DANOGEN Capsules (Danazol)

Table of Content

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory or for Specialist Use only

 Black Box Warning

Use of danazol in pregnancy is contraindicated. A sensitive test (e.g., beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy. Additionally, a non-hormonal method of contraception should be used during therapy. If a patient becomes pregnant while taking danazol, administration of the drug should be discontinued and the patient should be apprised of the potential risk to the foetus. Exposure to danazol in utero may result in androgenic effects on the female foetus; reports of clitoral hypertrophy, labial fusion, urogenital sinus defect, vaginal atresia, and ambiguous genitalia have been received.

Thromboembolism, thrombotic and thrombophlebitic events including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported.

Experience with long-term therapy with danazol is limited. Peliosis hepatis and benign hepatic adenoma have been observed with long-term use. Peliosis hepatis and hepatic adenoma may be silent until complicated by acute, potentially life-threatening intraabdominal haemorrhage. The physician therefore should be alert to this possibility. Attempts should be made to determine the lowest dose that will provide adequate protection. If the drug was begun at a time of exacerbation of hereditary angioneurotic oedema due to trauma, stress or other cause, periodic attempts to decrease or withdraw therapy should be considered.

Danazol has been associated with several cases of benign intracranial hypertension also known as pseudotumor cerebri. Early signs and symptoms of benign intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be screened for papilledema and, if present, the patients should be advised to discontinue danazol immediately and be referred to a neurologist for further diagnosis and care.

Qualitative and Quantitative Composition

DANOGEN 50

Each capsule contains:

Danazol…50 mg

DANOGEN 100

Each capsule contains:

Danazol…100 mg

DANOGEN 200

Each capsule contains:

Danazol…200 mg

Dosage Form(s) and Strength(s)

Capsules for oral use containing Danazol 50 mg, 100 mg and 200 mg.

Clinical Particulars

Therapeutic Indications

Endometriosis: Treatment of endometriosis where the required end-point of treatment is fertility, or for the control of symptoms when surgery is contraindicated or has been unsuccessful. To control pain, pelvic tenderness and other associated symptoms and to resolve or reduce the extent of endometriotic foci. Treatment of endometrios is associated symptoms or/and to reduce the extent of endometriosis foci. Danazol may be used either in conjunction with surgery or, as sole hormonal therapy, in patients not responding to other treatments.

Severe Cyclical Mastalgia: With or without nodularity (fibrocystic disease), unresponsive to counselling or analgesics, to reduce pain, tenderness and nodularity.

Breast Cysts: Control of benign, multiple or recurrent breast cysts in conjunction with aspiration.

Dysfunctional Uterine Bleeding (DUB): In DUB presenting as menorrhagia, to control excessive blood loss, to control associated dysmenorrhoea.

Symptomatic Gynaecomastia: Both idiopathic and drug induced, to reduce the size of breast, to control pain and tenderness.

Preoperative Thinning of Endometrium: Prior to hysteroscopic endometrial ablation.

Other Possible Uses: Hereditary angioneurotic oedema (HAE).

Posology and Method of Administration

DANOGEN should be given as a continuous course, with dosage being adjusted according to the severity of the condition and the patient’s response. A reduction in dosage once a satisfactory response has been achieved may prove possible. In fertile females, DANOGEN should be started during menstruation, preferably on the first day, to avoid exposing a pregnancy to its possible effects. Where doubt exists, appropriate checks should be made to exclude pregnancy before starting medication. Females of childbearing age should employ non-hormonal contraception throughout the course of treatment.

Endometriosis

In moderate-to-severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhoea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhoea may be considered depending upon patient response. For mild cases, an initial daily dose of 200-400 mg given in two divided doses is recommended and may be adjusted depending on patient response. Dosage should be increased if normal cyclical bleeding still persists after two months therapy, a higher dosage (not exceeding 800 mg per day) may also be needed for severe disease. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. It is essential that therapy continue uninterrupted for 3-6 months but may be extended to 9 months if necessary. After termination of therapy, if symptoms recur, treatment can be reinstituted.

