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Ketoconazole oral

Updated 2 Feb 2023 | Adrenocortical suppressants


Oral formulation of ketoconazole.

Drugs List

  • ketoconazole 200mg tablets
  • KETOCONAZOLE HRA 200mg tablets
  • Therapeutic Indications


    Cushing's syndrome

    Treatment of endogenous Cushing's syndrome in adults and adolescents above the age of 12 years.


    Ketoconazole daily dose should be periodically adjusted on an individual basis with the aim to normalise urinary free cortisol and/or plasma cortisol levels.



    The recommended dose at initiation is 400 to 600mg daily taken orally in two or three divided doses and this dose can be increased rapidly to 800 to 1200mg daily in 2 or 3 divided doses.


    400mg daily to a maximal dose of 1200mg daily taken orally in 2 to 3 divided doses. In most publications the maintenance dose varied between 600 and 800mg daily.

    A dose increase of 200mg daily every 7 to 28 days may be considered if urinary free cortisol and/or plasma cortisol levels are above the normal range, as long as the dose is tolerated by the patient.

    Block-and-replace regimen: The maintenance dose of ketoconazole should be further increased by 200mg and concomitant corticosteroid replacement therapy should be added.


    Children 12 years and older
    (See Dosage; Adults)

    Additional Dosage Information

    Adrenal Insufficiency

    The dose of ketoconazole should be decreased by at least 200mg daily or the treatment should be temporarily discontinued and/or a corticosteroid therapy should be added until the resolution of the event. Ketoconazole can be reintroduced thereafter at a lower dose.

    Hepatic function

    In the case of an increase in liver enzymes of less than 3 x ULN, more frequent monitoring of liver function tests should be performed and the daily dose should be decreased by at least 200mg.


    Children under 12 years
    Acute porphyria
    Hepatic disorder
    Hepatic enzymes above 2 times the upper limit of normal
    Long QT syndrome
    Torsade de pointes

    Precautions and Warnings

    Family history of long QT syndrome
    Females of childbearing potential
    Electrolyte imbalance
    Glucose-galactose malabsorption syndrome
    History of hepatic impairment
    History of torsade de pointes
    Lactose intolerance

    Correct electrolyte disorders before treatment
    Inflammatory/autoimmune disorder may occur after Cushing's remission
    Advise ability to drive/operate machinery may be affected by side effects
    Treatment to be initiated and supervised by a specialist
    Contains lactose
    Monitor hepatic function prior to treatment
    Perform ECG before treatment
    Adrenal insufficiency suspected: Monitor cortisol and reduce/suspend dose
    If adrenal insufficiency occurs, consider corticosteroid cover
    Monitor cortisol levels every few days/weeks during treatment initiation
    Monitor ECG within 1 week of initiation and then as clinically indicated
    Monitor hepatic function every 4 weeks for 6 months, or as indicated
    Monitor hepatic function weekly for 1 month after initiation
    Monitor LFTs at same frequency as when initiating with any dose increase
    Monitor serum electrolytes
    Once effective dose is established, monitor cortisol every 3 to 6 months
    Advise patient to report signs of hypocortisolism
    Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
    Discontinue if hepatitis develops
    Discontinue immediately following signs of acute hepatotoxicity
    Potentially hepatotoxic
    Discontinue if hepatic enzymes are equal to or greater than 3 x ULN
    Advise patient not to take paracetamol during treatment
    Advise patient not to take St John's wort concurrently
    Advise patient to avoid antacids for at least 2 hours after dose
    Advise patient to avoid alcohol during treatment
    Female: Ensure adequate contraception during treatment
    Block and replace regimen: Consider emergency card/glucocorticoid set

    Hepatic function

    It is required before starting the treatment to measure liver enzymes (AST, ALAT, gammaGT and alkaline phosphatase) and bilirubin.

    Patients should be informed about the risk of hepatotoxicity, including to stop treatment and to contact their doctor immediately if they feel unwell or in the event of symptoms such as anorexia, nausea, vomiting, fatigue, jaundice. abdominal pain or dark urine. If these occur, treatment should be stopped immediately and liver function tests should be performed.

