Consumer medicine information

Synacthen

Tetracosactide (tetracosactrin)

BRAND INFORMATION

Brand name

Synacthen

Active ingredient

Tetracosactide (tetracosactrin)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Synacthen.

What is in this leaflet

This leaflet answers some common questions about Synacthen.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up-to-date information on the medicine. Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you having Synacthen against the benefits they expect it will give you.

If you have any concerns about having this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What Synacthen is used for

Synacthen is used as a diagnostic test to find out if the adrenal glands, small glands next to the kidneys, are working as well as they should. The Synacthen test is given as a single injection into the muscle.

Synacthen is used as a test only. It is not used to treat poorly functioning adrenal glands.

Ask your doctor if you have any questions about why Synacthen has been prescribed for you. Your doctor may have prescribed it for another reason.

Synacthen is only available with a doctor's prescription. It is not habit-forming.

Before you are given Synacthen

When you must not have it

You should not be given Synacthen if you have ever had an allergic reaction to:

  • tetracosactide (tetracosactrin), the active ingredient in Synacthen
  • any of the other ingredients of Synacthen listed at the end of this leaflet
  • a similar medicine called ACTH or corticotrophin

Symptoms of an allergic reaction may include redness or pain at the injection site, rash, itching, hives or flushing of the skin, dizziness, nausea (feeling sick) or vomiting, difficulty breathing, swelling of the face, lips, tongue or other part of the body.

You should not be given Synacthen if you have any of the following healthproblems/medical conditions:

  • asthma or other allergic conditions
  • a viral illness or you have recently been vaccinated with a live virus
  • an infection, unless you are taking antibiotics for it
  • a stomach ulcer
  • severe heart disease
  • overactive adrenal glands (Cushing's syndrome)
  • adrenocortical insufficiency
  • (adrenal glands not working properly)
  • a mental illness with disturbances in thinking, feelings and behaviour

If you are unsure whether any of the above conditions apply to you, ask your doctor before you have the Synacthen test. This medicine could make your condition worse.

Do not have Synacthen if you are pregnant. This medicine may cause a miscarriage or affect your developing baby if you have it while you are pregnant.

Do not breast-feed while the Synacthen test is being done. There is not enough information to recommend breast-feeding while you are having Synacthen.

Before you start to have it

Tell your doctor if you have asthma or allergies, including any allergies to other medicines, foods, dyes or preservatives. If you have asthma or allergies, your chance of having an allergic reaction to Synacthen may be greater than normal. Your doctor can discuss this with you further.

Tell your doctor if you have any of the following medical conditions:

  • diabetes
  • high blood pressure

Your doctor may want to take special precautions if you have one of the above conditions.

Taking other medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription from a pharmacy, supermarket or health food shop.

These include medicines used to treat:

  • diabetes
  • high blood pressure
  • convulsions

It may be necessary to change the dose or in some cases to stop the medicine.

Some medicines may affect the results of the Synacthen test. These include:

  • some corticosteroid medicines, including cortisone and hydrocortisone
  • spironolactone, a medicine usually used to treat high blood pressure and fluid retention
  • oestrogens, including the birth control pill and hormone replacement therapy (HRT)

Your doctor may ask you to skip the morning dose of some medicines on the day of the Synacthen test so that the test results are not affected.

If you have not told your doctor about any of these things, tell him/her before you have the Synacthen test.

How Synacthen is given

You will be given a single injection of Synacthen into the muscle. You will have two blood samples taken, one before the dose of Synacthen and the other 30 minutes after the dose. These blood samples will show whether your adrenal glands are functioning as well as they should.

After having Synacthen

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert after you have had the Synacthen test until you know how it has affected you. Although Synacthen is unlikely to have affected your reactions, make sure before you drive or do anything else that could be dangerous.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are having the Synacthen test, even if you don't think it is connected with the medicine.

All medicines can have side effects. Sometimes they are serious, but most of the time they are not. You may need medical treatment if you get some of the side effects.

Tell your doctor or nurse immediately if you notice any of the following signs of a possible allergic reaction to Synacthen:

  • redness or pain at the injection site
  • rash, itching, hives or flushing of the skin
  • dizziness
  • nausea (feeling sick) or vomiting
  • difficulty breathing
  • swelling of the face, lips, tongue or other part of the body

Allergic reactions to Synacthen can happen rarely. Your doctor or nurse will watch you closely for signs of allergy during the Synacthen test and will have medicines to treat this type of reaction near at hand.