Severe Cyclical Mastalgia

200-300 mg daily; for 3-6 months.

Fibrocystic Breast Disease

The total daily dosage of danazol for fibrocystic breast disease ranges from 100-400 mg given in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with danazol. A non-hormonal method of contraception is recommended when danazol is administered at this dose, since ovulation may not be suppressed. In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2-3 months. Usually, elimination of nodularity requires 4-6 months of uninterrupted therapy. Regular menstrual patterns, irregular menstrual patterns, and amenorrhoea each occur in approximately one-third of patients treated with 100 mg of danazol. Irregular menstrual patterns and amenorrhoea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within 1 year. In this event, treatment may be reinstated.

Benign Breast Cysts

300 mg daily for 3-6 months.

DUB

200 mg daily for 3 months.

Gynaecomastia

200 mg daily in adolescents, which may be increased to 400 mg daily if no response is obtained after 2 months. Adults may be given 400 mg daily for 6 months.

Preoperative Thinning of the Endometrium

The usual dose is 400-800 mg daily given as a continuous course for 3-6 weeks.

Hereditary Angioneurotic Oedema

The dosage requirements for continuous treatment of hereditary angio-oedema with danazol should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. After a favourable initial response is obtained in terms of prevention of episodes of oedematous attacks, the proper continuing dosage should be determined by decreasing the dosage by 50% or less at intervals of 1-3 months or longer if frequency of attacks prior to treatment dictates. If an attack occurs, the daily dosage may be increased by up to 200 mg. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.

Contraindications

Danazol should not be administered to patients with the following:

  • Undiagnosed abnormal genital bleeding
  • Markedly impaired hepatic, renal, or cardiac function
  • Pregnancy
  • Breastfeeding
  • Porphyria – danazol can induce ALA synthetase activity and, hence, porphyrin metabolism
  • Androgen-dependent tumour
  • Active thrombosis or thromboembolic disease and history of such events
  • Hypersensitivity to danazol or to any of the excipients
  • Concomitant administration with simvastatin

Special Warnings and Precautions for Use

Warnings

A temporary alteration of lipoproteins in the form of decreased high-density lipoproteins and, possibly, increased low-density lipoproteins has been reported during danazol therapy. These alterations may be marked, and prescriber should consider the potential impact on the risk of atherosclerosis and coronary artery disease in accordance with the potential benefit of the therapy to the patient.

Until more is known, caution is advised in the use of danazol in the presence of known or suspected malignant disease. Before initiating therapy of fibrocystic breast disease with danazol, carcinoma of the breast should be excluded. However, nodularity, pain and tenderness due to fibrocystic breast disease may prevent recognition of underlying carcinoma before treatment is begun. Therefore, if any nodule persists or enlarges during treatment, hormone - dependent carcinoma should be considered and ruled out at least by careful clinical examination before initiating therapy with danazol.

Patients should be watched closely for signs of androgenic effects, some of which may not be reversible even when drug administration is stopped.

In the event of virilisation, danazol should be withdrawn. Androgenic reactions generally prove reversible, but continued use of danazol after evidence of androgenic virilisation increases the risk of irreversible androgenic effects.

Danazol should be stopped if any clinically significant adverse event arises, and particularly if there is evidence of papilloedema, headache, visual disturbances or other signs or symptoms of raised intracranial pressure, jaundice or other indication of significant hepatic disturbance, thrombosis or thromboembolism.

Whilst a course of therapy may need to be repeated, care should be observed as no safety data are available in relation to repeated courses of treatment over time. The long-term risk of 17-alkylated steroids (including benign hepatic adenomata, hepatocellular focal nodular hyperplasia, peliosis hepatis and hepatic carcinoma), should be considered when danazol, which is chemically related to those compounds, is used.

Data, from two case-control epidemiological studies, were pooled to examine the relationship between endometriosis, endometriosis treatments and ovarian cancer. These preliminary results suggest that the use of danazol might increase the baseline risk of ovarian cancer in - patients treated for endometriosis.

