Consumer medicine information

Synacthen Depot

Tetracosactide (tetracosactrin)

BRAND INFORMATION

Brand name

Synacthen Depot

Active ingredient

Tetracosactide (tetracosactrin)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Synacthen Depot.

What is in this leaflet

This leaflet answers some common questions about Synacthen Depot. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you or your child having Synacthen Depot against the benefits they expect it will provide.

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

Keep this leaflet with the medicine. You may need to read it again.

What Synacthen Depot is used for

Synacthen Depot has two very different uses:

  • It is used in people with multiple sclerosis who are experiencing a worsening of their symptoms
  • It is used in young children to treat some types of seizure (fit), such as infantile spasms.

Synacthen Depot works by causing the adrenal glands to increase the production of natural "steroid" hormones that can help to reduce the symptoms of certain diseases.

This medicine is not suitable for newborn babies, especially if they are premature, because it contains benzyl alcohol, which can cause severe side effects in very young babies. It must also be used with caution in children up to 3 years of age.

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

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

Before you have Synacthen Depot

When you must not have it

Do not have Synacthen Depot if you have an allergy to:

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

Some of the 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 parts of the body

Do not have Synacthen Depot if you have any of the following health problems/medical conditions:

  • a viral illness or you have recently been vaccinated with a live virus vaccine
  • an infection, unless you are taking antibiotics for it
  • a stomach ulcer
  • severe heart disease
  • abnormal functioning of your adrenal glands
  • a mental illness with disturbances in thinking, feelings and behaviour

If you are unsure whether any of the above conditions apply to you, your doctor can provide more information.

Do not have Synacthen Depot if you are pregnant. It may affect your developing baby or cause a miscarriage if you have it during pregnancy.

Do not breast-feed if you are having Synacthen Depot. There is not enough information to recommend breast-feeding while you are having this medicine.

Do not have Synacthen Depot after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. In that case, return it to your pharmacist.

If you are not sure whether you should have this medicine, talk to your doctor.

Before you start to have it

Tell your doctor if you have asthma or allergies to other medicines, foods, dyes or preservatives. Your chance of having an allergic reaction to Synacthen Depot may be greater than normal.

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

  • diabetes
  • high blood pressure
  • kidney problems
  • an inflammation of the bowel (e.g. ulcerative colitis or diverticulitis)
  • recent bowel surgery
  • blockage of a blood vessel by a clot (thromboembolism)
  • weak brittle bones (osteoporosis)
  • myasthenia gravis, a condition which causes extreme muscle weakness
  • an underactive thyroid gland
  • cirrhosis of the liver
  • tuberculosis
  • an eye infection caused by herpes simplex virus
  • an infection caused by an amoeba

If you are unsure about any of the above conditions, your doctor can provide more information.

Taking other medicines

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

Some medicines and Synacthen Depot may interfere with each other. These include medicines used to treat:

  • diabetes
  • high blood pressure
  • convulsions

It may be necessary to change the dose or in some cases stop the medicine while you are being treated with Synacthen Depot.

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

How Synacthen Depot is given

How much is given

For multiple sclerosis: the starting dose is usually a single daily injection of 1mg but it may be given twice a day in severe cases. Once the condition has improved, the number of injections can usually be reduced to one every 2 or 3 days or even once weekly.

For seizures in children: the starting dose is usually a single daily injection ranging from 0.25 to 1 mg, depending on the age of the child. Once the condition has improved, the number of injections can usually be reduced to one every 2 to 8 days.

How long treatment lasts

Synacthen Depot will not cure your condition but it may relieve some of the symptoms. The injections can be continued for as long as they provide a benefit. When treatment is stopped, it will usually be done gradually to help maintain the normal function of your adrenal glands.

While you are having Synacthen Depot

Things you must do

If you become pregnant while having this medicine, tell your doctor immediately. This medicine must not be used during pregnancy.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor will check for unwanted side effects. Some side effects such as change in blood pressure and in levels of sugar and other elements in the blood may only be found by doing regular tests. time to time to make sure the medicine is working and to prevent unwanted side effects. Children may need to have their heart checked and their growth monitored during long-term treatment.

