nafarelin

Action and Spectrum

Actions and Spectrum: 

Action: nafarelin is a synthetic analog of the body’s naturally occurring gonadotropin-releasing hormone (GnRH). Gonadotropin-releasing hormone (GnRH) triggers the secretion of (LH) and (FSH) from the pituitary gland. However, when administered in a pulsatile manner (as the body naturally secretes GnRH), it stimulates the release of LH and FSH. 

Spectrum: 

Endometriosis: nafarelin is used to manage the symptoms of endometriosis, a condition where tissue like the lining of the uterus grows outside the uterus. By suppressing LH and FSH production, nafarelin helps reduce estrogen levels, which can alleviate the symptoms associated with endometriosis. 

Central Precocious Puberty (CPP): CPP is a condition where children enter puberty earlier than usual. nafarelin can be used to delay puberty by suppressing the production of sex hormones in these children until an appropriate age for puberty to occur. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

Rhinitis (5%) 

Seborrhea (3%) 

Vaginal bleeding (8%) 

Breast enlargement (8%) 

Acne (10%) 

Emotional lability (6%) 

Increase in pubic hair (5%) 

Body odor (4%) 

Vaginal discharge (3%)  

Frequency Not Defined 

Arthralgia 

Eye pain 

Weakness 

Breast engorgement 

Maculopapular rash 

Palpitation 

Paresthesia 

Chloasma 

Black Box Warning

Black Box Warning:  

Cardiovascular Risk: 

nafarelin may cause an increased risk of cardiovascular events, including heart attack, stroke, and blood clots. 

It is contraindicated in patients with a history of cardiovascular disease. 

Intracranial Hypertension: 

nafarelin use may lead to an increase in intracranial pressure (ICP) leading to papilledema and potentially irreversible visual impairment. 

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: nafarelin should not be used in individuals who have a known hypersensitivity or allergic reaction to nafarelin or any of its components. 

Pregnancy and lactation: nafarelin is not indicated during pregnancy, and it should not be used by women who are pregnant or breastfeeding unless the potential benefits outweigh the risks.  

Undiagnosed vaginal bleeding: nafarelin should not be administered to patients with undiagnosed vaginal bleeding. Before starting treatment, any underlying cause of abnormal vaginal bleeding should be investigated. 

Primary ovarian failure: nafarelin is not suitable for use in women with primary ovarian failure, as it may not be effective in such cases. 

Active thrombophlebitis or thromboembolic disorders: nafarelin can increase the risk of blood clot formation, so it is contraindicated in individuals with active thrombophlebitis (inflammation of a vein with blood clot formation) or a history of thromboembolic disorders (blood clots that travel to other parts of the body). 

Severe renal impairment: nafarelin may be excreted through the kidneys, and its safety and efficacy in patients with severe renal impairment have not been established. Caution should be exercised in such cases. 

Severe hepatic impairment: The metabolism and elimination of nafarelin could be influenced in individuals with severe hepatic impairment. The use of nafarelin in these patients should be carefully evaluated, and alternative treatment options may be considered. 

Concomitant use of sex hormones: The concomitant use of nafarelin with sex hormones, such as estrogen and progestins, may interfere with the desired therapeutic effects of nafarelin and is generally not recommended. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: AU TGA pregnancy category: D
US FDA pregnancy category: X 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

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:  

nafarelin is a synthetic peptide analog of the natural gonadotropin-releasing hormone (GnRH). It is primarily used as a medication for the treatment of various hormone-related conditions. 

Pharmacodynamics:  

nafarelin is a powerful agonist that targets the GnRH receptor located in the pituitary gland. The GnRH receptor plays a vital role in triggering the release of (LH) and (FSH) from the anterior pituitary. When nafarelin persistently stimulates the GnRH receptor, it induces an initial surge in the release of LH and FSH, consequently resulting in a temporary elevation of sex hormone levels, including estrogen and testosterone, in the bloodstream.  

Pharmacokinetics: 

Absorption 

nafarelin is administered as a nasal spray, which allows for rapid absorption through the nasal mucosa. 

The absorption process involves the drug crossing the nasal epithelium and entering the systemic circulation. 

Distribution 

Once in the bloodstream, nafarelin is distributed throughout the body, including tissues and target organs. 

Its distribution may be limited to some extent due to its relatively large molecular size as a peptide. 

Metabolism 

nafarelin may undergo some metabolism in the liver and other tissues. 

Being a synthetic peptide, it is likely to be broken down into smaller peptide fragments or amino acids by proteolytic enzymes. 

Excretion and Elimination 

nafarelin and its metabolites are primarily excreted from the body through the urine and feces. 

The excretion process involves the elimination of the drug and its breakdown products from the body, mainly via the kidneys and gastrointestinal tract. 

Adminstartion

Administration:  

nafarelin is typically administered as a nasal spray. The nasal spray is self-administered by the patient following the prescribed dosage and schedule. 

The patient should follow these general steps for administering the nasal spray 

• Softly exhale through the nostrils to unclog the nasal passages 
• Shake the nasal spray container. 
•  Remove the cap and place the spray tip into one nostril.  
• Close the other nostril with a finger. e. Inhale deeply and press down on the pump to release the medication while breathing in through the nose. 
•  Repeat the process for the other nostril if instructed to do so. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: nafarelin 

Why do we use nafarelin?  

Endometriosis: nafarelin is a medication prescribed for the management of endometriosis. This condition leads to symptoms like pain and inflammation. By reducing the production of certain hormones, it helps in controlling the growth of endometrial tissue and alleviating the associated symptoms. 

Central Precocious Puberty (CPP): nafarelin is prescribed for children experiencing central precocious puberty, a condition where puberty starts at an abnormally early age. By inhibiting the release of certain hormones, it delays the onset of puberty and helps in normalizing growth and development. 

Assisted Reproductive Technologies: In certain infertility treatments, nafarelin can be used as a part of controlled ovarian hyperstimulation protocols. It helps in regulating the timing of ovulation during in vitro fertilization (IVF) and other assisted reproductive technologies. 

Uterine Fibroids: nafarelin may be used to shrink uterine fibroids (benign tumors in the uterus) before surgical removal, making the procedure more manageable. 

Prostate Cancer: In certain instances of advanced prostate cancer, nafarelin may be employed as a treatment option to reduce testosterone levels and inhibit the proliferation of cancer cells that rely on testosterone for their growth.