Precautions

Because danazol may cause some degree of fluid retention, conditions that might be influenced by this factor, such as epilepsy, migraine, or cardiac or renal dysfunction, polycythaemia and hypertension require careful observation and caution. Use with caution in patients with diabetes mellitus.

Since hepatic dysfunction manifested by modest increases in serum transaminases levels has been reported in patients treated with danazol capsules, periodic liver function tests should be performed.

Administration of danazol has been reported to cause exacerbation of the manifestations of acute intermittent porphyria.

Laboratory monitoring of the haematologic state should be considered.

In view of its pharmacology, known interactions and side effects, particular care should be observed when using danazol in patients with hepatic or renal disease, hypertension or other cardiovascular disease and in any state which may be exacerbated by fluid retention as well as in diabetes mellitus, polycythaemia, epilepsy, lipoprotein disorder, and in those who have shown marked or persistent androgenic reaction to previous gonadal steroid therapy.

Before treatment initiation, the presence of hormone-dependent carcinoma should be excluded at least by careful clinical examination, as well as if breast nodules persist or enlarge during danazol treatment.

Caution is advised in patients with migraine.

In addition to clinical monitoring in all patients, appropriate laboratory monitoring should be considered which may include periodic measurement of hepatic function and haematological state. For long-term treatment (> 6 months) or repeated courses of treatment, biannual hepatic ultrasonography is recommended.

The lowest effective dose of Danazol should always be sought. 

Drug Interactions

  1. Prolongation of prothrombin time occurs in patients stabilized on warfarin.
  2. Therapy with danazol may cause an increase in carbamazepine levels in patients taking both drugs.
  3. Danazol can cause insulin resistance. Caution should be exercised when used with antidiabetic drugs.
  4. Danazol may raise the plasma levels of cyclosporin and tacrolimus, leading to an increase of the renal toxicity of these drugs. Monitoring of systemic concentrations of these drugs and appropriate dose adjustments may be needed when used concomitantly with danazol
  5. Danazol can increase the calcemic response to synthetic vitamin D analogs in primary hypoparathyroidism.
  6. The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with statins such as simvastatin, atorvastatin and lovastatin. Caution should be exercised if used concomitantly. Consult the product labeling for statin drugs for specific information on dose restrictions in presence of danazol.

Laboratory Tests

Danazol treatment may interfere with laboratory determinations of testosterone, androstenedione and dehydroepiandrosterone. Other metabolic events include a reduction in thyroid-binding globulin and T4 with increased uptake of T3, but without disturbance of thyroid-stimulating hormone or of free-thyroxin index.

Use in Special Population

Pregnant Women

Pregnancy Category X.

There is epidemiological and toxicological evidence of hazard in human pregnancy. Danazol is known to be associated with the risk of virilization to the female foetus if administered during human pregnancy. Danazol should not be used during pregnancy.

Danazol should be initiated during menstruation. Women of childbearing age should be advised to use an effective, non-hormonal, method of contraception. If the patient conceives during therapy, danazol should be stopped.

Lactating Women

Contraindicated for lactation.

Danazol has the theoretical potential for androgenic effects in breastfed infants and therefore either danazol therapy or breast-feeding should be discontinued.

Paediatric Patients

Safety and effectiveness in paediatric patients have not been established.

Geriatric Patients

Clinical studies of danazol did not include sufficient numbers of subjects aged 65 years and over to determine the safety and effectiveness of danazol in elderly patients.

Effects on Ability to Drive and Use Machines

Danazol has no or negligible influence on the ability to drive and use machines.

Undesirable Effects

The following events have been reported in association with the use of danazol. For few reactions, a causal relationship to the administration of danazol has neither been confirmed nor refuted:

Androgenic effects: weight gain, acne, seborrhoea, hirsutism, oedema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris, fluid retention.

Other possible endocrine effects: Menstrual disturbances including spotting, alteration of the timing of the cycle and amenorrhoea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with danazol, persistent amenorrhoea has occasionally been reported. Flushing, sweating, vaginal dryness and irritation and reduction in breast size may reflect lowering of oestrogen.

