LUPRON DEPOT-PED KIT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LUPRON DEPOT-PED KIT (LUPRON DEPOT-PED KIT).

How it works

Leuprolide acetate, a GnRH agonist, initially stimulates pituitary gonadotropin release, but chronic administration suppresses LH and FSH secretion by downregulation of GnRH receptors, leading to reduced sex steroid production.

What the body does with it

Metabolism	Metabolized primarily by hydrolysis of the C-terminal amino acids to pentapeptide and tetrapeptide metabolites; not significantly metabolized by CYP450 enzymes.
Excretion	Renal (approximately 50% as unchanged drug and 50% as inactive metabolites); biliary/fecal excretion accounts for <5%
Half-life	Terminal elimination half-life is approximately 3 hours following subcutaneous administration; however, due to the depot formulation, the effective half-life is extended to about 1 month, driven by the slow release from the PLGA microspheres.
Protein binding	Approximately 46–50% bound to sex hormone-binding globulin (SHBG) and albumin in plasma.
Volume of Distribution	Volume of distribution (Vd) is approximately 0.3 L/kg, indicating distribution primarily into extracellular fluid and tissues with low intracellular penetration.
Bioavailability	Subcutaneous: Following depot injection, bioavailability is essentially 100% due to the controlled-release formulation; the mean peak serum concentration is achieved at approximately 1–2 hours post-injection, with sustained release over 4 weeks.
Onset of Action	Subcutaneous: Suppression of gonadotropin secretion occurs within 2–4 weeks after the first injection; GnRH agonist flare effect may be observed in the first week.
Duration of Action	After a single depot injection, therapeutic suppression of pituitary gonadotropins (LH, FSH) persists for at least 4 weeks, supporting monthly dosing intervals; maximal suppression is maintained with continued monthly administration.

Classification & Brands

Dosing & administration

Leuprolide acetate 3.75 mg IM monthly or 11.25 mg IM every 3 months; for central precocious puberty, 7.5 mg IM monthly or 22.5 mg IM every 3 months.

Dosage form	POWDER
Renal impairment	No specific GFR-based dose modifications recommended; clinical monitoring advised.
Liver impairment	No specific Child-Pugh based modifications recommended; caution in moderate to severe impairment.
Pediatric use	Central precocious puberty: 7.5 mg IM monthly (weighing <25 kg) or 11.25 mg IM monthly (weighing ≥25 kg); 45 mg 6-month depot available; initiate at diagnosis and titrate to suppress pubertal development.
Geriatric use	No specific dose adjustment required; monitor for cardiovascular risk and bone density loss due to prolonged androgen deprivation.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LUPRON DEPOT-PED KIT (LUPRON DEPOT-PED KIT).

Breastfeeding	Unknown if excreted in human milk; M/P ratio not determined. Caution advised; consider benefit of therapy versus potential infant exposure.
Teratogenic Risk	First trimester: Theoretical risk of spontaneous abortion and congenital anomalies based on leuprolide's mechanism (GnRH agonist); data limited. Second/third trimester: Not indicated for use; fetal risk cannot be excluded due to hormonal interference.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to leuprolide acetate, GnRH, GnRH agonist analogs, or any component of the formulation.","Non-hormonal causes of precocious puberty should be excluded before use."]

Clinical Precautions

Precautions

["Initial transient stimulation of sex steroids may cause temporary worsening of signs and symptoms of CPP.","May cause pseudotumor cerebri (idiopathic intracranial hypertension) and convulsions.","Monitor bone mineral density; risk of decreased bone density with prolonged use.","Hypersensitivity reactions including anaphylaxis have been reported.","Injection site reactions may occur."]

Clinical Tips & Counseling

Drug interactions

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LUPRON DEPOT-PED KIT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LUPRON DEPOT-PED KIT (LUPRON DEPOT-PED KIT).

How it works

What the body does with it

Metabolism	Metabolized primarily by hydrolysis of the C-terminal amino acids to pentapeptide and tetrapeptide metabolites; not significantly metabolized by CYP450 enzymes.
Excretion	Renal (approximately 50% as unchanged drug and 50% as inactive metabolites); biliary/fecal excretion accounts for <5%
Half-life	Terminal elimination half-life is approximately 3 hours following subcutaneous administration; however, due to the depot formulation, the effective half-life is extended to about 1 month, driven by the slow release from the PLGA microspheres.
Protein binding	Approximately 46–50% bound to sex hormone-binding globulin (SHBG) and albumin in plasma.
Volume of Distribution	Volume of distribution (Vd) is approximately 0.3 L/kg, indicating distribution primarily into extracellular fluid and tissues with low intracellular penetration.
Bioavailability	Subcutaneous: Following depot injection, bioavailability is essentially 100% due to the controlled-release formulation; the mean peak serum concentration is achieved at approximately 1–2 hours post-injection, with sustained release over 4 weeks.
Onset of Action	Subcutaneous: Suppression of gonadotropin secretion occurs within 2–4 weeks after the first injection; GnRH agonist flare effect may be observed in the first week.
Duration of Action	After a single depot injection, therapeutic suppression of pituitary gonadotropins (LH, FSH) persists for at least 4 weeks, supporting monthly dosing intervals; maximal suppression is maintained with continued monthly administration.

Classification & Brands

Dosing & administration

Leuprolide acetate 3.75 mg IM monthly or 11.25 mg IM every 3 months; for central precocious puberty, 7.5 mg IM monthly or 22.5 mg IM every 3 months.

Dosage form	POWDER
Renal impairment	No specific GFR-based dose modifications recommended; clinical monitoring advised.
Liver impairment	No specific Child-Pugh based modifications recommended; caution in moderate to severe impairment.
Pediatric use	Central precocious puberty: 7.5 mg IM monthly (weighing <25 kg) or 11.25 mg IM monthly (weighing ≥25 kg); 45 mg 6-month depot available; initiate at diagnosis and titrate to suppress pubertal development.
Geriatric use	No specific dose adjustment required; monitor for cardiovascular risk and bone density loss due to prolonged androgen deprivation.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LUPRON DEPOT-PED KIT (LUPRON DEPOT-PED KIT).

Breastfeeding	Unknown if excreted in human milk; M/P ratio not determined. Caution advised; consider benefit of therapy versus potential infant exposure.
Teratogenic Risk	First trimester: Theoretical risk of spontaneous abortion and congenital anomalies based on leuprolide's mechanism (GnRH agonist); data limited. Second/third trimester: Not indicated for use; fetal risk cannot be excluded due to hormonal interference.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to leuprolide acetate, GnRH, GnRH agonist analogs, or any component of the formulation.","Non-hormonal causes of precocious puberty should be excluded before use."]