Special Warning : אזהרת שימוש

4.4      Special warnings and precautions for use

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. If a patient becomes pregnant during treatment, administration of the drug must be discontinued and the patient must be informed of a potential risk to foetal development and/or miscarriage. As there is a risk of miscarriage in the patient population, a causal association with nafarelin acetate is uncertain.
NB Synarel® treatment will be stopped at least 3 days before fertilised embryos are placed in the uterine cavity.

As with other drugs in this class ovarian cysts have been reported to occur in the first two months of therapy with Synarel®. Many, but not all, of these events occurred in patients with polycystic ovarian disease. These cystic enlargements may resolve spontaneously, generally by about four to six weeks of therapy, but in some cases may require discontinuation of drug and/or surgical intervention.

After a course of therapy, if further treatment of endometriosis and fibroids with nafarelin acetate is contemplated, it is recommended that bone density be assessed before retreatment begins to ensure that values are within normal limits.

In adults, after six months of nafarelin acetate treatment there was very little, if any decrease in the mineral content of the distal radius and second metacarpal. There was a reduction in vertebral trabecular bone density and total vertebral mass, averaging 8.7% and 4.3%, respectively. Substantial recovery of bone occurred during the post-treatment period. Total vertebral bone mass, measured by dual photon absorptiometry (DPA) decreased by a mean of 5.9% at the end of treatment. Mean total vertebral mass, re-examined by DPA six months after completion of treatment, was 1.4% below pretreatment levels.

Controlled ovarian stimulation prior to in vitro fertilisation;

As with other GnRH agonists, there have been reports of ovarian hyperstimulation syndrome (OHSS), associated with the use of nafarelin in combination with gonadotropin. Patients being treated for controlled ovarian stimulation prior to in vitro fertilisation should be monitored carefully. If signs of OHSS develop, treatment should be discontinued (see section 4.8).

Transient ovarian cyst formation is a recognised complication of GnRH agonist use. These cysts tend to regress spontaneously over a number of weeks and are more common when GnRH agonists are commenced in the follicular phase of the cycle.

There are no clinical data available on the use of Synarel® in ovulation induction regimens involving patients with polycystic ovarian syndrome. Caution is advised in this patient group as they are at greater risk of excessive follicular recruitment when undergoing ovulation induction regimes.

Administration of nafarelin in therapeutic doses results in suppression of the pituitary-gonadal system. Normal function is usually restored within 8 weeks after treatment is discontinued.
Diagnostic tests of pituitary-gonadal function conducted during the treatment and up to 8 weeks after discontinuation of nafarelin therapy may therefore be misleading.

Sneezing during or immediately after dosing may impair absorption of nafarelin acetate. If sneezing occurs upon administration, repeating the dose may be advisable.

If the use of a nasal decongestant is required, it is recommended that the nasal decongestant be used at least 30 minutes after nafarelin acetate dosing (see Section 4.5) 
Synarel® contains the preservative benzalkonium chloride, which may cause contractions of the respiratory passage. The preservative (benzalkonium chloride) in nafarelin acetate may cause oedemas inthe nasal mucosa, especially on long term use. If a persistent oedema in the nasal mucosa is suspected, a medicinal product for nasal use without preservative should be chosen, if possible. If such products for nasal use are not available, the use of other formulations of the medicinal product should be considered.

There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH agonists, such as nafarelin acetate. Patients should be informed accordingly and treated as appropriate if symptoms occur.

Effects on Driving

4.7      Effects on ability to drive and use machines

Not applicable.