Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about Azol.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Azol against the benefits expected for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What Azol is used for

Azol is used in the following conditions:

• Endometriosis - a condition in which tissue similar to the lining of the uterus (womb) grows outside the uterus causing pain or bleeding
• Menorrhagia - abnormally heavy during menstruation
• Severe fibrocystic breast disease - lumps or cysts in the breast which are very painful
• Hereditary angioedema - an inherited condition associated with repeated episodes of stomach upset and swelling of the throat.

Azol contains the active ingredient danazol, which alters the level or the way certain chemicals in the body work.

Ask your doctor if you have any questions about why Azol has been prescribed for you. Your doctor may have prescribed Azol for another reason.

Azol is not recommended for use in children, as the safety and effectiveness in children has not been established.

Azol is available only with a doctor's prescription.

There is no evidence that Azol is addictive.

Before you take Azol

When you must not take it

Do not take Azol if you are allergic to medicines containing danazol or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include hayfever, skin rash, itching or hives.

Do not take Azol if you have any of the following medical conditions:

• severe liver, kidney or heart disease
• very high blood pressure
• pelvic infection
• porphyria - a blood disorder
• previous or present blockage of a blood vessel by a clot
• cancer of the ovary, womb, cervix, breast or prostate
• undiagnosed abnormal genital bleeding
• undiagnosed lumps or masses in the ovaries or womb
• past jaundice due to oral contraceptives.

Do not take Azol if you are pregnant. It is important that you are not pregnant when you start taking Azol, as Azol may cause female babies to develop male physical characteristics.

Do not take Azol if you are breastfeeding. Azol is not recommended during breastfeeding as it is not known whether it passes into breast milk or what effect it may have on your baby.

Do not take Azol if the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date, it may not work as well.

Do not take Azol if the packaging shows signs of tampering or the capsules do not look quite right.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you plan to become pregnant or breastfeed. Azol is not recommended during pregnancy or breastfeeding.

Tell your doctor if you have, or have had, any medical conditions, especially the following:

• diabetes
• liver or kidney disease
• high blood pressure or heart problems
• lipid disorders - blood fat abnormalities
• epilepsy - seizures or fits
• migraine
• polycythemia - too many red blood cells in the blood
• previous bad reaction to Azol or any similar treatment.

Your doctor may want to take special care if you have any of these conditions.

Tell your doctor if you have had male-like side effects while you were taking oral contraceptives or other sex hormones. These effects include hoarseness or deepening of the voice and facial hair.

If you have not told your doctor about any of the above, tell them before you start taking Azol.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may be affected by Azol, or may affect how well it works. These include:

• warfarin - a medicine used to prevent blood clots
• insulin and other medicines for diabetes
• medicines used for high blood pressure
• carbamazepine and phenytoin - medicines used to treat epilepsy
• oral contraceptives (birth control pills), sex hormones
• ciclosporin and tacrolimus - medicines used to prevent organ transplant rejection.

Your doctor can tell you what to do if you are taking any of these medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Azol.

How to take Azol

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the bottle, ask your doctor or pharmacist.

How much to take

The dose varies from person to person.

Your doctor will tell you how many capsules to take each day and when to take them. This depends on your condition and how you respond to this medicine.

Dose ranges are as follows:

• endometriosis, between 200 and 800 mg a day
• menorrhagia, between 200 to 400 mg a day
• hereditary angioedema, between 200 and 600 mg a day
• fibrocystic breast disease, between 200 and 400 mg a day.

Women starting Azol should begin treatment during menstruation. It is important that you are not pregnant when starting Azol, and do not become pregnant whilst taking Azol. You should use a non-hormonal, barrier method of contraception (such as a condom or diaphragm) while you are taking Azol.

Azol is not recommended for use in children.

How to take Azol

Swallow the capsules with a glass of water. Azol can be taken with or without food.

If you forget to take Azol

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take the missed dose as soon as you remember, and then go back to taking your capsules as you would normally.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you take too much Azol (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much Azol.

Do this even if there are no signs of discomfort or poisoning. You may need medical attention.

While you are taking Azol

Things you must do

If you are a woman, you should use a non-hormonal, barrier method of contraception (such as a condom or diaphragm) while you are being treated with Azol.

If you become pregnant while taking Azol, stop taking it and tell your doctor immediately.

Before starting any new medicine, tell your doctor or pharmacist that you are taking Azol.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Azol.

If you notice lumps in your breasts that become bigger or do not go away, tell your doctor immediately.

Visit your doctor regularly so that they can check on your progress. Your doctor may want to take some blood tests from time to time. This helps to prevent unwanted side effects.

If you are diabetic, tell your doctor if you notice a change in your blood or urine glucose test results. Azol can affect blood glucose levels.

If you have to have any blood tests, tell your doctor that you are taking Azol. Azol may affect the results of some tests.

Things you must not do

Do not use Azol to treat any other conditions unless your doctor tells you to.

