Synacthene

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Synacthene

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Medically reviewed

Marina Burgos

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Synacthene

Property Description
Active ingredient Tetracosactide (usually as Tetracosactide acetate)
Form Sterile solution for injection or suspension (Depot)
Pharmacological class Adrenocorticotropic agents
General purpose Stimulates adrenal hormone production
Origin Synthetic polypeptide

What Type of Medicine is Synacthene (Tetracosactide)?

Synacthene is a prescription-only medication whose active ingredient, Tetracosactide, is classified pharmacologically as an adrenocorticotropic agent. It is a synthetic polypeptide designed to function as an analogue of the body's natural adrenocorticotropic hormone (ACTH), which is clinically recognized for controlling the function of the adrenal glands.

The core substance, Tetracosactide, is chemically defined as the initial 24 amino acid sequence (alpha 1-24 corticotropin), representing the most active portion of the full, natural ACTH molecule. By manufacturing only this synthetic segment, the product ensures pharmaceutical consistency and predictable interaction with adrenal gland receptors, a key feature that makes it reliable for diagnostic use. Tetracosactide is considered an ACTH-like peptide, reflecting its role as an external trigger for the adrenal system.

How Does This Agent Work and What is Its General Purpose?

The general purpose of this synthetic agent is to deliver a direct, potent signal to the adrenal glands, prompting them to perform their essential function. Tetracosactide achieves this by stimulating the adrenal cortex to rapidly produce and release its own vital hormones, primarily glucocorticoids and mineralocorticoids.

This mechanism supports its typical use in diagnosing the functional capacity of the adrenal gland in cases where poor gland response is suspected. The ability to artificially trigger and observe the adrenal system's hormonal output means the agent can be used either to achieve a therapeutic increase in these natural steroids or to precisely assess the functional health of the adrenal gland itself.

Understanding the Form: Injectable Solution and Variations

Synacthene is prepared as a sterile solution or suspension, designated for parenteral administration, meaning it must be given by injection. This specific delivery method is necessary because the polypeptide structure of Tetracosactide would be rapidly broken down if taken orally.

Preparations of Tetracosactide exist in distinct forms based on their speed of action. The standard solution yields a rapid onset and short duration, which is advantageous for quick, acute signaling or diagnostic testing. In contrast, the long-acting depot suspension provides a slow, prolonged release of the active ingredient, differentiating it as a formulation designed for less frequent therapeutic intervention.

What side effects are possible with Synacthene?

Possible Side Effects and Safety Information

The safety profile of Synacthene (Tetracosactide) is characterized by effects stemming from two domains: rare reactions to the synthetic agent itself and the systemic consequences of stimulating the body’s own steroid hormones (glucocorticoids and mineralocorticoids), as documented in official regulatory labels.

Adverse Reaction Classification

The most acute safety concern is classified as Rare: severe hypersensitivity reactions, including anaphylactic shock, which official documents note are more likely in patients with a history of allergies, such as asthma. These reactions tend to occur within 30 minutes following administration.

Systemic Side Effects

The majority of documented adverse effects relate to the stimulated increase in endogenous steroid levels and are listed across numerous System-Organ Classes (SOC):

  • Metabolism and Nutrition: Effects include fluid retention, sodium retention, and hypokalaemia (low potassium).
  • Psychiatric: Disturbances such as changes in mood, severe depression, or psychotic manifestations are documented.
  • Vascular/Cardiac: Reactions include hypertension and potential manifestations of congestive cardiac failure or thromboembolism.
  • Gastrointestinal: Serious reactions such as peptic ulcer (with potential haemorrhage and perforation) are noted in regulatory texts.

Population and Exposure-Related Safety Patterns

Certain effects are specifically associated with the duration of use. Prolonged therapy is linked to the development of Posterior subcapsular Cataracts, Glaucoma, and osteoporosis. In children, the risk of growth retardation is a stated safety consideration with long-term exposure. Furthermore, repeated administration may lead to the formation of anti-ACTH antibodies, a documented safety restriction in official labeling.

