Drugs List

Therapeutic Indications

Uses

Benign fibrocystic breast disease - unresponsive to other treatment
Endometriosis - unresponsive to other treatment
Gynaecomastia
Menorrhagia
Thinning of uterine endometrium before or instead of surgery
Treatment of severe cyclical mastalgia with/without nodularity

Unlicensed Uses

Hereditary angioedema

Contraindications

Children under 12 years
Elderly
Androgen-dependent neoplasm
Breastfeeding
Galactosaemia
History of thrombosis
Porphyria
Pregnancy
Severe cardiac dysfunction
Severe hepatic impairment
Severe renal impairment
Thromboembolic disorder
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Children aged 12 to 18 years
Disorders aggravated by fluid retention
Females of childbearing potential
Marked or persistent androgenic reaction to previous gonadal steroids
Breast nodules
Cardiac impairment
Cardiovascular disorder
Diabetes mellitus
Disorder of lipoprotein metabolism
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hypertension
Lactose intolerance
Malignant neoplasm
Migraine
Polycythaemia
Renal impairment

Diabetes mellitus: May cause insulin resistance
Exclude malignancy before treatment
Not all available brands are licensed for all indications
Contains lactose
During treatment > than 6 months, perform biannual hepatic ultra sonography
Monitor haematological parameters periodically
Monitor hepatic function
Exclude cancer if breast nodules persist/enlarge during therapy
May increase baseline risk of ovarian carcinoma
May affect results of some laboratory tests
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if signs of raised intracranial pressure
Discontinue treatment if evidence of virilisation appears
Female: Barrier or non-hormonal contraception advised during treatment

Monitor hepatic function and haematological parameters periodically.
The long term risks of repeated courses of treatment should be considered as danazol is chemically related to steroids which have known long term risks of benign hepatic adenomata, peliosis hepatis and hepatic carcinoma. If treatment extends beyond 6 months, or repeated courses are given, biannual hepatic ultrasonography is recommended.

Pregnancy and Lactation

Pregnancy

Danazol is contraindicated during pregnancy.

Danazol should not be used during pregnancy as there is epidemiological and toxicological evidence of hazard. Danazol is known to be associated with a risk of virilisation of the female foetus if administered during pregnancy. If the patient conceives during pregnancy, danazol should be discontinued.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Danazol is contraindicated in breastfeeding.

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

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

"Spotting" bleeding
Acne
Altered glucose tolerance
Altered lipoproteins
Altered thyroid hormone levels
Amenorrhoea during and after treatment
Anxiety
Arterial thrombosis
Back pain
Benign hepatic adenomata
Benign raised intracranial pressure
Breast size reduction
Carpal tunnel syndrome
Cerebral thrombosis
Changes in libido
Cholestatic jaundice
Clitoral hypertrophy
Creatine phosphokinase increased
Depression
Dizziness
Emotional lability
Eosinophilia
Epigastric pain
Erythema multiforme
Exacerbation of epilepsy
Exfoliative dermatitis
Facial oedema
Fasciculation
Fatigue
Fever
Fluid retention
Flushing
Gastro-intestinal disturbances
Haematological disorders
Haematuria
Hair loss
Headache
Hepatic failure
Hepatic tumours
Hepatocellular damage
Hepatocellular jaundice
Hirsutism
Hypertension
Hypoglycaemia
Increase in serum glucose
Increase in serum transaminases
Increased appetite
Inflammatory erythematous nodules
Insulin resistance
Interstitial pneumonitis
Joint pain
Joint swelling
Leucopenia
Limb pain
Menstrual disturbances
Migraine
Muscle cramps
Muscle spasm
Myocardial infarction
Nausea
Nervousness
Oily skin
Palpitations
Pancreatitis
Peliosis hepatis
Photosensitivity
Pleuritic pain
Polycythaemia
Rash
Reduction in spermatogenesis (in male)
Seborrhoea
Skin pigmentation changes
Skin reactions
Splenic peliosis
Tachycardia
Thrombocytopenia
Tremor
Urticaria
Vaginal dryness
Vaginal irritation
Vertigo
Visual disturbances
Voice changes
Weight gain

Presentation

Capsules containing danazol

Drugs List

Therapeutic Indications

Uses

Benign fibrocystic breast disease - unresponsive to other treatment
Endometriosis - unresponsive to other treatment
Gynaecomastia
Menorrhagia
Thinning of uterine endometrium before or instead of surgery
Treatment of severe cyclical mastalgia with/without nodularity

