Synacthen Ampoules 250mcg

1. Name Of The Medicinal Product

Synacthen^® Ampoules 250mcg

2. Qualitative And Quantitative Composition

Tetracosactide acetate PhEur 250micrograms per ampoule.

3. Pharmaceutical Form

A clear colourless sterile solution in a clear glass ampoule.

4. Clinical Particulars

4.1 Therapeutic Indications

Diagnostic test for the investigation of adrenocortical insufficiency.

4.2 Posology And Method Of Administration

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.

4.3 Contraindications

History of hypersensitivity to ACTH, Synacthen or Synacthen Depot. Synacthen is contra-indicated in patients with allergic disorders (e.g. asthma).

4.4 Special Warnings And Precautions For Use

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.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None known.

4.6 Pregnancy And Lactation

The Synacthen test should not be utilised during pregnancy and lactation unless there are compelling reasons for doing so.

4.7 Effects On Ability To Drive And Use Machines

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

4.8 Undesirable Effects

Hypersensitivity reactions:

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.

Other side effects are unlikely to be observed with short-term use of Synacthen as a diagnostic tool. Should information be required on the side effects reported with therapeutic use of tetracosactide acetate, see Synacthen Depot Summary of Product Characteristics.

4.9 Overdose

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

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Tetracosactide acetate consists of the first 24 amino acids occurring in the natural corticotropic hormone (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.

5.2 Pharmacokinetic Properties

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.

5.3 Preclinical Safety Data

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.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Acetic acid, sodium acetate, sodium chloride and water.

6.2 Incompatibilities

None known.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

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

6.5 Nature And Contents Of Container

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

6.6 Special Precautions For Disposal And Other Handling

Shake well before use.

Administrative Data

7. Marketing Authorisation Holder

Alliance Pharmaceuticals Ltd

Avonbridge House

Bath Road

Chippenham

Wiltshire

SN15 2BB

8. Marketing Authorisation Number(S)

PL 16853/0017

9. Date Of First Authorisation/Renewal Of The Authorisation

25 June 1998

10. Date Of Revision Of The Text

February 2005

11. Legal Status

POM

Alliance, Alliance Pharmaceuticals and associated devices are registered Trademarks of Alliance Pharmaceuticals Ltd.