Laboratory tests: Abnormalities in laboratory tests may occur during therapy with danazol, including creatine phosphokinase (CPK), glucose tolerance, glucagon, thyroid-binding globulin, sex-hormone-binding globulin, other plasma proteins, lipids and lipoproteins.

Allergic: Urticaria, pruritus and rarely, nasal congestion.

CNS Effects: Headache, nervousness and emotional lability, depressed mood, dizziness and fainting, depression, fatigue, sleep disorders, tremor, paraesthesias, weakness, visual disturbances, and rarely, benign intracranial hypertension, anxiety, changes in appetite, chills, and rarely convulsions, Guillain- Barré syndrome, vertigo, migraine, aggravation of epilepsy, carpal tunnel syndrome.

Gastrointestinal: Gastroenteritis, nausea, vomiting, constipation and, rarely, pancreatitis and splenic peliosis, epigastric pain.

Musculoskeletal and Connective Tissue Disorders: Muscle cramps or spasms, or pains, joint pain, joint lockup, joint swelling, pain in back, neck, or extremities, muscle tremors, fasciculation. Rarely, carpal tunnel syndrome which may be secondary to fluid retention.

Cardiac Disorders: Hypertension, palpitations and tachycardia. Thrombotic events including sagittal sinus, cerebrovascular thrombosis as well as arterial thrombosis. Myocardial infarction.

Genitourinary: Haematuria with prolonged use in patients with hereditary angio-oedema, prolonged post-therapy amenorrhoea, pelvic pain, and nipple discharge.

In males, a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.

Haematologic: An increase in red cell and platelet count. Reversible erythrocytosis, leukocytosis or polycythaemia may be provoked. Eosinophilia, leukopenia, splenic peliosis and thrombocytopenia have also been noted.

Skin: Rashes (maculopapular, vesicular, papular, purpuric, petechial) and may be accompanied by fever or may take an urticarial form and may be accompanied by facial oedema) and rarely, sun sensitivity, Stevens-Johnson syndrome, inflammatory erythematosus nodules, changes in skin pigmentation, exfoliative dermatitis and erythema multiforme.

Eye Disorders: Visual disturbances such as blurring of vision, difficulty in focusing, difficulty in wearing contact lenses and refraction disorders requiring correction and, rarely, cataracts.

Respiratory, Thoracic and Mediastinal Disorders: Pleuritic pain, interstitial pneumonitis.

Hepatobiliary Disorders: Hepatic dysfunction, as evidenced by reversible elevated serum enzymes (transaminase) and/or jaundice, has been reported in patients receiving a daily dosage of danazol of 400 mg or more. It is recommended that patients receiving danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation.

Isolated increases in serum transaminase levels, serious hepatic toxicity including cholestatic jaundice, benign hepatic adenomata and pancreatitis, peliosis hepatis as well as malignant hepatic tumour, hepatocellular injury, hepatic failure, jaundice hepatocellular, hepatocellular focal nodular hyperplasia have been reported.

Metabolism and nutrition disorders: Increased insulin resistance, increase in plasma glucagon, mild impairment of glucose tolerance.

Increase in LDL cholesterol, decrease in HDL cholesterol, affecting all subfractions, and decrease in apolipoproteins AI and AII.

Induction of aminolevulinic acid (ALA) synthetase, and reduction in thyroid-binding globulin, T4, with increased uptake of T3 but without disturbance of thyroid-stimulating hormone or free levothyroxine index.

Other: Change in libido, bleeding gums, fever.

Reporting of side effects

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 18002677779. By reporting side-effects, you can help provide more information on the safety of this product.

Overdose

Available evidence suggests that acute overdosage would be unlikely to give rise to immediate serious reaction. In the case of acute overdose, consideration should be given to reducing the absorption of the drug with activated charcoal and the patient should be kept under observation in case of any delayed reactions.

