Lucrin Depot

Approved Indications:

• Advanced Prostate Cancer:
  Palliative treatment of hormone-dependent advanced prostate cancer.
• Breast Cancer (Premenopausal Women):
  Treatment of hormone receptor-positive breast cancer in premenopausal women, usually in combination with tamoxifen or aromatase inhibitors.
• Endometriosis:
  Management of endometriosis, including pain relief and reduction of endometrial lesions.
• Uterine Leiomyoma (Fibroids):
  Preoperative therapy to reduce fibroid size and correct anemia associated with fibroids.
• Central Precocious Puberty (CPP):
  Treatment of children with early onset of puberty (before 8 years in girls, 9 years in boys).
• Assisted Reproductive Technology (ART):
  Suppression of the pituitary gland during ovarian stimulation protocols to prevent premature luteinizing hormone (LH) surges.

Clinically Accepted Off-Label Uses:

• Preoperative Endometrial Thinning prior to endometrial ablation
• Hormone Suppression in Transgender Care (puberty blockers)

Route of Administration: Subcutaneous (SC) or Intramuscular (IM) injection

Adults:

• Prostate Cancer:
• 1 mg SC daily
• 7.5 mg IM every month
• 22.5 mg IM every 3 months
• 30 mg IM every 4 months
• 45 mg IM every 6 months
• Endometriosis:
• 3.75 mg IM monthly or 11.25 mg IM every 3 months
• Treatment duration: up to 6 months (longer with add-back therapy)
• Uterine Fibroids:
• 3.75 mg IM monthly, usually for 3 months before surgery
• Breast Cancer (Premenopausal):
• 3.75 mg IM every 4 weeks or 11.25 mg IM every 12 weeks
• Assisted Reproduction (ART):
• 0.5–1 mg SC daily starting in mid-luteal or early follicular phase

Pediatrics:

• Central Precocious Puberty (CPP):
• <25 kg: 7.5 mg IM every 4 weeks
• 25–37.5 kg: 11.25 mg every 4 weeks
• 37.5 kg: 15 mg every 4 weeks
  OR
• Depot options: 11.25 mg every 3 months, 30 mg every 6 months

Elderly:

• No adjustment needed

Renal/Hepatic Impairment:

• No specific dosage adjustment required; monitor if used long term

Leuprorelin Acetate is a synthetic gonadotropin-releasing hormone (GnRH) agonist. It initially stimulates the pituitary to secrete LH and FSH, causing a transient increase in sex hormones (estrogen and testosterone). Continued administration leads to receptor downregulation in the pituitary, resulting in suppressed secretion of LH and FSH, and thus decreased production of estrogen and testosterone. This reversible medical castration is beneficial in hormone-sensitive conditions like prostate cancer, breast cancer, endometriosis, and CPP.

• Absorption: Rapid and nearly complete after SC or IM administration
• Bioavailability: >90%
• Distribution: Widely distributed in body tissues; plasma protein binding is ~43%
• Metabolism: Primarily metabolized by peptidases into inactive peptides
• Half-Life:
• Immediate-release: ~3 hours
• Depot: Sustained release up to 6 months depending on formulation

• Excretion: Mainly via urine as inactive metabolites

• Pregnancy:
  Category X. Leuprorelin is contraindicated in pregnancy due to risk of fetal harm. It causes hormone suppression and can lead to pregnancy loss or fetal abnormalities.
• Lactation:
  Not recommended during breastfeeding. Unknown whether excreted in breast milk. Risk of serious adverse effects to the infant cannot be ruled out.

• Primary Class: Gonadotropin-Releasing Hormone (GnRH) Agonist
• Subclass: Long-acting synthetic peptide analog of natural GnRH

• Hypersensitivity to leuprorelin or its excipients
• Pregnancy
• Breastfeeding
• Undiagnosed vaginal bleeding
• High risk of spinal cord compression or urinary obstruction without antiandrogen co-administration in prostate cancer

• Tumor Flare: Initial hormone surge may worsen symptoms in prostate or breast cancer; antiandrogens may be needed at initiation.
• Bone Loss: Prolonged hypoestrogenism or hypogonadism may lead to osteoporosis. Monitor bone mineral density.
• Psychiatric Effects: Risk of depression, mood changes, and rarely, suicidal ideation.
• Metabolic Effects: May impair glucose tolerance and increase cardiovascular risks.
• Seizures: Reported in patients with or without prior neurological conditions.
• Injection Site Reactions: Swelling, pain, or abscess formation may occur.

Common (≥10%):

• Vasomotor: Hot flushes, night sweats
• Musculoskeletal: Joint pain, decreased bone density
• Neurologic: Headache, mood swings, fatigue
• Reproductive: Erectile dysfunction, decreased libido, amenorrhea
• Local: Pain or redness at injection site

Uncommon (1–10%):

• Weight gain
• Depression or anxiety
• Vaginal dryness
• Edema
• Gynecomastia

Serious (Rare):

• Seizures
• Anaphylaxis
• Myocardial infarction
• Spinal cord compression
• Osteoporotic fractures (long-term use)

• QT-Prolonging Drugs: Additive QT prolongation risk with antiarrhythmics, antipsychotics
• Antidiabetic Agents: May alter glucose tolerance; monitor closely
• Hormonal Agents: Use of estrogen or testosterone counteracts the effects of leuprorelin
• Alcohol: No direct interaction but may worsen vasomotor or psychiatric symptoms

• Prostate Cancer (NCCN): Leuprorelin remains first-line for androgen deprivation therapy.
• Breast Cancer (ASCO): Strongly recommended for ovarian suppression in premenopausal women with HR+ tumors.
• CPP Guidelines: Long-acting depot formulations preferred for consistent suppression.
• Osteoporosis Monitoring: Growing emphasis on monitoring bone health in long-term users.

• Temperature:
• Vials and syringes: Store at 2°C to 25°C
• Some depot formulations: Refrigerate at 2°C to 8°C (follow label-specific instructions)
• Humidity & Light: Protect from moisture and light
• Handling: Use reconstituted solution immediately; follow aseptic technique
• Reconstitution: Required for depot forms; use only diluent provided