nafarelin (Rx)

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

Psychiatric Disorders: Emotional lability, including crying, irritability, impatience, anger, and aggression; depression, including rare reports of suicidal ideation and attempt, in children treated for central precocious puberty

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

Convulsions reported in patients receiving GnRH agonists; reports with GnRH agonists have included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs; convulsions also reported in patients in the absence of any of the conditions listed

Psychiatric events reported in patients taking GnRH agonists; postmarketing reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression; monitor for development or worsening of psychiatric symptoms during treatment

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.

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)