Supprelin LA

• Supprelin LA^®
• Vantas^®

This section provides information on the proper use of a number of products that contain histrelin. It may not be specific to Supprelin LA. Please read with care.

A doctor or other trained health professional will give you this medicine. The histrelin implant will be placed under the skin in the inner area of the upper arm.

Your doctor will treat the upper arm with a numbing medicine (anesthetic) and then cut a small incision to insert the implant. The incision will be closed with either stitches or surgical strips. A pressure bandage will be placed over the arm and left in place for 24 hours.

Do not remove the surgical strips. Allow them to fall off on their own after several days. If the incision has been stitched, your doctor will remove the stitches or they will dissolve after several days.

After the implant is inserted, you should keep the arm clean and dry. Do not swim or bathe for 24 hours. You should avoid any heavy lifting or strenuous exercise for the first 7 days after the implant is inserted.

The implant will be left in place for one year (12 months) and then removed. If needed, your doctor will insert a new implant to continue treatment for another year.

This medicine may come with a Medication Guide and patient instructions. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

It is very important that your doctor check the progress of you or your child at regular visits to make sure the implant is in the proper place and is working properly. Blood tests may be needed to check for unwanted effects.

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

You may have some pain, redness, or bruising at the site where the implant is placed. If your arm has not healed within 2 weeks after you received the implant or if you continue to have redness or pain, call your doctor.

For children using Supprelin® LA:

• The medicine 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.
• This medicine may cause some children to be agitated, irritable, or display other abnormal behaviors. Make sure the doctor knows if your child is having trouble sleeping, gets upset easily, has a big increase in energy, or starts to act reckless. Also tell the doctor if your child has 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 this medicine may increase your child's risk of having seizures. Check with your doctor right away if your child starts to have convulsions, muscle spasm or jerking of all extremities, sudden loss of consciousness, or loss of bladder control.

For male patients:

• When you start using Vantas®, some of your symptoms might get worse for a short time. You might also have new symptoms such as bone pain, back pain, a tingling or numbness in the body, blood in the urine, or trouble urinating. The symptoms should improve in a few weeks. Tell your doctor if you have any new symptoms or your symptoms get worse.
• This medicine may cause your blood sugar level to increase. If you are diabetic and notice a change in the results of your blood or urine sugar tests, check with your doctor.
• This medicine may increase your risk of having a heart attack or stroke. Check with your doctor right away if you have chest pain or discomfort, difficulty with speaking, headache, pain or discomfort in the arms, jaw, back or neck, shortness of breath, sweating, or vomiting while using the medicine.
• Contact your doctor right away if you have any changes to your heart rhythm. You might feel dizzy or faint, or you might have a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you or anyone in your family has ever had a heart rhythm problem such as QT prolongation.

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

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 or nurse immediately if any of the following side effects occur:

• Bloody urine
• decreased frequency or amount of urine
• increased thirst
• loss of appetite
• lower back or side pain
• nausea
• swelling of the face, fingers, or lower legs
• trouble breathing
• unusual tiredness or weakness
• vomiting
• weight gain

• Bloating of the stomach
• dark urine
• discouragement
• feeling sad or empty
• irritability
• light-colored stools
• loss of interest or pleasure
• seizures
• stomach pain
• trouble concentrating
• trouble sleeping
• yellow eyes or skin

Some 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. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decrease in testicle size
• feeling of warmth
• local infection, irritation, pain, redness, or swelling on the skin where the implant was placed
• redness of the face, neck, arms, and upper chest
• sudden sweating

• Decreased interest in sexual intercourse
• difficulty having a bowel movement
• flushing or redness of the skin
• headache
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• swelling of the breast or breast soreness in both females and males
• unusually warm skin

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

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If your child's symptoms or health problems do not get better or if they become worse, call your child's doctor.
• Do not share your child's drug with others and do not give anyone else's drug to your child.
• Keep a list of all your child's drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child's doctor.
• Talk with your child's doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. If you have any questions about Supprelin LA, please talk with your child's doctor, nurse, pharmacist, or other health care provider.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Review Date: October 4, 2017

Supprelin LA is contraindicated in patients who are hypersensitive to gonadotropin releasing hormone (GnRH) or GnRH agonist analogs.

Supprelin LA is contraindicated in females who are or may become pregnant while receiving the drug. Supprelin LA may cause fetal harm when administered to pregnant patients. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. The possibility exists that spontaneous abortion may occur [see Use in Specific Populations (8.1)].

Overview: No formal drug-drug, drug-food, or drug-herb interaction studies were performed with Supprelin LA.