Overdose and Emergency Response

The official regulatory guidance for Synacthene (Tetracosactide) structures its emergency information around the risk of an acute systemic reaction and the consequences of excessive adrenocortical stimulation. Overdose is considered unlikely when used for diagnostic purposes. However, exposure resulting in exaggerated adrenocortical effects is documented and can include the development of Cushing's syndrome, fluid and sodium retention, hypokalaemia, and hypertension. Central nervous system effects may present as severe psychological disturbances, including euphoria, severe depression, or frank psychotic manifestations.

The primary life-threatening concern is the risk of an acute, severe hypersensitivity reaction, such as anaphylactic shock, which has rarely been associated with fatal outcomes. For this reason, medical personnel must be prepared to immediately combat any severe reaction by administering adrenaline and large doses of a corticosteroid. Individuals with a history of asthma or other allergic conditions are noted to have a higher susceptibility to these acute reactions.

Immediate medical attention must be sought if a severe reaction is suspected. Following administration, the patient must be kept under observation for at least 30 minutes. Management of the over-stimulation effects involves supportive measures like a low-salt diet and potassium substitution to address electrolyte and fluid imbalances.

Therapeutic Uses of Synacthene

What Synacthene Treats: Main Uses and Benefits

Synacthene is generally considered relevant for symptom management, and is also used as a diagnostic aid in specific contexts.

Diagnostic Use and Adrenal Support Benefit

Synacthene is relevant for managing symptoms that create noticeable physiological strain. It is used in situations involving certain distressing symptoms where an assessment helps address symptoms related to systemic imbalance, assisting with maintaining functional stability.

Support for Acute Symptomatic Flares

The medication is commonly used to help with managing symptoms that become more disruptive during flare-ups of certain inflammatory and autoimmune conditions, such as those associated with certain autoimmune or rheumatoid diseases. It is applied during phases when symptoms become temporarily overwhelming, providing support that helps ease the overall symptom burden.

Targeted Symptom Moderation in Specific Conditions

Synacthene may assist with managing symptoms in conditions presenting with acute or disruptive episodes, including specific challenging skin conditions or certain types of neurological disorders in children. It is used in situations involving distressing symptoms that create noticeable functional strain and supports general well-being during symptomatic phases.


Quick Fact: Relief for Symptom Burdens

Regulatory References

  1. Health Canada Product Monograph for Synacthen Depot

Eligibility and Restrictions for Use

Official Eligibility and Contraindications for Synacthene (Tetracosactide)

The population eligibility for using Synacthene is strictly defined by government regulatory documents, which establish clear restrictions and prohibitions based on age, pre-existing conditions, and physiological status.

Absolute Contraindications

Use of Synacthene is contraindicated and must be avoided in patients with a known hypersensitivity to tetracosactide or ACTH, and in those with:

  • Acute psychosis or untreated infectious diseases.
  • Peptic ulcer (active or latent).
  • Refractory heart failure or Cushing's syndrome.
  • Primary adrenocortical insufficiency (Addison's disease).

Age and Organ-Specific Rules

Population Group Regulatory Status
Neonates (under 1 month) Contraindicated (due to benzyl alcohol excipient).
Children (under 3 years) Not Recommended (due to benzyl alcohol excipient).
Pregnancy/Lactation Contraindicated by several authorities; otherwise, Not Recommended.

Use requires specific regulatory caution in populations with conditions such as renal insufficiency, cirrhosis of the liver, diabetes mellitus, hypertension, or osteoporosis. Therapeutic use is generally restricted in patients with asthma or other allergic conditions due to the risk of anaphylaxis.

What should I know about interactions with other medicines?

Interactions with Other Medicines and Products

The interaction profile for Synacthene (Tetracosactide) is defined by its core action: stimulating the adrenal glands to release natural corticosteroids, primarily glucocorticoids and mineralocorticoids. The majority of documented interactions are pharmacodynamic, reflecting the systemic effects of these stimulated hormones.