Pharmacological Properties

Pharmacodynamic Properties

Danazol suppresses the pituitary-ovarian axis. This suppression is probably a combination of depressed hypothalamic-pituitary response to lowered oestrogen production, the alteration of sex-steroid metabolism, and interaction of danazol with sex hormone receptors. The only other demonstrable hormonal effect is weak androgenic activity. Danazol depresses the output of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Danazol, 17a-pregna-2,4-dien-20-yno(2,3-d)-isoxazol-17-ol, is a synthetic steroid derived from ethisterone. Its pharmacological properties are as below:

  • Relatively marked affinity for androgen receptors, less marked affinity for progesterone receptors and least affinity for oestrogen receptors. In addition, anti-androgenic, progestogenic, anti-progestogenic, oestrogenic and anti-oestrogenic actions have been observed with danazol.
  • Interference with the synthesis of gonadal steroids, possibly by inhibition of the enzymes of steroidogenesis, including 3β hydroxysteroid dehydrogenase,17β hydroxysteroid dehydrogenase, 17 hydroxylase, 17, 20 lyase, 11β hydroxylase, 21 hydroxylase and cholesterol side chain cleavage enzymes, or alternatively by inhibition of the cyclic AMP accumulation usually induced by gonadotrophic hormones in granulosa and luteal cells.
  • Inhibition of the midcycle surge of FSH and LH as well as alterations in the pulsatility of LH. Danazol can also reduce the mean plasma levels of these gonadotropins after menopause.
  • A wide range of actions on plasma proteins, including increasing prothrombin, plasminogen, antithrombin III, alpha 2-macroglobulin, C1 esterase inhibitor, and erythropoietin and reducing fibrinogen, thyroid binding and sex hormone-binding globulins. Danazol increases the proportion and concentration of testosterone carried unbound in plasma.
  • The suppressive effects of danazol on the hypothalamic-pituitary-gonadal axis are reversible, cyclical activity reappearing normally within 60-90 days after therapy.

Recent evidence suggests a direct inhibitory effect at gonadal sites and a binding of danazol to receptors of gonadal steroids at target organs. In addition, danazol has been shown to significantly decrease IgG, IgM and IgA levels, as well as phospholipid and IgG isotope autoantibodies in patients with endometriosis and associated elevations of autoantibodies, suggesting this could be another mechanism by which it facilitates regression of the disease.

In the treatment of endometriosis, danazol alters the normal and ectopic endometrial tissue so that it becomes inactive and atrophic. Complete resolution of endometrial lesions occurs in the majority of cases.

Changes in vaginal cytology and cervical mucus reflect the suppressive effect of danazol on the pituitary-ovarian axis.

In the treatment of fibrocystic breast disease, danazol usually produces partial to complete disappearance of nodularity and complete relief of pain and tenderness. Changes in the menstrual pattern may occur.

Generally, the pituitary-suppressive action of danazol is reversible. Ovulation and cyclic bleeding usually return within 60-90 days when therapy with danazol is discontinued.

In the treatment of hereditary angio-oedema, danazol at effective doses prevents attacks of the disease characterized by episodic oedema of the abdominal viscera, extremities, face, and airway which may be disabling and, if the airway is involved, fatal. In addition, danazol corrects partially or completely the primary biochemical abnormality of hereditary angio-oedema by increasing the levels of the deficient C1 esterase inhibitor (C1EI). As a result of this action the serum levels of the C4 component of the complement system are also increased.

Pharmacokinetic Properties

Danazol is absorbed from the gastrointestinal tract, peak plasma concentrations of 50-80ng/ml being reached approximately 2-3 hours after dosing. Compared to the fasting state, the bioavailability has been shown to increase 3-fold when the drug is taken with a meal with a high fat content. It is thought that food stimulates bile flow which facilitates the dissolution and absorption of danazol, a highly lipophilic compound.

The apparent plasma elimination half-life of danazol in a single dose is approximately 3-6 hours. With multiple doses this may increase to approximately 26 hours.

None of the metabolites of danazol, which have been isolated, exhibits pituitary inhibiting activity comparable to that of danazol.

