Synacthen Ampoules 250mcg

Tetracosactide acetate PhEur 250micrograms per ampoule.

For a full list of excipients, see section 6.1.

A clear colourless sterile solution in a clear glass ampoule.

Diagnostic test for the investigation of adrenocortical insufficiency.

Adults: This preparation of Synacthen is intended for administration for diagnostic purposes only as a single intramuscular or intravenous dose; it is not to be used for repeated therapeutic administration.

The 30-minute Synacthen diagnostic test: This test is based on measurement of the plasma cortisol concentration immediately before and exactly 30 minutes after an intramuscular or intravenous injection of 250micrograms (1ml) Synacthen. Adrenocortical function can be regarded as normal if the post-injection rise in plasma cortisol concentration amounts to at least 200nmol/litre (70micrograms/litre).

Where the 30-minute test has yielded inconclusive results, or where it is desired to determine the functional reserve of the adrenal cortex, a 5-hour test can be performed with Synacthen Depot (see separate Summary of Product Characteristics). Furthermore, a 3-day test with Synacthen Depot may be used to differentiate between primary and secondary adrenocortical insufficiency.

Children: An intravenous dose of 250micrograms/1.73m² body surface area has been suggested. Thus for children aged 5 to 7 years, approximately half the adult dose will be adequate. For more accurate dosing of other ages, standard body surface area tables should be consulted.

Elderly: There is no evidence to suggest that dosage should be different in the elderly.

History of hypersensitivity to Adrenocorticotropic hormone (ACTH), Synacthen or Synacthen Depot. Synacthen is contra-indicated in patients with allergic disorders (e.g. asthma) (see Section 4.4 Special warnings and special precautions for use), acute psychosis, infectious diseases, peptic ulcer, refractory heart failure, Cushing's syndrome, and primary adrenocortical insufficiency.

Synacthen Ampoules should not be used during pregnancy or lactation unless there are compelling reasons to do so.

Before using Synacthen, the doctor should make every effort to find out whether the patient is suffering from, or has a history of, allergic disorders (see Section 4.3 “Contra-indications”). In particular, he should enquire whether the patient has previously experienced adverse reactions to ACTH, Synacthen or other drugs.

Synacthen should only be administered under the supervision of appropriate senior hospital medical staff (e.g. consultants).

If local or systemic hypersensitivity reactions occur after the injection (for example, marked redness and pain at the injection site, urticaria, pruritus, flushing, faintness or dyspnoea), Synacthen or other ACTH preparations should be avoided in the future. Hypersensitivity reactions tend to occur within 30 minutes of an injection. The patient should therefore be kept under observation during this time.

Preparation should be made in advance to combat any anaphylactic reaction that may occur after an injection of Synacthen. In the event of a serious anaphylactic reaction occurring, the following measures must be taken immediately: administer adrenaline (0.4 to 1ml of a 0.1% solution intramuscularly or 0.1 to 0.2ml of a 0.1% solution in 10ml physiological saline slowly intravenously) as well as a large intravenous dose of a corticosteroid (for example 100mg to 500mg hydrocortisone, three or four times in 24 hours), repeating the dose if necessary.

The hydrocortisone product information prepared by the manufacturer should also be consulted.

Synacthen Ampoules should not be used in the presence of active infectious or systemic diseases, when the use of live vaccine is contemplated or in the presence of a reduced immune response, unless adequate disease specific therapy is being given.

Use with care in patients with hypertension and thromboembolic tendencies.

The increased production of adrenal steroids may result in corticosteroid type effects:

• Psychological disturbances may be triggered or aggravated.

• Latent infections (e.g. amoebiasis, tuberculosis) may become activated.

• Ocular effects may be produced (e.g. glaucoma, cataracts).

• Dosage adjustments may be necessary in patients being treated for diabetes or hypertension.

Since Synacthen increases the adrenocortical production of glucocorticoids and mineralocorticoids, drug interactions of the type seen with these corticosteroids may occur (see Section 4.4 Special warnings and special precautions for use). Patients already receiving medication for diabetes mellitus or for moderate to severe hypertension must have their dosage adjusted if treatment with Synacthen is started.

