Drugs List

Therapeutic Indications

Uses

Diagnostic use
Investigation of adrenocortical insufficiency

Therapeutic use
1 mg/1 ml depot injection only
For short term therapy of conditions where glucocorticoids are indicated particularly in patients intolerant of oral glucocorticoid therapy or where normal therapeutic doses have been ineffective:
Crohn's disease
Ulcerative colitis
Juvenile rheumatoid arthritis
Adjunctive therapy in patients with rheumatoid arthritis
Adjunctive therapy in patients with osteoarthritis

Unlicensed Uses

Treatment of infantile spasms.

Administration

Tetracosactide solution for injection 250 micrograms/1 ml: for intravenous or intramuscular administration.

Tetracosactide suspension for injection 1 mg/1 ml: for intramuscular administration only.

Contraindications

Allergic disposition (for example, asthma)
Active peptic ulcer
Cardiac failure
Acute psychosis
Cushing's disease
Adrenogenital syndrome
Infectious diseases
Pregnancy
Children under 1 month
Hypersensitivity to benzyl alcohol

Precautions and Warnings

Tetracosactide may cause hypersensitivity reactions. It is therefore important to obtain patient history of allergic disorders before administering tetracosactide. Only administer under medical supervision and, for diagnostic use, under supervision of senior medical staff. It is important to monitor the patient for at least 30 minutes after administration as the majority of hypersensitivity reactions occur during this period. In the event of a serious anaphylactic reaction adrenaline and corticosteroid should be administered.

Discontinue and avoid future use if a serious anaphylactic reaction or other hypersensitivity reaction (redness/pain at the injection site, urticaria, pruritis, flushing, faintness, severe malaise or dyspnoea) occurs during or after an injection.

Do not administer tetracosactide treatment in the presence of an infective or systemic disease, when the use of a live vaccine may be required or if the immune system is compromised, unless satisfactory specific disease therapy is being given.

Relative insufficiency of the pituitary-adrenal axis is induced by prolonged administration, and may persist for several months after treatment has stopped, therefore appropriate adrenocortical therapy should be considered.
In patients who suffer an injury or undergo surgery during or within one year after treatment, the associated stress should be managed by an increase in or resumption of tetracosactide. Additional use of rapidly acting corticosteroids may be required. Use the lowest effective dose to control the condition. If the dose has to be reduced, this should be done gradually.

Children aged 1 month to 12 years.

Breastfeeding

Additional precautions for therapeutic use
Tetracosactide should be administered with caution to patients with the following conditions:
Non-specific ulcerative colitis
Diverticulitis,
Recent intestinal anastomosis,
Renal insufficiency,
Thromboembolic tendencies,
Osteoporosis,
Myasthenia gravis,
Hypertension,
Ocular Herpes simplex.

The effect of tetracosactide may be enhanced in patients with hypothyroidism or cirrhosis of the liver.

A increase in the production of adrenal steroids may result in corticosteroid type effects:
Salt and water retention (may respond to a low salt diet) Potassium supplementation may be required during long term therapy. Daily weight records may highlight any fluid retention.
Psychological disturbances may be aggravated or triggered.
Latent infections may become active (e.g. tuberculosis, amoebiasis). Monitor patients with tuberculin reactivity. Consider prophylactic anti-tuberculosis therapy if appropriate.
Ocular effects (glaucoma, cataracts) may occur.
Growth inhibition in children (unlikely if appropriate dose is administered correctly). Nevertheless, growth should be monitored in children undergoing long term treatment.
Reversible myocardial hypertrophy in rare cases following high doses in children up to 5 years. Echocardiographs readings should be taken regularly in order to detect any changes in the heart.
Dosage adjustments of concurrent therapy may be required for diabetics or patients with hypertension.

Pregnancy and Lactation

Pregnancy

Tetracosactide is contraindicated in pregnancy and should only be used if considered to be essential and the benefits outweigh the risks.

At the time of writing there is limited published information regarding the use of tetracosactide during pregnancy. Animal studies are insufficient with respect to reproductive toxicity. Schaefer 2007 states that inadvertent use is not grounds for pregnancy termination or for invasive diagnostic procedures.

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 tetracosactide with caution in breastfeeding.

It is unknown whether tetracosactide is excreted in breast milk. The UK drugs in Lactation Advisory Service considers tetracosactide to be safe to use in breastfeeding. Tetracosactide is a synthetic analogue of adrenocorticotropic hormone (ACTH), ACTH is a normal component of breast milk, therefore tetracosactide is likely to be excreted in breast milk. However, due to the drug's properties it is anticipated that it will not be absorbed from the infant's GI tract.

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

During diagnostic or therapeutic use, hypersensitivity reactions may be manifested in the following ways:
Anaphylactic shock
Skin reactions (injection site)
Dizziness
Nausea
Vomiting
Urticaria
Pruritus
Flushing
Malaise
Dyspnoea
Angioneurotic oedema
Quincke's oedema
Adrenal haemorrhage

During therapeutic use, general adverse of effects of glucocorticoids maybe seen including:
Osteoporosis
Muscle weakness
Muscular atrophy
Steroid myopathy
Loss of muscle mass
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathological fracture of long bones
Tendon rupture
Peptic ulceration with possible perforation and haemorrhage
Pancreatitis
Abdominal distension
Ulcerative oesophagitis
Impaired wound healing
Skin atrophy
Petechia
Ecchymosis
Erythema
Increased sweating
Suppression of skin test reactions
Acne
Skin pigmentation
Convulsions
Increased intracranial pressure with papilloedema (pseudotumour cerebri)
Vertigo
Headache
Psychiatric changes
Sodium retention
Fluid retention
Potassium loss
Hypokalaemic alkalosis
Calcium loss
Menstrual irregularities
Cushing's syndrome
Growth suppression in children
Secondary adrenocortical and pituitary unresponsiveness particularly in times of stress (trauma, surgery or illness)
Decreased carbohydrate tolerance
Hyperglycaemia
Manifestations of latent diabetes mellitus
Hirsutism
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Corneal perforation
Exophthalmos
Negative nitrogen balance due to protein catabolism
Hypertension
Necrotising vasculitis
Congestive heart failure
Reversible myocardial hypertrophy
Increased susceptibility to infection
Abscess
Thromboembolism
Weight gain
Increased appetite
Leucocytosis

Presentation

Suspension and solution for injection containing tetracosactide acetate

Drugs List

Therapeutic Indications

Uses

Diagnostic use
Investigation of adrenocortical insufficiency

Therapeutic use
1 mg/1 ml depot injection only
For short term therapy of conditions where glucocorticoids are indicated particularly in patients intolerant of oral glucocorticoid therapy or where normal therapeutic doses have been ineffective:
Crohn's disease
Ulcerative colitis
Juvenile rheumatoid arthritis
Adjunctive therapy in patients with rheumatoid arthritis
Adjunctive therapy in patients with osteoarthritis

Unlicensed Uses

Treatment of infantile spasms.

Dosage

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

Tetracosactide solution for injection 250 micrograms/1 ml: for intravenous or intramuscular administration.

Tetracosactide suspension for injection 1 mg/1 ml: for intramuscular administration only.

Contraindications

Allergic disposition (for example, asthma)
Active peptic ulcer
Cardiac failure
Acute psychosis
Cushing's disease
Adrenogenital syndrome
Infectious diseases
Pregnancy
Children under 1 month
Hypersensitivity to benzyl alcohol

Precautions and Warnings

Tetracosactide may cause hypersensitivity reactions. It is therefore important to obtain patient history of allergic disorders before administering tetracosactide. Only administer under medical supervision and, for diagnostic use, under supervision of senior medical staff. It is important to monitor the patient for at least 30 minutes after administration as the majority of hypersensitivity reactions occur during this period. In the event of a serious anaphylactic reaction adrenaline and corticosteroid should be administered.

Discontinue and avoid future use if a serious anaphylactic reaction or other hypersensitivity reaction (redness/pain at the injection site, urticaria, pruritis, flushing, faintness, severe malaise or dyspnoea) occurs during or after an injection.

Do not administer tetracosactide treatment in the presence of an infective or systemic disease, when the use of a live vaccine may be required or if the immune system is compromised, unless satisfactory specific disease therapy is being given.

Relative insufficiency of the pituitary-adrenal axis is induced by prolonged administration, and may persist for several months after treatment has stopped, therefore appropriate adrenocortical therapy should be considered.
In patients who suffer an injury or undergo surgery during or within one year after treatment, the associated stress should be managed by an increase in or resumption of tetracosactide. Additional use of rapidly acting corticosteroids may be required. Use the lowest effective dose to control the condition. If the dose has to be reduced, this should be done gradually.

Children aged 1 month to 12 years.

Breastfeeding

Additional precautions for therapeutic use
Tetracosactide should be administered with caution to patients with the following conditions:
Non-specific ulcerative colitis
Diverticulitis,
Recent intestinal anastomosis,
Renal insufficiency,
Thromboembolic tendencies,
Osteoporosis,
Myasthenia gravis,
Hypertension,
Ocular Herpes simplex.

The effect of tetracosactide may be enhanced in patients with hypothyroidism or cirrhosis of the liver.

A increase in the production of adrenal steroids may result in corticosteroid type effects:
Salt and water retention (may respond to a low salt diet) Potassium supplementation may be required during long term therapy. Daily weight records may highlight any fluid retention.
Psychological disturbances may be aggravated or triggered.
Latent infections may become active (e.g. tuberculosis, amoebiasis). Monitor patients with tuberculin reactivity. Consider prophylactic anti-tuberculosis therapy if appropriate.
Ocular effects (glaucoma, cataracts) may occur.
Growth inhibition in children (unlikely if appropriate dose is administered correctly). Nevertheless, growth should be monitored in children undergoing long term treatment.
Reversible myocardial hypertrophy in rare cases following high doses in children up to 5 years. Echocardiographs readings should be taken regularly in order to detect any changes in the heart.
Dosage adjustments of concurrent therapy may be required for diabetics or patients with hypertension.

Pregnancy and Lactation

Pregnancy

Tetracosactide is contraindicated in pregnancy and should only be used if considered to be essential and the benefits outweigh the risks.

At the time of writing there is limited published information regarding the use of tetracosactide during pregnancy. Animal studies are insufficient with respect to reproductive toxicity. Schaefer 2007 states that inadvertent use is not grounds for pregnancy termination or for invasive diagnostic procedures.

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 tetracosactide with caution in breastfeeding.

It is unknown whether tetracosactide is excreted in breast milk. The UK drugs in Lactation Advisory Service considers tetracosactide to be safe to use in breastfeeding. Tetracosactide is a synthetic analogue of adrenocorticotropic hormone (ACTH), ACTH is a normal component of breast milk, therefore tetracosactide is likely to be excreted in breast milk. However, due to the drug's properties it is anticipated that it will not be absorbed from the infant's GI tract.

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

As tetracosactide therapy can result in dizziness, patients should be warned of the potential hazards of driving or operating machinery.

Side Effects

During diagnostic or therapeutic use, hypersensitivity reactions may be manifested in the following ways:
Anaphylactic shock
Skin reactions (injection site)
Dizziness
Nausea
Vomiting
Urticaria
Pruritus
Flushing
Malaise
Dyspnoea
Angioneurotic oedema
Quincke's oedema
Adrenal haemorrhage

During therapeutic use, general adverse of effects of glucocorticoids maybe seen including:
Osteoporosis
Muscle weakness
Muscular atrophy
Steroid myopathy
Loss of muscle mass
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathological fracture of long bones
Tendon rupture
Peptic ulceration with possible perforation and haemorrhage
Pancreatitis
Abdominal distension
Ulcerative oesophagitis
Impaired wound healing
Skin atrophy
Petechia
Ecchymosis
Erythema
Increased sweating
Suppression of skin test reactions
Acne
Skin pigmentation
Convulsions
Increased intracranial pressure with papilloedema (pseudotumour cerebri)
Vertigo
Headache
Psychiatric changes
Sodium retention
Fluid retention
Potassium loss
Hypokalaemic alkalosis
Calcium loss
Menstrual irregularities
Cushing's syndrome
Growth suppression in children
Secondary adrenocortical and pituitary unresponsiveness particularly in times of stress (trauma, surgery or illness)
Decreased carbohydrate tolerance
Hyperglycaemia
Manifestations of latent diabetes mellitus
Hirsutism
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Corneal perforation
Exophthalmos
Negative nitrogen balance due to protein catabolism
Hypertension
Necrotising vasculitis
Congestive heart failure
Reversible myocardial hypertrophy
Increased susceptibility to infection
Abscess
Thromboembolism
Weight gain
Increased appetite
Leucocytosis

Effects on Laboratory Tests

Post administration total plasma cortisol levels during treatment with tetracosactide may be misleading in some clinical situations due to altered cortisol binding globulin levels. These situations include patients on oral contraceptives, post operative patients, critical illness, severe liver disease, and nephrotic syndrome. In these circumstances, use alternative parameters (e.g. salivary cortisol, free cortisol index, plasma free cortisol) to assess the integrity of the HPA axis.

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

Protect from light.

Store in a refrigerator (2 to 8 degrees C).

Further Information

Last Full Review Date: August 2014

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 characteristic: Synacthen Depot Ampoules 1mg/ml from Alliance Pharmaceuticals Ltd. Revised May 2014.

Summary of product characteristic: Synacthen Ampoules 250 micrograms/ml from Alliance Pharmaceuticals Ltd. Revised June 2014.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 01 September 2017.

UK Drugs in Lactation Advisory Service.
Available at: https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Last accessed: August 13, 2014