Nafarelin (Nasarel, Synarel) is a potent GnRH ( gonadotrophin-releasing hormone) agonist that inhibits the secretion of gonadotropins. It is used to treat early (precocious) puberty and females with endometriosis.

Nafarelin Uses:

• Central precocious puberty:

  • Used in the treatment of central precocious puberty (CPP) (gonadotropin dependent precocious puberty) in children of both sexes.

• Endometriosis:

  • Used in the management of endometriosis, including pain relief and reduction of endometriotic lesions.

Nafarelin (Nasarel, Synarel) Dose in Adults

Nafarelin (Nasarel, Synarel) Dose in the treatment of Endometriosis:

Intranasal: Females:

• One spray (200 mcg) into 1 nostril each morning and 1 spray (200 mcg) into the other nostril each evening starting between days 2 - 4 of the menstrual cycle (total: 2 sprays [400 mcg] daily).
• If regular menstruation persists after two months of therapy, may increase the dose to 2 sprays (400 mcg; 1 spray in each nostril) in the morning and evening (total: 4 sprays [800 mcg] daily).
• The total duration of therapy should not be more than 6 months due to decreases in bone mineral density; retreatment is not recommended by the manufacturer.

Nafarelin (Nasarel, Synarel) Dose in Childrens

Nafarelin (Nasarel, Synarel) Dose in the treatment of Central precocious puberty:

• Intranasal: Males/Females: (US labeling):

  • 2 sprays (400 mcg) into each nostril in the morning and 2 sprays (400 mcg) into each nostril in the evening (total: 8 sprays [1,600 mcg] daily).
  • If inadequate suppression may increase the dose to 3 sprays (600 mcg) into alternating nostrils 3 times a day(total: 9 sprays [1,800 mcg] daily).
  • Continue therapy until the resumption of puberty is desired.

Pregnancy Risk Category: X

• Contraindicated treatments for pregnant women should not be initiated.
• When used for endometriosis treatment, it can inhibit ovulation and stop menstruation. However, contraception cannot be guaranteed.
• It is not recommended to use hormonal contraception.
• It is not known if pregnancy rates are affected by or enhanced by the use of this drug.

Nafarelin use during breastfeeding:

• It is unknown if nafarelin can be found in breast milk.
• Contraindicated for lactating mothers

Nasarel Dose in Kidney Disease:

No dosage adjustments provided in the manufacturer's labeling (has not been studied).

Nasarel Dose in Liver disease:

No dosage adjustments provided in the manufacturer's labeling (has not been studied).

Adverse events may be more frequent in the first six weeks of treatment due to the stimulation of the pituitary-gonadal axis.

CPP (Central Precocious Puberty):

Side Effects of Nafarelin:

• Central Nervous System:

  • Emotional Lability

• Dermatologic:

  • Acne Vulgaris
  • Hypertrichosis
  • Body Odor
  • Seborrhea

• Endocrine & Metabolic:

  • Breast Hypertrophy
  • Vaginal Hemorrhage
  • Hot Flashes
  • Vaginal Discharge

• Hypersensitivity:

  • Hypersensitivity Reaction

• Respiratory:

  • Rhinitis

Endometriosis:

Common Side Effects Of Nafarelin (Nasarel):

• Central Nervous System:

  • Headache
  • Emotional Lability

• Dermatologic:

  • Acne Vulgaris

• Endocrine & Metabolic:

  • Hot Flash
  • Decreased Libido
  • Hyperphosphatemia
  • Hypocalcemia
  • Hypertriglyceridemia

• Genitourinary:

  • Vaginal Dryness

• Hematologic & Oncologic:

  • Change In WBC Count
  • Eosinophilia

Less Common Side Effects Of Nafarelin (Nasarel, Synarel):

• Cardiovascular:

  • Edema

• Central Nervous System:

  • Insomnia
  • Depression

• Dermatologic:

  • Hirsutism

• Endocrine & Metabolic:

  • Breast Atrophy
  • Hypercholesterolemia
  • Increased Libido

• Gastrointestinal:

  • Weight Gain
  • Weight Loss

• Neuromuscular & Skeletal:

  • Myalgia
  • Decreased Bone Mineral Density

• Respiratory:

  • Nasal Mucosa Irritation

Contraindications to Nafarelin (Nasarel, Synarel):

• Hypersensitivity to gonadotropin-releasing hormone (GnRH), GnRH-agonist analogs, or any component of the formulation
• Atypical vaginal bleeding that is not diagnosed
• Women who are pregnant or may become pregnant
• Breastfeeding

Warnings and precautions

• Reduced bone density

  • It has been reported that it may be irreversible.
  • Patients with bone loss risk factors (eg, chronic alcohol abuse, anticonvulsant and corticosteroid therapy, family history or osteoporosis) should be used cautiously.
  • Patients at high risk for bone loss should not be given repeat courses.

• Ovarian cysts

  • It may occur in the first two months of therapy.
  • These cysts can resolve themselves in about four to six weeks, although it is possible for them to require surgical intervention or discontinuation of therapy.

• Pituitary apoplexy

  • Administration GnRH agonist has been shown to be effective in rare cases of pituitary hypoplexy, which is often secondary to pituitary anadenoma. Usually, the symptoms last between 1 and 2 weeks.
  • You may experience sudden headaches, vomiting, visual and mental changes, or even cardiovascular collapse.

• Psychiatric events

  • Patients who have taken GnRH agonists have reported emotional lability such as crying, irritability and impatience.
  • GnRH agonists have been linked to depression in children with CPP.
  • Many of these patients had a history psychiatric illness, or other comorbidities that could increase the risk of depression.
  • Monitor for the development or worsening psychiatric symptoms during treatment.

• Seizures:

  • Patients who received GnRH agonists have experienced seizures.
  • Patients who have had seizures in the past, patients with cerebrovascular disorders, CNS abnormalities/tumors and patients taking concomitant medications that are associated with seizures are at higher risk.
  • It has been also reported in patients with no risk factors.

• Use this method for central precocious puberty.

  • Some signs of puberty may be present when CPP is treated. These should disappear within two months.

Nafarelin: Drug Interaction

Monitoring parameters:

Central precocious puberty:

• Bone mineral density
• GnRH testing (blood LH and FSH levels)
• measurement of bone age
• Tanner staging
• Monitor for development or worsening of psychiatric symptoms, including depression.

Endometriosis:

• Menstruation, vaginal bleeding or spotting which persists after 2 months of treatment

How to administer Nafarelin (Nasarel, Synarel)?

Nafarelin Nasal spray:

• Allow about 30 seconds to elapse between sprays.
• Sneezing during or immediately after dosing may decrease drug absorption.
• Do not use a topical nasal decongestant for at least 2 hours (US labeling) or at least 30 minutes after nafarelin use.

Mechanism of action of Nafarelin (Nasarel, Synarel):

• Potent synthetic decapeptide analog of gonadotropin-releasing hormone (GnRH; LHRH) which is approximately 200 times more potent than GnRH in terms of pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
• The length of the administration has an impact on the effects on the pituitary and sexhormones.
• Initial stimulation of the pituitary's release of LH/FSH is observed after acute administration
• The result is an increase in estrogens and androgens.
• However, continued administration of nafarelin reduces gonadotrope response to endogenous GnRH.
• This results in decreased secretion and FSH, and secondarily, lower ovarian and testicular steroids production.

Protein binding, plasma:

• ~80%

Metabolism:

• Degraded by peptidase; forms metabolites

Bioavailability:

• ~1% to 6%

Half-life elimination:

• ~3 hours; Metabolites: ~86 hours

Time to peak serum concentrations:

• 10 to 45 mins

Excretion:

• Urine (44% to 55%, ~3% as unchanged drug);
• feces (19% to 44%)

International Brands of Nafarelin:

• Synarel
• Nasanyl
• Nasarel
• Synarel
• Synarela
• Synrelin
• Synrelina

Nafarelin Brand Names in Pakistan:

No Brands Available in Pakistan.