Switching from Leuprolide to Relugolix: No Loading Dose Required
When transitioning a patient from leuprolide to relugolix, administer the standard relugolix loading dose of 360 mg on day 1, followed by 120 mg once daily, without waiting for testosterone recovery from leuprolide. 1
Transition Protocol
Timing of Switch
- Initiate relugolix at the time of the next scheduled leuprolide injection rather than waiting for testosterone recovery, as relugolix will immediately suppress any residual testosterone production 1
- No washout period is necessary between stopping leuprolide and starting relugolix 1
Standard Relugolix Dosing
- Day 1: 360 mg loading dose (three 120 mg tablets taken together) 1
- Day 2 onward: 120 mg once daily 1
- This loading dose achieves castrate testosterone levels (<50 ng/dL) in 56% of patients by day 4, compared to 0% with leuprolide 1
Key Advantages of This Approach
Rapid Testosterone Suppression
- Relugolix achieves castrate levels within 4 days in the majority of patients, eliminating any gap in androgen suppression that might occur if waiting for leuprolide washout 1
- By day 15, relugolix achieves profound castrate levels (<20 ng/dL) in significantly more patients than leuprolide 1
No Testosterone Surge
- Unlike leuprolide (a GnRH agonist that causes initial testosterone surge), relugolix is a GnRH antagonist that immediately blocks testosterone production without any surge phenomenon 2, 1
- This makes the transition safe even in patients with symptomatic metastatic disease where testosterone flare could worsen symptoms 2
Clinical Efficacy Evidence
Sustained Castration Rates
- Relugolix maintains castrate testosterone levels in 96.7% of patients through 48 weeks, compared to 88.8% with leuprolide 1
- This represents a 7.9 percentage point superiority (95% CI: 4.1 to 11.8; P<0.001) 1
Castration Resistance-Free Survival
- In the HERO study metastatic population, castration resistance-free survival rates at 48 weeks were 74.3% with relugolix versus 75.3% with leuprolide (HR 1.03; P=0.84), demonstrating equivalent oncologic efficacy 3
- When combined with radiotherapy, relugolix achieved 97% castration rates with no difference in castration resistance-free survival compared to leuprolide (HR 0.97; P=0.62) 4
Cardiovascular Safety Advantage
Major Adverse Cardiac Events
- Relugolix demonstrated a 54% lower risk of major adverse cardiovascular events (2.9%) compared to leuprolide (6.2%) with a hazard ratio of 0.46 (95% CI: 0.24-0.88) 1
- This cardiovascular benefit makes relugolix particularly advantageous for patients with pre-existing cardiac disease or risk factors 2, 1
Monitoring After Transition
Testosterone Levels
- Check testosterone at week 4 to confirm castrate levels (<50 ng/dL) have been achieved 1
- Continue monitoring testosterone every 3-6 months as per standard androgen deprivation therapy protocols 1
PSA Monitoring
- Monitor PSA at baseline, 4 weeks, then every 3 months to assess treatment response 3
- Rising PSA while castrate (>2 ng/mL above nadir, or ≥2 ng/mL with nadir <2 ng/mL) indicates potential castration resistance 3
Common Pitfalls to Avoid
- Do not reduce the loading dose – the full 360 mg loading dose is essential for rapid testosterone suppression regardless of prior leuprolide therapy 1
- Do not delay the switch waiting for testosterone recovery from leuprolide – this creates an unnecessary gap in androgen suppression 1
- Do not assume patients on leuprolide are already at castrate levels – 11.2% of leuprolide patients in HERO failed to maintain sustained castration 1
Adverse Effects Profile
- The adverse event profile of relugolix is consistent with testosterone suppression (hot flashes, fatigue, decreased libido) and similar to leuprolide 2, 1
- Grade 3 or higher adverse events are uncommon (<5%) and include hypertension, atrial fibrillation, and headache 4
- No new safety concerns emerged when relugolix was combined with radiotherapy 4