If you suffer an injury requiring medical attention or are going to have surgery either during treatment with Synacthen Depot or within 1 year after treatment has stopped, tell the doctor, surgeon or anaesthetist about this medicine. Prolonged treatment with Synacthen Depot may make your adrenal glands less able to cope with the stress to your body caused by an injury or surgery.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are having Synacthen Depot.

Tell any other doctors, dentists, and pharmacists who treats you that you are having this medicine.

Things you must not do

Do not have any vaccinations without first checking with your doctor. This medicine can change your response to vaccines and may prevent you from being successfully vaccinated against some diseases.

Do not take Synacthen Depot to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they seem to have the same condition as you.

Things to be careful of

Be careful driving or operating machinery or doing jobs that require you to be alert until you know how Synacthen Depot affects you. This medicine may cause headache and vertigo (spinning sensation) in some people. Make sure you know how it affects you before you drive or do anything else that could be dangerous.

If you are being treated for diabetes, be careful to check your blood sugar regularly and report any problems to your doctor. Synacthen Depot may change how well your diabetes is controlled. The dose of your diabetes medicines may need to be changed.

Be careful to avoid close contact with anyone who has an infectious disease. This medicine may make you more susceptible to infections than usual and these infections may be more serious.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are having Synacthen Depot.

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

Side effects can often be relieved by reducing the dose given at each injection or increasing the time between injections.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

During the injection of Synacthen Depot, tell your doctor immediately if you notice any of the following signs of a possible allergic reaction:

  • 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 any other parts of the body

Allergic reactions can happen rarely, usually within 30 minutes after the injection. During this period, your doctor or nurse will watch you closely for signs of allergy and will have medicines to treat this type of reaction near at hand.

Tell your doctor immediately if you notice any of the following symptoms at any time during treatment:

  • severe pain or tenderness in the stomach, which may be accompanied by nausea (feeling sick) and vomiting
  • vomiting blood or material that looks like coffee grounds
  • pain and ulceration along the food pipe leading from the throat to the stomach
  • convulsions (fits)
  • pain in the eye or difficulty seeing
  • sudden severe headache, sudden loss of coordination, slurred speech, numbness in the arm or leg, pain in the calves, thighs or chest
  • shortness of breath and swelling of the legs or ankles due to fluid build up
  • rapid change in mood from extreme happiness to depression, personality changes or other disturbances in thinking, feelings and behaviour
  • any infectious abscesses or wounds other than of a very minor nature
  • difficulty urinating or passing little or no urine

Tell your doctor if any of the following happen and they worry you:

  • headache
  • spinning sensation (vertigo)
  • difficulty sleeping
  • muscle weakness
  • feeling of bloating in the abdomen
  • changes to the skin such as thinning, darkening in colour, acne, stretch marks, red or purple pin head spots or bruising
  • red or moon-shaped face
  • increased sweating
  • excessive hair growth
  • changes in menstrual period
  • increased appetite
  • weight gain

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using Synacthen Depot

Storage

If you are storing Synacthen Depot at home, keep it in the fridge. Make sure that young people cannot reach it.

Disposal

If your doctor stops your treatment with Synacthen Depot or you find that the expiry date has passed, ask your pharmacist what to do with any medicine you have left over.

Product description

What it looks like

Synacthen Depot is available in a glass ampoule containing 1 mL of milky white liquid; one ampoule per carton.

