Eligard

Serious side effects have been reported. See the “Drug Precautions” section.

Common side effects include:

• hot flashes
• headache
• generalized pain
• irritation or pain at the site of injection
• mood changes
• fatigue
• acne
• rash
• swelling
• vaginal bleeding or discharge, dryness, and itching
• weight gain

This is not a complete list of Eligard side effects. Ask your doctor or pharmacist for more information.

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

Before taking Eligard, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic Eligard
• have a history of seizures
• have a history of brain trauma or injury
• have a history of heart attack
• have osteoporosis
• are unable to urinate
• have anemia
• have epilepsy
• are pregnant or planning to become pregnant
• are breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take Eligard exactly as prescribed.

Eligard comes as a long-acting suspension that is injected just under the skin by a healthcare provider in a medical office or clinic and is usually given every 1, 3, 4, or 6 months.

Leuprolide injection is a synthetic (man-made) hormone that is similar to a natural hormone that is produced in the brain. It is used to treat a number of medical problems including:

• Anemia caused by bleeding from uterine leiomyomas (fibroid tumors in the uterus), or
• Cancer of the prostate that is advanced or late-stage, or
• Central precocious puberty, a condition which causes early puberty in boys (before 9 years of age) and girls (before 8 years of age), or
• Pain due to endometriosis.

When given regularly to men, leuprolide decreases testosterone levels. Reducing the amount of testosterone in the body helps treat cancer of the prostate.

When given regularly to women, leuprolide decreases estrogen levels. Reducing the amount of estrogen in the body helps treat endometriosis. Leuprolide will also shrink tumors in the uterus, which decreases vaginal bleeding and helps prevent anemia.

When given regularly to boys and girls who have early puberty, leuprolide slows the development of the genital area for both sexes. Leuprolide will also slow breast development in girls. This medicine will delay puberty only as long as the child continues to receive it.

This medicine is available only with your doctor's prescription.

As with other similar agents, the use of gloves is recommended during mixing and administration.1

Eligard® is administered subcutaneously and provides continuous release of leuprolide acetate over a one-, three-, four-, or six-month treatment period (Table 1).  The injection delivers the dose of leuprolide acetate incorporated in a polymer formulation.

Table 1. Eligard® Recommended Dosing

As with other drugs administered by subcutaneous injection, the injection site should vary periodically.  The specific injection location chosen should be an area with sufficient soft or loose subcutaneous tissue.  In clinical trials, the injection was administered in the upper- or mid-abdominal area.  Avoid areas with brawny or fibrous subcutaneous tissue or locations that could be rubbed or compressed (i.e., with a belt or clothing waistband).

2.1 Mixing Procedure

IMPORTANT:  Allow the product to reach room temperature before mixing.  Once mixed, the product must be administered within 30 minutes or it should be discarded.

Follow the detailed instructions below to ensure proper preparation of Eligard® prior to administration:
Eligard® is packaged in two thermoformed trays. Each carton contains:

• One sterile syringe (Syringe A) pre-filled with the ATRIGEL® Delivery System
• One sterile syringe (Syringe B) pre-filled with leuprolide acetate powder
• One long white plunger rod for use with Syringe B
• One sterile needle  or One sterile safety needle
• Desiccant pack(s)

1.     On a clean field, open all of the packages and remove the contents.  Discard the desiccant pack(s).

2.     Pull out the short blue plunger rod with attached gray stopper from Syringe B and discard (Figure 1).  Twist the long, white replacement plunger rod into the gray primary stopper remaining in Syringe B (Figure 2).

3.     Unscrew and discard the clear cap from Syringe A (Figure 3).  Remove and discard the gray rubber cap from Syringe B (Figure 4).

4.     Join the two syringes together by pushing and twisting until secure (Figure 5).

5.     Inject the liquid contents of Syringe A into Syringe B that contains the leuprolide acetate powder.  Thoroughly mix the product for approximately 45 seconds by pushing the contents back and forth between both syringes to obtain a uniform suspension (Figure 6). When thoroughly mixed, the suspension will appear light tan to tan (Eligard® 7.5 mg) or colorless to pale yellow (Eligard® 22.5 mg, 30 mg and 45 mg). Please Note:  Product must be mixed as described; shaking will NOT provide adequate mixing of the product.

6.     After mixing, hold the syringes vertically with Syringe B on the bottom.  The syringes should remain securely coupled.  Draw the entire mixed product into Syringe B (short, wide syringe) by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger.  Unscrew Syringe A to decouple the syringes while continuing to push down on the Syringe A plunger (Figure 7).  Note:  Small air bubbles will remain in the formulation – this is acceptable.

