1. Clinical Overview
Leuprolide is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH). It acts as a potent GnRH agonist. Following initial stimulation, continuous administration leads to a profound suppression of pituitary gonadotropins (LH and FSH), resulting in a marked decrease in estrogen and testosterone levels. This makes it a cornerstone therapy for hormone-dependent conditions like prostate cancer, endometriosis, and central precocious puberty.
| Onset | Duration | Bioavailability |
|---|---|---|
| Initial gonadotropin surge occurs within 1-3 hours of administration. Significant suppression of sex hormones (testosterone/estradiol) is typically achieved within 2-4 weeks of continuous therapy. | The 1mg daily subcutaneous formulation provides a therapeutic effect for approximately 24 hours, requiring daily administration. Sustained suppression is maintained with continuous daily dosing. | Approximately 94% following subcutaneous injection. |
2. Mechanism of Action
Leuprolide is a potent agonist of the GnRH receptor in the anterior pituitary. Initial administration causes a transient surge in the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a temporary increase in gonadal steroidogenesis (testosterone or estradiol). This is the 'flare' effect. With continuous daily administration, the pituitary GnRH receptors become desensitized and downregulated. This results in a profound and sustained suppression of LH and FSH secretion, leading to a hypogonadal state with markedly reduced levels of testosterone in men and estradiol in women.
3. Indications & Uses
- Palliative treatment of advanced hormone-dependent prostate carcinoma
- Management of endometriosis (pain relief and reduction of lesions)
- Pre-operative management of uterine fibroids (leiomyomas) to reduce size and associated bleeding
4. Dosage & Administration
Adult Dosage: 1 mg (0.5 ml) administered subcutaneously once daily. For prostate cancer/endometriosis/fibroids, treatment duration is typically limited (e.g., 3-6 months for fibroids) due to bone density concerns.
Administration: For subcutaneous use only. Administer daily, rotating injection sites (abdomen, thigh, upper arm). The vial is for single use only; discard any unused portion. Allow the solution to reach room temperature before injection to minimize discomfort. Use aseptic technique.
5. Side Effects
Common side effects may include:
- Hot flashes (flushing)
- Increased sweating (diaphoresis)
- Headache
- Injection site reactions (pain, redness, swelling)
- Decreased libido
- Erectile dysfunction (in men)
- Vaginal dryness/dyspareunia (in women)
- Emotional lability, mood swings
- Initial worsening of bone pain or urinary symptoms (flare phenomenon)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Androgens (e.g., Testosterone) or Estrogens | Antagonizes the therapeutic effect of leuprolide. | Major |
| Drugs that prolong QT interval (e.g., Class IA/III antiarrhythmics, certain antipsychotics, antibiotics) | Additive risk of QT prolongation and cardiac arrhythmias. | Moderate |
| Corticosteroids (e.g., Prednisone) | May exacerbate bone mineral density loss. | Moderate |
| Other drugs metabolized by CYP450 enzymes | No significant interaction expected as leuprolide is not a CYP inhibitor/inducer. | None |
7. Patient Counselling
- DO administer the injection at the same time each day, as prescribed.
- DO rotate injection sites to prevent tissue irritation.
- DO store the vials in the refrigerator (2-8°C). Protect from light.
- DO use non-hormonal methods of contraception (e.g., condoms, copper-T) during and after treatment as advised by your doctor.
- DONT stop the injection suddenly without consulting your doctor.
- DONT use if the solution is discolored or contains particles.
- DONT share your injection device or medicine with anyone.
8. Toxicology & Storage
Overdose: Expected to be an extension of pharmacological effects: profound hypogonadism, severe hot flashes, cardiovascular effects (hypotension, QT prolongation). No specific acute overdose syndrome reported in humans.
Storage: Store unopened vials in a refrigerator at 2°C to 8°C. Do not freeze. Protect from light. Keep in the original carton. Once opened, the single-use vial should be used immediately and any unused portion discarded. Do not use if the solution is cloudy, discolored, or contains particulate matter.