What are the side effects of Synacthen (tetracosactide)?

Side Effects of Synacthen (Tetracosactide)

Synacthen (tetracosactide) can cause several significant side effects including anaphylactic reactions, hypertension, nephrotoxicity, and neurological symptoms that require careful monitoring during administration.

Common Side Effects

• Paresthesia occurs in approximately 7% of patients receiving tetracosactide 1
• Musculoskeletal pain is reported in about 5% of patients 1
• Headache, peripheral edema, nausea, nasal congestion, and dizziness are frequently reported adverse events 1
• Injection site reactions may occur at the location where the medication is administered 2

Serious Side Effects

Hypersensitivity Reactions

• Anaphylactic reactions can occur with tetracosactide administration, even after multiple prior doses without incident 3
• Two documented cases of anaphylaxis occurred after the 22nd and 6th injections respectively in patients with multiple sclerosis, with increased IgE immunoglobulin concentration and positive RAST to the drug 3
• Anti-ACTH antibodies can develop in patients receiving repeated tetracosactide depot injections, which may mediate adverse reactions 4

Cardiovascular Effects

• Hypertension is a common side effect that occurs more frequently in older patients 1
• If hypertension develops (measured on two separate occasions), the dose should be reduced by 25% to 50% 1
• If blood pressure does not normalize after dose reduction, discontinuation may be necessary 1

Renal Effects

• Nephrotoxicity is a potential serious side effect that requires monitoring 1
• Monthly serum creatinine levels should be monitored, with yearly glomerular filtration rates in patients on therapy for more than 1 year 1
• If serum creatinine elevates more than 25% above baseline on two occasions separated by 2 weeks, dose reduction of 25-50% is recommended 1

Neurological Effects

• Neurological side effects include tremor, asthenia, and fatigue 1
• Rare cases of pseudotumor cerebri have been reported in young patients taking concomitant tetracyclines 1
• Tetracosactide can lower the seizure threshold in patients with a history of seizures 1

Management of Side Effects

Hypersensitivity Reactions

• For grade 1/2 reactions: stop or slow the infusion rate and provide symptomatic treatment 1
• For grade 3/4 reactions: stop treatment immediately and provide aggressive symptomatic therapy 1
• Consider premedication with corticosteroids and antihistamines in high-risk patients 1

Hypertension Management

• Calcium channel blockers (particularly isradipine and amlodipine) are preferred for treating tetracosactide-induced hypertension 1
• Beta blockers and angiotensin-converting enzyme inhibitors are alternative options 1
• Avoid thiazide diuretics as they can increase nephrotoxicity 1
• Avoid potassium-sparing diuretics as they can cause hyperkalemia when combined with tetracosactide 1

Special Considerations

• Patients with a history of seizures should be warned about the potential for lowered seizure threshold 1
• Anti-ACTH antibodies may develop in up to 77% of patients receiving repeated tetracosactide injections 4
• When used for diagnostic purposes (adrenal insufficiency testing), side effects are typically minimal due to the short duration of exposure 2, 5
• The standard short Synacthen test involves a single dose of 0.25 mg administered intramuscularly or intravenously 2, 6

Monitoring Recommendations

• Monitor blood pressure regularly during treatment 1
• Check serum creatinine monthly and glomerular filtration rate yearly for long-term therapy 1
• If creatinine increases >25% above baseline on two occasions, reduce dose by 25-50% 1
• If creatinine does not decrease to within 25% of baseline after dose reduction, further reduce dose by 25-50% 1
• If creatinine remains >25% above baseline despite dose reductions, discontinue tetracosactide 1