leuprorelin

Action and Spectrum

Actions and spectrum: 

leuprorelin is a synthetic hormone analog that acts as an agonist of gonadotropin-releasing hormone (GnRH). It works by continuously stimulating the release of gonadotropins from the pituitary gland when used in a pulsatile fashion.

However, when used in a continuous manner, as is common in medical therapy, it initially stimulates gonadotropin release but suppresses it. This results in a decrease in the production of sex hormones, specifically testosterone in males and estrogen in females. 

leuprorelin is primarily used to treat conditions like prostate cancer, breast cancer, endometriosis, and precocious puberty by suppressing sex hormone production. It helps manage these conditions by reducing the levels of these hormones in the body. 

Drug Interaction

Adverse Reaction

Frequency not defined 

headache 

rash 

emotional lability 

vaginal bleeding 

acne 

Seborrhoea 

vaginitis 

ECG changes 

peripheral oedema 

Constipation 

vomiting 

myalgia 

insomnia 

sinus congestion 

Haematuria 

asthaenia 

high blood pressure 

Anorexia 

nausea 

anaemia 

dizziness 

UTI 

hirsutism 

paraesthesias 

Myalgia 

depression 

nervousness 

Vaginitis 

decreased libido 

emotional labilit 

breast tenderness 

Black Box Warning

Black Box Warning: 

There are no specific drug interactions associated with leuprorelin. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: leuprorelin should not be used in individuals who have a known hypersensitivity or allergy to leuprorelin or any of its components. 
• Undiagnosed Vaginal Bleeding: leuprorelin should not be used in cases of undiagnosed vaginal bleeding. It is important to determine the cause of the bleeding before starting treatment. 
• Children: leuprorelin is not typically used in pediatric patients for most of its indications, and its safety and effectiveness in children have not been established in many cases. 
• Bone Metastases: In some cases, leuprorelin may cause an initial increase in bone pain in patients with bone metastases. It is important to consider the risks and benefits when treating these patients.

Caution: 

• Cardiovascular Health: leuprorelin may cause changes in lipid profiles and may contribute to cardiovascular risk factors. Patients with preexisting cardiovascular conditions should be closely monitored, and appropriate measures to manage cardiovascular health, such as lifestyle modifications and medication, may be needed. 
• Liver Function: leuprorelin is metabolized in the liver, and its clearance may be affected in individuals with liver disease. Caution is advised when using leuprorelin in patients with severe liver impairment. 
• Psychiatric Effects: Some patients may experience mood changes, including depression or emotional lability, while on leuprorelin therapy. Healthcare providers should be vigilant for these symptoms, especially in patients with a history of mental health issues. 
• Pregnancy: leuprorelin is contraindicated during pregnancy. It causes harm to a developing fetus. If used during pregnancy, it should only be done under specific circumstances and with careful medical supervision. 
• Breastfeeding: leuprorelin may pass into breast milk and could potentially harm a nursing infant. Breastfeeding is typically not recommended during leuprorelin treatment.

Comorbidities: 

• Prostate or Breast Cancer: Depending on the type and stage of cancer, treatment with leuprorelin may be part of a broader therapeutic approach. Patients with cancer often have unique comorbidities associated with their specific cancer diagnosis. 
• Osteoporosis and Bone Health: leuprorelin therapy is associated with a risk of decreased bone density and an increased risk of osteoporosis. Patients with a history of osteoporosis or at risk of bone loss should be closely monitored and may require calcium & vitamin D supplementation. 
• Diabetes: leuprorelin can affect glucose metabolism and may lead to changes in blood sugar levels. Patients with diabetes or risk of diabetes should have their blood sugar levels closely monitored during treatment. 
• Mental Health Disorders: Some patients on leuprorelin treatment may experience mood changes, including depression or emotional lability. Patients with mental health issues should be monitored closely for these symptoms. 

Pregnancy / Lactation

Pregnancy consideration: Pregnancy Category: X 

Lactation: excreted into breast milk: unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

leuprorelin is a synthetic peptide analog of gonadotropin-releasing hormone (GnRH), a naturally occurring hormone that regulates the release of LH and FSH hormone from the pituitary gland. leuprorelin works by initially stimulating the pituitary gland to release LH and FSH, leading to an increase in the production of sex hormones like testosterone and estrogen.