Ingredients

Each ampoule of Synacthen Depot contains 1 mg of the active ingredient, tetracosactide (tetracosactrin) (in a zinc phosphate complex). It also contains;

  • benzyl alcohol
  • hydrochloric acid
  • sodium chloride
  • sodium hydroxide
  • sodium phosphate dibasic
  • zinc chloride
  • water for injections

Sponsor

Synacthen Depot is supplied in Australia by:

Clinect Pty Ltd
120-132 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 Depot AUST R 11060

Published by MIMS September 2020

BRAND INFORMATION

Brand name

Synacthen Depot

Active ingredient

Tetracosactide (tetracosactrin)

Schedule

S4

 

Notes

Distributed by Clinect Pty Ltd

1 Name of Medicine

Tetracosactide (tetracosactrin).

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.

2 Qualitative and Quantitative Composition

Tetracosactide (tetracosactrin) is the first corticotrophic preparation to be produced entirely by synthesis and displays all 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 tetracosactide (tetracosactrin) 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).
Synacthen Depot is administered only by the intramuscular route.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Injection, modified release.
Milky white suspension.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Synacthen Depot 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.
Synacthen Depot is supplied as a suspension in which the active substance is adsorbed onto an inorganic zinc complex so that the formulation provides for a protracted release. Following an intramuscular injection of 1 mg Synacthen Depot, the plasma cortisol concentration remains elevated for 24 to 36 hours.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Adsorption of tetracosactide (tetracosactrin) onto zinc phosphate provides for sustained release of the active substance from the intramuscular injection site. After an injection of 1 mg Synacthen Depot i.m., the radioimmunologically determined plasma concentrations of tetracosactide (tetracosactrin) lie for 12 hours between 200 and 300 picogram/mL.

Distribution.

Tetracosactide (tetracosactrin) has an apparent distribution volume of approximately 0.4 L/kg.

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 aminopeptidase 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 β1-24-corticotrophin, 95 to 100% of the radioactivity is excreted in the urine within 24 hours.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Neurological diseases.

Acute exacerbations in patients suffering from multiple sclerosis; hypsarrhythmia and/or infantile spasms.

4.3 Contraindications

If the patient's case history discloses any record of hypersensitivity reactions to ACTH treatment, tetracosactide (tetracosactrin) must not be used either for diagnosis or for treatment.
Hypersensitivity to tetracosactide (tetracosactrin) and/or ACTH of animal origin.
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).
Pregnancy and breastfeeding.
Adrenocortical insufficiency.
Adrenogenital syndrome.
In view of the increased risk of anaphylactic reactions, Synacthen Depot must not be employed to treat asthma or other allergic conditions.
Diabetes mellitus;
Moderate or severe hypertension.
Since Synacthen Depot contains benzyl alcohol, it is contraindicated in neonates (especially premature infants), in whom benzyl alcohol can cause severe poisoning.

4.4 Special Warnings and Precautions for Use

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 after administration of Synacthen Depot.
In patients who, in addition to the disease entity for which tetracosactide (tetracosactrin) is indicated, are also susceptible to allergies or are actually suffering from an allergic disorder (especially asthma), treatment with Synacthen Depot should only be resorted to if other therapeutic measures have failed to elicit the desired response and if the condition is severe enough to warrant such medication.
In these allergic patients the physician must be prepared in advance to treat any anaphylactic reaction occurring after the injection of Synacthen Depot.
Synacthen Depot should not be administered intravenously.

Hypersensitivity.

Before employing Synacthen Depot 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).
Synacthen Depot should only be administered under medical supervision.
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) treatment with tetracosactide (tetracosactrin) must be discontinued and all use of ACTH preparations avoided in the future.
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.

Salt and water retention.

Salt and water retention in response to Synacthen Depot can often be avoided or eliminated by prescribing a low salt diet. During prolonged treatment, potassium substitution may be required occasionally.

Pre-existing conditions.

Patients already receiving medication for diabetes mellitus or for moderate to severe hypertension must have their dosages readjusted if treatment with Synacthen Depot is instituted.
Use with caution in patients with nonspecific ulcerative colitis, diverticulitis, recent intestinal anastomosis, renal insufficiency, hypertension, predisposition to thromboembolism, osteoporosis and myasthenia gravis.
The effect of therapy with Synacthen Depot may be increased in patients with hypothyroidism or cirrhosis of the liver.

