SYNAREL- nafarelin acetate spray, metered
G.D. Searle LLC Division of Pfizer Inc
CENTRAL PRECOCIOUS PUBERTY (FOR ENDOMETRIOSIS, SEE REVERSE SIDE)
PHYSICIAN LABELING
DESCRIPTION
SYNAREL (nafarelin acetate) Nasal Solution is intended for administration as a spray to the nasal mucosa. Nafarelin acetate, the active component of SYNAREL Nasal Solution, is a decapeptide with the chemical name: 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-3-(2-naphthyl)-D-alanyl-L-leucyl-L-arginyl-L-prolyl-glycinamide acetate. Nafarelin acetate is a synthetic analog of the naturally occurring gonadotropin-releasing hormone (GnRH).
SYNAREL Nasal Solution contains nafarelin acetate (2 mg/mL, content expressed as nafarelin base) in a solution of benzalkonium chloride, glacial acetic acid, sodium hydroxide or hydrochloric acid (to adjust pH), sorbitol, and purified water.
After priming the pump unit for SYNAREL, each actuation of the unit delivers approximately 100 �L of the spray containing approximately 200 �g nafarelin base. The contents of one spray bottle are intended to deliver at least 60 sprays.
CLINICAL PHARMACOLOGY
Nafarelin acetate is a potent agonistic analog of gonadotropin-releasing hormone (GnRH). At the onset of administration, nafarelin stimulates the release of the pituitary gonadotropins, LH and FSH, resulting in a temporary increase of gonadal steroidogenesis. Repeated dosing abolishes the stimulatory effect on the pituitary gland. Twice daily administration leads to decreased secretion of gonadal steroids by about 4 weeks; consequently, tissues and functions that depend on gonadal steroids for their maintenance become quiescent.
Synarel Indications and Usage
FOR CENTRAL PRECOCIOUS PUBERTY
(For Endometriosis, See Reverse Side)
SYNAREL is indicated for treatment of central precocious puberty (CPP) (gonadotropin-dependent precocious puberty) in children of both sexes.
CONTRAINDICATIONS
Hypersensitivity to GnRH, GnRH agonist analogs or any of the excipients in SYNAREL;
Undiagnosed abnormal vaginal bleeding;
Use in pregnancy or in women who may become pregnant while receiving the drug. SYNAREL may cause fetal harm when administered to a pregnant woman. Major fetal abnormalities were observed in rats, but not in mice or rabbits after administration of SYNAREL during the period of organogenesis. There was a dose-related increase in fetal mortality and a decrease in fetal weight in rats (see Pregnancy Section). The effects on rat fetal mortality are expected consequences of the alterations in hormonal levels brought about by the drug. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus;
Use in women who are breast-feeding.
DOSAGE AND ADMINISTRATION
For the treatment of central precocious puberty (CPP), the recommended daily dose of SYNAREL is 1600 �g. The dose can be increased to 1800 �g daily if adequate suppression cannot be achieved at 1600 �g/day.
The 1600 �g dose is achieved by two sprays (400 �g) into each nostril in the morning (4 sprays) and two sprays into each nostril in the evening (4 sprays), a total of 8 sprays per day. The 1800 �g dose is achieved by 3 sprays (600 �g) into alternating nostrils three times a day, a total of 9 sprays per day. The patient's head should be tilted back slightly, and 30 seconds should elapse between sprays.
If the prescribed therapy has been well tolerated by the patient, treatment of CPP with SYNAREL should continue until resumption of puberty is desired.
There appeared to be no significant effect of rhinitis, i.e., nasal congestion, on the systemic bioavailability of SYNAREL; however, if the use of a nasal decongestant for rhinitis is necessary during treatment with SYNAREL, the decongestant should not be used until at least 2 hours following dosing with SYNAREL.
Sneezing during or immediately after dosing with SYNAREL should be avoided, if possible, since this may impair drug absorption.
At 1600 �g/day, a bottle of SYNAREL provides about a 7-day supply (about 56 sprays). If the daily dose is increased, increase the supply to the patient to ensure uninterrupted treatment for the duration of therapy.