Dosing and uses of Synarel (nafarelin)
Adult dosage forms and strengths
nasal spray
- 2mg/mL
Endometriosis
1 spray (200mcg) in one nostril qAM, 1 spray in the other nostril qPM (total 400 mcg/day) on days 2-4 of menstrual cycle (2 sprays/day)
May increase to 800 mcg/day if still menstruating after 2 month: 1 spray in each nostril twice daily
Maximum treatment duration: 6 months
Pediatric dosage forms and strengths
nasal spray
- 200mcg/spray
Central Precocious Puberty (>2 Years Old)
2 sprays (200 mcg/spray) in each nostril twice daily (total 1600 mcg/day)
May increase to 1800 mcg/day: 3 sprays (200 mcg/spray) into alternating nostrils three times daily (Total 9 sprays/day)
Discontinue when puberty onset is desired
Synarel (nafarelin) adverse (side) effects
1-10%
Acne (10%)
Breast enlargement (8%)
Vaginal bleeding (8%)
Seborrhea (3%)
Emotional lability (6%)
Vaginal discharge (3%)
Rhinitis (5%)
Body odor (4%)
Increase in pubic hair (5%)
Frequency not defined
Arthralgia
Breast engorgement
Chloasma
Maculopapular rash
Paresthesia
Weakness
Palpitation
Eye pain
Postmarketing Reports
Liver injury
Pituitary apoplexy
Seizures
Pituitary gland changes
Liver injury (rare)
Ovarian hyperstimulation syndrome
Warnings
Contraindications
Pregnancy, hypersensitivity, lactation, undiagnosed abnormal vaginal bleeding
Cautions
Goal in adult females is to suppress menstruation; max treatment period 6 mth
May cause increase in bone turnover & decrease in bone mineral content
Ovarian cysts may develop within first 2 months of therapy and occur more commonly in women with polycystic ovarian disease
Cases of pituitary apoplexy reported
Use caution in patients with risk factors for decreased bone mineral density
Irregular or incomplete daily doses may result in stimulation of the pituitary-gonadal axis; counsel caregivers to assure full compliance
During first month of treatment, may initially expect some signs of puberty, e.g., vaginal bleeding or breast enlargement, may occur; such changes should resolve soon after first month; if such resolution does not occur within first two months of treatment, this may be due to lack of compliance or presence of gonadotropin independent sexual precocity; if both possibilities excluded, the dose omay be increased to 1800 mcg/day administered as 600 mcg tid
Patients with intercurrent rhinitis should consult their physician for use of topical nasal decongestant; if use of topical nasal decongestant required during treatment decongestant should not be used until at least 2 hr after administering therapy; sneezing during or immediately after administering therapy should be avoided, if possible, since may impair drug absorption
Pregnancy and lactation
Pregnancy category: X
Lactation: Excretion in milk unknown, contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Synarel (nafarelin)
Mechanism of action
Synthetic decapeptide that is an agonist of LHRH, desensitizes response to endogenous GnRH, which in turn reduces secretion of LH and FSH and subsequently causes decreased ovarian and testicular production
Pharmacokinetics
Peak serum time: 10-45 min
Protein Bound: 78-84%
Metabolism: Degraded by peptidase
Metabolites: Dipeptide, tripeptide, pentapeptide, hexapeptide amide, D-naphthylalanine, 2-naphthylacetic acid (inactive)
Excretion: Urine (44-55%); feces (19-44%)
Half-Life: 3 hr
Bioavailability (1-6%)
Onset: 1 month (initial effect)
Peak effect: 12 wk (endometriosis); 4-8 hr (gonadotropin secretion stimulation)
