leuprolide

Action and Spectrum

Actions and Spectrum 

leuprolide is a man-made version of GnRH, a hormone that the hypothalamus naturally produces. It first stimulates the pituitary gland’s secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which is how it functions as an agonist. 

leuprolide desensitises the GnRH receptors in the pituitary by being administered continuously. This causes the synthesis of LH and FSH to be downregulated, which in turn causes a decrease in the production of sex hormones like testosterone in males and estrogen/progesterone in females.  

Advanced prostate cancer is frequently treated with leuprolide. It helps in slowing the growth and spread of cancer cells in the prostate gland by lowering testosterone production. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

For Fensolvi 

Nausea (8%) 

Emotional disorder (2%) 

Constipation (6%) 

Hot flush (5%) 

Irritability (2%) 

Upper respiratory tract infection (6%) 

Productive cough (6%) 

Abdominal pain (9%) 

Bronchospasm (6%) 

Injection site erythema (9%) 

Vomiting (6%)   

For Eligard 

<2% 

Gastrointestinal: Flatulence, dyspepsia, constipation 

General: syncope, rigors, weakness, Sweating, insomnia, lethargy 

Musculoskeletal: Tremor, muscle atrophy, limb pain, backache, joint pain 

Nervous: Disturbance of smell and taste, vertigo, depression 

Hematologic: Decreased red blood cell count, hemoglobin and hematocrit 

Metabolic: Weight gain  

Psychiatric: Insomnia, loss of libido, depression 

Reproductive: Testicular soreness/pain, breast soreness/tenderness, impotence, erectile dysfunction, penile disorder, reduced penis size, decreased libido, gynecomastia, testicular atrophy  

Skin: Alopecia, sweating increased, clamminess, night sweats 

Vascular: Hypertension, hypotension 

Renal: Difficulties with urination, nocturia aggravated, urinary retention, urinary urgency, incontinence, pain on urination, scanty urination, bladder spasm, blood in urine, nocturia 

For Lupron Depot-Ped  

Vasodilation (9%) 

<2% 

Hemic and lymphatic system: Purpura  

Nervous system: Somnolence, hyperkinesia 

Psychiatric system: Nervousness, depression 

Whole body: Allergic reaction, body odor, fever, aggravation of preexisting tumor and decreased vision, flu syndrome, hypertrophy, infection 

Metabolic and nutritional disorders: Growth retarded, weight gain, peripheral edema 

Musculoskeletal system: Arthralgia, myalgia, joint disorder, myopathy 

Respiratory system: Rhinitis, sinusitis, asthma, epistaxis, pharyngitis 

Endocrine system: feminization, goiter, accelerated sexual maturity  

Integumentary system: Nail disorder, skin hypertrophy, alopecia, hair disorder, hirsutism, leukoderma  

Laboratory abnormality: Antinuclear antibody present and increased sedimentation rate 

Urogenital system: Dysmenorrhea, gynecomastia/breast disorders, Cervix disorder/neoplasm, menstrual disorder, urinary incontinence 

Digestive System: Constipation, gingivitis, increased appetite, dyspepsia, dysphagia, nausea/vomiting 

Cardiovascular system: Bradycardia, hypertension, syncope, peripheral vascular disorder  

For Lupron Depot-Ped (3 months) 

Injection site swelling (2%) 

Increased weight (7%) 

Headache (2-7%) 

Altered mood (5%)  

For Lupron Depot  

<5%  

Laboratory abnormalities: Hyperglycemia, hyperuricemia, increased creatinine, decreased prostatic acid phosphatase, increased liver function tests, increased urine specific gravity, leukopenia, increased phosphorus, increased platelets, increased prostatic acid phosphatase, decreased albumin, decreased hemoglobin/hematocrit, decreased total protein, decreased urine specific gravity, increased total cholesterol, increased BUN  

