Posology : מינונים

4.2      Posology and method of administration

Synarel® is for administration by the intranasal route only.
The 60 dose unit bottle is sufficient for 30 days' treatment at 400 mcg (2 sprays) per day, and 15 days' treatment at 800 mcg (4 sprays) per day.
Patients should be advised that the use of the contents of the container beyond the abovementioned treatment-days may result in delivery of an insufficient amount of nafarelin acetate.

Controlled Ovarian Stimulation prior to in-vitro Fertilisation
400 mcg or 800 mcg daily administered as follows:

400 mcg: one spray (200mcg) to one nostril in the morning and one spray (200 mcg) to the other nostril in the evening.
800 mcg: one spray to each nostril (2x200 mcg) in the morning, and one spray to each nostril (2x200 mcg) in the evening.

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. However, in the use of Synarel® associated with controlled ovarian stimulation prior to in-vitro fertilisation, the aims of the treatment protocols are different, as follows:

In the "long protocol" administration, 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 estradiol <50pg/ml and serum progesterone <1ng/ml , and the majority of patients down-regulate within 4 weeks.

Therapy should be continued until down regulation is achieved; if this does not occur within 12 weeks nafarelin acetate should be discontinued.

Once down-regulation is achieved, controlled ovarian stimulation with gonadotrophines, e.g. hMG, is commenced, and the Synarel® dosage maintained until an appropriate stage of follicular development, when both are withdrawn and chorionic gonadatropin is given to induce ovulation The "short protocol" employs the flare effect as part of the gonadotrophin stimulation process, which is supplemented by concurrent administration of exogenous gonadotrophins. This usually takes 10-15 days, at which time, hCG is administered.

Treatment by the short protocol should begin in the early follicular phase (day 2). Treatment by the long protocol may begin in either the early follicular phase (day 2) or the mid-luteal phase (usually day 21).

Clinical trials using the long protocol have shown that achievement of down-regulation is more predictable when using a Synarel® dosage of 800 mcg per day.

Endometriosis
Experience with nafarelin for the treatment of endometriosis has been limited to women 18 years of age and older.

The recommended daily dose of nafarelin acetate is one spray (200 mcg of nafarelin free base) into one nostril in the morning and one spray into the other nostril in the evening (total of 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. Retreatment is not recommended.

The 400 mcg daily dose may not produce amenorrhea in all patients. For these patients, if the symptoms of endometriosis persist, the dose may be increased to 800 mcg daily. The 800 mcg dose is administered as one spray into each nostril in the morning (a total of two sprays) and again in the evening. This high dose should be maintained for 6 weeks and then reduced to 2 x 200 mcg/day.

Retreatment cannot be recommended since safety data beyond 6 months are not available.

Uterine Fibroids
The recommended dose of nafarelin acetate for uterine fibroid patients is one spray (200 mcg of nafarelin free base) to one nostril in the morning and one spray into the other nostril in the evening (400 mcg/day). The duration therapy should not exceed 3 months. Efficacy beyond 3 months has not been established.

Important Tips about using Synarel

• 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.


Priming the Spray Pump: 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.


               Using the Spray Pump

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.