Documented Pharmacodynamic and Exposure Interactions

Interaction Entity Interaction Outcome and Restriction
Antidiabetic Agents Requires dosage adjustment of the antidiabetic medicine due to the effect of stimulated glucocorticoids on carbohydrate tolerance.
Antihypertensive Agents Requires dosage adjustment of the antihypertensive medicine due to the mineralocorticoid effect causing salt/water retention and blood pressure elevation.
Live Virus Vaccines Should not be administered during therapeutic use due to the risk of a decreased antibody response.
Valproate (Pediatric Use) Co-administration is not recommended or to be avoided in the pediatric population due to a documented risk of severe jaundice.
Certain Anticonvulsants Co-administration with agents like phenytoin or phenobarbital may increase the risk of liver damage (hepatotoxicity).

Timing and Diagnostic Constraints

Interactions that compromise the accuracy of the Synacthene diagnostic test require specific timing constraints:

  • Estrogen-Containing Drugs: Must be discontinued four to six weeks prior to diagnostic testing to ensure accurate measurement of plasma total cortisol levels.
  • Other Steroids (e.g., Cortisone, Hydrocortisone): Pre-test doses of these agents must be omitted on the day of the diagnostic test.

Population and Dietary Notes

An enhanced effect of corticotropin therapy is documented for patients with hypothyroidism or cirrhosis of the liver. Regarding drug–food interactions, a low-sodium diet is a documented measure to avoid or eliminate the salt and water retention associated with mineralocorticoid effects.

Mechanism of Action

Targeting the Adrenal Gland’s Melanocortin Receptor 2 (MC2R)

The mechanism of action for Synacthene begins with the synthetic peptide, Tetracosactide, acting as a full agonist at the Melanocortin Receptor 2 (MC2R) located specifically on the cells of the adrenal cortex. This targeted binding event initiates a signal, leading to rapid pathway activation, which functions as an external command that surpasses basal ACTH signaling.

The Steroidogenesis Signaling Cascade

Activation of the MC2R triggers a signal transduction cascade inside the adrenal cells, characterized by a surge in the second messenger cAMP. This cellular signal directly drives the rate-limiting enzymatic step that converts cholesterol into pregnenolone, the gateway molecule for all adrenal hormone production, thereby stimulating the pathway towards its maximal potential output.

Resulting Endogenous Hormone Release

The direct consequence of this pathway stimulation is a marked and rapid increase in the body’s own endogenous steroid hormones in the bloodstream, primarily the glucocorticoid cortisol and, to a lesser extent, the mineralocorticoid aldosterone. This specific, high-magnitude hormonal change is the primary physiological consequence resulting from the drug's mechanism.

Dosage and Administration Information

The administration of Tetracosactide (Synacthene) follows a precise protocol dependent on the specific formulation being used. The medicine is prepared in two distinct forms: a standard solution (250 mcg/mL) primarily for diagnostic use, and a long-acting suspension (Depot, 1 mg/mL) for therapeutic use.

The approved route of administration is strictly defined by the product type. The 250 mcg/mL solution may be administered via intramuscular (IM) or intravenous (IV) injection or infusion. In contrast, the 1 mg/mL Depot suspension is designated for IM injection only and must not be administered intravenously. The Depot ampoule is required to be shaken thoroughly before use to ensure the suspension is uniformly mixed, and both forms require administration under medical supervision.

Dosing schedules are determined by the general principle of use. For the adrenal function diagnostic test, the standard adult regimen is a single dose of 250 mcg IM or IV. For therapeutic use, the regimen is cycling: treatment begins with an initial dose of 1 mg IM daily and transitions to a less frequent maintenance schedule, such as 1 mg every two to three days.

Usage instructions for specific populations are also established. Pediatric dosing for therapeutic use follows an age-adjusted regimen that ranges from 0.25 mg to 1 mg. If prolonged therapeutic use is discontinued, the instruction is to reduce the dosage gradually. No specific dose adjustment is considered necessary for older adults.