Few data on excretion routes and rates exist. In the monkey 36% of a radioactive dose was recoverable in the urine and 48% in the faeces within 96 hours.

Absorption

After oral administration of a 400 mg dose to healthy male volunteers, peak plasma concentrations of danazol are reached between 2 and 8 hours, with a median Tmax value of 4 hours. Steady-state conditions are observed following 6 days of twice daily dosing of danazol.

The pharmacokinetic parameters for danazol after administering a 400 mg oral dose to healthy males are summarized in the following table:

Parameters

Mean ± SD (n=15)

Cmax (ng/mL)

69.6 ± 29.9

Tmax (h)

2.47 ± 1.62

AUC0-∞ (ng*h/mL)

601 ± 181

t1/2 (h)

9.70 ± 3.29

Total Body Clearance (L/h)

727 ± 221

The pharmacokinetic parameters for danazol after oral administration of 100, 200 and 400 mg single doses to healthy female volunteers are summarized in the following table:

Dose

(mg)

Mean Cmax ± SD

(ng/mL)

Mean Tmax

(h)

Mean AUC0-∞ ± SD

(ng*h/mL)

 

Fasting

Fed

Fasting

Fed

Fasting

Fed

100

45.9 ± 23.9

113.8 ± 46.0

1-8

2-6

484 ± 263

741 ± 265

200

63.8 ± 27.7

159 ± 57.3

1-6

2-4

681 ± 363

1252 ± 307

400

60.4 ± 30.0

253.7 ± 105.5

1-6

2-4

754 ± 443

1851 ± 605

Dose Proportionality

Bioavailability studies indicate that blood levels do not increase proportionally with increases in the administered dose.

Single-dose administration of danazol in healthy female volunteers found that a 4-fold increase in dose produced only a 1.6- and 2.5-fold increase in AUC and a 1.3 and 2.2-fold increase in Cmax in the fasted and fed states, respectively. A similar degree of non-dose proportionality was observed at steady state.

Food Effect

Single dose administration of 100 mg and 200 mg capsules of danazol to female volunteers showed that both the extent of availability and the maximum plasma concentration increased by 3- to 4- fold, respectively, following a meal (>30 grams of fat), when compared to the fasted state. Further, food also delayed mean time to peak concentration of danazol by about 30 minutes. It is thought that food stimulates bile flow, which facilitates the dissolution and absorption of danazol, a highly lipophilic compound.

Even after multiple dosing under less extreme food/fasting conditions, there remained approximately a 2-to 2.5- fold difference in bioavailability between the fed and fasted states.

Distribution

Danazol is lipophilic and can partition into cell membranes, indicating the likelihood of distribution into deep tissue compartments.

Metabolism and Excretion

Danazol appears to be metabolized and the metabolites are eliminated by renal and faecal pathways. The two primary metabolites excreted in the urine are 2-hydroxymethyl danazol and ethisterone. At least ten different products were identified in faeces. The reported elimination half-life of danazol is variable across studies. The mean half-life of danazol in healthy males is 9.7 hours. After 6 months of 200 mg three times-a-day dosing in endometriosis patients, the half-life of danazol was reported as 23.7 hours.

Non-Clinical Properties

Animal Toxicology or Pharmacology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Current data are insufficient to assess the carcinogenicity of danazol.

Description

Danazol is a synthetic steroid derived from ethisterone.

Pharmaceutical Particulars

Shelf Life

Refer Pack

Packaging Information

DANOGEN 50.......................Strip pack of 10 capsules

DANOGEN 100.....................Strip pack of 10 capsules

DANOGEN 200.....................Strip pack of 10 capsules

Storage and Handling Instructions

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light and excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach.