Infectious diseases.

Synacthen Depot may activate latent amoebiasis. It is recommended that latent or active amoebiasis be ruled out before initiating therapy.
If Synacthen Depot is indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary because the disease may be reactivated. During prolonged therapy, such patients should receive chemoprophylaxis.
Synacthen Depot should be used cautiously in patients with ocular herpes simplex owing to possible corneal perforation.
Do not administer live virus vaccines to patients being treated with Synacthen Depot. Any other immunisation procedures must be undertaken with caution because of the decrease in antibody response.

Adrenocortical insufficiency.

Relative adrenocortical insufficiency can follow termination of prolonged ACTH treatment and may persist for several months after stopping treatment. The risk can be reduced by keeping the dose of Synacthen Depot to the lowest possible level for the shortest duration (see Section 4.2 Dose and Method of Administration). Treatment should be withdrawn gradually.
In patients who suffer an injury or undergo surgery during or within one year after treatment, the associated stress may be managed by an increase or resumption of treatment with Synacthen Depot. Additional use of rapidly acting corticosteroids may be required. The lowest effective dose should be used and, if the dose has to be reduced, it should be done gradually.

Antibody formation.

There have been occasional instances of antibodies being formed in individuals during therapy with synthetic ACTH. The clinical significance of these is not clear.

Effects on the eye.

Prolonged therapy may be associated with development of posterior subcapsular cataracts and glaucoma.

Psychological disturbances.

Psychological disturbances may occur during treatment with Synacthen Depot (e.g. euphoria, insomnia, mood swings, personality changes, severe depression or even frank psychotic manifestations). Existing emotional instability or psychotic tendencies may be aggravated.

Use in hepatic impairment.

The effect of therapy with Synacthen Depot may be increased in patients with cirrhosis of the liver.

Use in renal impairment.

Use with caution in patients with renal insufficiency.

Use in the elderly.

No data available.

Paediatric use.

Provided the dosage is carefully individualised, Synacthen Depot is unlikely to inhibit growth in children. Nevertheless, in children undergoing long-term treatment, growth should be monitored.
In infants and small children treated with Synacthen Depot, echocardio-graphic recordings should be made regularly, because during long-term treatment with high doses reversible myocardial hypertrophy may occur.
Due to the presence of benzyl alcohol, Synacthen Depot is not recommended in infants and children up to 3 years old, as it may cause toxic reactions and allergic reactions.

Effects on laboratory tests.

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Lack of diagnostic accuracy.

4.5 Interactions with Other Medicines and Other Forms of Interactions

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 (see Section 4.4 Special Warnings and Precautions for Use).

Anticipated interactions to be considered.

Since Synacthen Depot increases the adrenocortical production of glucocorticoids and mineralocorticoids, drug interactions of the type seen with these corticosteroids may occur. Patients already receiving medication for diabetes mellitus or hypertension may need adjustment to their drug regimen if treatment with Synacthen Depot is instituted.

Lack of diagnostic accuracy.

Postadministration 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.
Synacthen Depot contains an active substance that may interfere with routine drug testing in athletes.

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 Depot 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 initiate treatment with Synacthen Depot must be with recognition to the individual case history. Mothers must not breastfeed during the period of its use.

4.8 Adverse Effects (Undesirable Effects)

Hypersensitivity reactions.

Synacthen Depot 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 reactions may include skin reactions at the injection site, dizziness, nausea, vomiting, urticaria, flushing, malaise, dyspnoea, angioneurotic oedema or Quincke's oedema.
A number of deaths have been reported in association with administration of Synacthen or Synacthen Depot. The incidence of mortality in recipients is estimated to be about 0.002%, which is very low and comparable to that associated with the use of penicillin. However, it should be borne in mind that the outcome has been fatal in 15% of all adverse reactions reported. Allergic reactions account for 74% of all reactions.