Do not give Azol to anyone else, even if they have the same condition as you.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Azol. Like all other medicines, Azol may have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Tell your doctor if you notice any of the following and they worry you:

• nausea (feeling sick), vomiting, indigestion, constipation
• weight gain
• muscle cramps
• joint, back or neck pain
• hot flushes, sweating
• headache
• changes in appetite
• menstrual disturbances such as spotting, irregular periods, no periods
• vaginal dryness and irritation.

The above list includes the common and milder side effects of your medicine.

Tell your doctor immediately if you notice any of the following:

• gradual blurring or loss of vision
• acne, oily skin or hair
• facial hair in women
• voice deepening or hoarseness in women
• enlarged clitoris
• decrease in testicle size
• continuing pain or tenderness in abdomen or stomach
• anxiety, depression
• symptoms of sunburn such as redness, itching, swelling, blistering, which may occur more quickly than normal
• yellowing of the eyes or skin, dark coloured urine, light coloured stools, continuing loss of appetite
• bleeding or bruising more easily than normal
• frequent infections such as fever, severe chills, sore throat or mouth ulcers
• worsening of epilepsy.

The above list includes serious side effects which may require medical attention.

If any of the following happen, stop taking Azol and tell your doctor immediately, or go to Accident and Emergency at the nearest hospital:

• problems with your vision such as blurred vision or difficulty focusing, with headache, nausea, vomiting
• chest pain
• skin rash, itching or hives
• measles-like rash, often with fever, sore throat, headache, diarrhoea
• severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
• pain or swelling and redness in the legs
• difficulty breathing.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using Azol

Storage

Keep Azol where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep your capsules in a cool dry place where the temperature stays below 30°C.

Do not store Azol or any other medicine in the bathroom or near a sink.

Do not leave Azol in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking Azol, or your capsules have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Azol is available in 2 capsule strengths:

• Azol 100 - dark grey and light grey capsule printed G and DL100
• Azol 200 - orange and white capsule printed G and DL200.

Each bottle contains 100 capsules.

Ingredients

The active ingredient in Azol is danazol.

• Each Azol 100 capsule contains 100 mg of danazol.
• Each Azol 200 capsule contains 200 mg of danazol.

The capsules also contain the following inactive ingredients:

• lactose
• lactose monohydrate
• microcrystalline cellulose
• colloidal anhydrous silica
• povidone
• sodium starch glycollate
• sodium lauryl sulfate
• magnesium stearate
• titanium dioxide
• gelatin
• iron oxide black [Azol 100 only]
• erythrosine [Azol 200 only]
• iron oxide red [Azol 200 only]
• iron oxide yellow [Azol 200 only].

The capsules are gluten free.

Manufacturer

Azol is made in Australia by:

Alphapharm Pty Limited
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration numbers:
Azol 100 - AUST R 10001
Azol 200 - AUST R 10011

This leaflet was prepared on 28 August 2019.

Published by MIMS October 2019

1 Name of Medicine

Danazol.

6.7 Physicochemical Properties

Danazol is a white or pale yellow crystalline powder.
It is practically insoluble in water, but soluble in chloroform and in acetone. It has a melting point of 225°C with some decomposition.
Chemical name: 17α-pregna-2,4- dien-20-yno(2,3-d) isoxazol-17β-ol. Molecular formula: C₂₂H₂₇NO₂. Molecular weight: 337.5.

Chemical structure.

CAS number.

2 Qualitative and Quantitative Composition

Each Azol capsule contains 100 mg or 200 mg of danazol as the active ingredient.

Excipients of known effect.

3 Pharmaceutical Form

Azol 100 capsules: light grey body with dark grey cap, marked G on the cap and DL100 on the body in black.
Azol 200 capsules: white body with orange cap, marked G on the cap and DL200 on the body in black.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Endometriosis and menorrhagia.

Hereditary angioedema.

Fibrocystic breast disease.

Clinical trials.

Endometriosis and menorrhagia.

Hereditary angioedema.

Fibrocystic breast disease.

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

4 Clinical Particulars

4.1 Therapeutic Indications

Endometriosis.

Menorrhagia.

Hereditary angioedema.

Fibrocystic breast disease.

4.3 Contraindications

Undiagnosed abnormal genital bleeding.
Markedly impaired liver, renal or cardiac function, including oedema.
Past jaundice with oral contraceptives.
Undiagnosed ovarian/uterine masses.
Pelvic infection.
Neoplasia of primary or secondary sexual organs.
Hypertension WHO II or worse.
Known hypersensitivity to danazol.
Pregnancy*.
Breastfeeding*.
Porphyria (danazol can induce ALA synthetase activity and hence porphyrin metabolism).
Androgen-dependent tumour.
Active thrombosis, thromboembolic disease or history of such events.
(* See Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy, Use in lactation.)