[Applies to Eligard® single use kit of a two syringe-mixing system with sterile needle]

7.     Hold Syringe B vertically.  Remove and discard the cap on the bottom of the sterile needle cartridge by twisting it (Figure 8).  Attach the needle cartridge to the end of Syringe B (Figure 9) by pushing in and turning the needle until it is firmly seated.  Do not overtwist the needle onto the syringe because the thread may become stripped.  Pull off the clear needle cartridge cover prior to administration (Figure 10).

[Applies to Eligard® single use kit of a two syringe-mixing system with sterile safety needle]

8.     Hold Syringe B vertically.  Open the sterile safety needle package by peeling back the paper tab and remove the safety needle (Figure 11).  Secure the needle to the end of Syringe B by holding the protective needle sheath and twisting the syringe clockwise to fully seat the needle (Figure 12).  Do not overtwist the needle onto the syringe because the thread may become stripped. Remove the protective needle sheath prior to administration (Figure 13).

2.2 Administration Procedure

IMPORTANT:  Allow the product to reach room temperature before mixing.  Once mixed, the product must be administered within 30 minutes or it should be discarded. 

1.     Choose an injection site on the abdomen, upper buttocks, or another location with adequate amounts of subcutaneous tissue that does not have excessive pigment, nodules, lesions, or hair. Since you can vary the injection site for subcutaneous injections, choose an area that hasn’t recently been used.

2.     Cleanse the injection-site area with an alcohol swab.

3.     Using the thumb and forefinger of your non-dominant hand, grab and bunch the area of skin around the injection site.

4.     Using your dominant hand, insert the needle quickly at a 90° angle to the skin surface. The depth of penetration will depend on the amount and fullness of the subcutaneous tissue and the length of the needle. After the needle is inserted, release the skin with your nondominant hand.

5.     Inject the drug using a slow, steady push.  Press down on the plunger until the syringe is empty.

6.     Withdraw the needle quickly at the same 90° angle used for insertion.

[Step 7 only applies to Eligard® single use kit of a two syringe-mixing system with sterile safety needle]

7.     Immediately following the withdrawal of the needle, activate the safety shield on the needle by using a thumb (Figure 14) or finger (Figure 15) or a flat surface (Figure 16) to push the safety shield forward until it completely covers the needle tip and locks into place.  An audible and tactile “click” verifies a locked position for the safety shield (Figure 17).

8.     Discard all components safely in an appropriate biohazard container.

Eligard® is an injectable suspension of leuprolide acetate available in a single use kit.  The kit consists of a two-syringe mixing system, a sterile needle or a sterile safety needle (Table 2), a silica gel desiccant pouch to control moisture uptake, and a package insert for constitution and administration procedures.  Each syringe is individually packaged.  One contains the ATRIGEL® Delivery System and the other contains leuprolide acetate powder.  When constituted, Eligard® is administered as a single dose.

Table 2.  Eligard® Needle Specifications

4.1 Hypersensitivity

Eligard® is contraindicated in patients with hypersensitivity to GnRH, GnRH agonist analogs or any of the components of Eligard®.  Anaphylactic reactions to synthetic GnRH or GnRH agonist analogs have been reported in the literature.

4.2 Pregnancy

Eligard® may cause fetal harm when administered to a pregnant woman. Expected hormonal changes that occur with Eligard® treatment increase the risk for pregnancy loss and fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].  Eligard® is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to the fetus.

No pharmacokinetic drug-drug interaction studies were conducted with Eligard®.

8.1  Pregnancy

Pregnancy category X.  [See ‘Contraindications’ section]

Eligard® is contraindicated in women who are or may become pregnant while receiving the drug. Expected hormonal changes that occur with Eligard® treatment increase the risk for pregnancy loss. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to the fetus and the potential risk for pregnancy loss.

In non-clinical studies in rats, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation.  There were increased fetal mortality and decreased fetal weights in rats and rabbits.  The effects of fetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug. The possibility exists that spontaneous abortion may occur.

8.3  Nursing Mothers

Eligard® is not indicated for use in women [see Indications and Usage (1)]. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Eligard®, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4  Pediatric Use

The safety and effectiveness of Eligard® in pediatric patients have not been established.

8.5  Geriatric Use

The majority of the patients (approximately 70%) studied in the clinical trials were age 70 and older.

