Leuprolide Dosage and Administration
Leuprolide is administered as a 1 mg (0.2 mL) daily subcutaneous injection for daily formulations, or as depot formulations ranging from 3.75 mg to 30 mg given intramuscularly at intervals of 1 to 3 months, depending on the specific indication and formulation used. 1
Daily Subcutaneous Formulation
- Administer 1 mg (0.2 mL or 20 unit mark) as a single daily subcutaneous injection 1
- Rotate injection sites periodically to minimize local tissue reactions 1
- Inspect solution for discoloration and particulate matter before each use 1
Depot Formulations by Indication
Advanced Prostate Cancer
- Monthly depot: 3.75 mg or 7.5 mg intramuscularly or subcutaneously every 4 weeks 2, 3
- Serum leuprolide peaks within 3 hours post-injection (13.1-54.5 ng/ml), then declines to a steady plateau by 5 weeks 3
- Castration levels of testosterone are achieved and maintained within 3 weeks in all patients 3
- The 3.75 mg monthly dose is as effective as higher doses for hormonal suppression 3
Central Precocious Puberty
- Treatment-naive children: Start with depot 11.25 mg intramuscularly every 3 months 4
- Alternative dosing: 3.75 mg to 15 mg intramuscularly every 28 days, with the minimal effective dose averaging 0.15 ± 0.07 mg/kg per 28 days 5
- For more advanced puberty: 30 mg depot every 3 months may be required, as this achieves 95.2% LH suppression compared to 78.4% with 11.25 mg 4
- Dosage correlates directly with bone age and pubertal stage—children with more advanced puberty require higher doses 5
- Monitor with GnRH stimulation testing at 6-month intervals, as 5 patients in one study required dose escalation 5-10 months after initial suppression 5
Endometriosis
- Depot 3.75 mg intramuscularly or subcutaneously monthly for up to 6 months maximum 2
- Duration is limited to 6 months due to reduction in bone mineral density 2
- Efficacy is comparable to danazol 800 mg/day or buserelin 900 mcg/day 2
Fertility Preservation (Neoadjuvant Therapy with Cyclophosphamide)
- Administer leuprolide in relation to cyclophosphamide exposure timing 6
- This indication is specifically for women desiring future childbearing who are receiving intravenous cyclophosphamide for lupus nephritis 6
In Vitro Fertilization
- 0.5 to 1 mg daily subcutaneously to prevent premature luteinization 2
- Reduces risk of cancelled cycles for oocyte retrieval 2
Pharmacokinetic Considerations
- Bioavailability exceeds 90% with direct action on GnRH receptors 2
- Initial "flare" effect occurs within first 3 hours to 3 weeks: transient rise in gonadotropins and sex hormones before suppression 2, 3
- Sustained suppression achieved by 3-5 weeks with continued administration 3
- Dose-dependent area under the curve (0-35 days) correlates directly with administered dose 3
Critical Monitoring Parameters
For Prostate Cancer
- Serum testosterone levels should reach castration range (<50 ng/dL) within 3 weeks 3
- Monitor LH and FSH suppression at 5 weeks 3
For Precocious Puberty
- Perform abbreviated GnRH stimulation test (samples at 20 and 40 minutes) every 6 months to confirm adequate suppression 5
- Peak-stimulated LH should be suppressed to <4 IU/L 4
- Monitor growth velocity, pubertal progression, and bone age advancement 4
- Bone mineral content should be assessed during treatment 7
For Endometriosis
- Assess uterine volume and symptom reduction 2
- Monitor bone mineral density due to treatment-related reduction 2
Common Pitfalls to Avoid
- Do not exceed 6 months of treatment for endometriosis due to bone density concerns 2
- Do not assume initial dose adequacy in precocious puberty—some patients require dose escalation after 5-10 months despite initial suppression 5
- Do not use the 11.25 mg 3-month depot as first-line in children with very advanced puberty—the 30 mg formulation provides superior LH suppression (95.2% vs 78.4%) 4
- Anticipate the initial testosterone flare in prostate cancer patients within the first 3 weeks, which may temporarily worsen symptoms 3