Patient Counselling Information

  1. What DANOGEN is and what it is used for?

DANOGEN contains a medicine called danazol. It works by changing the way some hormones act in your body. It is used to treat:

  • Endometriosis – an illness where some of the tissues that line the womb are found elsewhere in the body. One way of treating this is to have an operation and to take DANOGEN as well. DANOGEN can also be used on its own, where other treatments have not worked
  • Breast cysts (lumps) which may be painful, but not malignant. DANOGEN is used where other treatments have not worked or when they cannot be taken.
  1. Before you take danazol

Do not take this medicine and tell your doctor if:

  • You are allergic (hypersensitive) to danazol or any of the other ingredients of DANOGEN. Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.
  • You have a rare inherited illness which affects your metabolism (called ‘porphyria’)
  • You are pregnant, might become pregnant, or think you may be pregnant.
  • You are breast-feeding
  • You have severe kidney, liver or heart disease
  • You have ever had blood clots (thrombosis)
  • You have a type of cancer which is affected by hormones
  • You have unusual vaginal bleeding which has no been checked by a doctor
  • You are taking cholesterol lowering medicine (Simvastatin)

Do not take if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking danazol.

Take special care with danazol. Check with your doctor or pharmacist before taking your medicine if:

  • You have any liver or kidney problems
  • You have an illness which could be made worse by fluid retention
  • You have high blood pressure or heart disease
  • You have diabetes
  • You have an illness in which the blood gets thicker (called ‘polycythaemia’)
  • You have fits (epilepsy)
  • You have blood fat problems (called ‘lipid disorders’)
  • You have ever had a bad reaction to a hormonal treatment similar to danazol
  • You get migraines
  • You have cancer or possible breast cancer.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking danazol.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because danazol can affect the way some other medicines work. Also, some medicines can affect the way danazol works.

In particular, tell your doctor if you are taking any of the following:

  • Steroids such as testosterone, estrogen, progesterone (including ‘the Pill’ or hormone replacement therapy - known as HRT)
  • Statins such as simvastatin. Danazol may increase the risk of muscle weakness or rapid breakdown of muscle.

Danazol may increase the effect of the following medicines:

  • Medicines for epilepsy, fits or convulsions (anticonvulsants)
  • Medicines used to thin the blood (anti-coagulants such as warfarin)
  • Anaesthetics
  • Ciclosporin and tacrolimus - used to stop the rejection of organs after a transplant. Danazol can increase the levels of these medicines in your blood and may damage your kidneys
  • Alpha calcidol (a form of vitamin D) used for vitamin D deficiency and illness where there is not enough calcium in the blood

Danazol may lower the effect of the following medicines:

  • Medicines for diabetes
  • Medicines for high blood pressure (anti-hypertensives)
  • Medicines for migraine

Operations or tests

If you are due to have an operation, tell your doctor you are taking danazol. This is because danazol can increase the effect of some anaesthetics.

If you have to take danazol for more than six months your doctor will arrange for an ultrasound test to check your liver.

Taking danazol with food and drink

Do not drink alcohol while you are taking danazol. This is because drinking alcohol while taking danazol can make you feel sick or short of breath.

Pregnancy and breastfeeding

Do not take danazol if you are pregnant, might become pregnant or think you may be pregnant. If you think you may have become pregnant while taking danazol, stop taking it straight away and talk to your doctor.

Do not breastfeed if you are taking danazol. This is because small amounts may pass into mothers’ milk. If you are planning to breast-feed, talk to your doctor or pharmacist. Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breastfeeding.

  1. How to take DANOGEN

Always take DANOGEN exactly as your doctor has told you.

You should check with your doctor or pharmacist if you are not sure.

Taking this medicine

  • Take this medicine by mouth
  • Swallow the capsules whole with a drink of water
  • If you feel the effect of your medicine is too weak or too strong, do not change the dose yourself, but ask your doctor
  • It is important that you do not become pregnant while taking danazol. Start taking the capsules on the first day of your period. Use reliable contraception (such as an Intra Uterine Device or barrier method in conjunction with contraceptive foam or jelly). The contraceptive pill should not be used until your treatment with danazol has finished.

How much to take

The usual dose depends on your needs and the illness being treated:

  • Endometriosis: 200 to 800mg a day for three to six months
  • Breast cysts: 300mg a day for three to six months

The dose for each day may be split between two and four separate doses.