Recent Clinical Evidence

Recent Clinical Evidence

Evidence for Monotherapy

Research has explored the potential for changes in clinical outcomes in patients with moderately active Rheumatoid Arthritis (RA) when used as a single agent. The first major study reported findings related to changes in measures of pain and inflammation over a 24-week period. Furthermore, research evaluated joint health parameters, including progression of damage. A long-term follow-up examined the safety profile of the drug and reported on the timing of symptom changes observed during the treatment course. Studies evaluated clinical and laboratory measures in this patient group.


Evidence for Combination Therapy

Studies have extensively investigated whether combining the drug with Methotrexate (MTX) compared against using either agent alone. The combination was associated with different changes in disease activity scores compared to monotherapy, as reported by the study authors. Research explored the potential impact of starting combination therapy at different stages of the disease course.


Unstudied Applications

While the primary indication is RA, early research has examined if the drug was evaluated for its potential in Psoriatic Arthritis (PsA). Though evidence remains limited, initial findings suggest a need for further investigation in this patient population. This text describes only research that has been conducted and does not constitute advice for use outside of approved indications.

Key Studies & References American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis

Frequently Asked Questions (FAQ)

Common questions about Synacthene (FAQ)

Q: What is the main difference between Synacthene and a standard steroid injection?

Synacthene is a synthetic hormone (an ACTH analogue) that works indirectly. It stimulates your own adrenal glands to produce and release natural steroid hormones inside your body. In contrast, a standard steroid injection directly introduces a synthetic form of those hormones into your system.

Q: Is Synacthene a natural or synthetic hormone replacement?

The active ingredient in Synacthene, Tetracosactide, is classified as a synthetic polypeptide. It is specifically manufactured to act like your body's natural ACTH (adrenocorticotropic hormone), which signals your adrenal glands to produce their own hormones.

Q: How quickly should I expect to feel any effects from a Synacthene shot?

Official product information states that serious reactions, particularly severe allergic responses, tend to occur within 30 minutes of administration. Regulatory documents state that patients should be kept under medical observation immediately following administration. The onset of therapeutic effects may vary.

Q: What are the most commonly reported mood changes from Synacthene?

The systemic effects from the stimulated hormones can cause psychological disturbances. These can include mood swings, euphoria (feeling unusually energized), insomnia (difficulty sleeping), or changes in personality. Official documents also note the possibility of severe depression or psychotic manifestations.

Q: Can Synacthene cause long-term weight gain?

Weight gain is listed as a possible undesirable effect in official labeling. The drug stimulates hormones that can cause sodium and fluid retention in the body. This fluid retention is a common side effect of the stimulated steroids and can contribute to an increase in body weight.

Q: How long does Synacthene stay active in your system after the injection?

Regulatory documents indicate that the active substance, Tetracosactide, is rapidly distributed throughout the body. The drug is quickly broken down by enzymes in the bloodstream into inactive components after it has delivered its signal to the adrenal gland.

Q: Is it common to have pain or swelling at the Synacthene injection site?

Local skin reactions at the injection site, such as redness or pain, are documented as possible signs of a hypersensitivity reaction. Regulatory warnings indicate that if these signs occur, they may be part of a reaction which typically requires discontinuation under medical guidance.

Q: What should I avoid eating or drinking when I am on Synacthene treatment?

The hormone effects stimulated by Synacthene can cause the body to retain salt and water. A low-sodium (low-salt) diet is a specific dietary measure documented in the official labeling to help manage or prevent this fluid retention effect.

Q: Is there any research on Synacthene's use for conditions other than adrenal issues?

Official indications can vary by region. Synacthene is approved in certain countries for the treatment of specific inflammatory conditions, such as Rheumatoid Arthritis, Psoriatic Arthritis, and Ulcerative Colitis. Official prescribing information restricts use to approved indications in each region.

Q: What happens if I forget about an upcoming Synacthene appointment or injection?

Since Synacthene is always administered by a healthcare professional (a doctor or nurse), official consumer information states that a missed dose is unlikely. Patients should address any concerns about their treatment schedule or upcoming appointment with their managing care team.

Q: Can Synacthene affect blood sugar levels, especially for non-diabetics?

