nafarelin

Acts as a synthetic analogue of gonadotropin-releasing hormone (GnRH). Initially increases pituitary production of luteinizing hormone and follicle-stimulating hormone, which cause ovarian steroid production. Chronic administration leads to decreased production of gonadotropins. Endometriotic lesions are sensitive to ovarian hormones.

Therapeutic effects:

Reduction in lesions and associated pain in endometriosis.
Arrest and regression of puberty in children with central precocious puberty.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following intranasal administration.

Distribution: Unknown.

Metabolism/Excretion: 20–40% excreted in feces; 3% excreted unchanged by the kidneys.

Half-Life: 3 hr.

Time/Action Profile ⬆ ⬇

(↓ ovarian steroid production)

ROUTE	ONSET	PEAK	DURATION
Intranasal	within 4 wk	3–4 wk	3–6 mo‡

‡Relief of symptoms of endometriosis following discontinuation.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to GnRH, its analogues, or sorbitol;
OB: Pregnancy ;
Lactation: Lactation.

Use Cautiously in:

Rhinitis;
Seizures, cerebrovascular disorders, CNS tumor, or concurrent use of bupropion or selective serotonin reuptake inhibitors.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, MI

Derm: acne, hot flushing, hirsutism, seborrhea

EENT: nasal irritation

Endo: ↓breast size, hyperglycemia

GU: ↓fertility, ↓libido, cessation of menses, vaginal dryness

Metab: weight gain

MS: ↓bone density, myalgia

Neuro: headache, aggression, anger, depression, impatience, insomnia, intracranial hypertension (children), irritability, SEIZURES, STROKE, SUICIDAL ATTEMPT/IDEATION (IN CHILDREN)

Misc: hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

Concurrent topical nasal decongestants may ↓ absorption (administer decongestant at least 2 hr after nafarelin).
Concurrent use with bupropion or SSRIs may ↑ risk of seizures.

Route/Dosage ⬆ ⬇

Endometriosis

(Adults ): 1 spray (200 mcg) in one nostril in the morning and 1 spray in the other nostril in the evening (400 mcg/day). May ↑ to 1 spray in each nostril in the morning and evening (800 mcg/day).

Central Precocious Puberty

(Children ): 2 sprays in each nostril in the morning and in the evening (1600 mcg/day); may ↑ up to 1800 mcg/day (3 sprays in alternating nostrils 3 times daily).

Availability ⬆ ⬇

Nasal spray: 2 mg/mL (200 mcg/spray)

Assessment ⬆ ⬇

Endometriosis: Assess patient for endometriotic pain periodically during therapy.
Central Precocious Puberty: Prior to therapy, a complete physical and endocrinologic examination including height, weight, hand and wrist x-ray, total sex steroid level (estradiol or testosterone), adrenal steroid level, beta human chorionic gonadotropin level, GnRH stimulation test, pelvic/adrenal/testicular ultrasound, and CT of the head must be performed. These parameters are monitored after 6–8 wk and every 3–6 mo during therapy.
- Assess patient for signs of precocious puberty (menses, breast development, testicular growth) periodically during therapy.
- Nafarelin is discontinued when the onset of normal puberty is desired. Monitor the onset of normal puberty and assess menstrual cycle, reproductive function, and final adult height.

Implementation ⬆ ⬇

Endometriosis: Treatment should be started between days 2 and 4 of the menstrual cycle and continued for up to 6 mo.

Patient/Family Teaching ⬆ ⬇

Instruct patient on the correct technique for nasal spray: The head should be tilted back slightly; wait 30 sec between sprays.
- Advise patient to consult health care professional if rhinitis occurs during therapy. If a topical decongestant is needed, do not use decongestant until 2 hr after nafarelin dosing. If possible, avoid sneezing during and immediately after nafarelin dose.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and to avoid breastfeeding during therapy.
Endometriosis: Inform patient that 1 spray should be administered into one nostril in the morning and 1 spray into the other nostril in the evening for the 400-mcg/day dose. If dose is increased to 800 mcg/day, administer 1 spray to each nostril (2 sprays) morning and evening; 1 bottle should provide a 30-day supply at the 400 mcg/day dose.
- Advise patient to use a form of contraception other than oral contraceptives during therapy. Inform patient that amenorrhea is expected. Instruct patient to notify health care professional if regular menstruation persists or if successive doses are missed.
- Advise patient that medication may cause hot flashes. Notify health care professional if these become bothersome.
Central Precocious Puberty: Instruct patient on correct timing and number of sprays. The 1600-mcg/day dose is achieved by 2 sprays to each nostril in the morning (4 sprays) and 2 sprays to each nostril in the evening (4 sprays), for a total of 8 sprays. The 1800 mcg/day dose is achieved by 3 sprays into alternating nostrils 3 times per day, for a total of 9 sprays. Inform patient and parents that if doses are not taken as directed pubertal process may be reactivated. One bottle should provide a 7-day supply at the 1600-mcg/day dose.
- Advise patient and parents that during 1st mo of therapy some signs of puberty (vaginal bleeding, breast enlargement) may occur. These should resolve after the 1st mo of therapy. If these signs persist after the 2nd mo of therapy, notify health care professional.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