Drugs List

Therapeutic Indications

Uses

Differential diagnosis in ACTH-dependent Cushing's syndrome
Management of Cushing's syndrome
Resistant oedema (in conjunction with glucocorticosteroids) due to increased aldosterone secretion in cirrhosis, nephrosis and congestive heart failure

Administration

For oral administration.

Should be taken with milk or after food to minimise nausea and vomiting which can lead to impaired absorption.

Contraindications

Pregnancy (see Pregnancy section)
Breastfeeding (see Lactation section)
Primary adrenocortical insufficiency (Addison's Disease)
Porphyria

Precautions and Warnings

Should only be used under the supervision of a specialist.

When used for diagnostic purposes, patient should be hospitalised.

The ability of the adrenal cortex to respond to ACTH should be demonstrated before using metyrapone as a diagnostic test. Acute adrenal insufficiency may be induced by metyrapone in patients with reduced adrenal function and / or gross hypopituitarism.

Transient adrenocortical insufficiency can be triggered if the adrenocortical or anterior pituitary function is more severely compromised than indicated by the results of the test. (This can be corrected with appropriate administration of corticosteroids.)

Corticosteroid replacement therapy may be necessary if high doses are used.

Hypothyroidism: urinary steroid levels may rise very slowly or not at all.

Hepatic impairment: delayed response to the diagnostic test is likely (see Dosage - Hepatic Impairment ).

A significant number of drugs can interfere with the metyrapone test, and unless they are withdrawn, the test may be inappropriate. Seek expert advice, but anticonvulsants, anti-depressants, neuroleptics, anti-thyroid agents and hormones that affect the hypothalamo-pituitary axis may influence the results of the test.

Long-term use may cause hypertension - monitor blood pressure regularly.

The ability to drive or operate machinery may be affected by side effects..

Patients with ectopic Cushing�s syndrome may be at risk of developing opportunistic infections such as Pneumocystis jirovecii pneumonia (previously Pneumocystis carinii pneumonia) during metyrapone treatment. Appropriate prophylactic treatment should be considered for these patients.

Use in Porphyria

The European Porphyria initiative classes metyrapone as 'probably porphyrogenic'.

Pregnancy and Lactation

Pregnancy

Metyrapone is a competitive inhibitor of cortisol biosynthesis used for the evaluation of ACTH secretion in the rare cases when Cushing's disease is suspected and it can impair the biosynthesis of foetal-placental steroids. Schaefer (2007) states that inadvertent use of metyrapone during pregnancy never justifies termination of the pregnancy. No congenital abnormalities have been reported after exposure to metyrapone during pregnancy but as other diagnostic methods exist, there is no indication for metyrapone use during pregnancy.

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 14-17 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

Metyrapone and its active metabolites are excreted in very small amounts into breast milk and are unlikely to affect a breastfed infant. Exposure can be further minimised by avoiding nursing for 2 to 2.5 hours after each dose. The manufacturer advises that nursing mothers should refrain from breastfeeding their infants during treatment with metyrapone.

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

Nausea
Vomiting
Abdominal pain
Headache
Dizziness
Sedation
Hypotension
Hypertension (on long term use)
Hypersensitivity reactions
Transient adrenocortical insufficiency
Acute adrenal insufficiency
Hirsutism
Allergic dermatitis
Bone marrow failure
Alopecia

Presentation

Capsules containing metyrapone 250mg

Drugs List

Therapeutic Indications

Uses

Differential diagnosis in ACTH-dependent Cushing's syndrome
Management of Cushing's syndrome
Resistant oedema (in conjunction with glucocorticosteroids) due to increased aldosterone secretion in cirrhosis, nephrosis and congestive heart failure

Dosage

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For oral administration.

Should be taken with milk or after food to minimise nausea and vomiting which can lead to impaired absorption.

Contraindications

Pregnancy (see Pregnancy section)
Breastfeeding (see Lactation section)
Primary adrenocortical insufficiency (Addison's Disease)
Porphyria

Precautions and Warnings

Should only be used under the supervision of a specialist.

When used for diagnostic purposes, patient should be hospitalised.

The ability of the adrenal cortex to respond to ACTH should be demonstrated before using metyrapone as a diagnostic test. Acute adrenal insufficiency may be induced by metyrapone in patients with reduced adrenal function and / or gross hypopituitarism.

Transient adrenocortical insufficiency can be triggered if the adrenocortical or anterior pituitary function is more severely compromised than indicated by the results of the test. (This can be corrected with appropriate administration of corticosteroids.)

Corticosteroid replacement therapy may be necessary if high doses are used.

Hypothyroidism: urinary steroid levels may rise very slowly or not at all.

Hepatic impairment: delayed response to the diagnostic test is likely (see Dosage - Hepatic Impairment ).

A significant number of drugs can interfere with the metyrapone test, and unless they are withdrawn, the test may be inappropriate. Seek expert advice, but anticonvulsants, anti-depressants, neuroleptics, anti-thyroid agents and hormones that affect the hypothalamo-pituitary axis may influence the results of the test.

Long-term use may cause hypertension - monitor blood pressure regularly.

The ability to drive or operate machinery may be affected by side effects..

Patients with ectopic Cushing�s syndrome may be at risk of developing opportunistic infections such as Pneumocystis jirovecii pneumonia (previously Pneumocystis carinii pneumonia) during metyrapone treatment. Appropriate prophylactic treatment should be considered for these patients.

Use in Porphyria

The European Porphyria initiative classes metyrapone as 'probably porphyrogenic'.

Pregnancy and Lactation

Pregnancy

Metyrapone is a competitive inhibitor of cortisol biosynthesis used for the evaluation of ACTH secretion in the rare cases when Cushing's disease is suspected and it can impair the biosynthesis of foetal-placental steroids. Schaefer (2007) states that inadvertent use of metyrapone during pregnancy never justifies termination of the pregnancy. No congenital abnormalities have been reported after exposure to metyrapone during pregnancy but as other diagnostic methods exist, there is no indication for metyrapone use during pregnancy.

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 14-17 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

Metyrapone and its active metabolites are excreted in very small amounts into breast milk and are unlikely to affect a breastfed infant. Exposure can be further minimised by avoiding nursing for 2 to 2.5 hours after each dose. The manufacturer advises that nursing mothers should refrain from breastfeeding their infants during treatment with metyrapone.

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

Effects on Ability to Drive and Operate Machinery

The ability to drive or operate machinery may be affected by side effects.

Counselling

Advise patients the ability to drive or operate machinery may be affected by side effects.

Side Effects

Nausea
Vomiting
Abdominal pain
Headache
Dizziness
Sedation
Hypotension
Hypertension (on long term use)
Hypersensitivity reactions
Transient adrenocortical insufficiency
Acute adrenal insufficiency
Hirsutism
Allergic dermatitis
Bone marrow failure
Alopecia

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 ).

Shelf Life and Storage

Store below 30 degrees C.
Protect from heat and moisture

Further Information

Last Full Review Date: June 2012

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Metopirone capsules 250 mg. HRA Pharma UK and Ireland Limited. Revised December 2016.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 11 September 2017

The Drug Database for Acute Porphyria
https://www.drugs-porphyria.com/languages/UnitedKingdom/s1.php?l=gbr
Metyrapone Last revised 1 October 2004
Last accessed 18th June 2012

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Metyrapone Last revised: 23, March 2010
Last accessed: 18th June 2012