Tetracosactid

Uses and Administration

Tetracosactide is a synthetic polypeptide with general properties similar to those of corticotropin ( Refer to ). Tetracosactide is used diagnostically to investigate adrenocortical insufficiency ( Refer to ).

Although tetracosactide, like corticotropin, has also been used therapeutically for most of the conditions in which systemic corticosteroid therapy is indicated, it is now rarely used for such indications.

Tetracosactide is usually used in the form of the acetate although doses are often expressed in terms of tetracosactide itself.

For diagnostic purposes tetracosactide acetate is used intramuscularly or intravenously as a plain injection in the first instance then, if results are inconclusive, intramuscularly as a long-acting depot injection. The initial test using the plain injection is based on the measurement of plasma-cortisol concentrations immediately before and exactly 30 minutes after an intramuscular or intravenous injection equivalent to 250 micrograms of tetracosactide; adrenocortical function may be regarded as normal if there is a rise in the cortisol concentration of at least 200 nanomoles/litre (70 micrograms/litre). In some cases the dose may be given by intravenous infusion over 6 hours to provide a greater stimulus of the adrenal glands, with cortisol concentrations measured before and at the end of the infusion. A low-dose test using 1 microgram has also been used (see Diagnostic Use, Refer to ).

If the results of this test are equivocal, or where functional reserve of the adrenal cortex is to be determined, the long-acting depot preparation may be used, the dose being 1 mg of tetracosactide acetate given intramuscularly. Adrenocortical function is regarded as normal if plasma-cortisol concentrations have steadily increased to 1000 to 1800 nanomoles/litre 5 hours after the injection. A 3-day test, for example with 1 mg of the depot preparation given each morning, is also used to differentiate between primary and secondary adrenocortical insufficiency; this is preceded on the first day and followed on the fourth day by the test using the plain injection. A marked improvement in the second assessment suggests secondary adrenocortical insufficiency.

For therapeutic purposes tetracosactide acetate has been given by intramuscular injection as the long-acting depot preparation. The usual initial dose of tetracosactide acetate has been 1 mg daily (or 1 mg every 12 hours in acute cases), reduced after the acute symptoms have been controlled to 0.5 to 1 mg every 2 or 3 days or 1 mg weekly.

For doses used in children, see Refer to .

(last reviewed 2010-07-28; last modified 2010-08-31)

Administration in children

For diagnostic use, children may be given an intravenous or intramuscular dose of the plain injection of tetracosactide 145 micrograms/m2, to a maximum of 250 micrograms. The BNFC also includes a low-dose test of 300 nanograms/m2.

Tetracosactide acetate in a long-acting depot preparation has been given intramuscularly for therapeutic use in conditions requiring systemic corticosteroid therapy. For children aged 3 to 5 years old, an initial dose of 250 to 500 micrograms has been given daily, and then every 2 to 8 days for maintenance. A dose of 0.25 to 1 mg has been used similarly in children aged 5 to 12 years.

Tetracosactide has also been used to manage infantile spasms (see Epilepsy, Refer to ). For children aged 1 month and older, the BNFC suggests using the depot preparation in a dose of 500 micrograms by intramuscular injection, given on alternate days and adjusted according to response.

(last reviewed 2010-07-28; last modified 2014-01-07)

Diagnostic use

Tetracosactide is widely used in the diagnosis of adrenal insufficiency ( Refer to ). It is usually given by intramuscular or intravenous injection in a dose of 250 micrograms, with plasma-cortisol concentrations measured before and 30 minutes after the injection. The sensitivity of this test has been questioned, as such a high dose may produce a cortisol response in patients with partial adrenal gland atrophy, resulting in a missed diagnosis of secondary adrenal insufficiency. A low-dose test using an intravenous dose of 1 microgram has been proposed as a more sensitive test.

A meta-analysis1 concluded that high- and low-dose tests performed similarly in the diagnosis of secondary adrenal insufficiency. However, the high-dose test was favoured because of the lack of a commercially available low-dose preparation. A later review2 advocated the use of the low-dose test for diagnosing secondary insufficiency, but recommended the high-dose test for diagnosis of suspected primary adrenal insufficiency. Both considered that more study was needed of the use of these tests in critically ill patients.1,2

(last reviewed 2010-07-28; last modified 2010-06-24)

References

1. Dorin RI, et al.. Diagnosis of adrenal insufficiency.Ann Intern Med. 2003; 139: 194–204. PubMed

2. Magnotti M, Shimshi M. Diagnosing adrenal insufficiency: which test is best—the 1-microgram or the 250-microgram cosyntropin stimulation test?Endocr Pract. 2008; 14: 233–8. PubMed

Post-dural puncture headache

There are anecdotal reports of the relief of post-dural puncture headache by corticotropin or, more recently, tetracosactide.1-5Intramuscular injection and intravenous infusion have both been used, but a controlled study6 in 18 women found that a single intramuscular dose of tetracosactide 1 mg was no more beneficial than sodium chloride 0.9%. As discussed on Refer to , many patients respond to conservative measures.

