nafarelin
Regulatory sources consulted
Approved indications
- Genital or extragenital endometriosis in adults and pituitary suppression in controlled ovarian stimulation before in vitro fertilization.
Contraindications
Absolute
- Pregnancy or possibility of pregnancy, breastfeeding, undiagnosed vaginal bleeding, hypersensitivity to GnRH/analogs, or prior 6-month nafarelin treatment.
Clinical warnings
- Major warning · Use nonhormonal barrier contraception. Missed doses may permit ovulation and pregnancy; stop if pregnancy occurs. During ovarian stimulation, monitor for ovarian hyperstimulation syndrome and stop if signs develop. — CIMA/AEMPS, ficha técnica 60079
- Major warning · Hypoestrogenism reduces bone density; limit endometriosis treatment to 6 months and assess bone density before retreatment. Symptoms may transiently worsen and ovarian cysts may develop. — CIMA/AEMPS, ficha técnica 60079
Drug interactions
- ModerateNasal decongestants such as oxymetazoline
Mechanism: They may substantially reduce nasal nafarelin absorption.
Recommendation: Discourage concomitant use; if essential, separate dosing and reassess clinical suppression.
CIMA/AEMPS, ficha técnica 60079https://cima.aemps.es/cima/dochtml/ft/60079/FT_60079.html
Adverse events
Common (≥1%)
Hot flushes · Headache · Mood lability or decreased libido · Rhinitis or nasal irritation · Acne or seborrhea · Myalgia · Vulvovaginal dryness
Rare but serious
Ovarian hyperstimulation syndrome · Marked bone-density loss · Severe hypersensitivity
Pregnancy and lactation
Contraindicated during pregnancy and breastfeeding; use nonhormonal contraception and stop immediately if pregnancy occurs.
Recent literature (PubMed)
Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens? An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief. Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted. A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected. Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded. Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or 'draw-back' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A