    In the case of an increase in liver enzymes of less than 3 times the upper limit of normal , more frequent monitoring of liver function tests should be performed and the daily dose should be decreased by at least 200mg.

    Adrenal function

    Adrenal insufficiency can occur:

    Under conditions of a relative cortisol deficiency due to an increased glucocorticoid demand (e.g. in case of stress, surgery, or infection).

    In case of ketoconazole overtreatment in patients treated with a block-only regime.

    In insufficient glucocorticoid replacement therapy in patients treated with a block-and-replace regimen.

    Block and replace regimen

    Patients treated with a block-and-replace regime should be taught to adjust their glucocorticoid replacement therapy dose under conditions of stress.

    Gastric acidity

    Absorption of ketoconazole is impaired with decreased gastric acidity.

    In patients with achlorhydria, e.g. certain AIDS patients and those on acid secretion suppressors (such as H2-antagonists, proton pump inhibitors), it is advisable to administer ketoconazole with an acidic beverage e.g. cola, orange juice.

    If acid secretion suppressors are added to or removed from the concomitant medication then ketoconazole dose should be adjusted according to cortisol levels.

    Treatment of Infections

    The CHMP has recommended that the use of oral ketoconazole to treat fungal infections should be suspended. The CHMP concluded that the risk of hepatotoxicity associated with oral ketoconazole is greater than the benefit in treating fungal infections. An alternative available treatment should be used.

    Pregnancy and Lactation


    Ketoconazole is contraindicated during pregnancy.

    Use of ketoconazole during pregnancy is contraindicated by the manufacturer. Pre-clinical data show that ketoconazole crosses the placenta and is teratogenic.

    Animal studies have shown teratogenic effects. There are insufficient data regarding the use of ketoconazole in pregnant women and as such a potential risk cannot be ruled out.

    Schaefer reports the use of ketoconazole in several occasions in pregnancy with good maternal and fetal outcome (Schaefer 2015). Also, Schaefer reports some studies showing no evidence of an increased risk of malformation (Schaefer 2015).


    Ketoconazole is contraindicated during breastfeeding.

    The manufacturer suggests because ketoconazole is excreted in breast milk, patients should not breastfeed whilst being treated.

    Briggs reports a case where the exposure to ketoconazole on a breastfeed infant did not appear to be clinically significant (Briggs 2015).

    LactMed (2018) indicates that if oral ketoconazole is required by the mother, it may not be a reason to discontinue breastfeeding. Taking the dose just before the infant's longest sleep period or avoiding breastfeeding from 2 to 5 hours after the dose might decrease the infant's exposure to ketoconazole.

    Side Effects

    Abdominal pain
    Abnormal liver function tests
    Adrenal insufficiency
    Alcohol intolerance
    Anaphylactic reaction
    Anaphylactic shock
    Anaphylactoid reaction
    Bulging fontanelles in infants
    Decrease in plasma testosterone (transient)
    Dry mouth
    Dry skin
    Erectile dysfunction
    Erythema multiforme
    Hepatic failure
    Hepatic impairment
    Hepatic necrosis
    Hot flushes
    Hypersensitivity reactions
    Increased appetite
    Increases in hepatic enzymes
    Menstrual disturbances
    Peripheral oedema
    Raised intracranial pressure
    Reduced platelet count
    Tongue discolouration
    Transient adrenocortical insufficiency


    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 ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: April 2020.

    Reference Sources

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

    Summary of Product Characteristics: Ketoconazole HRA 200mg tablets. Laboratoire HRA Pharma. Revised August 2017.

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Ketoconazole Available at:
    Last revised: 03 December 2018.
    Last accessed: 25 February 2020.

    European Medicines Agency (EMA).
    Committee for Medicinal Products for Human Use (CHMP).
    Available at:
    Last accessed: 06 April 2020.

    NICE Evidence Services Available at: Last accessed: 25 February 2020.

    The Norwegian Porphyria Centre (NAPOS).
    Available at:
    Last revised: October 2018
    Last accessed: 25 February 2020.

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