DO NOT TAKE more than 8 of the 100mg capsules or 4 of the 200mg capsules in one day.

If you take more DANOGEN than you should

If you take more capsules than you should, tell a doctor or go to a hospital casualty department straight away. Take the medicine pack with you. This is so the doctor knows what you have taken.

If you forget to take DANOGEN

If you forget a dose, take it as soon as you remember it. However, if it is nearly time for the next dose, skip the missed dose. Do not take a double dose to make up for a forgotten dose.

If you stop taking DANOGEN

Keep taking DANOGEN until your doctor tells you to stop taking it. Do not stop taking DANOGEN just because you feel better. If you stop your illness may get worse.

Blood tests

Your doctor may carry out regular blood tests to check your liver is working properly and your blood levels are normal.

Also, taking danazol may affect the results of some other blood tests. These include the following tests:

  • Hormone testosterone levels
  • Liver and thyroid function
  • Lipids (fats), sugars and protein levels in your blood

If you are going to have a blood test, it is important to tell your doctor you are taking danazol.

  1. What are the possible side effect of danazol?

Like all medicines, danazol can cause side effects, although not everybody gets them.

Stop taking danazol and see a doctor or go to a hospital straight away if:

  • You have an allergic reaction. The signs may include a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue
  • Pain or tightness in the chest, jaw or arm.

These could be signs of a heart attack.

Stop taking danazol and tell a doctor straight away if you notice any of the following side effects (frequency not known) – you may need urgent medical treatment:

  • Severe headache and vomiting (being sick)
  • Clitoris becomes larger
  • Blurred vision, problems with eyesight, difficulty wearing contact lenses
  • Liver problems that may cause the eyes or skin to go yellow (jaundice)
  • Pain in the liver or liver failure may cause a swollen abdomen, mental disorientation and confusion (this may be due to a liver injury or non-cancerous liver tumour).
  • Pain when moving arms or legs (this may be due to a blood clot)
  • Feeling weak together with numb arms or legs which you may not be able to move (this may be a stroke)
  • Bruising more easily, getting more infections than usual. These could be signs of a blood problem

Any other severe symptoms which you cannot explain

Tell your doctor as soon as possible if you have any of the following side effects (frequency not known):

  • Hair loss (similar to male baldness)
  • More hair than usual on the body or face
  • Sore throat, hoarse voice or your voice sounds higher or lower than usual
  • Skin rashes or blistering. Changes in skin colour or sensitivity to the sun.
  • Blood in the urine
  • Migraines which are worse than usual
  • Your epilepsy gets worse
  • Stomach or chest pain

Tell your doctor or pharmacist if any of the following side effects (frequency not known) gets serious or lasts longer than a few days:

  • Putting on weight, or increased appetite
  • Spots, acne, greasy skin or rashes
  • Changes to your menstrual period, vaginal dryness, changes to your sex drive (libido)
  • High temperature with skin rashes
  • Backache, muscle cramps, twitching of the muscles, pain or swelling in your joints, arms or legs
  • Headache, feeling tired
  • Flushing
  • Feeling depressed, anxious or more nervous than usual
  • If your breasts get smaller
  • Water retention or bloating
  • Feeling sick, dizzy or balance problems (vertigo)
  • Palpitations, fast heartbeat, high blood pressure
  • Lowered fertility in men (may be caused by a lowering in the level of sperm)

Reporting of side effects

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 18002677779. By reporting side effects, you can help provide more information on the safety of this product.

How to Store Danogen

Store at a temperature not exceeding 25ºC. Protect from light and moisture.

Details of Manufacturer

Synokem Pharmaceuticals Ltd., Plot No.: 56-57, Sec-6A, IIE (SIDCUL), Ranipur (BHEL)

Haridwar-249403 (Uttarakhand)

Marketed by - Cipla House, Peninsula Business Park, Ganpatrao Kadam Marg, Lower Parel, Mumbai, Maharashtra, India

Details of Permission or Licence Number with Date

27/UA/SC/P-2018

Date of Revision

Last update: 01/06/2021