However, with continued use, leuprorelin desensitizes the pituitary gland, LH and FSH release in a pulsatile, rather than continuous, manner. This desensitization suppresses the production of sex hormones in both men and women. As a result, leuprorelin is used in the treatment of conditions such as prostate cancer, breast cancer, and certain gynecological disorders where reducing sex hormone levels is beneficial.  

Pharmacodynamics: 

• Initial Stimulation: When administered, leuprorelin stimulates the release of LH & FSH. This initial surge in LH and FSH leads to increased production of sex hormones, such as testosterone in males and estrogen in females. 
• Desensitization: With continued use, leuprorelin causes desensitization of the pituitary gland. It desensitizes the GnRH receptors, leading to reduced LH and FSH secretion. This desensitization is referred to as a “flare effect” and is followed by a sustained decrease in LH and FSH production. 
• Hormone Suppression: Prolonged exposure to leuprorelin results in the suppression of sex hormone production. In men, it lowers testosterone levels, while in premenopausal women, it reduces estrogen levels. This hormone suppression is valuable in treating hormone-dependent conditions like prostate cancer and certain gynecological disorders. 
• Therapeutic Applications: By lowering sex hormone levels, leuprorelin is used to manage conditions like advanced prostate cancer, endometriosis, uterine fibroids, and central precocious puberty. It is also utilized as a part of assisted reproductive techniques. 
• Reversible Effects: Importantly, the effects of leuprorelin on hormone levels are reversible upon discontinuation of the drug, allowing for flexibility in treatment. 

Pharmacokinetics: 

Absorption 

leuprorelin is not orally active, which means it cannot be taken by mouth and absorbed through the digestive system. Instead, it is typically administered by injection or implantation. Common routes of administration include subcutaneous (under the skin) injection and intramuscular (into a muscle) injection. The drug is absorbed slowly and steadily from the injection site into the bloodstream. 

Distribution 

Once in the bloodstream, leuprorelin is distributed throughout the body. It has a short half-life, which means it remains effective for a limited duration before it needs to be administered again. The drug’s distribution is within the circulatory system, where it can interact with its target receptors in the pituitary gland. 

Metabolism 

leuprorelin is not extensively metabolized in the body. It acts as a synthetic analog of gonadotropin-releasing hormone (GnRH), and its primary mechanism of action is to bind to GnRH receptors in the pituitary gland. The drug is designed to resist rapid enzymatic breakdown, allowing it to maintain its activity over time. 

Elimination and excretion 

leuprorelin is primarily eliminated from the body through renal (kidney) clearance. It is filtered from blood by kidneys and excreted in the urine in its unchanged form. Since leuprorelin is administered at controlled intervals, the body can eliminate it gradually as it loses its pharmacological effect. 

Adminstartion

Administration: 

Subcutaneous Injection: 

• leuprorelin is often administered as a subcutaneous injection, it is injected just beneath the skin. This can be done in various parts of the body, such as the abdomen or thigh. 
• The injection site is typically cleaned and prepared, and the drug is administered using a syringe with a fine needle. 
• The injection may need to be repeated at regular intervals, depending on the treatment plan. 

Intramuscular Injection: 

• In some cases, leuprorelin may be administered as an intramuscular injection, where it is injected directly into a muscle. This method may be used for certain long-acting formulations. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: leuprorelin 

Pronounced: (loo-pro-REL-in)  

Why do we use leuprorelin? 

• Prostate Cancer: leuprorelin is often used in the treatment of advanced prostate cancer. It belongs to a class of drugs called luteinizing hormone-releasing hormone (LHRH) agonists. By continuously stimulating the pituitary gland, leuprorelin suppresses the testosterone production, which helps to slow the growth of prostate cancer cells. 
• Breast Cancer: In some cases, leuprorelin may be used in the hormone receptor-positive breast cancer, especially in premenopausal women. By reducing estrogen levels, it can help control the growth of certain breast cancer cells. 
• Central Precocious Puberty (CPP): leuprorelin is used to treat children with central precocious puberty, a condition where puberty starts at an abnormally early age. By suppressing the release of certain hormones, it can delay puberty until a more appropriate age. 
• Endometriosis: leuprorelin is sometimes prescribed to manage endometriosis, where tissue like the lining of uterus grows outside the uterus. By reducing estrogen levels and inhibiting ovulation, it can alleviate symptoms and slow the growth of endometrial tissue. 
• Uterine Fibroids: In some cases, leuprorelin may be used to shrink uterine fibroids before surgical removal. It can reduce the size of fibroids and make surgery more manageable.