Tell your doctor if you notice anything else that is making you feel unwell. It is possible that other side effects not listed above may happen in some people.

Product description

What it looks like

Synacthen is available in a glass ampoule containing 1 mL of liquid; one ampoule per carton. Each ampoule contains 250 micrograms of tetracosactide (tetracosactide).

Ingredients

Each ampoule of Synacthen contains 250 micrograms of the active ingredient, tetracosactide (tetracosactrin) (as the hexa- acetate salt). It also contains:

  • acetic acid
  • sodium acetate
  • sodium chloride
  • water for injections

This medicine does not contain any preservative.

Sponsor

Synacthen is distributed in Australia by:

Clinect Pty Ltd
20-132 Atlantic Drive, Keysborough
VIC 3173, Australia
Free Call Australia: 1800 899 005

®= Registered Trademark

This leaflet was prepared in March 2020

Australian Registration Number
Synacthen ampoules AUST R 11058

Published by MIMS August 2020

BRAND INFORMATION

Brand name

Synacthen

Active ingredient

Tetracosactide (tetracosactrin)

Schedule

S4

 

Notes

Distributed by Link Medical Products Pty Ltd

1 Name of Medicine

Tetracosactide (tetracosactrin).

2 Qualitative and Quantitative Composition

Synacthen is the first corticotrophic preparation to be produced entirely by synthesis and displays all of the pharmacological properties of endogenous ACTH. It is a long-chain polypeptide composed of the first 24 of the 39 amino acids contained in the naturally occurring ACTH (corticotrophin) molecule.
In contrast to ACTH preparations obtained by extraction, the composition of Synacthen is not subject to variation, so that dosage can be expressed in terms of weight. For the purposes of clinical use, Synacthen 1 mg corresponds approximately to 100 international units of ACTH (as defined in the Third International Working Standard). Studies have shown that a single test dose of Synacthen 250 microgram (corresponding to 25 IU) administered by intramuscular injection is sufficient to elicit a marked rise in plasma cortisol within 30 minutes.
Synacthen ampoules contain 250 microgram tetracosactide (tetracosactrin) (as the hexa-acetate salt) per 1 mL of solution.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

As a diagnostic aid in the assessment of suspected adrenocortical hypofunction.

4.2 Dose and Method of Administration

See Section 4.4 Special Warnings and Precautions for Use, Effects on laboratory tests; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for information on drugs that may interfere with test results.

Synacthen 30 minute test.

This test is based on the increase in plasma cortisol recorded 30 minutes after an intramuscular injection of Synacthen 250 microgram. Two blood specimens should be taken, the first immediately before and the second exactly 30 minutes after the injection of Synacthen. If the plasma cortisol rises to at least 200 nanomoles/L (70 microgram/L) above the initial level, or if the plasma cortisol level attained 30 minutes after injection exceeds 500 nanomoles/L (180 microgram/L), irrespective of the basal level, then adrenocortical function can be regarded as normal.

4.3 Contraindications

If the patient's case history discloses any record of hypersensitivity reactions to ACTH treatment, tetracosactide (tetracosactrin) must not be used.
Hypersensitivity to tetracosactide (tetracosactrin) and/or ACTH of animal origin or to any component of the formulation.
Synacthen must not be used to treat asthma or other allergic conditions due to the increased risk of anaphylactic reactions (also see Section 4.4 Special Warnings and Precautions for Use).
Viral diseases or recent vaccination with live virus.
Acute psychoses.
Infections (unless antibiotics are being administered at the same time).
Peptic ulcer.
Cushing's syndrome.
Heart failure (refractory).
Treatment of primary adrenocortical insufficiency.
Pregnancy and breastfeeding.
Adrenogenital syndrome.
In view of the increased risk of anaphylactic reactions, Synacthen as a diagnostic agent is not recommended in patients with asthma or other allergic conditions (see Section 4.4 Special Warnings and Precautions for Use, Hypersensitivity).

4.4 Special Warnings and Precautions for Use

Synacthen should only be administered under medical supervision.

Hypersensitivity.

