Relugolix
Relugolix
Generic Name
Relugolix
Mechanism
- Competitive, reversible inhibition of GnRH receptors in the pituitary.
- ↓ Secretion of LH and FSH → ↓ testicular/ovarian steroidogenesis.
- Direct, dose‑dependent suppression of serum testosterone or estrogen within 48 h.
- No “flare” due to absence of initial pulsatile stimulation of the receptors.
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Pharmacokinetics
| Parameter | Key Findings |
| Route | Oral (tablet) |
| Bioavailability | ~46% after PO administration; dose‑dependent up to 120 mg. |
| Absorption | Peak plasma 4–6 h post‑dose; food effect minimal. |
| Metabolism | Esterase‑mediated hydrolysis → inactive metabolite; modest CYP3A4 involvement. |
| Half‑life | ~24–30 h (steady‑state ~48 h with loading dose). |
| Excretion | Mainly fecal (≥80 %); renal elimination <10 % of unchanged drug. |
| Drug interactions | Moderate inhibitors of CYP3A4 (e.g., ketoconazole) ↑ plasma exposure by ~1.5‑fold. No major drug‑drug interactions in clinical trials. |
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Indications
- Advanced or metastatic prostate cancer (androgen‑deprivation therapy).
- Uterine fibroids in pre‑menopausal women when surgery is deferred.
- Endometriosis when hormonal therapy is indicated.
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Contraindications
- Contraindicated in pregnancy, postpartum lactation, or active hepatitis B/C.
- Absolute contraindications: hypersensitivity to relugolix or any excipient.
- Warnings:
- *Osteoporosis*: Long‑term estrogen suppression increases fracture risk.
- *Fluid retention* (rare) in patients with heart failure.
- *Potential tumor flare* in prostate cancer (transient PSA rise).
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Dosing
| Condition | Loading Dose | Maintenance Dose | Duration |
| Prostate cancer | 240 mg once | 120 mg daily | 6 mo+ (lifelong if disease persists) |
| Fibroids / Endometriosis | 120 mg daily | 120 mg daily | 6 mo or as clinically indicated |
• Administration: Take PO with a full glass of water. Avoid high‑fat meals; no strict timing relative to food.
• Titration: If PSA/estrogen levels remain above target, add aromatase inhibitor (e.g., letrozole) or switch to surgical castration after counseling.
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Adverse Effects
| Common (≥10 %) | Serious (≤1 %) |
| Hot flashes | Osteopenia/osteoporosis (fracture risk) |
| Headache | Acute tumor flare (PSA burst) |
| Nausea | Hypocalcemia (rare) |
| Vaginal dryness | Hormone‑related rebound on discontinuation |
| Fatigue | Serotonin syndrome (when combined with serotonergic agents) |
> Monitoring: Baseline and periodic DEXA scans, electrolytes, and hormonal assays.
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Monitoring
- Serum PSA (prostate cancer) 3–6 wk post‑initiation.
- Testosterone / estradiol levels 4–6 wk after loading dose.
- Bone mineral density at baseline, 6 mo, then annually.
- Liver function tests if hepatic impairment is suspected.
- Electrolytes (Ca²⁺, Mg²⁺) if concurrent bisphosphonate therapy.
- Adverse events: Document hot flashes, arthralgias, GI disturbances.
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Clinical Pearls
- *Convenient oral therapy* eliminates the need for injections and surgical castration, improving adherence in men with prostate cancer.
- Loading dose (240 mg) reduces early PSA rise by 90 % compared with maintenance alone.
- Bone protection: Initiate bisphosphonates or denosumab concurrently; calcium‑vitamin D supplementation is essential.
- Drug interaction vigilance: Although metabolism is primarily non‑CYP, strong CYP3A4 inhibitors (e.g., ritonavir) can elevate exposure—adjust dose only with close monitoring.
- Switching strategy: Transition from an GnRH agonist to relugolix is smooth if the flare window is bridged with anti‑androgen therapy.
- Endometriosis management: Relugolix can serve as the first line in young, fertility‑intending patients when combined with progestins or when surgery is postponed.
- Safety profile: Early phase data show no significant increase in cardiovascular events compared with placebo.
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• *For the most current dosing guidelines and drug–drug interaction updates, consult the latest prescribing information and peer‑reviewed pharmacology reviews.*