Unlicensed Uses

Hereditary angioedema

Dosage

Adults

Adolescents

Contraindications

Children under 12 years
Elderly
Androgen-dependent neoplasm
Breastfeeding
Galactosaemia
History of thrombosis
Porphyria
Pregnancy
Severe cardiac dysfunction
Severe hepatic impairment
Severe renal impairment
Thromboembolic disorder
Undiagnosed gynaecological haemorrhage

Precautions and Warnings

Children aged 12 to 18 years
Disorders aggravated by fluid retention
Females of childbearing potential
Marked or persistent androgenic reaction to previous gonadal steroids
Breast nodules
Cardiac impairment
Cardiovascular disorder
Diabetes mellitus
Disorder of lipoprotein metabolism
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hypertension
Lactose intolerance
Malignant neoplasm
Migraine
Polycythaemia
Renal impairment

Diabetes mellitus: May cause insulin resistance
Exclude malignancy before treatment
Not all available brands are licensed for all indications
Contains lactose
During treatment > than 6 months, perform biannual hepatic ultra sonography
Monitor haematological parameters periodically
Monitor hepatic function
Exclude cancer if breast nodules persist/enlarge during therapy
May increase baseline risk of ovarian carcinoma
May affect results of some laboratory tests
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if signs of raised intracranial pressure
Discontinue treatment if evidence of virilisation appears
Female: Barrier or non-hormonal contraception advised during treatment

Monitor hepatic function and haematological parameters periodically.
The long term risks of repeated courses of treatment should be considered as danazol is chemically related to steroids which have known long term risks of benign hepatic adenomata, peliosis hepatis and hepatic carcinoma. If treatment extends beyond 6 months, or repeated courses are given, biannual hepatic ultrasonography is recommended.

Pregnancy and Lactation

Pregnancy

Danazol is contraindicated during pregnancy.

Danazol should not be used during pregnancy as there is epidemiological and toxicological evidence of hazard. Danazol is known to be associated with a risk of virilisation of the female foetus if administered during pregnancy. If the patient conceives during pregnancy, danazol should be discontinued.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Danazol is contraindicated in breastfeeding.

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

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

"Spotting" bleeding
Acne
Altered glucose tolerance
Altered lipoproteins
Altered thyroid hormone levels
Amenorrhoea during and after treatment
Anxiety
Arterial thrombosis
Back pain
Benign hepatic adenomata
Benign raised intracranial pressure
Breast size reduction
Carpal tunnel syndrome
Cerebral thrombosis
Changes in libido
Cholestatic jaundice
Clitoral hypertrophy
Creatine phosphokinase increased
Depression
Dizziness
Emotional lability
Eosinophilia
Epigastric pain
Erythema multiforme
Exacerbation of epilepsy
Exfoliative dermatitis
Facial oedema
Fasciculation
Fatigue
Fever
Fluid retention
Flushing
Gastro-intestinal disturbances
Haematological disorders
Haematuria
Hair loss
Headache
Hepatic failure
Hepatic tumours
Hepatocellular damage
Hepatocellular jaundice
Hirsutism
Hypertension
Hypoglycaemia
Increase in serum glucose
Increase in serum transaminases
Increased appetite
Inflammatory erythematous nodules
Insulin resistance
Interstitial pneumonitis
Joint pain
Joint swelling
Leucopenia
Limb pain
Menstrual disturbances
Migraine
Muscle cramps
Muscle spasm
Myocardial infarction
Nausea
Nervousness
Oily skin
Palpitations
Pancreatitis
Peliosis hepatis
Photosensitivity
Pleuritic pain
Polycythaemia
Rash
Reduction in spermatogenesis (in male)
Seborrhoea
Skin pigmentation changes
Skin reactions
Splenic peliosis
Tachycardia
Thrombocytopenia
Tremor
Urticaria
Vaginal dryness
Vaginal irritation
Vertigo
Visual disturbances
Voice changes
Weight gain

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: December 2013

Reference Sources

Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on December 16, 2013]

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Paediatric Formulary Committee. BNF for Children 2013-2014. London: BMJ Group, Pharmaceutical Press, and RCPCH Publications; 2013. Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications https://www.medicinescomplete.com [Accessed on December 16, 2013].

Summary of Product Characteristics: Danol 200mg capsules.Sanofi. Revised August 2013.
Summary of Product Characteristics: Danazol 200mg capsules. Generics UK Ltd. Revised February 2013.