In the U.S.—

• Gonadotropin inhibitor
• gonadotropin-releasing hormone analog

Histrelin ( his-TREL-in) is a hormone similar to one normally released from the hypothalamus gland in the brain. Histrelin is used in the treatment of central precocious puberty (CPP), a condition that causes early puberty in boys (before 9.5 years of age) and in girls (before 8 years of age). Histrelin works by decreasing the amount of estrogen and testosterone in the blood.

When given regularly to boys and girls, this medicine helps to delay early puberty, slowing down the development of breasts in girls and the development of genital areas in boys and girls. This medicine delays puberty in a child only as long as the child continues to receive it.

Suppressing estrogen can cause thinning of the bones or slowing of their growth. Slowing the growth of bones is a positive effect in girls and boys whose bones grow too fast when puberty begins too early. Boys and girls may benefit by adding inches to their adult height when histrelin helps their bones grow at the proper and expected rate for children.

This medicine is available only with your doctor's prescription, in the following dosage form(s):

Parenteral
• Injection (U.S.)

In deciding to use a medicine, the risks of using the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For histrelin, the following should be considered:

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to histrelin or to gonadotropin-releasing hormone-like medicines. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.

Pregnancy—Histrelin use is not recommended during pregnancy. Histrelin has not been studied in pregnant women. It has been shown to cause problems in animals, such as low birth weights and a decrease in the number of successful pregnancies.

Breast-feeding—It is not known whether histrelin passes into breast milk. However, use of histrelin is not recommended during breast-feeding because it may cause unwanted effects in nursing babies.

Children—When used to treat a child for central precocious puberty, histrelin will stop having an effect soon after the child stops using it, and puberty should occur normally. It is not known if using histrelin around the time of puberty will cause changes in a boy's or a girl's future ability to have babies. Their chances of having children are thought to be normal.

It is especially important that you discuss with the child's doctor the good that this medicine may do as well as the risks of using it.

You will be given a fact sheet with your prescription for histrelin that explains how to prepare and give the injection. Carefully read the fact sheet. If you have any questions about using histrelin, ask your health care professional.

There are several important steps that will help you successfully prepare the histrelin injection. To draw the histrelin up into the syringe correctly, you need to follow these steps:

• Remove a bottle of medicine from the refrigerator and allow it to warm to room temperature before injecting it.
• Wash your hands with soap and water.
• Open the syringe packaging.
• Look at the medicine to make sure it is clear and colorless. Do not use it if it seems to be even a little discolored.
• Remove the colored protective cap on the bottle. Do not remove the rubber stopper.
• Wipe the top of the bottle with an alcohol swab.
• Pull the plunger on the syringe back until it is at the amount you were asked to inject.
• Remove the needle cover from the syringe.

How to prepare the histrelin dose:

• Gently push the needle through the top of the rubber stopper with the bottle standing upright.
• Push plunger in all the way to inject air into the bottle.
• Turn the bottle with syringe upside down in one hand. Be sure the tip of the needle is covered by the histrelin. With your other hand, draw the plunger back slowly to draw the correct dose of histrelin into the syringe.
• Check the dose. Hold the syringe with the scale at eye level to see that the proper dose is withdrawn and to check for air bubbles. To remove air bubbles, tap gently on the measuring scale of the syringe to move any bubbles to the top of the syringe near the needle. Then, push the histrelin slowly back into the bottle and draw up the dose again.
• If the dose measures too low in the syringe, withdraw more solution from the bottle. If there is too much histrelin in the syringe, put some back into the bottle. Then check the dose again.
• Remove the needle from the bottle and re-cover the needle with its plastic cap.

Choose the proper area of the body, such as the upper arms, thighs, or abdomen, to inject the dose of histrelin. The site should be changed between injections as directed by your doctor.

How to inject the histrelin dose:

• After you have prepared the syringe and chosen the area of the body to inject, you are ready to inject the histrelin into the fatty part of the skin.
  • Clean the area where the injection is to be given with an alcohol swab or with soap and water. Let the area dry.
  • Pinch up a large area of skin and hold it firmly. With your other hand, hold the syringe like a pencil. Push the needle straight into the pinched-up skin at a 45-degree angle for a child. Be sure the needle is all the way in. It is not necessary to draw back on the syringe each time to check for blood (also called routine aspiration).
  • Push the plunger all the way down, using less than 5 seconds to inject the dose. Let go of the skin. Hold an alcohol swab near the needle and pull the needle straight out of the skin in the same direction that you inserted it.
  • Press the alcohol swab against the injection area for several seconds. Do not rub.
  • Throw away the vial with any remaining medicine in it. It does not have a preservative and will not keep until the next day.

For patients using disposable syringes:

• Manufacturers of disposable syringes recommend that they be used only once, because the sterility of a reused syringe cannot be guaranteed. The syringe should be thrown away safely. It should not be used even once if the needle is bent or has come into contact with any surface other than the cleaned, swabbed area of the skin. Do not wipe the needle with alcohol.
• Used syringes and needles should be destroyed. Be careful when you recap, bend, or break a needle, because these actions increase the chances of a needle-stick injury. It is best to put used syringes and needles in a disposable container that is puncture-resistant (such as an empty plastic liquid laundry detergent or bleach bottle) or to use a needle-clipping device. The chance of a syringe being reused by someone else is lower if the plunger is taken out of the barrel and broken in half when you dispose of a syringe.

Use this medicine only as directed by your doctor. Do not use more or less of it, and do not use it more often than your doctor ordered. The exact amount of medicine you need has been carefully worked out. Using too much may increase the chance of unwanted side effects, while using too little may not control the onset of puberty.

Many boys and girls who have central precocious puberty will not feel sick or will not understand the importance of using the medicine regularly. It is very important that the medicine is used exactly as directed and that the proper amount is used at the proper time. It works best when there is a constant amount in the blood. To help keep the amount of histrelin in the blood constant, histrelin must be given on a regular schedule.

Dosing—

The dose of histrelin 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 histrelin. If your dose is different, do not change it unless your doctor tells you to do so.

• For injection dosage form:
  • Central precocious puberty:
    • Children up to 2 years of age—Use and dose must be determined by the doctor.Children 2 years of age and older—10 micrograms (mcg) per kilogram (kg) (4.5 micrograms per pound) of body weight injected under the skin once a day and given every twenty-four hours.

Missed dose—

Check with your doctor if you miss a dose of this medicine.

Storage—

To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Store in the refrigerator. However, keep the medicine from freezing.
• Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

All scheduled visits to the doctor should be kept. This is especially important for children using the medicine for treatment of central precocious puberty as their condition improves. The child's progress still must be checked by the doctor after the medicine is no longer being used.

Tell the doctor if histrelin does not stop puberty from progressing within 6 to 8 weeks after starting treatment with histrelin . You may notice puberty progressing in your child for the first few weeks of therapy. These signs should stop within 4 weeks after your child begins treatment with histrelin.

This medicine may cause blurred vision, difficulty in reading, or other changes in vision. It may also cause some people to feel dizzy or lightheaded and impair their ability to use machines or do dangerous tasks. If these problems occur, report them to your doctor.

In the first few weeks of therapy, you may notice puberty progressing in your child, including light vaginal bleeding and breast enlargement in girls. Within 4 weeks after histrelin has had time to begin working properly, you should see signs in boys and girls that puberty is stopping.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Less common
  • Bloody mucus in nose or unexplained nosebleeds;  convulsion;  difficulty in swallowing ;  feeling of fast or irregular heartbeat;  flushing of skin;  increased blood pressure ;  itching or redness of skin;  lightheadedness;  loss of consciousness;  migraine headaches;  swelling of skin ;  trouble in breathing 
  
  

Check with your doctor as soon as possible if any of the following side effects occur:

• More common
  • Headache;  redness, swelling, and itching of skin at place of injection;  skin rash;  vaginal bleeding (for a short-term, occurring within first 3 weeks of therapy initiation);  white vaginal discharge  
  
  

• Less common
  • Anxiety;  blood in urine;  breast swelling, pain, or discharge;  brownish vaginal discharge with odor;  chills;  conduct disorder;  cough;  difficulty in seeing;  dizziness;  earache;  feeling of warmth;  frequent urge to urinate;  hair loss ;  increased sensitivity of eyes to light;  irritation or itching of vaginal area;  loss of appetite;  lower back pain;  mental depression;  nervousness;  pain in chest, legs, joints, or neck;  pain or burning while urinating;  paleness of skin;  red or purple spots on skin, varying in size from pinpoint to large bruises ;  seeing two objects instead of just one;  sore throat;  sudden sweating;  thickened patches of skin;  trembling or shaking;  unusual tiredness or weakness 
  
  

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:

• More common
  • Abdominal pain or cramping;  diarrhea ;  nausea;  vomiting 
  
  

• Less common
  • Constipation;  increased appetite;  increased thirst 
  
  

Other side effects not listed above also may occur in some patients. If you notice any other effects, check with your doctor.