(last reviewed 2010-07-28; last modified 2006-03-04)

References

1. Collier BB. Treatment for post dural puncture headache.Br J Anaesth. 1994; 72: 366–7. PubMed

2. Foster P. ACTH treatment for post-lumbar puncture headache.Br J Anaesth. 1994; 73: 429. PubMed

3. Kshatri AM, Foster PA. Adrenocorticotropic hormone infusion as a novel treatment for postdural puncture headache.Reg Anesth. 1997; 22: 432–4. PubMed

4. Carter BL, Pasupuleti R. Use of intravenous cosyntropin in the treatment of postdural puncture headache.Anesthesiology. 2000; 92: 272–4. PubMed

5. Cánovas L, et al.. Use of intravenous tetracosactin in the treatment of postdural puncture headache: our experience in forty cases.Anesth Analg. 2002; 94: 1369. PubMed

6. Rucklidge MWM, et al.. Synacthen Depot® for the treatment of postdural puncture headache.Anaesthesia. 2004; 59: 138–41. PubMed

Adverse Effects, Treatment and Precautions

Adverse Effects, Withdrawal, and Precautions

As for Corticotropin, Refer to . Although hypersensitivity reactions, including anaphylaxis, may occur with the use of tetracosactide, it is reported to be less immunogenic than corticotropin; US licensed product information suggests that patients with a history of hypersensitivity to corticotropin may tolerate tetracosactide. In the UK, however, previous hypersensitivity to corticotropin or to tetracosactide is considered a contra-indication to tetracosactide use. Tetracosactide is also contra-indicated in patients with a history of allergic disorders such as asthma.

Since hypersensitivity reactions may occur up to 1 hour after injection, sufficient time should be allowed for recovery after use at the hospital or surgery. Self-administration is not recommended.

(last reviewed 2010-07-28; last modified 2010-06-24)

Porphyria

The Drug Database for Acute Porphyria, compiled by the Norwegian Porphyria Centre (NAPOS) and the Porphyria Centre Sweden, classifies tetracosactide as not porphyrinogenic; it may be used as a drug of first choice and no precautions are needed.1

(last reviewed 2010-07-28; last modified 2011-11-15)

References

1. The Drug Database for Acute Porphyria. Available at: Link (accessed 17/10/11)

Interactions

As for Corticosteroids, Refer to .

(last reviewed 2010-07-28; last modified 2005-08-03)

Pharmacokinetics

On intravenous injection tetracosactide has triphasic pharmacokinetics. It is rapidly eliminated from plasma, mostly by distribution to the adrenal glands and kidneys. It is metabolised by serum endopeptidases into inactive oligopeptides, and then by aminopeptidases into free amino acids. Most of a dose is excreted in urine within 24 hours. The terminal half-life of tetracosactide is about 3 hours.

(last reviewed 2010-07-28; last modified 2010-06-24)

Preparations: Single-Ingredient

The following preparations list represents a compilation of all available salt forms or related substances for this drug product.

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

ARGENTINA: Synacthen;AUSTRALIA: Synacthen;AUSTRIA: Synacthen;BELGIUM: Cortrosyn¤; Synacthen;BRAZIL: Cortrosina¤;CANADA: Cortrosyn; Synacthen Depot;CHILE: Synacthen;CZECH REPUBLIC: Synacthen¤;DENMARK: Synacthen;FRANCE: Synacthene;GERMANY: Synacthen Depot; Synacthen;GREECE: Cortrosyn¤; Nuvacthen; Synacthene;HONG KONG: Cortrosyn¤;IRELAND: Synacthen Depot¤; Synacthen¤;ISRAEL: Cortrosyn¤; Synacthen¤;ITALY: Cortrosyn¤; Synacthen;NETHERLANDS: Cortrosyn¤; Synacthen;NORWAY: Synacthen¤;NEW ZEALAND: Synacthen;PORTUGAL: Synacthen;RUSSIAN FEDERATION: Synacthen (Синактен)¤; Synacthen Depot (Синактен Депо)¤;SOUTH AFRICA: Synacthen Depot;SINGAPORE: Synacthen;SPAIN: Nuvacthen Depot;SWEDEN: Synacthen;SWITZERLAND: Synacthen Depot; Synacthen;THAILAND: Cortrosyn;TURKEY: Synacthen Depot;UNITED KINGDOM: Synacthen Depot; Synacthen;UNITED STATES: Cortrosyn;VENEZUELA: Synacthen;

Preparations: Pharmacopoeial

The following preparations list represents a compilation of all available salt forms or related substances for this drug product.

BP 2019: Tetracosactide Injection; Tetracosactide Zinc Injection;

Therapeutic Use

• Corticosteroids

Last Updated 1/21/20