Nafarelin

VERBATIM UK SPC §4.2 (Synarel 2mg/ml Nasal Spray), ENDOMETRIOSIS: 'In the use of Synarel in endometriosis, the aim is to induce chronic pituitary desensitisation, which gives a menopause-like state maintained over many months. The recommended daily dose of Synarel is 200 mcg taken twice daily as one spray (200 mcg of nafarelin) to one nostril in the morning and one spray into the other nostril in the evening (400 mcg/day). Treatment should be started between days 2 and 4 of the menstrual cycle. The recommended duration of therapy is six months; only one 6-month course is advised. In clinical studies the majority of women have only received up to six-months treatment with Synarel.' VERBATIM, IVF DOWN-REGULATION: 'In the use of Synarel associated with controlled ovarian stimulation prior to in vitro fertilisation, the long protocol should be employed, whereby Synarel is continued through a period of transient gonadotrophin stimulation lasting 10-15 days (the "flare effect") through to pituitary desensitisation (down-regulation). Down-regulation may be defined as serum oestradiol ≤50pg/ml and serum progesterone ≤1ng/ml, and the majority of patients down-regulate within 4 weeks. The recommended daily dose of Synarel is 400 mcg taken twice daily as one spray to each nostril in the morning, and one spray to each nostril in the evening (800 mcg/day). Once down-regulation is achieved, controlled ovarian stimulation with gonadotrophins, e.g. hMG, is commenced, and the Synarel dosage maintained until the administration of hCG at follicular maturity (usually a further 8-12 days). If patients do not down-regulate within 12 weeks of starting Synarel, it is recommended that Synarel therapy be discontinued and the cycle cancelled. Treatment may begin in either the early follicular phase (day 2) or the mid-luteal phase (usually day 21).' SUPERSEDES THE PREVIOUS HOLD: this page was previously held because only the US SYNAREL label — whose DOSAGE AND ADMINISTRATION section covers CENTRAL PRECOCIOUS PUBERTY at 1600–1800 micrograms/day — was in the bundle. The UK SPC has now been recovered and it carries the adult gynaecological posology this page exists for. The US paediatric CPP regimen is a different indication in a different population and MUST NOT be applied to endometriosis or IVF down-regulation. SCOPE: §4.2 of the UK SPC is COMPLETE in the bundle (no truncation marker) and contains exactly these two indications — endometriosis and IVF down-regulation — both of which are quoted above, so no licensed regimen has been omitted. NO MAXIMUM DOSE is populated: the SPC states no ceiling for endometriosis, and the 800 micrograms/day of the IVF regimen is a different indication's dose, not an endometriosis ceiling — importing it would overstate the endometriosis maximum by twofold. BOTTLE CAPACITY IS A DOSING CONSTRAINT, verbatim: 'Bottles contain either 30 or 60 doses and should not be used for a greater number of doses. The 60 dose-unit bottle is sufficient for 30 days' treatment at 400mcg (2 sprays) per day, and 15 days treatment at 800mcg (4 sprays) per day. The 30 dose-unit bottle is sufficient for 15 days' treatment at 400mcg (2 sprays) per day, and 7 days' treatment at 800mcg (4 sprays) per day. Patients should therefore be advised that continued use after this time may result in delivery of an insufficient amount of nafarelin.' ADMINISTRATION TECHNIQUE: prime the pump before first use (about 5–7 presses) — this is done once only; clean the spray tip before and after every use to prevent clogging and an incorrect dose; bend the head forward slightly, close one nostril and aim towards the back and outer side of the nose, then bend the head backwards for a few seconds after spraying. Do not enlarge the hole in the spray tip and do not remove the pump from the bottle. RETREATMENT IS NOT RECOMMENDED (§4.3): a small loss of trabecular bone mineral content occurs during 6 months of treatment; although mostly reversible within 6 months of stopping, there are no data on the effects of repeat courses, so retreatment or use for longer than 6 months is not recommended. If further treatment of endometriosis or fibroids is contemplated, §4.4 recommends bone density be assessed before retreatment begins. CONTRACEPTION (§4.4): 'When regularly used at the recommended dose, nafarelin inhibits ovulation. Patients should be advised to use non-hormonal, barrier methods of contraception. In the event of missed doses there may be breakthrough ovulation and a potential for conception.' For IVF, 'Synarel treatment will be stopped at least 3 days before fertilised embryos are placed in the uterine cavity.' A nasal decongestant, if required, should not be used until at least 2 hours after a Synarel dose (US label). §4.4 IS TRUNCATED in the bundle, so the warnings captured here are partial.