Before employing Synacthen the physician must ascertain whether the patient is suffering from an allergic disorder (especially asthma) or is susceptible in general to allergies. He should also enquire whether the patient has been treated with ACTH preparations in the past, and if so, ensure that the treatment did not give rise to hypersensitivity reactions (see Section 4.3 Contraindications).
In rare instances in patients without a history of allergy, but more frequently in the presence of a history of asthma or other forms of allergy, severe anaphylactic reactions have occurred, some with fatal outcome. Usually, such reactions were manifest within 30 minutes of administration of Synacthen. In these allergic patients, the Synacthen test should only be performed if no ACTH preparations have previously been given. The physician must at all events be prepared in advance to combat at once any anaphylactic reaction occurring after the injection of Synacthen.
Hypersensitivity reactions tend to occur within 30 minutes of injection. The patient should be kept under observation during this time. Should a serious anaphylactic reaction occur, despite all precautions, the following immediate measures must be taken: administer adrenaline (0.4 to 1 mL of a 1 mg/mL solution intramuscularly or 0.1 to 0.2 mL of a 1 mg/mL solution in 10 mL physiological saline slowly intravenously), as well as large intravenous doses of water-soluble corticosteroids, repeating the dose if necessary.
If local or systemic hypersensitivity reactions occur during or after an injection (e.g. marked redness and pain at the injection site, urticaria, pruritus, flushing, severe malaise, or dyspnoea), all use of ACTH preparations must be avoided in the future.

Pre-existing conditions.

Synacthen should be used with caution in patients with diabetes mellitus or moderate to severe hypertension.

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

Post administration total plasma cortisol levels during the Synacthen test might be misleading in some special clinical situations due to altered cortisol binding globulin levels. These situations include patients on oral contraceptives, postoperative patients, critical illness, severe liver disease, nephrotic syndrome. Hence in these circumstances, alternative parameters (e.g. salivary cortisol, free cortisol index, plasma free cortisol) can be used to assess the integrity of HPA axis.
Because spironolactone metabolites fluoresce, erroneously high plasma cortisol concentrations may be reported in patients receiving spironolactone when fluorometric analysis is used but not when radioimmunoassay or competitive protein binding methods are used. Therefore, patients should not receive pretest doses of spironolactone on the day of testing when the fluorometric method is used. Since prednisone, dexamethasone and betamethasone are not detectable by the fluorometric method, therapy with these drugs can be maintained.
In patients with increased plasma bilirubin concentrations or with free haemoglobin in their plasma, falsely elevated fluorescence measurements may occur.
Synacthen contains an active substance that may interfere with routine drug testing in athletes.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Patients receiving cortisone or hydrocortisone on the test day may exhibit abnormally high baseline plasma cortisol concentrations and a paradoxical decrease in plasma cortisol concentrations following administration of Synacthen. Patients should not receive pretest doses of cortisone or hydrocortisone on the day of testing.

Observed interactions resulting in concomitant use not being recommended.

Severe jaundice has been observed for concurrent use of Synacthen and valproate in pediatric population. Their concurrent use should be avoided.

Observed interactions to be considered.

Concurrent use of Synacthen and other anticonvulsants (e.g. phenytoin, clonazepam, nitrazepam, phenobarbital, primidone) may increase the risk of liver damage, thus, Synacthen should be used with caution at minimum possible doses and for minimum duration for concurrent treatment.
Endogenous and synthetic estrogens can cause an increase in total cortisol levels and therefore, it is considered appropriate to use alternative methods (e.g. salivary cortisol, free cortisol index, plasma free cortisol) for interpretation of the results of the HPA axis examination.
Live virus immunisation procedures must not be undertaken during treatment with Synacthen because of the decrease in antibody response.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
There have been some reports of miscarriage or fetal malformation occurring in pregnant women treated with tetracosactide (tetracosactrin). Therefore, Synacthen must not be administered during pregnancy.
Australian characterisation of pregnancy definition: Category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
 The administration of tetracosactide (tetracosactrin) during lactation has not been reported. Any decision to administer Synacthen as a diagnostic aid must be with recognition to the individual case history. Mothers must not breastfeed during the period of its use.