Nervous system: Insomnia/sleep disorders; neuromuscular disorders, Agitation 

Respiratory system: Emphysema, lung edema, sputum increased and hemoptysis  

Urogenital system: Breast enlargement, urinary tract infection and Balanitis 

Musculoskeletal system: Myalgia 

Cardiovascular system: Angina, congestive heart failure 

Skin and appendages: Hair disorder, skin reaction 

Hemic and lymphatic system: Ecchymosis 

Digestive system: Dysphagia, eructation, peptic ulcer, Anorexia 

Whole body: Headache, injection site reaction, neoplasm, Asthenia, cellulitis, fever  

For Lupron Depot  

Headache (6.4%) 

Insomnia/sleep disorders (8.5%) 

Asthenia (7.4%)  

Vertigo (6.4%) 

Respiratory disorders (6.4%) 

Neuromuscular disorders (9.6%) 

Skin reaction (8.5%)  

<5% 

Whole body: Enlarged abdomen, fever   

Special senses: Abnormal vision, dry eyes, tinnitus, amblyopia 

Digestive system: Anorexia, increased appetite, thirst/dry mouth, duodenal ulcer  

Respiratory system: Epistaxis, pleural effusion, pharyngitis, pneumonia  

Urogenital system: Gynecomastia, testis disorders, impotence, penis disorders 

Cardiovascular system: Hypertension, hypotension, arrhythmia, bradycardia, heart failure, varicose vein 

Laboratory abnormalities: Increased WBC, hyperphosphatemia, abnormal liver function tests, increased PT, increased BUN, hyperglycemia, hyperlipidemia, increased PTT, decreased platelets, decreased potassium 

Nervous system: Hypesthesia, libido decreased, anxiety, delusions, depression, nervousness, paresthesia 

Hemic and lymphatic system: anemia, lymphedema 

Metabolic and nutritional disorders: dehydration, edema  

>10% 

For Fensolvi 

Nasopharyngitis (22%) 

Cough (13%) 

Headache (16%) 

Injection site pain (31%) 

Pyrexia (17%)   

For Lupron Depot-Ped (monthly)  

Vaginal bleeding or discharge (13%) 

Rash including erythema multiforme (12%) 

General pain (12%) 

Headache (11%) 

Acne/seborrhea (13%)  

Injection site reactions including abscess (37%) 

Emotional lability (19%)  

For Lupron Depot-Ped (3 months) 

Injection site pain (19-21%)  

For Lupron Depot (3 months) 

Gastrointestinal disorders (16%)  

Urinary disorders (14.9%) 

Joint disorders (11.7%) 

Testicular atrophy (20.2%) 

Injection site reaction (13.8%) 

Hot flashes/sweats (58.5%) 

General pain (26.6%)  

Post marketing Reports 

For fensolvi 

Metabolic: Diabetes mellitus 

General: Chest pain, fatigue, weight decrease, decreased appetite, weight increase   

Reproductive system: Vaginal bleeding, breast enlargement 

Respiratory: Dyspnea 

Pseudotumor cerebri  

Vascular: Hypotension, hypertension 

Musculoskeletal and connective tissue: Arthralgia, muscle spasms, myalgia 

Skin and subcutaneous tissue: Injection-site reactions  

Neurologic: paralysis, insomnia, peripheral neuropathy, convulsion 

Psychiatric: Rare reports of suicidal ideation and attempt, emotional lability, depression 

Laboratory abnormalities: Decreased WBC 

Allergic Reactions: Anaphylactic, urticaria, photosensitivity reactions and rash  

For Eligard  

Respiratory System: Interstitial lung disease 

Nervous System: Convulsions 

Patients presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, pituitary apoplexy occurred within 2 weeks of the initial dose 

For Lupron Depot 

Cardiovascular system: Pulmonary embolism, hypotension, myocardial infarction  

Central/peripheral nervous system: Spinal fracture/paralysis, Convulsion, peripheral neuropathy  