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

Usage in pregnancy: There is limited amount of data in the use of tetracosactide in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see Section 5.3 Preclinical safety data). Usage in pregnancy is contraindicated (see Section 4.3 Contraindications).Therefore the Synacthen test should not be utilised during pregnancy and lactation unless there are compelling reasons for doing so.

Usage in lactation: It is not known whether tetracosactide enters breast milk or not. Usage in lactation is contraindicated (see Section 4.3 Contraindications).

Fertility: Animal studies are insufficient with respect to reproductive toxicity (see Section 5.3 Preclinical safety data).

Patients should be warned of the potential hazards of driving or operating machinery if they experience side effects such as dizziness.

Synacthen may provoke hypersensitivity reactions. In patients suffering from, or susceptible to, allergic disorders (especially asthma) this may take the form of anaphylactic shock (see Section 4.3 “Contra-indications”).

Hypersensitivity may be manifested as skin reactions at the injection site, dizziness, nausea, vomiting, urticaria, pruritus, flushing, malaise, dyspnoea, angioneurotic oedema and Quinke's oedema.

The undesirable effects related to glucocorticoid and mineralocorticoid effects are unlikely to be observed with short-term use of Synacthen as a diagnostic tool, but may be reported when Synacthen is used in therapeutic indications. Should information be required on the side effects reported with therapeutic use of tetracosactide acetate, see Synacthen Depot Summary of Product Characteristics.

Adverse reactions in Table 1 are ranked under heading of frequency where known, the most frequent first, using the following convention: very common (greater than or equal to 1 in 10); common (less than or equal to 1 in 100, less than 1 in 10); uncommon (greater than or equal to 1 in 1,000, less than 1 in 100); rare (greater than or less than 1 in 10,000, less than 1 in 1,000) very rare (less than 1 in 10,000), not known (where no valid estimate of the incidence has been derived).

Table 1. Adverse events

1) Particularly in times of stress, e.g. after trauma, surgery, or illness

2) Also see section 4.4

Overdosage is unlikely to be a problem when the product is used as a single dose for diagnostic purposes.

Pharmacotherapeutic group: anterior pituitary lobe hormones and analogues – ACTH.

ATC code: H01AA02.

Tetracosactide acetate consists of the first 24 amino acids occurring in the ACTH sequence and displays the same physiological properties as ACTH. In the adrenal cortex, it stimulates the biosynthesis of glucocorticoids, mineralocorticoids, and, to a lesser extent androgens.

The site of action of ACTH is the plasma membrane of the adrenocortical cells, where it binds to a specific receptor. The hormone-receptor complex activates adenylate cyclase, stimulating the production of cyclic AMP (adenosine monophosphate) and so promoting the synthesis of pregnenolone from cholesterol. From pregnenolone the various corticosteroids are produced via different enzymatic pathways.

Following an intravenous injection, elimination of tetracosactide acetate from the plasma consists of 3 phases. The half-lives of these phases are approximately 7 minutes (0 to 1 hour), 37 minutes (1 to 2 hours) and 3 hours thereafter.

Tetracosactide acetate has an apparent volume of distribution of approximately 0.4L/kg.

In the serum, tetracosactide acetate is broken down by serum endopeptidases into inactive oligopeptides and then by aminopeptidases into free amino acids. The rapid elimination from plasma is probably not attributable to this relatively slow cleavage process, but rather to the rapid concentration of the active substance in the adrenal glands and kidneys.

Following an iv dose of ¹³¹I-labelled tetracosactide acetate, 95 to 100% of the radioactivity is excreted in the urine within 24 hours.

There are no pre-clinical data of relevance to the prescriber, which are additional to those already included in other sections of the Summary of Product Characteristics.

Acetic acid, sodium acetate, sodium chloride and water.

None known.

5 years.

Synacthen should be protected from light and stored in a refrigerator (2 - 8°C).

The ampoules are colourless glass PhEur type I. Five ampoules are packed in a cardboard box.

Any unused product or waste material should be disposed of in accordance with local requirements.

Alliance Pharmaceuticals Ltd

Avonbridge House

Bath Road

Chippenham

Wiltshire

SN15 2BB

PL 16853/0017

25 June 1998

04 January 2011