs and symptoms, it is important to have a neurology evaluation done immediately.

• Thromboembolic Events: [US Boxed Warning]

  • There have been reports of thromboembolism, blood clots, and thrombotic events (including sagittal sinusthrombosis, life-threatening strokes, or fatal strokes).

• A benign breast disorder is associated with cyclic breast pain (mastalgia).

  • Second-line agent for benign conditions only. This is when the pain is not responding to other analgesics.

• Diabetes:

  • Diabetes patients may experience an increase in insulin use. Be careful.

• Conditions that are edematous:

  • Patients with underlying conditions like migraine, heart disease, or renal impairment should be cautious when using edema.

• Porphyria

  • Patients with porphyria should not be given this medication as it can worsen AIP.

Danazol: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Liver and kidney function tests (periodically);
• hematologic parameters;
• lipid panel.
• Signs and symptoms of intracranial hypertension (papilledema, headache, nausea, vomiting), androgenic changes, and/or fluid retention.
• Hereditary angioedema, long-term prophylaxis:
  • CBC, urinalysis, liver function test, and lipid profile (baseline, every 6 months while on therapy and 6 months following discontinuation);
  • liver ultrasound (baseline and then yearly);
  • blood pressure (every 6 months)

Cyclic breast pain (mastalgia) secondary to benign  breast disorders:

• Pain and side effects; in most studies, this was done (at a minimum) following 1, 3, and 6 months of therapy.

How to administer Danazol (Danocrine)?

Endometriosis: therapy is started in menstruation. Pregnancy must be avoided during treatment.

Mechanism of action of Danazol (Danocrine):

• Reduces abnormal breast tissue proliferation, atrophy local and ectopic endometrial growth, and increases C-4 complement levels to reduce hereditary angioedema spells.
• This is done by suppressing FSH/LH production from pituitary.

The onset of action:

• Immune thrombocytopenia (off-label use):
  • Initial response: 14 to 90 days;
  • Peak response: 28 to 180 days.

Metabolism:

• major site: hepatic, mainly to 2-hydroxymethyl danazol and ethisterone

Half-life elimination:

• 9.7 ± 3.29 hours (variable; up to 24 hours following long-term use for endometriosis)

Time to peak, serum:

• 4 hours (range: 2 to 8 hours)

Excretion:

• Urine and feces

International Brand Names of Danazol:

• Cyclomen
• Anargil
• Azol
• Cipladanogen
• Cyclolady
• D-Zol
• Dana
• Danamet
• Danarem
• Danasin
• Danatrol
• Danazol
• Danazol Jean Marie
• Danazol-ratiopharm
• Danocil
• Danocrine
• Danodiol
• Danogar
• Danogen
• Danokrin
• Danol
• Danoval
• Dazol
• Dorink
• Ectopal
• Elle
• Gonablock
• Gonablok
• Gong Fu Yi Kang
• Kupdina
• Ladazol
• Ladogal
• Lozana
• Mastodanatrol
• Nazol
• Novaprin
• Vabon
• Winobanin
• Zendol

Danazol Brand Names in Pakistan: