Drugs List

Therapeutic Indications

Uses

Intractable hypoglycaemia

Unlicensed Uses

Resistant hypertension

Contraindications

Breastfeeding
Labour

Precautions and Warnings

Left-to-right cardiovascular shunt
Aortic stenosis
Cardiac failure
Cerebrovascular disorder
Coarctation of the aorta
History of gout
Hyperuricaemia
Ischaemic heart disease
Poor cardiac reserve
Pregnancy
Reduced serum proteins
Renal impairment
Right-to-left cardiovascular shunt

May cause hypokalaemia - give potassium replacement therapy
Assess growth, bone and psychological maturation regularly in children
Maintain urine output in excess of 1 litre/day in severe renal impairment
Monitor blood glucose
Monitor blood pressure regularly
Monitor uric acid levels
Patients with fluid retention should be treated with diuretics
Perform regular white blood cell and platelet counts
Increased risk of hypotension with diuretics and other antihypertensives
Consider dose reduction in renal impairment

Retention of sodium and water is likely thus patients may need to be treated with an oral diuretic such as furosemide (up to 1 g daily). It must be expected that if diuretics are administered then both the hypotensive and hyperglycaemic actions of diazoxide will be potentiated, thus the dosage of diazoxide will require adjustment downwards.

Use with caution in patients in whom sodium and water retention may worsen or precipitate congestive heart failure, e.g. cardiac failure or impaired cardiac reserve. Such retention may have a direct effect on cardiac function.

The very rapid, almost complete protein binding of diazoxide requires careful dosage consideration in patients whose plasma proteins may be lower than normal.

Pregnancy and Lactation

Pregnancy

Use diazoxide with caution during pregnancy.

Diazoxide also inhibits uterine activity during labour. The degree and duration of inhibition is dose dependant (Briggs, 2015).

Although it has been used to treat severe hypertension in pregnancy, there are safer alternatives and the long term effect on the infant has not been evaluated. Diazoxide is known to cross the placenta readily and foetal plasma concentrations reach levels similar to maternal levels. If diazoxide is necessary during pregnancy, small doses should be used (Briggs, 2015).

The use of oral diazoxide in the last 19 to 69 days of pregnancy has been associated with alopecia, hypertrichosis lanuginosa and decreased ossification of the wrist in the neonate (Briggs, 2015).

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

Use of diazoxide is contraindicated during breastfeeding.

At the time of writing there was insufficient information to assess the effect/s of diazoxide on a breast feeding infant.

Briggs (2015) suggests that the molecular weight (about 231) is low enough that passage into milk should be expected.

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

Abdominal pain
Albuminuria
Anaemia
Anorexia
Arrhythmias
Azotaemia
Bleeding
Blurred vision
Cardiac failure
Cardiomegaly
Cataracts (transient)
Cogwheel rigidity
Constipation
Decrease in creatinine clearance
Decrease in haemoglobin and haematocrit
Dermatitis
Diarrhoea
Diplopia
Dizziness
Dysgeusia
Dyspnoea
Eosinophilia
Extrapyramidal effects
Fever
Fluid retention
Galactorrhoea
Haematuria
Haemorrhage
Headache
Hirsutism
Hyperglycaemia
Hyperosmolar non-ketotic coma
Hypersensitivity reactions
Hypertrichosis
Hyperuricaemia
Hypogammaglobulinaemia
Hypotension
Ileus
Immunoglobulin abnormalities
Increase in alkaline phosphatase
Increase in AST level
Increased serum androgens
Ketoacidosis
Lacrimation
Leucopenia
Lichenoid rash
Musculoskeletal pain
Nausea
Nephrotic syndrome
Oculogyric crisis
Pancreatitis
Parkinsonian tremor
Pruritus
Pulmonary hypertension
Rash
Reduced libido
Scotoma
Sodium retention
Subconjunctival haemorrhage
Taste disturbances
Thrombocytopenia
Tinnitus
Visual disturbances
Voice changes
Vomiting

Presentation

Oral formulations containing diazoxide

Drugs List

Therapeutic Indications

Uses

Intractable hypoglycaemia

Unlicensed Uses

Resistant hypertension

Dosage

Adults

Children

Neonates

Contraindications

Breastfeeding
Labour

Precautions and Warnings

Left-to-right cardiovascular shunt
Aortic stenosis
Cardiac failure
Cerebrovascular disorder
Coarctation of the aorta
History of gout
Hyperuricaemia
Ischaemic heart disease
Poor cardiac reserve
Pregnancy
Reduced serum proteins
Renal impairment
Right-to-left cardiovascular shunt

May cause hypokalaemia - give potassium replacement therapy
Assess growth, bone and psychological maturation regularly in children
Maintain urine output in excess of 1 litre/day in severe renal impairment
Monitor blood glucose
Monitor blood pressure regularly
Monitor uric acid levels
Patients with fluid retention should be treated with diuretics
Perform regular white blood cell and platelet counts
Increased risk of hypotension with diuretics and other antihypertensives
Consider dose reduction in renal impairment

Retention of sodium and water is likely thus patients may need to be treated with an oral diuretic such as furosemide (up to 1 g daily). It must be expected that if diuretics are administered then both the hypotensive and hyperglycaemic actions of diazoxide will be potentiated, thus the dosage of diazoxide will require adjustment downwards.

Use with caution in patients in whom sodium and water retention may worsen or precipitate congestive heart failure, e.g. cardiac failure or impaired cardiac reserve. Such retention may have a direct effect on cardiac function.

The very rapid, almost complete protein binding of diazoxide requires careful dosage consideration in patients whose plasma proteins may be lower than normal.

Pregnancy and Lactation

Pregnancy

Use diazoxide with caution during pregnancy.

Diazoxide also inhibits uterine activity during labour. The degree and duration of inhibition is dose dependant (Briggs, 2015).

Although it has been used to treat severe hypertension in pregnancy, there are safer alternatives and the long term effect on the infant has not been evaluated. Diazoxide is known to cross the placenta readily and foetal plasma concentrations reach levels similar to maternal levels. If diazoxide is necessary during pregnancy, small doses should be used (Briggs, 2015).

The use of oral diazoxide in the last 19 to 69 days of pregnancy has been associated with alopecia, hypertrichosis lanuginosa and decreased ossification of the wrist in the neonate (Briggs, 2015).

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

Use of diazoxide is contraindicated during breastfeeding.

At the time of writing there was insufficient information to assess the effect/s of diazoxide on a breast feeding infant.

Briggs (2015) suggests that the molecular weight (about 231) is low enough that passage into milk should be expected.

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

Abdominal pain
Albuminuria
Anaemia
Anorexia
Arrhythmias
Azotaemia
Bleeding
Blurred vision
Cardiac failure
Cardiomegaly
Cataracts (transient)
Cogwheel rigidity
Constipation
Decrease in creatinine clearance
Decrease in haemoglobin and haematocrit
Dermatitis
Diarrhoea
Diplopia
Dizziness
Dysgeusia
Dyspnoea
Eosinophilia
Extrapyramidal effects
Fever
Fluid retention
Galactorrhoea
Haematuria
Haemorrhage
Headache
Hirsutism
Hyperglycaemia
Hyperosmolar non-ketotic coma
Hypersensitivity reactions
Hypertrichosis
Hyperuricaemia
Hypogammaglobulinaemia
Hypotension
Ileus
Immunoglobulin abnormalities
Increase in alkaline phosphatase
Increase in AST level
Increased serum androgens
Ketoacidosis
Lacrimation
Leucopenia
Lichenoid rash
Musculoskeletal pain
Nausea
Nephrotic syndrome
Oculogyric crisis
Pancreatitis
Parkinsonian tremor
Pruritus
Pulmonary hypertension
Rash
Reduced libido
Scotoma
Sodium retention
Subconjunctival haemorrhage
Taste disturbances
Thrombocytopenia
Tinnitus
Visual disturbances
Voice changes
Vomiting

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: January 2017

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: Eudemine 50mg Tablets. RPH Pharmaceuticals AB. Revised May 2015.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 28 June 2017.