Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
The hormonal management of endometriosis, including pain relief and reduction of endometriotic lesions.
Use in controlled ovarian stimulation programmes prior to in-vitro fertilisation, under the supervision of an infertility specialist.
Synarel is for administration by the intranasal route only.
Experience with the treatment of endometriosis has been limited to women 18 years of age and older.
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.
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).
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.
The pump should produce a fine mist, which can only happen by a quick and firm pumping action. It is normal to see some larger droplets of liquid within the fine mist. However, if Synarel comes out of the pump as a thin stream of liquid instead of a fine mist, Synarel may not work as well, and the patient should talk to a pharmacist.
Be sure to clean the Spray Tip after priming (at the time of the first use). The spray tip should then be cleaned before and after every use. Failure to do this may result in a clogged tip that may cause the patient not to get the right amount of medicine that is prescribed for them. Always replace the safety clip and the plastic dust cap on the nasal piece after use to help prevent the tip becoming clogged.
The pump is made to deliver only a set amount of medicine, no matter how hard you pump it.
Do not try to make the tiny hole in the spray tip larger. If the hole is made larger the pump will deliver a wrong dose of Synarel.
Before the patient uses a bottle of Synarel for the first time, they have to prime the spray pump. This only needs to be done once, before they use the first dose.
1. Remove and save the safety clip and the plastic dust cap to uncover the nasal piece. Hold the bottle with in an upright position away from you with two fingers on the ‘shoulders’ and your thumb on the bottom of the bottle.
2. Prime the pump by pressing the bottle upwards several times firmly and quickly until the air is expelled and a fine spray appears. This usually requires about 5-7 presses. It is not necessary to prime the pump again during subsequent use. You will waste your medicine if you prime the pump every time you use it.
3. Clean the Spray Tip after Priming:
Hold the bottle in a horizontal position and rinse the spray tip with warm water, while wiping the tip with your finger or a clean soft cloth for 15 seconds.
Do not clean the spray tip with a pointed object. This could cause an improper dose of the spray to be delivered. Do not remove the pump from the bottle, as this will release the priming pressure.
Wipe the tip dry with a clean soft cloth or tissue.
1. Gently blow the nose to clear the nostrils.
2. Remove the safety clip and the plastic cap to uncover the nasal piece. Hold the bottle as shown previously.
3. Clean the tip of pump.
Hold the bottle in a horizontal position and rinse the spray tip with warm water, while wiping the tip with your finger or a clean soft cloth for 15 seconds.
Do not clean the spray tip with a pointed object. This could cause an improper dose of the spray to be delivered. Do not remove the pump from the bottle, as this will release the priming pressure.
Wipe the tip dry with a clean soft cloth or tissue.
4. Bend head forward slightly. Close one nostril and put the spray tip into the other, aiming towards the back and outer side of the nose.
5. Press the bottle firmly up between thumb and fingers once only whilst gently breathing in through the nostril. For patients using 4 sprays per day, Synarel should now be sprayed into the other nostril.
6. Remove the sprayer from the nostril. Bend head backwards for a few seconds to let the spray spread over back of the nose.
7. Clean the tip of pump. Hold the bottle in a horizontal position and rinse the spray tip with warm water, while wiping the tip with your finger or a clean soft cloth for 15 seconds.
Do not clean the spray tip with a pointed object. This could cause an improper dose of the spray to be delivered. Do not remove the pump from the bottle, as this will release the priming pressure.
Wipe the tip dry with a clean soft cloth or tissue.
Cleaning the spray tip before and after use is important to prevent clogging of the tip that may cause you to get the wrong dose of medicine.
8. Replace the safety clip and the plastic dust cap on the nasal piece. This is important as it helps to prevent the spray tip becoming clogged.
In animals, subcutaneous administration of up to 60 times the recommended human dose (expressed on a mcg/kg basis) had no adverse effects. Orally-administered nafarelin is subject to enzymatic degradation in the gastro-intestinal tract and is therefore inactive. At present there is no clinical experience with overdosage of nafarelin.
Based on studies in monkeys, nafarelin is not absorbed after oral administration.
2 years.
Store upright below 25°C. Avoid heat above 30°C. Protect from light and freezing.
White, high density polyethylene bottles with a 0.1ml metered spray pump, containing 6.5ml or 10ml.
PVC-coated glass bottles with an internal conical reservoir in the base and a valois pump, with either an aluminium crimp-on cap or a polypropylene snap-on cap, containing 4ml or 8ml.
Not all pack sizes may be marketed.
In order to ensure that the correct dose of medicine is administered, it is important that the spray tip is cleaned after priming (at the time of the first use). The spray tip should then be cleaned before and after every use to avoid the tip becoming clogged (see section 4.2).
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