Sermorelin Acetate

Sermorelin acetate is the acetate salt of sermorelin, a synthetic amidated 29-amino-acid peptide identical to the amino-terminal sequence (1-29) of human growth hormone-releasing hormone (GHRH), the shortest fragment with full biological activity.

It was the active ingredient of Geref (sermorelin acetate for injection), FDA-approved for subcutaneous treatment of idiopathic growth hormone deficiency in children with growth failure, and of Geref Diagnostic for intravenous evaluation of pituitary growth hormone secretory capacity. Geref was discontinued in the US in 2008, and no FDA-approved sermorelin product is currently marketed.

• Former FDA labeling (Geref, subcutaneous): treatment of idiopathic growth hormone deficiency in children with growth failure.
• Former FDA labeling (Geref Diagnostic, intravenous): single-dose evaluation of the pituitary's ability to secrete growth hormone.
• Prescribers use compounded sermorelin injections for individualized evaluation and support of the growth hormone axis in patients with intact pituitary function.

Sermorelin binds the GHRH receptor, a Gs-coupled receptor on anterior pituitary somatotrophs. Receptor activation stimulates adenylate cyclase, raising intracellular cAMP and activating protein kinase A, which increases growth hormone gene transcription, synthesis and pulsatile release. Released growth hormone raises hepatic IGF-I. Because the response depends on a functioning pituitary and remains subject to somatostatin and IGF-I feedback, it is self-limiting compared with direct growth hormone replacement.

Sermorelin has a short plasma half-life (minutes) and low subcutaneous bioavailability. It is cleared quickly by plasma and tissue peptidases. The growth hormone response peaks within about an hour of dosing. Oral bioavailability is negligible.

• Hypersensitivity to sermorelin acetate or any excipient, including the preservative.

• Thyroid and metabolic status: untreated hypothyroidism blunts the response and should be corrected first; obesity, hyperglycemia and elevated plasma fatty acids also reduce response.
• Malignancy: growth hormone and IGF-I can stimulate cell growth; avoid in active malignancy and use caution with a history of cancer.
• Intracranial lesions: evaluate for pituitary or hypothalamic tumors before treatment and monitor patients with a history of such lesions.
• Immunogenicity and hypersensitivity: antibodies to sermorelin have been reported; their clinical significance is unclear. Stop for signs of a systemic allergic reaction.

• Glucocorticoids, somatostatin and somatostatin analogs can suppress the growth hormone response.
• Drugs that affect growth hormone release, such as clonidine, levodopa, insulin, arginine, propranolol and antimuscarinics like atropine, can alter the response or confound testing.
• Thyroid status affects response: hypothyroidism should be treated, and thyroid replacement doses may need review once therapy starts. Cyclooxygenase inhibitors such as aspirin and indomethacin may also alter the response.

The most frequent effects in Geref labeling were injection-site reactions (pain, swelling, redness). Others include facial flushing, headache, nausea, vomiting, dizziness, altered taste, somnolence, hyperactivity and, rarely, hypersensitivity reactions.

No adequate data in pregnant women; Geref was labeled pregnancy category C. Use is not recommended in pregnancy. It is not known whether sermorelin passes into breast milk; use is not recommended while breastfeeding.

Monitor serum IGF-I, thyroid function, fasting glucose and HbA1c, and clinical response. In children, follow growth velocity and bone age. Watch for injection-site reactions and hypersensitivity, and reassess therapy if no response occurs.

• Geref (sermorelin acetate for injection) Prescribing Information (archived, discontinued).
• Geref Diagnostic (sermorelin acetate for injection) Prescribing Information (archived, discontinued).