Adrenal haemorrhage.

Isolated cases have been reported with Synacthen Depot.
In rare cases the benzyl alcohol contained in Synacthen Depot may also give rise to hypersensitivity reactions, especially in children below 3 years of age (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

Other adverse reactions.

Synacthen Depot induces the adrenal cortex to increase its production of glucocorticoids and mineralocorticoids, and androgens to a lesser extent. Side effects therefore tend to be of the type found with these corticosteroids.

Musculoskeletal.

Osteoporosis, muscle weakness, steroid myopathy, loss of muscle mass, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathological fracture of long bones, tendon rupture.

Gastrointestinal.

Abdominal discomfort/ distension, peptic ulcer with possible perforation and haemorrhage, pancreatitis, ulcerative oesophagitis.

Dermatological.

Hyperpigmentation, acne, striae of the skin, thin fragile skin, petechiae and ecchymosis, facial erythema, increased sweating, suppression of skin test reactions, impaired wound healing, abscess.

Neurological.

Headache, vertigo, psychological changes, convulsions, increased intracranial pressure with papilloedema (pseudotumour cerebri), usually after treatment.

Endocrine.

Fluid retention, electrolyte disturbance (e.g. hypernatraemia, hypokalaemia, hypokalaemic alkalosis, negative calcium balance), hirsutism, hyperglycaemia, glycosuria, Cushing's syndrome (moon face, plethora), suppression of growth in children, secondary adrenocortical and pituitary unresponsiveness particularly in times of stress (e.g. after trauma, surgery or illness), decreased carbohydrate tolerance, menstrual irregularities, increased appetite, weight gain.

Ophthalmic.

Posterior subcapsular cataracts, increased intraocular pressure, glaucoma, exophthalmos.

Metabolic.

Negative nitrogen balance due to protein catabolism.

Cardiovascular.

Hypertension, necrotising angiitis, congestive heart failure, thromboembolism. In infants and small children treated over a prolonged period with high dosages, reversible myocardial hypertrophy may occur in isolated instances.

Haematological.

Leucocytosis.

Immunological.

Lowered resistance to infectious agents.

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.

4.2 Dose and Method of Administration

By intramuscular injection only.
Before an injection of Synacthen Depot, the ampoule containing the relatively thin, slightly opalescent suspension should be shaken until it becomes uniformly cloudy. The preparation should be stored in a refrigerator (2-8°C).

Adults.

Initially 1 mg daily; in acute or critical conditions, treatment can be initiated with 1 mg every 12 hours. Once the acute manifestations have subsided, the usual maintenance dosage is 1 mg every two or three days; in patients who respond well, it is often possible to reduce the dose to as little as 0.5 mg every two or three days or 1 mg weekly.

Infants.

Initially: 0.25 mg daily; for maintenance: 0.25 mg every two to eight days.

Small children.

Initially: 0.25 to 0.5 mg daily; for maintenance: 0.25 to 0.5 mg every two to eight days.

Children of school age.

Initially: 0.25 to 1 mg daily; for maintenance: 0.25 to 1 mg every two to eight days.

4.7 Effects on Ability to Drive and Use Machines

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

4.9 Overdose

Overdosage may lead to temporary water retention and to signs of excessive adrenocortical activity (Cushing's syndrome). In such circumstances, Synacthen Depot should be withdrawn for a time or, alternatively, given in reduced doses either by halving the dosage or by prolonging the interval between injections to, say, 5 to 7 days in adults.
In infants or children, tetracosactide (tetracosactrin) should be discontinued and the case history and dosage schedule carefully reviewed.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription only medicine.

6 Pharmaceutical Particulars

6.1 List of Excipients

Benzyl alcohol, dibasic sodium phosphate dodecahydrate, hydrochloric acid, sodium chloride, sodium hydroxide, water for injection, zinc chloride.

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: 1mg/mL, 1 mL ampoules; containers of 1 AUST R 11060.

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.

Summary Table of Changes