Drug-Laboratory Interactions: Therapy with Supprelin LA results in suppression of the pituitary-gonadal system. Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after Supprelin LA therapy may be affected. Supprelin LA decreased mean serum insulin-like growth factor-1 (IGF-1) levels by approximately 11% in one study (Study 1). Supprelin LA increased the serum concentration of dehydroepiandrosterone (DHEA) in 8 of 36 patients in another study (Study 2).

8.1 Pregnancy

Pregnancy category X [see Contraindications (4)].
SUPPRELIN LA is contraindicated in females who are, or may become, pregnant while receiving the drug. Supprelin LA can cause fetal harm when administered to a pregnant patient. The possibility exists that spontaneous abortion may occur.

Animal Data: Major fetal abnormalities were observed in rabbits at 3 times human therapeutic exposure but not in rats after administration of histrelin acetate throughout gestation. There was dose-related increased fetal mortality during organogenesis in both rats given 1, 3, 5 or 15 mcg/kg/day (at less than therapeutic exposures using body surface area comparisons, based on a 65 mcg per day human dose) and in rabbits at 20, 50 or 80 mcg/kg/day (at 3 times human exposure using body surface area comparisons, based on a 65 mcg/day dose in humans).

8.4 Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years have not been established. The use of Supprelin LA in children under 2 years is not recommended.

SUPPRELIN LA is a sterile, non-biodegradable, diffusion-controlled, hydrogel polymer reservoir containing histrelin acetate, a synthetic nonapeptide analog of the naturally occurring gonadotropin releasing hormone (GnRH) possessing a greater potency than the natural sequence hormone. Supprelin LA is designed to deliver approximately 65 mcg histrelin acetate per day over 12 months.

The Supprelin LA implant looks like a small thin flexible tube and consists of a 50-mg histrelin acetate drug core inside a 3.5 cm by 3 mm, cylindrical, hydrogel polymer reservoir (Figure 1). The implant may appear partially to completely full with variation in color from off-white to light brown. The color may be uneven within the core.

Figure 1. Supprelin LA Implant Diagram (not to scale)

The chemical name of histrelin acetate is: L-Pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-N-benzyl-D-histidyl-L-leucyl-L-arginyl-L-proline N-ethylamide, acetate salt.

The molecular formula for histrelin acetate is C66H86N18O12 x 2 CH3COOH and its molecular weight is 1443.70 (or 1323.52 as free base). Histrelin is also chemically described as 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-Nt-benzyl-D-histidyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide diacetate. The chemical structure of the free base (histrelin) is represented below in Figure 2.

 Figure 2. Structure of Histrelin

The drug core also contains the inactive ingredient stearic acid NF. The hydrogel polymer reservoir is a hydrophilic cartridge composed of 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, trimethylolpropane trimethacrylate, benzoin methyl ether, Perkadox-16, and Triton X-100. Each implant is packaged hydrated in a glass vial containing 2 mL of sterile 1.8% sodium chloride solution, so that it is primed for immediate release of the drug upon insertion.

A single use, sterile, Insertion Tool is provided along with the implant that can be used for the placement of the Supprelin LA implant into the subcutaneous tissue of the inner aspect of the upper arm. The Insertion Tool is enclosed in a sterile bag and is provided separately from the implant in the Implantation Kit [see Recommended Procedure for Implant Insertion and Removal (2.2)].

Supprelin LA (NDC 67979-002-01) is supplied in a corrugated shipping carton that contains 2 inner cartons: a small one for the vial containing the Supprelin LA implant, which is shipped with a cold pack inside a polystyrene cooler that must be refrigerated upon arrival, and a larger one comprising the Implantation Kit, which must not be refrigerated, for use during insertion or removal of Supprelin LA.

The Supprelin LA implant contains 50 mg of histrelin acetate. The Supprelin LA implant carton contains a cold pack for refrigerated shipment and a small carton containing an amber plastic pouch. Inside the pouch is a glass vial with a Teflon-coated stopper and an aluminum seal, containing the implant in 2 mL of sterile 1.8% sodium chloride solution. (Note:  the 3.5 mL vial is not completely filled with saline). 

Upon receipt, refrigerate the small carton containing the amber plastic pouch and glass vial (with the implant inside) until the day of insertion. The implant vial should not be opened until just before the time of insertion.

SUPPRELIN LA is stable when stored refrigerated, in its sealed vial, pouch, and carton, at 2-8 °C (36-46 °F) until the expiration date provided. Excursion permitted to 25 °C (77 °F) for 7 days. Do not freeze. Protect from light.