4.7 Effects on Ability to Drive and Use Machines

Since Synacthen may have an effect on the central nervous system, patients should be cautious when driving a vehicle or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

Frequency estimate: very common ≥ 10%; common ≥ 1% to < 10%; uncommon ≥ 0.1% to < 1%; rare ≥ 0.01% to < 0.1%; very rare < 0.01%.

Hypersensitivity reactions.

Rare.

Synacthen may provoke hypersensitivity reactions which tend to be more severe (anaphylactic shock) in patients susceptible to allergies, especially asthma (see Section 4.4 Special Warnings and Precautions for Use, Hypersensitivity). Hypersensitivity reactions may include skin reactions at the injection site, dizziness, nausea, vomiting, urticaria, flushing, malaise, dyspnoea, angioneurotic oedema or Quincke's oedema.

Adrenal haemorrhage.

Isolated cases have been reported with Synacthen.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at https://www.tga.gov.au/reporting-problems.

4.9 Overdose

There have not been any reports that administration of Synacthen in recommended dosage, as a diagnostic aid, has resulted in signs and symptoms associated with overdosage. However, for information on this subject, reference may be made to the Product Information for Synacthen Depot.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Synacthen has the same physiological action as endogenous ACTH. In the normally functioning adrenal cortex it stimulates the biosynthesis of glucocorticoids, mineralocorticoids and (to a lesser extent) androgens. This accounts for its therapeutic effect in conditions responsive to glucocorticoid treatment. Its pharmacological activity, however, is not comparable to that of the corticosteroids, because under ACTH treatment, in contrast to treatment with a single glucocorticoid, the tissues are exposed to a physiological spectrum of corticosteroids such as desoxycorticosterone, corticosterone, cortisol and aldosterone.
Prolonged treatment with high doses of ACTH induces hyperplasia and hypertrophy of the adrenal cortex and continuous high output of cortisol, corticosterone and weak androgens. The binding sites of ACTH are located in the plasma membrane of the adrenocortical cells, where it becomes bound to a specific receptor. The hormone-receptor complex activates adenyl cyclase, thereby stimulating the production of cyclic AMP (adenosine monophosphate). Cyclic AMP activates protein kinase, which promotes the synthesis of pregnenolone from cholesterol. From pregnenolone the various corticosteroids are produced via a variety of enzymatic pathways.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Distribution.

Tetracosactide (tetracosactrin) has an apparent distribution volume of approx. 0.4 litres/kg. The half-lives of its elimination from the plasma following an intravenous injection are approximately 7 minutes in the first phase (lasting approximately 1 hour), approximately 37 minutes in the next phase (also lasting approximately 1 hour) and, thereafter, approximately 3 hours.

Metabolism.

In the serum, tetracosactide (tetracosactrin) is broken down first by serum endopeptidases (such as trypsin, plasmin, thrombin, and kallikrein) into inactive oligopeptides, and then by aminopeptidases into free amino acids. Its rapid elimination from the plasma is probably attributable, not only to this relatively slow process of cleavage, but rather to the fact that the active substance becomes rapidly concentrated in the adrenals and kidneys.

Elimination.

Following an intravenous dose of 131I-labelled beta1-24-corticotrophin, 95 to 100% of the radioactivity is excreted in the urine within 24 hours.

5.3 Preclinical Safety Data

Genotoxicity.

Appropriate studies have not been performed to evaluate mutagenic potential.

Carcinogenicity.

Appropriate studies have not been performed to evaluate carcinogenic potential

6 Pharmaceutical Particulars

6.1 List of Excipients

Acetic acid, sodium acetate, sodium chloride, water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Protect from light and store in a refrigerator (2-8°C).

6.5 Nature and Contents of Container

Injection.

250 microgram/mL, 1 mL ampoule; containers of 1. AUST R 11058.

6.6 Special Precautions for Disposal

The release of medicines into the environment should be minimised. Medicines should not be disposed of via wastewater and disposal through household waste should be avoided. Unused or expired medicine should be returned to a pharmacy for disposal.

6.7 Physicochemical Properties

Chemical structure.

Active ingredient.

Tetracosactide (tetracosactrin).

Empirical formula.

C136H210N40O31S.

Molecular weight.

2933.5.

Amino acid sequence.

Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-Lys-Val-Tyr-Pro.

CAS number.

60189-34-6.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription only medicine.

Summary Table of Changes