Drug reference

Nafarelin

GnRH Analogue · Gonadal Suppressant, Endocrine Agent

Also known as Synarel

GnRH AnalogueGonadal Suppressant, Endocrine AgentATC null

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

—

none in our sources

PREGNANCY

Avoid—teratogenic in animal studies. Pregnancy should be excluded before treatment.

FDA category + note

Mechanism

Nafarelin is a synthetic analog of Gonadotropin-Releasing Hormone (GnRH) that initially binds to specific GPCRs on gonadotrophs in the anterior pituitary, activating the Gq/11 pathway and stimulating LH and FSH release. However, sustained, non-pulsatile administration of Nafarelin desensitizes the pituitary gonadotrophs, leading to a profound inhibition of FSH and LH secretion. This results in hypogonadotropic hypogonadism and consequent suppression of gonadal steroid production.

Indications

EndometriosisUterine fibroidsCentral precocious pubertyAssisted reproductive technology procedures (controlled ovarian stimulation/pituitary down-regulation)Prostate cancer (off-label, for GnRH analogs in general)Gonadal suppression in early adolescents who are transgender or gender diverse (off-label)Androgen deprivation therapy (ADT) for all forms of advanced prostate cancerAssisted reproduction (to suppress endogenous LH surge during controlled ovarian hyperstimulation)Advanced estrogen dependent carcinoma breastAdvanced androgen dependent carcinoma prostate

Dosing

Adult: Endometriosis: 200 µg intranasally into alternate nostril twice daily for up to 6 months. Uterine fibroids: 200 µg intranasally twice daily for 3–6 months. For pituitary down-regulation in assisted reproductive technology: Administered usually within 4 weeks (then maintained for 8–12 days during gonadotrophin administration), discontinue if down-regulation not achieved within 12 weeks.…
Pediatric: Central precocious puberty: 800 µg twice daily by nasal spray.
Max dose: For endometriosis or IM 11.25mg injection: use longer than 6 months is contraindicated and treatment should not be repeated.

Pharmacokinetics

Onset

Down-regulation in assisted reproductive technology: usually within 4 weeks.

Duration

Duration of action varies based on formulation, from several hours for daily administration to 1, 3, 6, or 12 months for depot forms.

Half-life

2–6 hours for long-acting GnRH agonists (subcutaneous and intranasal forms).

Bioavailability

low (~4%) for intranasal formulation

Contraindications

Undiagnosed vaginal bleeding
Use for longer than 6 months for endometriosis (do not repeat)
Pregnancy
Hormone-dependent malignancies (prostate, breast) must be excluded
Pregnant women

Side effects

Common

Appetite decreasedArthralgiaBone painBreast abnormalitiesDepressionDizzinessFatigueGynaecomastiaHeadacheHepatic disordersHot flushHyperhidrosisInjection site necrosisInsomniaMood alteredMuscle weaknessParaesthesiaPeripheral oedemaSexual dysfunctionTesticular atrophyVulvovaginal drynessWeight changeLoss of libidoOsteoporosisEmotional labilityHot flashesDecreased bone densityVaginal dryness (women)Vaginal atrophy (women)Erectile dysfunction (men)Vasomotor instabilityImpotenceGynecomastiaAnemiaWeight gainDecreased insulin sensitivityAltered lipid profilesFracturesLoss of muscle massVaginal dryness

Serious

Alopecia
Diarrhoea
Fever
Myalgia
Palpitations
Visual impairment
Vomiting
Haemorrhage
Anaemia
Impaired glucose tolerance
Hypertension
Hypotension
Interstitial lung disease
Leucopenia
Paralysis
Pulmonary embolism
QT interval prolongation
Seizure
Spinal fracture
Thrombocytopenia
Urinary tract obstruction
Tumour 'flare' (leading to spinal cord compression, ureteric obstruction, or increased bone pain) in prostate cancer patients
Allergic reactions
risk of osteoporosis (with long-term use)
estrogen withdrawal symptoms (e.g., hot flashes)
Testosterone flare (transient rise in testosterone leading to acute stimulation of prostate cancer growth and symptoms, typically lasting 2 to 3 weeks)
Increased risk of diabetes
Increased risk of coronary heart disease