SYNACTHEN

What it is

Synacthen contains tetracosactide (tetracosactrin), the first corticotrophic preparation to be produced entirely by synthesis and displaying 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 is not subject to variation, so that dosage can be expressed in terms of weight. Synacthen Depot is supplied as a milky white suspension for injection with modified release properties. Synacthen Depot is administered only by the intramuscular route.

Approved indications

— Acute exacerbations in patients suffering from multiple sclerosis — Hypsarrhythmia and/or infantile spasms

Dosing overview

Adults are initially given 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 2 or 3 days; in patients who respond well, it is often possible to reduce the dose to as little as 0.5 mg every 2 or 3 days or 1 mg weekly. Infants are initially given 0.25 mg daily; for maintenance, 0.25 mg every 2 to 8 days. Small children are initially given 0.25 to 0.5 mg daily; for maintenance 0.25 to 0.5 mg every 2 to 8 days. Children of school age are initially given 0.25 to 1 mg daily; for maintenance 0.25 to 1 mg every 2 to 8 days.

Key safety warnings

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 allergic patients the physician must be prepared in advance to treat any anaphylactic reaction occurring after the injection of Synacthen Depot. 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. 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. 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. Treatment should be withdrawn gradually. Prolonged therapy may be associated with development of posterior subcapsular cataracts and glaucoma. Psychological disturbances may occur during treatment with Synacthen Depot (for example, euphoria, insomnia, mood swings, personality changes, severe depression or even frank psychotic manifestations).

Contraindications

Synacthen Depot must not be used if the patient's case history discloses any record of hypersensitivity reactions to ACTH treatment, or if there is hypersensitivity to tetracosactide and/or ACTH of animal origin. Synacthen Depot is contraindicated in 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, refractory heart failure, pregnancy and breast feeding, adrenocortical insufficiency, adrenogenital syndrome, and in view of the increased risk of anaphylactic reactions, it must not be employed to treat asthma or other allergic conditions. Synacthen Depot is also contraindicated in diabetes mellitus, moderate or severe hypertension, and in neonates (especially premature infants) because it contains benzyl alcohol which can cause severe poisoning.

PBS listing

Synacthen Depot is listed on the PBS as a compound depot injection 1 mg in 1 mL with one PBS item. The listing is restricted, with an ex-manufacturer price of A$53.20.

Regulatory history

Synacthen Depot (ARTG 11060) was first listed on the Australian Register of Therapeutic Goods on 2 August 1991 as a tetracosactide zinc complex 1 mg/1 mL injection ampoule. In March 2021, the PBAC deferred a change request for hypsarrhythmia and/or infantile spasms seeking to change from Restricted Benefit to Unrestricted Benefit. In May 2021, the PBAC advised that delisting would result in an unmet clinical need for patients with hypsarrhythmia and/or infantile spasms, and that there is no clinical need for tetracosactide in the treatment of multiple sclerosis. Therefore, the current restriction for hypsarrhythmia and/or infantile spasms should remain unchanged.