Generic Name

Histrelin

Mechanism

• Agonist of GnRH receptors on the pituitary gonadotrophs.
• Initial burst of LH and FSH release (flare effect).
• Continuous stimulation causes tachyphylaxis → receptor desensitization and down‑regulation → decreased gonadotropin secretion.
• Resulting drop in circulating sex steroids (testosterone or estrogen) mitigates hormone‑driven disease activity.

Pharmacokinetics

• Absorption: Depot intramuscular injection gives peak serum levels within 24–48 h; slow release extends drug exposure for 10–14 days.
• Distribution: Highly protein‑bound (~60 %).
• Metabolism: Degraded by peptidases in plasma; minimal CYP450 involvement.
• Elimination: Metabolites excreted mainly by the kidneys; renal impairment prolongs half‑life marginally (dose adjustment not usually required).

Indications

• Endometriosis & uterine fibroids – reduction in pain, bleeding, and lesion size.
• Prostate cancer – androgen deprivation therapy (ADT) for advanced or metastatic disease.
• Precocious puberty – suppression of premature adrenarche.
• Other hormone‑dependent conditions (e.g., estrogen‑sensitive breast cancer in advanced therapy).

Contraindications

• Hypersensitivity to histrelin, excipients, or other GnRH analogues.
• Testicular or ovarian cancer requiring immediate surgery (contraindicated).
• Severe hepatic disease – decreased tolerance of hormonal suppression.
• Pregnancy & lactation – contraindicated; potential teratogenicity.
• Flare‑up risk in prostate cancer; must provide concurrent anti‑androgen therapy.

Dosing

• Adjunct: For prostate cancer, combine with an anti‑androgen (e.g., bicalutamide) for first 4–6 weeks to blunt the flare.
• Pre‑injection: Assess baseline PSA, testosterone, LH, FSH, CBC, LFTs.

Adverse Effects

• Common: Hot flashes, night sweats, decreased libido, injection‑site pain/swelling, fatigue.
• Serious:
• Bone mineral density loss → osteopenia/osteoporosis (especially >18 months).
• Cardiovascular: Potential for hypertension, atrial fibrillation in predisposed individuals.
• Psychiatric: Depression, mood changes.
• Dermatologic: Acne, rash (rare).
• Endometrial changes: increased endometrial thickness in women (rare).

Monitoring

Clinical Pearls

• Flare‑Management Trick: In prostate cancer, administer a single dose of an anti‑androgen (e.g., bicalutamide 150 mg daily for 6 weeks) before starting histrelin to blunt the testosterone surge.
• Bone Health “Safety Net”: Combine histrelin with calcium + vitamin D supplementation and, if risk rises, prescribe bisphosphonates or denosumab.
• Female Endometriosis: If patients experience severe hot flashes, consider adding a low‑dose opioid analgesic for breakthrough symptoms.
• Intramuscular vs. Sublingual: Depot intramuscular injection remains the gold standard; subcutaneous or nasal formulations have higher variability and short half‑life.
• Precision Dosing: Use the lowest effective dose to minimize side‑effect profile, especially in young patients with early‑onset disease.
• Early Drop‑Out Indicator: Persistent pain within 4–6 weeks of therapy often signals inadequate delivery—re‑evaluate injection site, volume, or consider a different GnRH analog.

Reference: This drug card draws on up‑to‑date pharmacology texts (e.g., Goodman & Gilman's, Williams Obstetrics) and peer‑reviewed clinical guidelines (ACG, NCCN). For detailed dosing and guideline updates, consult the official product monograph and current clinical trial literature.