LUPRODEX 3.75MG

Indications

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty
• Gender dysphoria (as part of hormone therapy)

Dosage

Adults: The recommended adult

Mechanism of action

Leuprolide functions as a GnRH receptor superagonist. Initially, it binds to GnRH receptors on the anterior pituitary, stimulating the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This results in a temporary increase in testosterone and estradiol levels. However, with continuous administration over 2-4 weeks, it leads to downregulation of GnRH receptors, causing a significant reduction in LH and FSH secretion and, consequently, lower sex hormone levels. This feedback inhibition results in therapeutic benefits while the effects are reversible upon discontinuation.

Pharmacodynamics

Leuprolide's initial stimulation of steroid production leads to an increase in testosterone in men and estradiol in women, which can worsen symptoms in conditions like endometriosis. Prolonged use results in decreased steroid levels, similar to other forms of androgen-deprivation therapy. Adverse effects may include loss of bone mineral density, increased risk of cardiovascular events, and exacerbation of depressive symptoms in susceptible individuals. In female patients, the initial rise in estradiol can lead to increased pain and bleeding.

Pharmacokinetics

Leuprolide is administered via subcutaneous or intramuscular injection, with peak plasma concentrations typically occurring within a few hours post-injection. It has a half-life of approximately 3 hours and is metabolized by proteolytic enzymes. The drug is excreted primarily through the urine as inactive metabolites. Continuous administration leads to altered pharmacokinetic profiles due to receptor downregulation.

Contra-indications

• Pregnancy
• Hypersensitivity to leuprolide or any of the excipients
• Undiagnosed abnormal vaginal bleeding
• Hormone-sensitive cancers

Adverse effects

• Hot flashes
• Injection site reactions
• Decreased libido
• Erectile dysfunction
• Mood changes
• Fatigue
• Nausea
• Osteoporosis
• Bone pain
• Galactorrhea
• Vaginal dryness
• Endometrial hyperplasia

Interactions

• Caution with norethisterone due to increased risk of severe adverse effects
• Potential interaction with other hormonal therapies

Precautions

• Monitor for signs of depression, particularly in patients with a history of mood disorders
• Assess bone mineral density prior to and during treatment
• Consider potential effects on cardiovascular health in at-risk populations
• Evaluate pregnancy status in women prior to initiation of therapy

Pregnancy

Leuprolide is contraindicated during pregnancy due to potential harm to the fetus.

Breast-feeding

It is advised to avoid breastfeeding during treatment with leuprolide, as it may affect milk production and composition.

Storage

Store at controlled room temperature, away from light. Protect from moisture.

Formulations

• Injectable solution (e.g., depot formulation)
• Subcutaneous implant

Mechanism of action

Gonadotropin-releasing hormone (GnRH) is a naturally occurring decapeptide that modulates the hypothalamic-pituitary-gonadal (HPG) axis. GnRH binds to corresponding receptors (GnRHRs) on the anterior pituitary gonadotropes, which in turn release luteinizing hormone (LH) and follicle-stimulating hormone (FSH); these, in turn, affect the downstream synthesis and release of the sex hormones testosterone, dihydrotestosterone, estrone, and estradiol. Despite the variety of conditions indicated for treatment with leuprolide, the mechanism of action underlying efficacy is the same in all cases. As a GnRHR agonist, leuprolide binds to and initially activates downstream LH and FSH release; this initial spike in gonadotropin levels is responsible for some of the adverse effects associated with treatment. After 2-4 weeks of treatment, continuous stimulation of GnRHR results in feedback inhibition and significant downregulation of LH, FSH, and their corresponding downstream effects, producing a therapeutic benefit. These effects are reversible upon treatment discontinuation. Like naturally occurring luteinizing hormone-releasing hormone, initial or intermittent administration of leuprolide stimulates release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary. Luteinizing hormone and follicle-stimulating hormone release from the anterior pituitary transiently increases testosterone concentration in males. However, continuous administration of leuprolide in the treatment of prostatic carcinoma suppresses secretion of gonadotropin-releasing hormone, with a resultant fall in testosterone concentrations and a "medical castration". Initial stimulation of gonadotropins form the anterior pituitary is followed by prolonged suppression. Gonadotropin release from the anterior pituitary transiently increases estrone and estradiol concentrations in females. However, continuous administration of leuprolide in the treatment of endometriosis produces a fall in estrogens to postmenopausal levels. As a consequence of suppression of ovarian function, both normal and ectopic endometrial tissues become inactive and atrophic. As a result, amenorrhea occurs.

Pharmacodynamics

Leuprolide is a gonadotropin-releasing hormone (GnRH) analogue that functions as a GnRH receptor superagonist. After an initial spike in GnRH-mediated steroidal production, including testosterone and estradiol, prolonged use results in a significant drop in circulating steroid levels, in line with those produced through other forms of androgen-deprivation therapy (ADT). The corresponding hormonal/steroidal changes produce specific adverse effects in different patient populations. In women undergoing treatment for endometriosis or uterine leiomyomata, careful consideration regarding pregnancy status is advised. The initial increase in estradiol levels may worsen symptoms such as pain and bleeding. Long-term use of leuprolide is associated with loss of bone mineral density. Patients co-administered with [norethisterone] may experience sudden vision loss, proptosis, diplopia, migraine, thrombophlebitis, and pulmonary embolism and may also be at higher risk of cardiovascular disease. Patients with a history of depression may experience severe recurrence of depressive symptoms. In men undergoing palliative treatment for advanced/metastatic prostate cancer, short-term spikes in testosterone levels may cause tumour flare and associated symptoms such as bone pain, hematuria, neuropathy, bladder and/or ureteral obstruction, and spinal cord compression. In addition, patients are at increased risk of developing hyperglycemia, diabetes, and cardiovascular disease, which may manifest through myocardial infarction, stroke, cardiac death, or prolonged QT/QTc interval. In addition, Leuprolide may cause convulsions and embryo-fetal toxicity. In pediatric patients undergoing treatment for central precocious puberty (CPP), the initial steroidal spike may be associated with increased clinical signs of puberty within 2-4 weeks of treatment initiation. In addition, leuprolide may cause convulsions and psychiatric symptoms, including irritability, impatience, aggression, anger, and crying.