Urogenital system: Prostate pain 

Endocrine system: Diabetes 

Hemic and lymphatic system: Decreased WBC 

Musculoskeletal system: Tenosynovitis-like symptoms 

Hepatobiliary disorder: Serious drug-induced liver injury 

Respiratory, thoracic and mediastinal disorder: Interstitial lung disease  

Frequency not defined 

For Lupron Depot-Ped  

Administration site conditions and General disorders: Injection site hematoma, injection site induration, injection site warmth, asthenia, gait disturbance, injection site abscess sterile, irritability   

Skin and subcutaneous tissue disorders: Hyperhidrosis 

Metabolic and nutritional disorders: Decreased appetite, obesity  

Thoracic, respiratory and mediastinal disorders: Cough 

Vascular disorders: Pallor 

Connective tissue disorders: Musculoskeletal pain, pain in extremity 

Psychiatric disorders: Crying, tearfulness 

Nervous system disorders: Dizziness 

Gastrointestinal disorders: Abdominal pain, nausea 

Black Box Warning

Black Box Warning 

None  

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• People with history of allergies or hypersensitivity to leuprolide acetate or any of its ingredients should not use leuprolide. 

Caution: 

• leuprolide usage in children should be done so with caution since safety and efficacy can differ depending on the specific indication.  
• people with cardiovascular illness, cerebrovascular disease, seizure disorders, bone disorders, or psychiatric problems, leuprolide should be used with caution.  
• leuprolide medication may cause alterations in glycaemic control in those with metabolic diseases including diabetes or a tendency towards glucose intolerance. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion into human milk is unknown  

Pregnancy Categories:         

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  

leuprolide functions as a strong agonist of pituitary GnRH receptors. It encourages the pituitary gland to release the hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH). leuprolide produces downregulation and desensitization of the GnRH receptors, albeit, when it is taken continuously. As a result, less LH and FSH are secreted, which lowers the amount of sex hormones produced. 

Pharmacodynamics 

Castration is performed medically when testosterone production in men is suppressed by leuprolide medication. The treatment of illnesses like advanced prostate cancer benefits from this drop in testosterone levels. 

leuprolide increases LH and FSH levels in females, which causes the levels of estrogen and progesterone to initially rise. leuprolide medication that is prolonged results in a reduction in LH and FSH secretion, which profoundly suppresses the generation of estrogen and progesterone. 

Pharmacokinetics 

Absorption   

leuprolide is released into the bloodstream over a prolonged period and is given as an intramuscular injection.  

These formulations have a quicker beginning of effect than depot formulations because they absorb more rapidly. The formulation will have an impact on the absorption rate. 

Distribution 

leuprolide is distributed throughout the body. It strongly binds to plasma proteins, especially albumin. leuprolide may be distributed differently depending on the tissue or organ that it is intended to treat. 

Metabolism 

leuprolide is metabolised by enzymes, mostly in the liver and kidneys. leuprolide metabolism’s precise metabolic pathways are not completely understood. 

Elimination and excretion 

Its metabolites and a little amount of the drug’s unchanged form are largely excreted via the kidneys, and they are eliminated by urine. leuprolide’s elimination half-life might vary from hours to days depending on the formulation employed. 

Adminstartion

Administration 

leuprolide injectable depot formulations, such as leuprolide acetate depot, are injected intramuscularly (IM). The gluteal (buttock) muscle or, less frequently, the thigh muscle is the target of the injections.  

leuprolide is also available in formulations for subcutaneous injection, which is administered most frequently in the upper thigh or abdomen. leuprolide is available as a nasal spray formulation for certain indications. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: leuprolide 

Why do we use leuprolide? 

Male with advanced prostate cancer is treated with leuprolide. It is used to inhibit testosterone production, which can aid in reducing the growth and metastasis of prostate cancer cells.  

In order to treat endometriosis, a condition in which the tissue that ordinarily borders the uterus develops outside of it, leuprolide is used. Uterine fibroids that form in the uterus and can be treated with leuprolide. It is used to treat central precocious puberty, a disorder in which children have early onset of puberty.