Yes, regulatory documents list hyperglycemia (high blood sugar) and a decrease in carbohydrate tolerance as possible undesirable effects. The stimulation of natural steroid hormones can also potentially bring out previously undiagnosed diabetes mellitus.

Q: Does taking Synacthene increase the risk of developing infections?

Official product information lists an increased susceptibility to infection as a possible undesirable effect. The medication may also activate a latent or dormant infection, such as tuberculosis, due to the effects of the stimulated hormones on the immune system.

Q: Does Synacthene require any special monitoring like blood tests?

Due to the potential for adverse effects like changes in potassium levels or effects on carbohydrate tolerance, patients may require monitoring, such as blood tests, as determined by the prescriber. This ensures safe management of the stimulated hormone levels.

Q: Can Synacthene cause problems with sleep or insomnia?

Insomnia, or the inability to fall or stay asleep, is specifically listed in the official documents as one of the possible psychological disturbances that may occur during Synacthene treatment.

Q: Will using Synacthene affect my ability to drive or operate machinery?

Official product information advises caution when performing tasks requiring alertness, such as driving or operating machinery. This caution is advised because the medication can cause systemic effects that might affect attention or reaction time.

Q: What should I do if I experience nausea or stomach upset from Synacthene?

Nausea and vomiting are documented as symptoms associated with general hypersensitivity reactions to the drug. If a patient experiences these or any other persistent or concerning symptoms, they should be reported promptly to the healthcare professional managing their care.

Q: Why is Synacthene only available as a prescription drug?

Synacthene is classified as a Prescription Only Medicine (POM) by regulatory authorities. This classification is due to the nature of its pharmacological effects, the need for it to be administered under medical supervision, and the potential for serious adverse reactions that require professional management.

Q: Are there any known side effects on vision from Synacthene?

The official product labeling lists several potential effects on the eyes. These include an increase in pressure inside the eye (glaucoma), the formation of cataracts behind the lens, and bulging of the eyeballs (exophthalmoses).

Q: Is it normal to feel a bit flushed or warm right after receiving Synacthene?

Flushing of the skin is documented as a possible symptom of a hypersensitivity (allergic) reaction. Because flushing may be a symptom of a hypersensitivity reaction, regulatory information stresses that patients should be monitored for this and other related signs (such as itching or dizziness).

Q: Does Synacthene show up on a standard drug screening test?

The active substance in Synacthene, Tetracosactide, may interfere with routine drug testing in athletes. Regulatory documents state that patients may be required to disclose this medication to testing authorities, particularly in athletic competitions.

Q: Does Synacthene have any impact on fertility or reproductive health?

Regulatory documents indicate that no specific data is available on the effects of Synacthene on human fertility. For both pregnancy and breastfeeding, the drug is generally not recommended by regulatory authorities.

Q: What are the signs of a serious allergic reaction to Synacthene I should look out for?

Signs of a severe allergic reaction may include marked redness and pain at the injection site, hives (urticaria), intense itching, dizziness, difficulty breathing, or swelling of the face, lips, or tongue. If any of these signs occur, immediate medical attention is required.

Q: Why do patients sometimes call Synacthene a 'steroid' even though it's a hormone?

Synacthene is correctly classified as a hormone analogue, not a steroid. However, because its job is to trigger the release of your body's own powerful natural steroid hormones (glucocorticoids), its overall physiological effect is similar to receiving external steroid therapy. This similarity likely leads to the common usage of the term 'steroid' by patients.

How should Synacthene be stored and disposed of?

How to Store and Dispose of Synacthene (Tetracosactide)

Synacthene must be stored under controlled conditions as specified in official regulatory documents to maintain its stability. The medicine must be kept in a refrigerator at a temperature range of mathbf2 C to mathbf8 C. It is strictly required that the product must not be frozen.

Storage Protection and Handling

The injection must be kept in the original container to ensure it is protected from light. For child safety, Synacthene must be stored out of the sight and reach of children.

Disposal Requirements

Unused or expired Synacthene must be disposed of in accordance with local requirements. The product must not be thrown away with household waste or disposed of via wastewater.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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