4.4 Special Warnings and Precautions for Use

Thromboembolism, thrombotic and thrombophlebitic events including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported.
Experience with long-term danazol therapy is limited. Serious toxicity (including cholestatic jaundice) has been reported. Peliosis hepatis, benign hepatic adenoma and hepatic carcinoma have been observed with long-term use. Peliosis hepatis, hepatic adenoma and hepatic carcinoma may be silent until complicated by acute, potentially life-threatening intra-abdominal haemorrhage. The physician, therefore, should be alert to this possibility. In patients with HAE, 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 HAE 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 pseudotumour cerebri. Early signs and symptoms of benign intracranial hypertension include papilloedema, headache, nausea and vomiting and visual disturbances. Patients with these symptoms should be screened for papilloedema and, if present, should be advised to discontinue danazol immediately and be referred to a neurologist for further diagnosis and care.
Patients should be watched closely for signs of androgenic effects and warned to report voice change promptly, as this effect may persist even when drug administration has stopped. Specific caution should be exercised when considering the use of danazol in professional singers.
Danazol should be stopped if there is evidence of virilisation (failure to stop danazol increases the risk of irreversible androgenic effects).
A treatment related 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 hence the potential impact on the risk of atherosclerosis and coronary artery disease in accordance with the potential benefit of the therapy to the patient should be considered. Clinical evidence suggests that on cessation of danazol therapy, plasma lipoprotein levels return to pre-treatment levels.
Patients taking danazol may show decreased glucose tolerance. The significance of this aberration for diabetic patients taking danazol is not known, but such patients should be carefully monitored.
Before initiating treatment, a thorough medical history and examination of abdomen, breast and pelvis should be undertaken to exclude the presence of carcinoma. During treatment, if breast nodules persist or enlarge, the presence of carcinoma should be excluded before continuing danazol.
Preliminary epidemiological data suggest that the use of danazol in patients undergoing treatment for endometriosis may increase the baseline risk of ovarian cancer.
Fluid retention may be produced to such a degree as to necessitate the use of diuretics. However, in some cases, fluid retention may be controlled by restriction of salt intake. Patients with conditions which may be influenced by fluid retention, such as epilepsy, migraine or cardiac or renal dysfunction, require careful observation.
Periodic blood counts should be performed.
Administration of danazol has been reported to cause exacerbation of the manifestations of acute intermittent porphyria (see Section 4.3 Contraindications).
While a course of therapy may need to be repeated, care should be observed. The risk of long-term exposure to 17-alkylated steroids should be borne in mind since danazol is chemically related to these compounds.
Danazol should be stopped if any clinically significant adverse event arises and particularly if there is any evidence of jaundice or other indication of significant hepatic disturbance, thrombosis or thromboembolism. The lowest effective dose of danazol should be sought.
In view of its pharmacology, known interactions and side effects, particular care should be observed in using danazol in those with hepatic disease, hypertension or other cardiovascular disease, lipoprotein disorder, polycythemia, a history of marked or persistent androgenic reaction to previous gonadal steroid therapy, or epilepsy induced or worsened by previous gonadal steroid therapy. However, close clinical monitoring is advised in all patients.
Also see Section 4.2 Dose and Method of Administration, Instructions to patients.

Use in hepatic impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Warfarin.

Anticonvulsants.

Ciclosporin and tacrolimus.

Oral contraceptives.

Antidiabetic therapy.

Concomitant steroids.

Antihypertensives.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.8 Adverse Effects (Undesirable Effects)

In general, the side effects associated with danazol therapy are attributable to the pharmacological activity of the drug; these effects may reflect danazol's weak androgenic and anabolic activity and/or the gonadal suppression which results from therapy.
CIOMS frequency estimates: Very common: ≥ 10%; common: ≥ 1 to < 10%; uncommon: ≥ 0.1 to < 1%; rare: ≥ 0.01 to < 0.1%; very rare: < 0.01%.

Androgenic/ anabolic effects.

Endocrine effects.

Hepatic effects.

Biochemical abnormalities.

Allergic.

Dermatological.

Gastrointestinal.

Genitourinary.

Musculoskeletal.

Central nervous system.

Haematological.

Cardiovascular.

Ophthalmic.

Other.

Reporting suspected adverse effects.

4.2 Dose and Method of Administration

In women of reproductive age, therapy should begin during menstruation. A sensitive test (e.g. beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy to ensure the patient is not pregnant. Additionally, a non-hormonal method of contraception should always be used during danazol therapy (see Section 4.4 Special Warnings and Precautions for Use).

Endometriosis.

Menorrhagia.

Hereditary angioedema.

Fibrocystic breast disease.

Instructions to patients.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Not reported in humans. LD₅₀ could not be determined in animals but danazol was found not to cause death after single oral doses from 5,000 mg/kg in rabbits and dogs, to 16,000 mg/kg in rats and mice.

Symptoms.

Treatment.

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Azol 100 capsules contain the following inactive ingredients: colloidal anhydrous silica, gelatin, iron oxide black, lactose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate, sodium starch glycollate and titanium dioxide.
Azol 200 capsules contains the following inactive ingredients: colloidal anhydrous silica, erythrosine, gelatin, iron oxide red, iron oxide yellow, lactose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate, sodium starch glycollate and titanium dioxide.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Container type: bottle (HDPE).
Pack size: 100.
Some strengths, pack sizes and/or pack types may not be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

Summary Table of Changes