Eligard® is a sterile polymeric matrix formulation of leuprolide acetate, a GnRH agonist, for subcutaneous injection.  It is designed to deliver leuprolide acetate at a controlled rate over a one-, three-, four- or six-month therapeutic period.

Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin releasing hormone (GnRH) that, when given continuously, inhibits pituitary gonadotropin secretion and suppresses testicular and ovarian steroidogenesis.  The analog possesses greater potency than the natural hormone.  The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt) with the following structural formula:

Eligard® is prefilled and supplied in two separate, sterile syringes whose contents are mixed immediately prior to administration.  The two syringes are joined and the single dose product is mixed until it is homogenous.  Eligard® is administered subcutaneously, where it forms a solid drug delivery depot.

One syringe contains the ATRIGEL® Delivery System and the other contains leuprolide acetate.  ATRIGEL® is a polymeric (non-gelatin containing) delivery system consisting of a biodegradable poly (DL-lactide-co-glycolide) (PLGH or PLG) polymer formulation dissolved in a biocompatible solvent, N-methyl-2-pyrrolidone (NMP).

Refer to Table 5 for the delivery system composition and constituted product formulation for each Eligard® product.

Table 5.  Eligard® Delivery System Composition and Constituted Product Formulation

Applies to leuprolide: kit, powder for solution, powder for suspension, powder for suspension 1 month, powder for suspension 3 month, powder for suspension 4 month, powder for suspension 6 month, solution

Along with its needed effects, leuprolide (the active ingredient contained in Eligard) 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 while taking leuprolide:

• Fast or irregular heartbeat

• Bone, muscle, or joint pain
• fainting
• fast or irregular breathing
• numbness or tingling of the hands or feet
• puffiness or swelling of the eyelids or around the eyes
• skin rash, hives, or itching
• sudden, severe decrease in blood pressure and collapse
• tightness in the chest
• troubled breathing

• Arm, back, or jaw pain
• bloody or cloudy urine
• blurred vision
• chest pain or discomfort
• difficult, burning, or painful urination
• difficulty with moving
• dizziness
• frequent urge to urinate
• headache
• increased urge to urinate during the night
• muscle pain or stiffness
• nausea
• nervousness
• pain in the joints
• pale skin
• pounding in the ears
• slow or fast heartbeat
• sweating
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness
• waking to urinate at night

• Pain in the groin or legs (especially in the calves)

• Altered mental status
• cardiovascular collapse
• double vision
• visual changes
• vomiting

• Anxiety
• deepening of voice
• increased hair growth
• mental depression
• mood changes

• Body pain
• burning, itching, redness, or swelling at the injection site

• Vaginal bleeding (continuing)
• white vaginal discharge (continuing)

Some side effects of leuprolide 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:

• Sudden sweating and feelings of warmth (hot flashes)

• Bleeding, bruising, burning, itching, pain, redness, or swelling at the injection site
• decreased interest in sexual intercourse
• swelling of the feet or lower legs
• swelling or increased tenderness of the breasts
• trouble sleeping
• weight gain

• Light, irregular vaginal bleeding
• stopping of menstrual periods

• Burning, dryness, or itching of the vagina
• pelvic pain

• Back pain
• chills
• constipation
• cough
• diarrhea
• fever
• general feeling of discomfort or illness
• loss of appetite
• pain or discomfort at the injection site
• redness of the face, neck, arms, and occasionally, upper chest
• runny nose
• shivering
• sore throat
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

• Decreased size of the testicles
• inability to have or keep an erection

Use is contraindicated. AU TGA pregnancy category: D US FDA pregnancy category: X Comments: -If a patient becomes pregnant during treatment, use should be discontinued. 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 the fetus. -Patients should be advised that if they miss any doses, breakthrough bleeding or ovulation may occur with the potential for conception. -This drug may cause spontaneous abortion.

Animal studies have shown reproductive toxicity. Additionally, there was increased fetal mortality and decreased fetal weights in animals. There are no controlled data in human pregnancy. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Leuprolide overstimulates the body's own production of certain hormones, which causes that production to shut down temporarily. Leuprolide reduces the amount of testosterone in men or estrogen in women.

Leuprolide is used in men to treat the symptoms of prostate cancer (but does not treat the cancer itself). Leuprolide is used in women to treat symptoms of endometriosis (overgrowth of uterine lining outside of the uterus) or uterine fibroids.

Leuprolide is also used to treat precocious (early-onset) puberty in both male and female children.

Leuprolide may also be used for purposes not listed in this medication guide.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.