Nafarelin Nasal

In the U.S.

• Synarel

Available Dosage Forms:

• Spray

Therapeutic Class: Endocrine-Metabolic Agent

Pharmacologic Class: Luteinizing Hormone Releasing Hormone Agonist

Use nafarelin only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. Do not change your dose or stop using nafarelin without checking first with your doctor.

nafarelin comes with patient instructions. Read and follow these instructions carefully and make sure you understand:

• How to prepare the nasal spray.
• How to use the spray.
• How long the spray can be stored.

nafarelin is only used in the nose. Do not get it in your eyes or on your skin. If it does get on these areas, rinse them with water right away and call your doctor.

To use nafarelin spray:

• Before you use each new bottle of nafarelin, the spray pump needs to be primed first. To do this, point the bottle away from you and pump the bottle firmly about 7 times until a fine mist spray appears. This only needs to be done once for each new bottle of nafarelin. Be careful not to breathe in this spray. You could inhale extra doses of nafarelin, since the medicine is dissolved in the spray.
• Before you use nafarelin spray, blow your or your child's nose gently to clear the nostrils. You can also use a bulb syringe to clean your child's nose.
• For central precocious puberty:
  • Tilt your child's head back slightly. Put the tip of the bottle into your child's nostril.
  • Close the other nostril with your finger. At the same time, let your child sniff in the spray as you pump the bottle once.
  • Allow 30 seconds between sprays in the same nostril.
  • Keep your child's head tilted back for a few seconds after spraying nafarelin to let the spray get onto the back of the nose.
• For endometriosis:
  • Lean your head forward. Put the spray tip into one nostril. Aim the tip toward the back and outside of your nostril. You do not need to put the tip too far into your nose.
  • Close your other nostril with your finger. At the same time, sniff in the spray as you pump the bottle once.
  • Do not spray nafarelin in your other nostril unless your doctor tells you to.
  • Tilt your head backwards for a few seconds after spraying nafarelin to let the spray get onto the back of your nose.
• Repeat these steps for each dose of the medicine.
• Each time you use the spray bottle, wipe off the tip with a clean tissue or cloth. Keep the white safety clip and plastic cap on the bottle when you are not using it.
• Be sure to clean the tip of the spray bottle before and after every use. To do this, hold the bottle sideways. Rinse the tip with warm water, while wiping the tip with your finger or a soft cloth for about 15 seconds. Dry the tip with a soft cloth or tissue. Replace the cap right after use. Be careful not to get water into the bottle, since this could dilute the medicine.
• Do not try to make the tiny hole in the spray tip larger. Doing so, may deliver a wrong dose of the medicine.

If you are also using a nasal decongestant, do not use it at the same time you are using nafarelin. Wait at least 2 hours after using nafarelin spray before using the nasal decongestant.

Avoid sneezing when spraying and immediately after using the medicine. If you sneeze, the medicine may not be absorbed as well.

Many boys and girls who have central precocious puberty will not feel sick or will not understand the importance of taking nafarelin regularly. Nafarelin must be given on a regular schedule.

Women with endometriosis should start using nafarelin between the 2nd and 4th day of their menstrual period, unless instructed otherwise by your doctor. nafarelin is used for six months.

Dosing

The dose of nafarelin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of nafarelin. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For nasal dosage form (spray):
  • For treatment of central precocious puberty:
    • Children—Two sprays in each nostril two times a day, taken in the morning and in the evening. This provides a total dose of 8 sprays a day. Some patients may need a larger dose by using 3 sprays in alternating nostrils three times a day to provide a total of 9 sprays per day.
  • For treatment of endometriosis:
    • Adults—One spray in one nostril in the morning and one spray into the other nostril in the evening, taken for 6 months. Begin your treatment on Day 2, 3, or 4 of your menstrual period.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of nafarelin, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep the bottle upright. Do not freeze. After you prime the bottle, there will only be 60 doses or sprays. Keep track of the number of sprays you use. Throw the bottle away after you use 60 sprays (for 30 days) even if some liquid remains.

It is very important that your doctor check the progress of you or your child at regular visits to make sure that nafarelin is working properly. Blood tests may be needed to check for unwanted effects. Be sure to keep all appointments.

For female patients: You should not use nafarelin if you are pregnant or may become pregnant. Using nafarelin while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment with nafarelin. If you think you have become pregnant while using the medicine, tell your doctor right away.

For children using nafarelin spray for central precocious puberty (CPP): nafarelin can cause a brief increase in blood levels of some hormones. During this time, you may notice more signs of puberty in your child, including light vaginal bleeding and breast enlargement in girls. If your child's symptoms do not improve within 4 weeks, or if they get worse, call your doctor.

For adult women using nafarelin spray for endometriosis:

• For the first few days of treatment, the symptoms of your condition may get worse. This is normal. Do not stop using nafarelin. Talk with your doctor if you have concerns about this.
• During the time you are using nafarelin, your menstrual period may not be regular or you may not have a menstrual period at all. This is to be expected when being treated with nafarelin. If regular menstruation does not begin within 2 to 3 months after you stop using nafarelin, check with your doctor.
• During the time you are using nafarelin spray, you should use birth control methods that do not contain hormones, such as condoms, IUD, a diaphragm or a cervical cap with a spermicide. If you have any questions about this, check with your doctor.
• Use a water-based vaginal lubricant product if dryness of the vagina causes problems, such as pain during sexual intercourse. Make sure the lubricant you choose can be used with a latex birth control device if you are using one. Some lubricants contain oils, which can break down the latex rubber of condoms, a cervical cap, or a diaphragm, and cause them to rip or tear.
• nafarelin can cause your bone mineral density to decrease, which may lead to osteoporosis or weakened bones. Talk with your doctor about how this risk will affect you.
• If you suspect you may have become pregnant, stop using nafarelin and check with your doctor right away. There is a chance that continued use of nafarelin during pregnancy could cause birth defects or a miscarriage.

nafarelin may cause some people to be agitated, irritable, or display other abnormal behaviors. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell the doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. If you or your caregiver notice any of these side effects, tell your doctor right away.

Using nafarelin may increase your risk of having seizures. Check with your doctor right away if you start to have convulsions, muscle spasm or jerking of all extremities, sudden loss of consciousness, or loss of bladder control.

Nafarelin spray can increase your risk of having cysts in the ovaries. Talk to your doctor about this risk.

Before you have any medical tests, tell the medical doctor in charge that you are using nafarelin. The results of some tests may be affected by nafarelin.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Do not miss any doses of this medicine. Skipping doses or not using nafarelin nasal correctly may cause a hormonal imbalance that could lead to unwanted side effects.

Nafarelin nasal is usually given 2 times per day, or once every 12 hours. Use the medicine at the same times each day.

Before your first use, prime the spray bottle by pumping it 5 to 10 times until a fine spray appears.

To use the nasal spray:

• Blow your nose gently. Keep your head upright and insert the tip of the bottle into one nostril. Press your other nostril closed with your finger. Breathe in quickly and gently spray the medicine into your nose.

• Tilt your head back for a few seconds to allow the medicine to flow to the back of your nose. Try not to sneeze right after using the nasal spray.

• If you use more than one spray, wait at least 30 seconds before using the second spray.

• Do not use the nasal spray in your other nostril unless your doctor has told you to.

• Do not blow your nose for at least a few minutes after using the nasal spray.

• If the spray gets in your eyes or mouth or on your skin, rinse with water.

Rinse the tip of the spray bottle with warm water before and after each use.

Do not use a nafarelin nasal spray bottle for longer than 30 days, even if it still contains some medicine. After 30 days of regular use, the amount of medicine left in the bottle will not be enough for you to receive a full dose. If your doctor increases your dose, you may need to get a new bottle to be sure you have enough medicine for full doses.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

When you first start using nafarelin nasal to treat precocious puberty, you may notice an increase in signs of puberty, such as enlarged breasts or vaginal bleeding. These are normal side effects during the first month of use.

Call your doctor if pubertal signs continue for longer than 1 month.

Use nafarelin nasal regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

To be sure this medicine is helping your condition and is not causing harmful effects, your doctor will need to check your progress on a regular basis.

Store nafarelin nasal in an upright position at room temperature, away from moisture, heat, and light. Do not freeze. Keep the bottle tightly capped when not in use.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

It is very important that you DO NOT MISS A DOSE of this medicine.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Usual Adult Dose for Endometriosis:

200 mcg (as 1 spray into 1 nostril) intranasally 2 times a day
-Maximum dose: 800 mcg/day (as 1 spray into each nostril 2 times a day)
-Duration of therapy: 6 months

Comments:
-Doubling the recommended dose should be considered in compliant patients who experience menstruation for 2 months after starting treatment.
-Treatment should begin between days 2 and 4 of the menstrual cycle.
-Patients receiving the recommended dose should alternate nostrils, with administration into one nostril in the morning and the other nostril in the evening.

Use: Management of endometriosis, including pain relief and reduction of endometriotic lesions

Usual Pediatric Dose for Precocious Puberty:

800 mcg (as 2 sprays into each nostril) intranasally 2 times a day
-Maximum dose: 1800 mcg/day (as 3 sprays into alternating nostrils 3 times a day)

Comments:
-If patients do not have symptom resolution within the first 2 months of treatment, compliance and gonadotropin independent sexual precocity should be evaluated; the dose may be increased to 1800 mcg/day if both etiologies are excluded.
-Signs of puberty may occur early in treatment, but should resolve after the first month.
-Treatment may continue until the resumption of puberty is appropriate.

Use: Treatment of central/gonadotropin-dependent precocious puberty

Applies to nafarelin: nasal spray

Cardiovascular

Hot flashes occurred commonly in adult women who were treated for endometriosis. Approximately 3% of children developed transient hot flashes.[Ref]

Very common (10% or more): Hot flashes/hot flush (up to 90%)
Common (1% to 10%): Chest pain, edema, hyper/hypotension
Frequency not reported: Palpitations
Postmarketing reports: Arterial thromboembolism, deep vein thrombosis, myocardial infarction, venous thromboembolism[Ref]

Psychiatric

Very common (10% or more): Decreased libido (up to 23%), emotional/affect lability (up to 15%)
Common (1% to 10%): Depression, increased libido, insomnia
Postmarketing reports: Aggression, anger, impatience, irritability, suicidal ideation, suicide attempt[Ref]

Genitourinary

Very common (10% or more): Vaginal dryness (up to 19%)
Common (1% to 10%): Transient breast enlargement, breast atrophy/decreased breast size, vulvovaginal dryness, artificial menopause, uterine hemorrhage, vaginal bleeding, white/brown vaginal discharge
Uncommon (0.1% to 1%): Ovarian cyst
Frequency not reported: Ovarian hyperstimulation syndrome[Ref]

Nervous system

Very common (10% or more): Headache (up to 18%)
Common (1% to 10%): Paresthesia
Frequency not reported: Migraines
Postmarketing reports: Convulsions, stroke, transient ischemic attack[Ref]

Dermatologic

Very common (10% or more): Acne (up to 14%)
Common (1% to 10%): Transient increase in pubic hair, body odor, seborrhea, pruritus, rash, urticaria, hirsutism
Uncommon (0.1% to 1%): Alopecia[Ref]

Respiratory

Common (1% to 10%): Rhinitis, dyspnea, nasal irritation
Frequency not reported: Shortness of breath
Postmarketing reports: Interstitial pneumonitis, pulmonary embolism, pulmonary fibrosis[Ref]

Musculoskeletal

Common (1% to 10%): Myalgia, decreased bone mineral density
Uncommon (0.1% to 1%): Arthralgia
Postmarketing reports: Arthritic symptoms[Ref]

Endocrine

Common (1% to 10%): Estrogen deficiency
Frequency not reported: Pituitary enlargement/asymmetry/pituitary gland changes (size and shape)
Postmarketing reports: Pituitary apoplexy[Ref]

Metabolic

Common (1% to 10%): Increased/decreased weight
Frequency not reported: Increased serum alkaline phosphatase, increased total cholesterol/triglycerides[Ref]

Hypersensitivity

Common (1% to 10%): Drug hypersensitivity[Ref]

Oncologic

Frequency not reported: Adrenal rest tumor of the testis, pituitary gland adenoma[Ref]

A patient with congenital adrenal hyperplasia developed an adrenal rest tumor 8 months after discontinuing treatment; however, correlation to treatment is unlikely.

Pituitary gland adenomas have been observed in a few children receiving treatment; however, the relationship to treatment is unknown.[Ref]

Hepatic

Frequency not reported: Increased AST/ALT, serious liver injury[Ref]

Ocular

Frequency not reported: Blurred vision[Ref]

Other

Postmarketing reports: Crying

Some side effects of nafarelin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Administration advice:
-Patients should tilt their heads slightly back during administration.
-If multiple sprays are required in one nostril, doses should be separated by 30 seconds.
-Patients who sneeze during/immediately after administration should consider repeating the dose.

Storage requirements:
-Protect from light and freezing; store upright when not in use.

General:
-When used to treat endometriosis, this drug produces a menopause-like state via induction of chronic pituitary desensitization.
-Controlled ovulation stimulation should be supervised by an infertility specialist.
-Alternative etiologies should be ruled out in patients with central precocious puberty prior to beginning treatment (e.g., hypothalamic/pituitary/testicular tumors, increased intracranial pressure, congenital adrenal hyperplasia, testotoxicosis, autonomous feminizing/masculinizing disorders).

Monitoring:
-Pregnancy tests prior to treatment and in any patient who misses a dose
-Bone density, especially in patients with a high risk of reduced bone mass and/or receiving 2 or more courses of therapy
-Estradiol and progesterone levels, especially in patients on treatment for controlled ovulation or precocious puberty
-Luteinizing hormone, especially patients on treatment for precocious puberty
-Growth and bone age velocity in patients on treatment for precocious puberty
-Development/worsening of psychiatric symptoms

Patient advice:
-Patients should be advised to speak to their healthcare provider if they are pregnant, intend to become pregnant, or are breastfeeding; patients should be told to use non-hormonal, barrier contraceptives during treatment.
-Patients and/or caregivers should be instructed to maintain complete compliance during treatment; if included, the informational pamphlet should be read prior to use.
-Patients should be told to contact their healthcare providers if doses are missed or menstruation occurs despite compliance.
-Patients should contact their healthcare provider if nasal congestion or rhinitis occurs to determine appropriate treatments. Topical nasal decongestants should be separated by at least 30 minutes.